Development of recurrent pressure ulcers, risk factors in older patients: a prospective observational study.

OBJECTIVE: Prevention of recurrent pressure ulcers (PU) is one of the most important challenges in wound care, furthermore, the risk factors for recurrent PUs are still not fully understood. This study aimed to explore the risk factors for recurrent PU development within two weeks, including biophysical skin properties, pro-inflammatory cytokine (tumour necrosis factor [TNF]-α) levels and bacterial species, in older patients. METHOD: This prospective study was conducted in a long-term care facility with patients whose PU had healed within two months. Biophysical skin properties were evaluated by stratum corneum hydration, pH, sebum content and transepidermal water loss. TNF-α level was measured using skin blotting. Skin bacteria were collected using tape stripping and determined by species-specific gene amplification. These parameters, along with Braden scale and interface pressure, were evaluated every two weeks for a total period of eight weeks. A penalised generalised estimating equation analysis was used to determine the risk factors for recurrent PUs. RESULTS: In total, 20 patients were included in this study, with 57 observations. Of these, recurrent PU was seen in eight observations. Elevation of pH (p=0.049; odds ratio [OR] per 1 unit=3.91, 95% confidence interval [CI]:1.01-15.15), presence of Acinetobacter spp. (p=0.039; OR versus culture-negative=6.28, 95%CI:1.10-35.86) and higher interface pressure (p=0.008; OR per 1 mmHg=1.06, 95%CI:1.01-1.10) on the healed PU were significantly related to the development of recurrent PU. CONCLUSION: Higher pH, existence of Acinetobacter spp. and higher interface pressure on the site of the healed PU were associated with the development of recurrent PUs in older patients undergoing conservative treatments.

Comparison of wiping methods for the removal of cleaning agent residue from hair follicles.

PURPOSE: This study aimed to clarify the influence of different wiping methods on cleaning agent residue in hair follicles when using skin cleaning agents that are "removable-by-wiping." METHODS: A total of 18 male volunteers were recruited and a cleaning agent containing 10% fluorescein sodium salt (cleaning agent) was used in this study. After gentle washing, the cleaning agent was removed via the washing method (control) or three distinct wiping methods (experiment). Hairs were obtained from the measurement area. The fluorescence intensities of the residual cleaning agent on the hair root and hair bulb were then evaluated after normalizing for autofluorescence from the hair. Fluorescence intensity was used to estimate the amount of cleaning agent residue. RESULTS: No significant differences were found among cleaning agent removal methods (hair root: P = 0.67, hair bulb: P = 0.62) with respect to the amount of residual cleaning agent on hair. CONCLUSION: Cleaning agent residual index did not differ according to removal method. Cleaning agent remained in the hair follicle (hair roots, hair bulbs) despite removal from the skin by washing or wiping. Further studies are required to apply "removable-by-wiping" cleaning agents for people with vulnerable skin.

Comparison of ceramide retention in the stratum corneum between dry skin and normal skin using animal model with fluorescent imaging method.

BACKGROUND/PURPOSE: Skin care via moisturization compensates for the lack of skin barrier function. However, moisturizer application methods are not clearly decided. Here, we focused on and examined the retention of externally applied ceramide in the stratum corneum (SC) using fluorescent imaging method. This study aimed to compare ceramide retention in the SC between normal skin and dry skin using an animal model. METHODS: Nine-week-old Sprague-Dawley rats were divided into two groups: normal skin and dry skin model. The dry skin model group was treated with acetone-diethyl ether solution. A fluorescently labeled ceramide solution was prepared and applied to rats' back skin. Skin samples were taken at 0 minute and 12 hours after ceramide application. Fluorescently labeled ceramide was evaluated and observed under a microscope. RESULTS: The intensity of externally applied ceramide in the normal skin group showed no significant change from 0 minute to 12 hours after application. In contrast, in the dry skin model group, the intensity of externally applied ceramide increased significantly from 0 minute to 12 hours after application. CONCLUSION: Our findings demonstrate that the externally applied ceramide penetrated the SC of dry skin more than that of normal skin.

Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair.

Serotonin 2C receptors (5-HT2 C Rs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5-HT2 C R mRNA undergoes adenosine-to-inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non-edited 5-HT2 C R INI-isoform (INI) or the fully edited VGV-isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety-like behaviour, and depression-like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno-associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5-HT2 C R RNA editing, and its impairment may be linked to mood disorders.

Effectiveness of Three Types of Moisturizers on Senile Dry Skin: A Randomized Controlled Pilot Trial.

Background: For dry skin, the application of a hypoallergenic moisturizer twice daily is recommended in elderly individuals. However, it is not known which is the most effective and appropriate moisturizer among the commercially available moisturizers. Aims: In this study, we aimed to investigate the efficacy of the three widely used moisturizers for the treatment of senile dry skin. Patients/Methods. This interventional study involved elderly individuals aged >65 years who were living in a nursing home. The participants were randomly divided into the interventional (moisturizers A, B, and C) and conventional care groups. Moisturizers A, B, and C were applied on the skin of each member of the three intervention groups twice daily for 8 weeks. The water content of the stratum corneum and transepidermal water loss (TEWL) were evaluated before and after the intervention. Changes in these parameters among the groups were compared using two-way analysis of variance and a posthoc test. Results: Moisturizers A, B, and C and conventional care groups comprised six, seven, five, and four participants, respectively. The water content of the stratum corneum was significantly higher in the moisturizer A (p = 0.01) and B (p = 0.047) groups than in the conventional care group. There was no significant difference in TEWL among the groups. Conclusions: In terms of the appearance of the skin, white powder and small scales were both reduced in group A. Taken together with the water content, this was considered a clinically significant change.

Stability of Skin Microbiome at Sacral Regions of Healthy Young Adults, Ambulatory Older Adults, and Bedridden Older Patients After 2 Years.

OBJECTIVE: The sacral skin of bedridden older patients often develops a dysbiotic condition. To clarify whether the condition changes or is sustained over time, we analyzed the skin microbiome and the skin physiological functions of the sacral skin in patients who completed our 2017 study. METHODS: In 2019, we collected the microbiome on the sacral region and measured sacral skin hydration, pH, and transepidermal water loss from 7 healthy young adults, 10 ambulatory older adults, and 8 bedridden older patients, all of whom had been recruited for the 2017 study. For microbiome analysis, 16S ribosomal RNA-based metagenomic analysis was used. RESULTS: No significant differences in the microbial compositions or any alpha diversity metrics were found in the bedridden older patients between the 2017 and 2019 studies; the higher gut-related bacteria were still observed on the sacral skin of the bedridden older patients even after 2 years. Only skin pH showed a significant decrease, approaching normal skin condition, in the bedridden older patients over 2 years. CONCLUSION: This study indicated that gut-related bacteria stably resided in the sacral skin in bedridden patients, even if the patient had tried to restore skin physiological functions using daily skin care. We propose the importance of skin care that focuses more on bacterial decontamination for the sacral region of bedridden older patients, in order to decrease the chances of skin/wound infection and inflammation.

Skin Physiology and its Microbiome as Factors Associated with the Recurrence of Pressure Injuries.

BACKGROUND: Preventing recurrent pressure injuries (RPIs) is one of the important challenges faced in healthcare, but the risk factors of RPIs have not been fully revealed. This study aims to explore factors associated with RPIs, by focusing on skin physiology and its microbiome as local factors crucial for the health of healed tissue after pressure injury healing. METHODS: This prospective observational study was conducted in a long-term care facility in Japan with patients whose PIs had healed within 1 month. Skin physiology was evaluated by stratum corneum (SC) hydration, pH, and transepidermal water loss. Skin bacteria was collected by tape stripping, followed by 16S ribosomal RNA-based metagenomics analysis. These parameters were evaluated every two weeks over a period of six weeks. RESULTS: A total of 30 patients were included in this study, and 8 patients (26.7%) had an RPI within 6 weeks. In this study, significantly lower SC hydration and a higher rate of Staphylococcus species on the healed site were found in the RPI group. DISCUSSION: A high rate of RPIs (about one in four) points out the necessity of a further care strategy on the healed PIs. Lower skin hydration and/or the increase in Staphylococcus bacteria may have a potential to be used as a biomarker for the prediction of RPIs, or may be an intervention point for the prevention of RPIs by, for example, skin cleansing with moisturizing care.

Distinct Skin Microbiome and Skin Physiological Functions Between Bedridden Older Patients and Healthy People: A Single-Center Study in Japan.

With the increase in the older populations, the number of bedridden older patients is becoming a matter of concern. Skin microbiome and skin physiological functions are known to change according to lifestyle and community; however, such changes in case of movement- and cleaning-restricted bedridden older patients have not yet been revealed. To address this issue, we analyzed skin microbiome and skin physiological functions, including pH, hydration, sebum level, and transepidermal water loss (TEWL), of bedridden older patients, compared with those of ambulatory older and young individuals. For this analysis, we enrolled 19 healthy young and 18 ambulatory older individuals from the community and 31 bedridden older patients from a single, long-term care hospital in Japan. The area of interest was set to the sacral (lower back) skin, where pressure injuries (PIs) and subsequent infection frequently occurs in bedridden older patients. We observed a higher number of gut-related bacteria, fewer commensals, higher skin pH, and lower TEWL on the sacral skin of bedridden older patients than on that of young or ambulatory older individuals. In addition, we observed that 4 of the 31 bedridden older patients developed PIs during the research period; a higher abundance of pathogenic skin bacteria were also observed inside the PI wounds. These findings imply distinct skin microbiome and skin physiological functions in bedridden older patients in comparison with healthy individuals and may suggest the need for more stringent cleaning of the skin of bedridden older patients in light of the closeness of skin and wound microbiome.

Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene.

The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR)-arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR-Tango system. This novel tool is useful for in vitro high-throughput targeted 5-HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models.

Increased alcohol consumption in relaxin-3 deficient male mice.

Relaxin-3 is a neuropeptide expressed in the brainstem, and predominantly localized in the gray matter of the midline dorsal pons termed the nucleus incertus. Relaxin-3-expressing neurons densely project axons rostrally to various forebrain regions including the septum, hippocampus, and lateral hypothalamus. Several relaxin-3 functions have been reported including food intake, stress responses, neuroendocrine function, emotion, and spatial memory. In addition, recently relaxin-3 and its receptor, RXFP3, were shown to regulate alcohol intake using an RXFP3 antagonist and RXFP3 gene knockout mice. In the present study, we investigated alcohol consumption in relaxin-3 knockout mice, and found that male but not female mice significantly drank more alcohol than wild-type mice in the two-bottle choice test. However, after chronic alcohol vapor exposure, wild-type and mutant mice did not show this difference in alcohol intake, although both genotypes exhibited increased alcohol consumption compared with non-alcohol-exposed control mice. There was no genotype difference in sucrose or quinine preference. These results suggest that the relaxin-3 neuronal system modestly affects alcohol preference and consumption.

Behavioral analysis of relaxin-3 deficient mice.

Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral tests of sensory/motor functions and emotion-related behaviors. Relaxin-3 KO mice exhibited normal growth and appearance. There was no difference in bodyweight among genotypes in both normal and high fat diet feeding. In addition, there were no significant differences between wild-type and KO mice in social interaction, depression-like behavior, and short memory test. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the open field test. Taken together, these results indicate that relaxin-3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior.