I Sms Skin E63 By Ichiki Zip
Harriet Wehrenberg
Purpose: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash.
Ichiki has a vibrant purple haircolor, complemented by a spiky ponytail style on the back, and a gray and orange earpiece. With his hair down, it goes down to his shoulder height. Ichiki has white skin and dark blue eyes. His orange and gray jacket has decoration resembling speakers on the shoulders, as well as red cords coming from the sides, leading some to think that they might actually be speakers. He also wears a white shirt with an orange star in the middle, and a blue collar. For the bottom, he wears white jeans and blue shoes. Ichiki's preferred look is very colorful, which comes off as a surprise when people learn that a Septagunner's signature color is gray.
Epidermal ceramides are indispensable lipids that maintain the functions of the stratum corneum. Esterified omega-hydroxyacyl-sphingosine (EOS) ceramide with a linoleate moiety is one of the most important ceramide species for forming cornified lipid envelopes. This linoleate moiety is eventually metabolized to trihydroxy-linoleic acid (triol, 9,10,13-trihydroxy-11E-octadecenoic acid). Thus, we assumed that a decrease of triols might reflect skin barrier dysfunction. Against this background, the purposes of this study were to measure the triols by a simple tape-stripping method and to determine the correlation between the amount of triols and transepidermal water loss (TEWL) as an indicator of barrier dysfunction in atopic dermatitis patients. Twenty Japanese subjects with normal skin and 20 atopic dermatitis patients were enrolled in this study. TEWL was measured and triols of the stratum corneum were analyzed by tape-stripping. The results showed for the first time that triols in the stratum corneum could be simply measured using the tape-stripping method. The triol levels in atopic dermatitis patients were much higher than those in healthy subjects. Moreover, the triol levels correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis. The results suggest that the assaying of triol levels via non-invasive tape-stripping could be beneficial for monitoring barrier function in atopic dermatitis.
The barrier function of the skin is mainly provided by the stratum corneum. Although individual corneocytes in the stratum corneum act as a major structure forming a physical barrier, extracellular lamellar lipids (ECLLs) containing abundant ceramides also play an important role in the barrier structure [1]. These are often described as brick (corneocytes) and mortar (ECLLs) structures. There is also a single thin layer between corneocytes (crosslinked protein) and ECLLs, which can be observed using an electron microscope, called the corneocyte lipid envelope (CLE); this is considered to be an integral component for combining the corneocyte envelope with ECLLs [1, 2] (Fig 1a). Thus, insufficiency of CLE formation induces skin symptoms and increased transepidermal water loss (TEWL) since an appropriate stratum corneum cannot be constructed [3, 4].
Accordingly, the objectives of the current study were: i) to develop a simple and practical method for measuring trihydroxy-linoleic acid using stripped tape specimens; ii) to compare the amount of trihydroxy-linoleic acid between healthy subjects and atopic dermatitis patients, with the latter representing CLE construction failure and skin barrier impairment; and iii) to determine the correlation of the amount of trihydroxy-linoleic acid with barrier function (TEWL).
(a) Analysis of a mixture of authentic triols-1 to -8 (2 ng) as a standard, (b) triols of forehead skin in normal subjects and (c) atopic dermatitis patients, and (d) triols of forearm skin in normal subjects and (e) atopic dermatitis patients.
As shown in Table 1, the mean TEWL in normal subjects was 32.9 20.0 g/m2h in forehead and 12.6 6.9 g/m2h in forearm. In contrast, the mean values for non-lesional skin in atopic dermatitis patients were 49.2 35.5 g/m2h in forehead and 20.6 13.4 g/m2h in forearm; this is indicative of the impairment of skin barrier function, as also described in a previous report [26, 27]. SCORAD also correlated with serum markers of atopic dermatitis, however, the values of TEWL and SCORAD were not necessarily correlated in our study (S3 Table). The mean concentrations of total trihydroxy-linoleic acids in normal subjects were 0.75 0.74 pg/cm2 in forehead skin and 0.26 0.16 pg/cm2 in forearm skin. In the atopic dermatitis group, the corresponding values were 2.08 3.43 and 1.03 2.28 pg/cm2, respectively. Next, we corrected the trihydroxy-linoleic acid amount with the protein amount of corneum. The mean concentrations of total trihydroxy-linoleic acids in normal subjects were calculated as 6 5 pg/μg protein in forehead skin and 4 4 pg/μg protein in forearm skin. In the atopic dermatitis group, the corresponding values were 15 22 and 37 58 pg/μg protein, respectively.
We confirmed that TEWL and the amount of trihydroxy-linoleic acids were increased in atopic dermatitis patients; therefore, we next examined the correlation between them. In forehead skin, TEWL had no correlation with the amount of trihydroxy-linoleic acids (Fig 3a). On the other hand, TEWL in forearm skin was positively correlated with the amount of trihydroxy-linoleic acids (R2 = 0.47, p < 0.01; Fig 3b). We also analyzed the correlations of clinical laboratory data such as IgE, peripheral eosinophil count, TARC, LDH, and SCORAD with the amount of trihydroxy-linoleic acids in the atopic dermatitis group, but found no significant results (S4 Table).
Moreover, in atopic dermatitis patients who have impaired skin barrier function, ceramide levels are altered. Several mechanisms have been suggested to contribute to the decrease in ceramide content in such cases. For example, an increase of kallikrein activity in atopic dermatitis suppresses ceramide-generating enzymes such as acidic sphingomyelinase and β-glucocerebrosidase [31]. In addition, the upregulation of interferon gamma expression in atopic dermatitis downregulates the epidermal synthesis of ceramides [32]. Namely, the percentage and amount of ceramide EOS as a source of triols were decreased in non-lesional skin of atopic dermatitis patients [33].
Intriguingly, trihydroxy-linoleic acid levels were positively correlated with TEWL of non-lesional forearm skin in patients with atopic dermatitis (R2 = 0.47, p < 0.01). Although these triols may reflect inefficient metabolization, the biological action of trihydroxy-linoleic acid for skin barrier function is still unknown. An increase of trihydroxy linoleic acid might be possible to downregulate ceramide EOS synthesis. On the other hand, TEWL of non-lesional forehead skin had a low correlation with triols. This may have been because the amount of triols was lower than that of forearm or due to another anatomical difference associated with this site [34]. In healthy subjects, such correlation was not observed in both forehead and forearm skin.
Respiratory-swallowing coordination is critical for safely and efficiently transporting foods and liquids from the mouth into the esophagus. In healthy adults, the timing of swallow initiation typically corresponds with a pause in the expiratory phase of quiet breathing at mid-to-low lung volumes7,8,10,11,12. This coordinative pattern (1) serves as a vital mechanism for airway protection, (2) facilitates physiological events beneficial to swallowing safety and efficiency, such as tongue base retraction, laryngeal elevation, and pharyngoesophageal segment opening, and (3) subsequently aids in bolus clearance13,14,15. However, it is well-documented that the coordination of breathing with swallowing is significantly disrupted in patients with dysphagia, resulting in impairments in the swallowing mechanism and significant decreases in health and quality of life. Traditional swallowing interventions typically use a single-system approach, focusing on increasing the strength and range of motion of oral, pharyngeal, and laryngeal structures1,16. Current methods enable detection of swallowing events and respiratory phase with piezoresistive/surface electromyography sensors mounted on the neck, but they rely on wired hardware that cannot be easily adapted for use in home settings or during natural daily activities without patient burden17. As such, despite demonstrated positive outcomes of these schemes, most patients continue living with swallowing impairments. More recently, a novel intervention that trains patients with dysphagia to initiate swallowing during the expiratory phase of the breathing cycle has shown to decrease aspiration and improve swallowing biomechanics in some patient populations18. However, three significant methodologic challenges exist in the rehabilitation of swallowing function: (1) the ability to unambiguously detect the occurrence of swallowing and swallowing coordinated with breathing without the use of expensive, non-portable imaging and respiratory recording equipment; (2) the ability to ensure the fidelity of the swallowing intervention and provide visual cueing to enhance performance in real-time, and (3) the ability to facilitate stability of the acquired swallowing skills through ambulatory monitoring and cueing. The work presented here addresses these challenges with a device technology that captures subtle and gross motions at the surface of the skin using soft, miniaturized wireless sensors mounted near the base of the neck.
This paper summarizes a sensor and a corresponding set of analysis algorithms specially designed to support simultaneous, real-time monitoring of swallowing and breathing behaviors for patients with dysphagia. Specifically, the device monitors movements captured from the surface of the skin at two distinct locations on the neck and adjacent regions (SN/SM or SN/LP) to capture both swallow and respiratory phase signatures, applicable across a wide range of individuals, including patients with dysphagia. A differential sensing mode allows for reliable operation even during natural daily activities. A real-time graphical user interface and an optional haptic module support visual and haptic feedback, respectively. Benchtop and pilot studies on healthy subjects and patients with PD highlight key features of the devices and their potential for broad utility in clinical research and at-home settings to guide the treatment of patients with dysphagia. Simple algorithms for identifying swallowing events and corresponding respiratory phase offer excellent performance with modest computational load, thereby allowing for reliable, real-time analysis on portable electronic devices. Developing advanced approaches based on machine learning represents an area of current work. This technology platform has strong potential for the treatment and care of patients suffering from dysphagia, directly through its use in improved training protocols and indirectly through its use in studies of swallow dynamics.
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