-
Frontiers in Microbiology 2023The bacterial communities of the human skin impact its physiology and homeostasis, hence elucidating the composition and structure of the healthy skin bacteriome is...
The bacterial communities of the human skin impact its physiology and homeostasis, hence elucidating the composition and structure of the healthy skin bacteriome is paramount to understand how bacterial imbalance (i.e., dysbiosis) may lead to disease. To obtain an integrated view of the spatial diversity of the skin bacteriome, we surveyed from 2019 to 2023 five skin regions (belly button, behind ears, between toes, calves and forearms) with different physiological characteristics (dry, moist and sebaceous) in 129 healthy adults (579 samples - after data cleaning). Estimating bacterial diversity through 16S rRNA metataxonomics, we identified significant ( < 0.0001) differences in the bacterial relative abundance of the four most abundant phyla and 11 genera, alpha- and beta-diversity indices and predicted functional profiles (36 to 400 metabolic pathways) across skin regions and microenvironments. No significant differences, however, were observed across genders, ages, and ethnicities. As previously suggested, dry skin regions (forearms and calves) were more even, richer, and functionally distinct than sebaceous (behind ears) and moist (belly button and between toes) regions. Within skin regions, bacterial alpha- and beta-diversity also varied significantly for some of the years compared, suggesting that skin bacterial stability may be region and subject dependent. Our results, hence, confirm that the skin bacteriome varies systematically across skin regions and microenvironments and provides new insights into the internal and external factors driving bacterial diversity.
PubMed: 37795302
DOI: 10.3389/fmicb.2023.1257276 -
The Journal of Allergy and Clinical... Aug 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
OBJECTIVE
This study aimed to identify historical and clinical features and biomarkers associated with AD severity.
METHODS
A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity.
RESULTS
Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001).
CONCLUSIONS
In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.
Topics: Humans; Dermatitis, Atopic; Ectropion; Respiratory Sounds; Phenotype; Biomarkers; Allergens; Conjunctivitis; Immunoglobulin E; Blepharitis; Severity of Illness Index
PubMed: 37182563
DOI: 10.1016/j.jaip.2023.04.052 -
The Oncologist Jul 2023Alpelisib is a specific oral PI3K inhibitor used combined with fulvestrant for the treatment of patients with HR+/HER2-/PIK3CA-mutated metastatic breast cancer. Adverse...
Alpelisib is a specific oral PI3K inhibitor used combined with fulvestrant for the treatment of patients with HR+/HER2-/PIK3CA-mutated metastatic breast cancer. Adverse drug reactions with alpelisib are common, including hyperglycemia and rash. Here we describe extraordinary and life-threatening reactions beyond skin rash in two patients with progressive PIK3CA-mutated metastatic cancer in whom alpelisib was initiated. Case-A (vaginal cancer): After 10 days on treatment, she developed dry eyes, generalized rash and itching. Alpelisib was interrupted and symptomatic treatment initiated. Because of an initial tumor response, a rechallenge was done. Ninety minutes after a reduced dose of alpelisib, she developed an anaphylactic reaction with angioedema, hypotension, and skin rash. Case-B (breast cancer): After 11 days on treatment, she developed skin rash and alpelisib was interrupted. At re-initiation, she felt tingles in her face and ears and some skin erythema. Given the mild rash, a second rechallenge with premedication was performed. Ninety minutes after a reduced dose of alpelisib, she developed a type-1 allergic reaction with angioedema, tingles, and skin rash. In both cases, a type-1 allergic reaction was diagnosed and symptomatic treatment was initiated, alpelisib was permanently discontinued and the patients fully recovered the next week(s). This report underlines the critical importance to consider type-I allergic reactions in the differential diagnosis in cases of rash associated with alpelisib. Even if a reaction develops after days on treatment, a type-I allergic reaction cannot be excluded. A rechallenge can be dangerous and should always be well contemplated or even avoided.
Topics: Female; Humans; Receptor, ErbB-2; Anaphylaxis; Phosphatidylinositol 3-Kinases; Breast Neoplasms; Exanthema; Class I Phosphatidylinositol 3-Kinases; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37086483
DOI: 10.1093/oncolo/oyad092 -
Progress in Lipid Research Jan 2024The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a... (Review)
Review
The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters. The balance of these skin surface lipids in terms of their relative abundance, composition, molecular organisation and dynamics, and their intricate interactions play a crucial role in the maintenance of healthy skin. For that reason, even minuscule alterations in skin surface lipid properties or overall lipid profile have been implicated in the aetiology of many common skin diseases including atopic dermatitis, psoriasis, xerosis, ichthyosis and acne. Novel lipid-based interventions aimed at correcting the skin surface lipid abnormalities have the potential to repair skin barrier integrity and the symptoms associated with such skin diseases, even though the exact mechanisms of lipid restoration remain elusive.
Topics: Humans; Lipids; Skin; Epidermis; Skin Diseases; Cholesterol; Ceramides; Fatty Acids
PubMed: 37940006
DOI: 10.1016/j.plipres.2023.101264 -
Deutsches Arzteblatt International Oct 2023Hydration disturbances are common in old age: the reported prevalence of dehydration in elderly patients ranges from 19% to 89%, depending on the definition and the... (Review)
Review
BACKGROUND
Hydration disturbances are common in old age: the reported prevalence of dehydration in elderly patients ranges from 19% to 89%, depending on the definition and the population in question. However, the clinical assessment of patients' hydration status is difficult. In this review, we discuss the diagnostic value of currently used methods that may or may not be suitable for assessing older patients' hydration status.
METHODS
We conducted a selective literature search for relevant studies concerning patients aged 65 and above. Of the 355 articles retrieved by the initial search, a multistep selection process yielded 30 that were suitable for inclusion in this review.
RESULTS
107 different methods for the diagnostic assessment of dehydration in older persons were evaluated on the basis of the reviewed publications. High diagnostic value, especially for the determination of hyperosmolar dehydration, was found for serum osmolality, serum sodium concentration, inferior vena cava ultrasonography, a history (from the patient or another informant) of not drinking between meals, and axillary dryness. On the other hand, a variety of clinical signs such as a positive skin turgor test, sunken eyes, dry mouth, tachycardia, orthostatic dysregulation, and dark urine were found to be of inadequate diagnostic value.
CONCLUSION
Only five of the 107 methods considered appear to be suitable for determining that a patient is dehydrated. Thus, the available scientific evidence indicates that all clinicians should critically reconsider their own techniques for assessing hydration status in elderly patients. To optimize the clinical assessment of patients' hydration status, there seems to be a need for the rejection of unsuitable methods in favor of either newly developed criteria or of a combination of the best criteria already in use.
Topics: Aged; Humans; Aged, 80 and over; Dehydration; Osmolar Concentration
PubMed: 37583084
DOI: 10.3238/arztebl.m2023.0182 -
Dermatology Practical & Conceptual Oct 2023Atopic dermatitis (AD) causes dry and itchy skin and inflammation that severely impairs the quality of life of affected children and adults. While topical... (Review)
Review
INTRODUCTION
Atopic dermatitis (AD) causes dry and itchy skin and inflammation that severely impairs the quality of life of affected children and adults. While topical glucocorticosteroid application is typically the first-line treatment of choice, steroid treatment is associated with side effects and, increasingly, patient concerns about prolonged use. Novel drugs and drug delivery vehicles are required for patients with AD.
OBJECTIVES
To summarize the current literature on novel topical agents for atopic dermatitis and novel delivery vehicles.
METHODS
A literature search was conducted, and a narrative review was compiled to summarize recent evidence.
RESULTS
Novel topical drugs approved or in late-phase clinical trials for the treatment of AD include the Janus kinase inhibitor ruxolitinib, the phosphodiesterase-4 inhibitors crisaborole, and roflumilast, and the aryl hydrocarbon receptor activator tapinarof. While current topical drugs for AD are delivered via creams, ointments, gels, and related vehicles, novel delivery approaches such as electrospun patches, sprays, liposomes, nanoparticles, and lasers are being developed to enhance transdermal delivery, reduce side effects, and increase treatment adherence.
CONCLUSIONS
Topical application of creams or ointments is currently the predominant vehicle for the delivery of atopic dermatitis drugs. In vitro studies on novel vehicles show promising results to overcome the issues associated with topical delivery. Still, these findings have to be corroborated by controlled studies with human patients in the future.
PubMed: 37992345
DOI: 10.5826/dpc.1304a216 -
Sensors (Basel, Switzerland) Dec 2023Evaluations of new dry, high-density EEG caps have only been performed so far with serial measurements and not with simultaneous (parallel) measurements. For a first...
Evaluations of new dry, high-density EEG caps have only been performed so far with serial measurements and not with simultaneous (parallel) measurements. For a first comparison of gel-based and dry electrode performance in simultaneous high-density EEG measurements, we developed a new EEG cap comprising 64 gel-based and 64 dry electrodes and performed simultaneous measurements on ten volunteers. We analyzed electrode-skin impedances, resting state EEG, triggered eye blinks, and visual evoked potentials (VEPs). To overcome the issue of different electrode positions in the comparison of simultaneous measurements, we performed spatial frequency analysis of the simultaneously measured EEGs using spatial harmonic analysis (SPHARA). The impedances were 516 ± 429 kOhm (mean ± std) for the dry electrodes and 14 ± 8 kOhm for the gel-based electrodes. For the dry EEG electrodes, we obtained a channel reliability of 77%. We observed no differences between dry and gel-based recordings for the alpha peak frequency and the alpha power amplitude, as well as for the VEP peak amplitudes and latencies. For the VEP, the RMSD and the correlation coefficient between the gel-based and dry recordings were 1.7 ± 0.7 μV and 0.97 ± 0.03, respectively. We observed no differences in the cumulative power distributions of the spatial frequency components for the N75 and P100 VEP peaks. The differences for the N145 VEP peak were attributed to the different noise characteristics of gel-based and dry recordings. In conclusion, we provide evidence for the equivalence of simultaneous dry and gel-based high-density EEG measurements.
Topics: Humans; Evoked Potentials, Visual; Reproducibility of Results; Electroencephalography; Electrodes; Electric Impedance
PubMed: 38139591
DOI: 10.3390/s23249745 -
Frontiers in Toxicology 2023Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical... (Review)
Review
Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.
PubMed: 37547228
DOI: 10.3389/ftox.2023.1067942 -
Journal of Medical Genetics Jul 2023Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter...
BACKGROUND
Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk.
METHODS
Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers.
RESULTS
We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants around (7 065 298-7 272 682 bp in GRCh37/hg19 genome build) in males, and of common GI disorder and asthma/anaemia risk variants around (7 866 804-7 895 780 bp) in males and females, respectively. Deletion carriers were overwhelmingly in favour of cardiac screening implementation.
CONCLUSION
Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Topics: Humans; Male; Female; Ichthyosis, X-Linked; Heterozygote; Surveys and Questionnaires; Heart Defects, Congenital; Heart
PubMed: 36379544
DOI: 10.1136/jmg-2022-108862