Language-to-music transfer effects depend on the tone language: Akan vs. East Asian tone languages.

Recent research suggests that speaking a tone language confers benefits in processing pitch in nonlinguistic contexts such as music. This research largely compares speakers of nontone European languages (English, French) with speakers of tone languages in East Asia (Mandarin, Cantonese, Vietnamese, Thai). However, tone languages exist on multiple continents-notably, languages indigenous to Africa and the Americas. With one exception (Bradley, Psychomusicology, 26(4), 337-345, 2016), no research has assessed whether these tone languages also confer pitch processing advantages. Two studies presented a melody change detection task, using quasirandom note sequences drawn from Western major scale tone probabilities. Listeners were speakers of Akan, a tone language of Ghana, plus speakers from previously tested populations (nontone language speakers and East Asian tone language speakers). In both cases, East Asian tone language speakers showed the strongest musical pitch processing, but Akan speakers did not exceed nontone speakers, despite comparable or better instrument change detection. Results suggest more nuanced effects of tone languages on pitch processing. Greater numbers of tones, presence of contour tones in a language's tone inventory, or possibly greater functional load of tone may be more likely to confer pitch processing benefits than mere presence of tone contrasts.

Why Does Facial Eczema Differ From Body Eczema?

BACKGROUND: The pathophysiology of atopic dermatitis (AD) is multifactorial, influenced by genetics, skin barrier dysfunction, and environmental stressors. There is a lack of research comparing the etiologies and pathologic mechanisms accounting for differences in facial vs body eczema. OBJECTIVES: To explore reasons why facial eczema may differ from body eczema. RESULTS: There are key differences in the environments of the face and body that may lead to AD exacerbation. These include differences in the skin microbiome, sebaceous glands concentration, and levels of natural moisturizing factor. The face is exposed to more environmental stress compared with the rest of the body. These stresses include aeroallergens, ultraviolet radiation, and cosmetic products. Management of facial eczema also differs from that of body eczema due to the avoidance of high potency topical steroids on the face. Topical steroids increase microbiome diversity, and lack of topical steroid use on the face can lead to decreased microbiome diversity and increased AD severity. CONCLUSION: Facial and body eczema differ due to differences seen in anatomical structure and environmental exposures. These differences should be further researched and used in the management of facial vs body eczema and can also be used in the development of new AD treatments. J Drugs Dermatol. 2022;21(10): 1119-1123. doi:10.36849/JDD.6354.

Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab.

BACKGROUND: IL-22 is potentially a pathogenic cytokine in patients with atopic dermatitis (AD), but the molecular effects of IL-22 antagonism have not been defined in human subjects. OBJECTIVE: We sought to evaluate the cellular and molecular effects of IL-22 blockade in tissues from patients with moderate-to-severe AD. METHODS: We assessed lesional and nonlesional skin from 59 patients with moderate-to-severe AD treated with anti-IL-22 (fezakinumab) versus placebo (2:1) using transcriptomic and immunohistochemistry analyses. RESULTS: Greater reversal of the AD genomic profile was seen with fezakinumab versus placebo, namely 25.3% versus 10.5% at 4 weeks (P = 1.7 × 10-5) and 65.5% versus 13.9% at 12 weeks (P = 9.5 × 10-19), respectively. Because IL-22 blockade showed clinical efficacy only in patients with severe AD, we used baseline median IL-22 mRNA expression to stratify for high (n = 30) and low (n = 29) IL-22 expression groups. Much stronger mean transcriptomic improvements were seen with fezakinumab in the IL-22-high drug-treated group (82.8% and 139.4% at 4 and 12 weeks, respectively) than in the respective IL-22-high placebo-treated group (39.6% and 56.3% at 4 and 12 weeks) or the IL-22-low groups. Significant downregulations of multiple immune pathways, including TH1/CXCL9, TH2/CCL18/CCL22, TH17/CCL20/DEFB4A, and TH22/IL22/S100A's, were restricted to the IL-22-high drug group (P < .05). Consistently, tissue predictors of clinical response were mostly genes involved in T-cell and dendritic cell activation and differentiation. CONCLUSIONS: This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by robust effects in patients with high IL-22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in patients with AD.

Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial.

BACKGROUND: Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. OBJECTIVE: Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). METHODS: We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. RESULTS: At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. LIMITATIONS: The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. CONCLUSION: Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders.

The presence of actinic keratoses (AKs) increases a patient's risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.

Metabolomic stability of exercise-induced sweat.

Due to increased interest in the use of excreted sweat for biomarker discovery, data must be generated supporting sample collection and handling methods to allow for controlled, large-scale biomarker discovery studies to be performed. In this manuscript, twelve amino acids were quantitated from exercise-induced excreted sweat held at room temperature or a simulated body temperature of 37 °C for up to 90 min. The data illustrate a large dynamic range exists among amino acids in sweat. Additionally, the amino acid quantities vary across individuals and among the same individual under different storage conditions, with alanine, arginine, and threonine showing a significant statistical difference between sampling events (p < 0.05). Furthermore, the results establish amino acids are relatively invariant, at both storage temperatures tested, for up to 90 min illustrated by <10% (15/156) of the amino acids measurements demonstrating change greater than 10% from the time zero value. An untargeted metabolomics approach was also applied to the data set to evaluate global changes to the metabolome. The results show more than 88% of all data points fall within the established limits, regardless of temperature condition and ionization mode. Collectively, this study demonstrates that sweat is largely invariant at two distinct temperatures for up to 90 min. These results establish sweat collection and sample handling is possible for up to 90 min with minimal changes in metabolite abundances.

Speech error elicitation and co-occurrence restrictions in two Ethiopian Semitic languages.

This article reports the results of speech error elicitation experiments investigating the role of two consonant co-occurrence restrictions in the productive grammar of speakers of two Ethiopian Semitic languages, Amharic and Chaha. Higher error rates were found with consonant combinations that violated co-occurrence constraints than with those that had only a high degree of shared phonological similarity or low frequency of co-occurrence. Sequences that violated two constraints had the highest error rates. The results indicate that violations of consonant co-occurrence restrictions significantly increase error rates in the productions of native speakers, thereby supporting the psychological reality of the constraints.

Use of 308 nm excimer laser for the treatment of chronic hand and foot eczema.

BACKGROUND: Chronic hand and foot eczema (CHFE), a prevalent debilitating disorder affecting approximately 15% of the population, presents a socioeconomic and psychosocial burden for patients and often follows a chronic course, refractory to conventional therapies. Thus, a large need exists for more effective therapeutics; the excimer laser (308 nm) is effective for some inflammatory skin diseases, but its efficacy has not been evaluated for CHFE. METHODS: The study is a retrospective chart review conducted on 30 patients with recalcitrant CHFE (19 with hand involvement, four with foot involvement, and seven with both) treated twice weekly with excimer laser (308 nm) single wavelength ultraviolet (UV)B radiation between January 2013 and December 2014. RESULTS: Improvements in clinical scores included a 69% reduction in average physician's global assessment (PGA) scores (from 2.77 at baseline to 0.87 after treatment, P < 0.0001) with a parallel reduction in average modified total lesion/symptom scores of 70% (from 10.2 to 3.1, P < 0.0001). Only mild sunburn-like reactions were observed. CONCLUSION: This report evaluates excimer laser for patients with refractory CHFE and shows excellent and sustained efficacy for this treatment. Compared to other UV therapies, excimer laser offers lower cumulative doses of UV radiation by targeting specific areas. This effective treatment should be considered alone or in combination with other established or newer therapies.

Rapid genotyping of Bacillus anthracis strains by real-time polymerase chain reaction.

Rapid and accurate identification of Bacillus anthracis is critical for patient care as well as outbreak control. We have developed 3 separate PCR based assays using fluorescence resonance energy transfer (FRET) to detect the presence of pXO1, pXO2 plasmids and a chromosomal marker. A set of amplification primers and probes were used in each assay. The probes were ad jacently placed inside the primer sites and were 1-bp apart. The upstream probe was labeled with fluorescein at the 3' end, and the downstream probe had Cy5 attached at the 5' end. The probes are included in the PCR reactions and hybridize with the PCR products as they are formed. Binding of probes to PCR products results in transfer of energy from fluorescein to Cy5, resulting in emission from Cy5. Increase in fluorescence, indicating amplification, was monitored in real time on a LightCycler((TM)) LC24. Initial denaturation of target sequences was accomplished at 95 degrees C for 1 min, followed by 28 cycles of denaturation at 95 degrees C for 0 sec, annealing at 58 degrees C for 15 sec, and elongation at 72 degrees C for 5 sec. These assays are specific and can be performed on as little as 25 ng of total DNA or crude cell lysate a from fresh colony. It is thus possible to deter mine the genotype of B. anthracis strains in less than 1 hour.