Applications of hydroxy acids: classification, mechanisms, and photoactivity

Hydroxy acids (HAs) represent a class of compounds which have been widely used in a number of cosmetic and therapeutic formulations in order to achieve a variety of beneficial effects for the skin. We review and discuss the most frequently used classes of these compounds, such as α-hydroxy acids, β-hydroxy acids, polyhydroxy acids, and bionic acids, and describe their applications as cosmetic and therapeutic agents. Special emphasis is devoted to the safety evaluation of these formulations, in particular on the effects of their prolonged use on sun-exposed skin. Furthermore, we summarize the very limited number of studies dealing with the modifications evoked by topical application of products containing HAs on photocarcinogenesis. In spite of the large number of reports on the cosmetic and clinical effects of HAs, their biological mechanism(s) of action still require more clarification. Some of these mechanisms are discussed in this article along with important findings on the effect of HAs on melanogenesis and on tanning. We also emphasize the important contribution of cosmetic vehicles in these types of studies. Thus, HAs play an important role in cosmetic formulations, as well as in many dermatologic applications, such as in treating photoaging, acne, ichthyosis, rosacea, pigmentation disorders, and psoriasis

Effects of Cosmetic Formulations Containing Hydroxyacids on Sun-Exposed Skin: Current Applications and Future Developments

This paper describes recent data on the effects of various skin formulations containing hydroxyacids (HAs) and related products on sun-exposed skin. The most frequently used classes of these products, such as α- and β-hydroxyacids, polyhydroxy acids, and bionic acids, are reviewed, and their application in cosmetic formulations is described. Special emphasis is devoted to the safety evaluation of these formulations, particularly on the effects of their prolonged use on sun-exposed skin. We also discuss the important contribution of cosmetic vehicles in these types of studies. Data on the effects of HAs on melanogenesis and tanning are also included. Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, are presented

Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial

BACKGROUND Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders. METHODS Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response. RESULTS Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms. LIMITATIONS This was a pilot feasibility and acceptability trial; results should be interpreted with caution. CONCLUSIONS Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety.This work was supported by a Postdoctoral National Research Service Award from the National Institutes of Health [F32 MH098490] to K. Ellard. (F32 MH098490 - Postdoctoral National Research Service Award from the National Institutes of Health)Accepted manuscrip

The adenovirus E4-ORF3 protein stimulates SUMOylation of general transcription factor TFII-I to direct proteasomal degradation

Modulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3-dependent manner was the general transcription factor II–I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4-ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I-repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection

Altered Auditory Feedback In-The-Ear Devices

Purpose: This study examined objective and subjective measures of the effect of a self-contained ear-level device delivering altered auditory feedback (AAF) for those who stutter 12 months following initial fitting with and without the device. Method: Nine individuals with developmental stuttering participated. In Experiment 1, the proportion of stuttering was examined during reading and monologue. A self-report inventory inquiring about behavior related to struggle, avoidance and expectancy associated with stuttering was examined in Experiment 2. In Experiment 3, naive listeners rated the speech naturalness of speech produced by the participants during reading and monologue. Results: The proportions of stuttering events were significantly (p < 0.05) reduced at initial fitting and remained so 12 months post follow-up. After using the device for 12 months, self- reported perception of struggle, avoidance and expectancy were significantly (p < 0.05) reduced relative to pre-fitting. Naive listeners rated the speech samples produced by those who stutter while wearing the device significantly more natural sounding than those produced without the device for both reading and monologue (p < 0.0001). Conclusions: These findings support the notion that a device delivering AAF is a viable therapeutic alternative in the treatment of stuttering

Community-based infant hearing screening in a developing country: parental uptake of follow-up services

<p>Abstract</p> <p>Background</p> <p>Universal newborn hearing screening is now considered an essential public health care for the early detection of disabling life-long childhood hearing impairment globally. However, like any health interventions in early childhood, parental support and participation is essential for achieving satisfactory uptake of services. This study set out to determine maternal/infant socio-demographic factors associated with follow-up compliance in community-based infant hearing screening programmes in a developing country.</p> <p>Methods</p> <p>After health educational/counselling sessions, infants attending routine childhood immunisation clinics at four primary care centres were enrolled into a two-stage infant hearing screening programme consisting of a first-stage screening with transient-evoked otoacoustic emissions and second-stage screening with automated auditory brainstem response. Infants referred after the second-stage screening were scheduled for diagnostic evaluation within three months. Maternal and infant factors associated with completion of the hearing screening protocol were determined with multivariable logistic regression analysis.</p> <p>Results</p> <p>No mother declined participation during the study period. A total of 285 out of 2,003 eligible infants were referred after the first-stage screening out of which 148 (51.9%) did not return for the second-stage, while 32 (39.0%) of the 82 infants scheduled for diagnostic evaluation defaulted. Mothers who delivered outside hospitals were significantly more likely to return for follow-up screening than those who delivered in hospitals (Odds ratio: 1.62; 95% confidence intervals: 0.98 – 2.70; p = 0.062). No other factors correlated with follow-up compliance for screening and diagnostic services.</p> <p>Conclusion</p> <p>Place of delivery was the only factor that correlated albeit marginally with infant hearing screening compliance in this population. The likely influence of issues such as the number of return visits for follow-up services, ineffective tracking system and the prevailing unfavourable cultural perception towards childhood deafness on non-compliance independently or through these factors warrant further investigation.</p

Diagnostic accuracy of non-specialist versus specialist health workers in diagnosing hearing loss and ear disease in Malawi.

OBJECTIVE: To determine whether a non-specialist health worker can accurately undertake audiometry and otoscopy, the essential clinical examinations in a survey of hearing loss, instead of a highly skilled specialist (i.e. ENT or audiologist). METHODS: A clinic-based diagnostic accuracy study was conducted in Malawi. Consecutively sampled participants ≥ 18 years had their hearing tested using a validated tablet-based audiometer (hearTest) by an audiologist (gold standard), an audiology officer, a nurse and a community health worker (CHW). Otoscopy for diagnosis of ear pathologies was conducted by an ENT specialist (gold standard), an ENT clinical officer, a CHW, an ENT nurse and a general nurse. Sensitivity, specificity and kappa (κ) were calculated. 80% sensitivity, 70% specificity and kappa of 0.6 were considered adequate. RESULTS: Six hundred and seventeen participants were included. High sensitivity (>90%) and specificity (>85%) in detecting bilateral hearing loss was obtained by all non-specialists. For otoscopy, sensitivity and specificity were >80% for all non-specialists in diagnosing any pathology except for the ENT nurse. Agreement in diagnoses for the ENT clinical officer was good (κ = 0.7) in both ears. For other assessors, moderate agreement was found (κ = 0.5). CONCLUSION: A non-specialist can be trained to accurately assess hearing using mobile-based audiometry. However, accurate diagnosis of ear conditions requires at least an ENT clinical officer (or equivalent). Conducting surveys of hearing loss with non-specialists could lower costs and increase data collection, particularly in low- and middle-income countries, where ENT specialists are scarce