The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

A microRNA focus on acne

Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. Driven by complex interactions between the pilosebaceous unit and Cutibacterium acnes (C. acnes) bacteria, the disease is characterised by comedonal lesions, papules, pustules and nodules that appear predominantly on the face. Acne and sequelae such as scarring and pigment changes affect health-related quality of life negatively. Approvals for nucleic acid therapies (NATs) such as short-interfering RNA (siRNA) drugs and antisense oligonucleotides (ASOs) have surged in recent years, for rare disorders with little or no effective treatments. These advances, along with clinical trials for microRNA (miRNA) modulation in skin contexts, raise the possibility that NATs may have potential for future acne treatment regimens. In this review, we highlight potential miRNA targets for anti-acne therapy. We provide a brief overview of acne pathophysiology and highlight roles of C. acnes. We then focus on recently discovered differential effects of planktonic and biofilm C. acnes on a Toll-like receptor 2 (TLR2) axis spanning miR-146a-5p. We appraise miR-146a-5p in sebocytes before addressing the putative contributions of miR-21-5p, miR-233-3p and miR-150-5p to inflammatory axes in acne. We conclude with translational perspectives and considerations of patient involvement in miRNA-related research for acne

Patient-reported outcome measures for acne: a mixed-methods validation study (acne PROMs).

OBJECTIVES: To examine the acceptability and validity of two patient-reported outcome measures (PROMs) for adult acne, comparing them to the validated Acne-specific Quality of Life (Acne-QoL) measure. DESIGN: Mixed-methods validation study. SETTING: Participants were recruited by (1) mail-out through primary care if they had ever consulted for acne and received a prescription for acne treatment within the last 6 months, (2) opportunistically in secondary care and (3) poster advertisement in community venues. PARTICIPANTS: 221 (204 quantitative and 17 qualitative) participants with acne, aged 18-50 years. OUTCOME MEASURES: Quantitative sub-study participants completed Acne-QoL, Skindex-16 and Comprehensive Acne Quality of Life Scale (CompAQ) at baseline, 24 hours and 6 weeks. Qualitative sub-study participants took part in cognitive think-aloud interviews, while completing the same measures. Transcribed audio recordings were analysed using inductive thematic analysis. RESULTS: Quantitative analyses suggested high internal consistency (Cronbach's alpha 0.74-0.96) and reliability (intraclass correlation coefficient values 0.88-0.97) for both questionnaires. Both scales showed floor effects on some subdomains. Skindex-16 and CompAQ showed good evidence of construct validity when compared with Acne-QoL with Spearman's correlation coefficients 0.54-0.81, and good repeatability over 24 hours.Qualitative data uncovered wide-ranging views regarding usability and acceptability. Interviewees held strong but differing views about layout, question/response wording, redundant/similar questions and guidance notes. Similarly, interviewees differed in perceptions of acceptability of the different scales, particularly on relatability of questions and emotive reactions to scales. CONCLUSIONS: All PROMs performed well in statistical analyses. No PROM showed superior usability and acceptability in the qualitative study. Any PROM should be acceptable for further research in adult acne but researchers should consider the different domains and whether they will measure only facial or facial and trunk acne before making a selection. A new PROM or further evaluation of novel PROMs may be beneficial

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

Systematic review of clinical practice guidelines for acne vulgaris published between January 2017 and July 2021

Background: Acne is very common, can cause considerable negative impact on quality of life and there is increasing concern over the use of long courses of oral antibiotics for this condition. Objectives: (1) To critically appraise reporting in acne guidelines and compare this with previous systematic review of acne guidelines. (2) Examine acne treatment guidance on pre-specified acne treatments of interest and compare between acne guidelines. Methods: Searches for new or updated guidelines were carried out in MEDLINE, Embase, Google Scholar, LILACS from 1 January 2017 to 31 July 2021, supplemented by searching a guideline-specific depository and checking for updates to guidelines included in previous review. We included guidelines, consensus statements or care protocols on the medical treatment of acne vulgaris in adults and/or children and excluded those that focused on a single intervention or subgroup of acne, regional adaptations of guidelines or guidelines included in previous review. AGREE II checklist was applied to critically appraise reporting of guidelines. Results were synthesised narratively. Results: Of 807 abstracts identified nine guidelines were identified that were eligible for inclusion. All guidelines had AGREE II scores above average in at least one domain and reporting was substantially improved compared to the systematic review of acne carried out 5 years previously. There was consensus between guidelines on the key role of topical treatments as first-line acne treatment and most recommended continuing topical treatments as maintenance therapy. There was considerable variation between guidelines on classification of severity, indications for commencing oral antibiotics and on maximum duration of oral antibiotics. However, there was consensus on the need for co-prescription of a non-antibiotic topical treatment when using oral antibiotics. There were notable differences on recommendations regarding provision of information for patients on how to use topical treatments or how to mitigate against side effects. Conclusions: Substantial differences in classification of acne severity hampered comparisons between guidelines. Although development and reporting of guidelines has improved over the past 5 years, differences in key recommendations remain, possibly reflecting uncertainties in the underlying evidence base. Differences between guidelines could have substantial implications for prevalence of antibiotic prescribing for acne

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA

Honey, a Gift from Nature to Health and Beauty: A Review

Benefits of honey are contributed by the composition of its elements such as glucose, fructose, glucose oxidase, vitamins and phenolic compounds. For health, honey can be used to treat wounds due to the antibacterial activity conferred by the hydrogen peroxide produced by glucose oxidase in honey. Anti-inflammatory, anti-oxidant, deodorizing and tissue regeneration activities in honey also help in the wound healing process. It can also be an alternative sweetener for diabetic patients to ensure compliance to a healthy diet. Moreover, honey exerts several effects such as lowering low density lipids and increasing high density lipids, thus reducing risk of atherosclerosis. In terms of beauty, honey can be used on skin and hair. It moisturizes skin through its natural humectant properties contributed by high contents of fructose and glucose. Honey treats acne on the skin due to its antibacterial activity, anti-inflammatory action and tissue repair. The hair can benefit from honey in such a way that the hair has abundance, and becomes easier to comb. However, there have not been as many studies regarding the use of honey in skin in comparison to its use for health. Therefore, future studies on honey could research its use, action and benefits in both cosmetics and dermatology