High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells.

Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.

Mapping prohormone processing by proteases in human enteroendocrine cells using genetically engineered organoid models.

Enteroendocrine cells (EECs) secrete hormones in response to ingested nutrients to control physiological processes such as appetite and insulin release. EEC hormones are synthesized as large proproteins that undergo proteolytic processing to generate bioactive peptides. Mutations in EEC-enriched proteases are associated with endocrinopathies. Due to the relative rarity of EECs and a paucity of in vitro models, intestinal prohormone processing remains challenging to assess. Here, human gut organoids in which EECs can efficiently be induced are subjected to CRISPR-Cas9-mediated modification of EEC-expressed endopeptidase and exopeptidase genes. We employ mass spectrometry-based analyses to monitor peptide processing and identify glucagon production in intestinal EECs, stimulated upon bone morphogenic protein (BMP) signaling. We map the substrates and products of major EECs endo- and exopeptidases. Our studies provide a comprehensive description of peptide hormones produced by human EECs and define the roles of specific proteases in their generation.

Resemblances in the early development of two sea urchins: Toxopneustes roseus (Euechinoidea: Echinacea) and Rhyncholampas pacificus (Euechinoidea: Irregularia) from different habitats in the southern Mexican Pacific.

Sea urchins play a key role in the marine environment, contributing to maintain a balance in benthic ecosystems. Toxopneustes roseus acts as a regulator of rhodolith beds and is a key species as a bioturbation promoter, while Rhyncholampas pacificus moderates the detritus content of sediment through various mechanisms and contributes to accelerating the circulation of organic matter. However, nothing is known about their early development, so the objective of this research is to characterize the embryonic and larval development of specimens of the two species from the southern Mexican Pacific and identify the causes that produce their differences. The embryonic development of T. roseus lasted approximately 20 â€‹h; the echinopluteus larva appeared at 23 â€‹h and culminated in around 12 days with an eight-armed larva. Metamorphosis was reached at 18 days. The embryonic development of R. pacificus lasted about 15 â€‹h; the larva emerged at 20 â€‹h and culminated in about two days with an eight-armed larva. The metamorphosis was completed in 9 days. The reproductive output of both species determines their development time and the structure of their larvae; therefore, the energy of R. pacificus is invested in reaching metamorphosis earlier to ensure that its larvae, which are not very abundant, settle and recruit to the population. Regarding T. roseus, the longest permanence in the plankton is efficiently maintained by its numerous larvae through the presence of mobile arms and the shift of the swimming function to the epauletes. This is the first work that characterizes the early development of a species of the genus Toxopneustes and of the only living species of the genus Ryncholampas. The information generated in this work is essential to gaining knowledge about these groups of echinoids, especially the effect of the environment on their early development.

Patient and Provider Experiences and Views on the Use of Telehealth in Genetics Clinics in Response to the COVID-19 Pandemic.

Introduction: The 2019 Coronavirus Disease (COVID-19) pandemic necessitated a mass transition in genetics clinics nationwide from in-person care to virtual care through telehealth. Before the COVID-19 pandemic, there was limited research on the use of telehealth in genetics specialties. Therefore, the COVID-19 pandemic presented a unique opportunity to study this emerging mode of care delivery in the setting of genetics clinics. This study described the scope of telehealth use in genetics clinics nationally and determined how COVID-19 influenced patients' decisions regarding their genetic care. Methods: Two anonymous surveys for patients and providers were developed. The patient survey was offered online to all genetics patients seen through telehealth at a Manhattan-based practice between March and December 2020. The provider survey was distributed through several listservs to genetics providers nationwide. Results: Patients (n = 242) and providers (n = 150) responded. Telehealth was used in all specialty genetics clinics for both initial and follow-up visits. Telehealth was both effective and satisfactory to patients for both visit types and across specialties; however, Asian and Hispanic/Latino patients had significantly lower mean satisfaction scores compared with White patients (p = 0.03 and 0.04, respectively). Patients appreciated telehealth for its convenience and to avoid COVID-19 exposure. Providers across specialties and provider types preferred telehealth for follow-up rather than initial visits. Several clinic initiatives related to telehealth were identified. Discussion: Telehealth was generally well received by both patients and providers, and is expected to become permanent option in genetics clinics. Further studies are needed to identify barriers to accessing telehealth.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes.

Cascade testing, the site-specific genetic testing of relatives within families with an inherited condition, is underutilized. Long wait times for appointments in specialty genetics clinics are a known barrier to genetic testing access. In our cancer genetics, New Patient Clinic (NPC), the long wait time for an appointment (on average 5 months for routine referrals), was identified by both providers and patients as a barrier to uptake of cascade testing. Timely testing of at-risk relatives is essential to maximize the benefits of cascade testing and reduce cancer morbidity and mortality. Our objective was to improve access via implementation of a different clinical model that designated appointments for patients seeking cascade testing. A secondary goal was to improve use of genetic counselor time. We implemented a dedicated Cascade Testing Clinic (CTC) with an expedited triaging and unique scheduling model to decrease patient wait time to appointment and optimize clinician time. We report on the process and outcomes here. Between October 2016 and February 2020, the average wait time between referral date and first scheduled appointment date was 46 days for the CTC compared to 144 days for the NPC (p < 0.0001). No-show/cancelation/rescheduling rate was 11.7% in the CTC compared to 29.7% in the NPC (p < 0.0001). Genetic counselors saw approximately twice as many patients per half-day clinic in the CTC compared to the NPC (p < 0.00001). Modifications to clinic staffing and appointment times were made based on provider feedback. Implementation of a dedicated clinic specifically for patients seeking cascade testing significantly shortened wait times for this population, reduced patient drop-off, and improved clinician efficiency. The relatively straightforward indications and generally uncomplicated medical histories made this an ideal population for expedited appointments.

Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.

The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.

Chitinase 3-like 1 is not a target antigen in patients with multiple sclerosis.

Autoimmunity to chitinase 3-like 1 (CHI3L1) has recently been reported in hepatic and bowel inflammatory conditions. Considering that CHI3L1 plays a role as prognostic biomarker in multiple sclerosis (MS), here we investigated CHI3L1 as potential autoantigenic target in the disease. We determined serum CHI3L1 autoantibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 60 untreated MS patients with different clinical forms of the disease and 20 healthy controls (HC). IgG levels to CHI3L1 were similar between patients with relapsing-remitting MS, primary and secondary progressive MS, and HC. These findings do not support a role for CHI3L1 autoantibodies in MS pathogenesis.

Fruit consumption and cardiometabolic risk in the PREDIMED-plus study: A cross-sectional analysis.

BACKGROUND AND AIMS: Total fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters. METHODS AND RESULTS: A total of 6633 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (≥3 servings/d) had lower waist circumference (WC) (ß = -1.04 cm; 95%CI:-1.81, -0.26), fasting glucose levels (ß = -2.41 mg/dL; 95%CI(-4.19, -0.63) and LDL-cholesterol (ß = -4.11 mg/dL; 95%CI:-6.93, -1.36), but, unexpectedly, higher systolic blood pressure (BP) (ß = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (ß = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (<1 servings/d). Participants consuming ≥1 serving/day of total fruit juice had lower WC (ß = -0.92 cm; 95%CI:-1.56, -0.27) and glucose levels (ß = -1.59 mg/dL; 95%CI:-2.95, -0.23) than those consuming <1 serving/month. The associations with cardiometabolic risk factors differed according to the color of fruits. CONCLUSION: Fruit consumption is associated with several cardiometabolic risk factors in Mediterranean elders with metabolic syndrome. The associations regarding BP levels could be attributed, at least partially, to reverse causality bias inherent to the cross-sectional design of the study.

Detection of factors influencing circadian rhythms on Intensive Care inpatients and hospitalization: Protocol for an observational study.

AIMS: Identify the prevalence of circadian health disorders in ICU and hospitalized patients. Stablish the relationship of the circadian system with light, temperature, noise and nursing activities. BACKGROUND: Commonly, self-assessment through subjective questionnaires is used for research about sleep quality. However, more reliable and valid measures should be applied objectively to find out the real prevalence of the problem. There is a negative relationship between circadian rhythms and hospitalization. In this study, we will analyse sleep patterns and hospital environments to implement measures to improve the quality of care related to sleep. DESIGN: Descriptive observational study. It is estimated that 975 patients from 13 hospitals need to be recruited from ICU and hospitalization units. The sample should meet the following criteria: Patients over 18 admitted to ICU and medical units, length of stay between 96-148 hr, with no visual, hearing or moderate-severe cognitive impairment. Variables: Sleep variables are collected with an electronic device (named Kronowise® and Kronobed®), circadian and infrared light exposure, environmental noise, temperature, unit structural characteristics, nursing care (from 0 to 6 a.m.) and, characteristics of hospitalization period. The study, registered on Clinical Trials, initiated in December 2019 and it will continue up to December 2022. DISCUSSION: Using objective and subjective measures of sleep and circadian rhythms, this study will shed light on the factors that negatively affect the hospitalized patients' sleep quality and circadian health. The ultimate goal is to design hospital guidelines to minimize the adverse effects on the dependent variables studied. Arguably, these guidelines will contribute to reducing the risk of these alterations and it will also serve to improve the nursing activities. CONCLUSION: We expect to obtain adequate results for the creation of a protocol to improve the circadian health, quality of care and health outcomes related to sleep in patients.

Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults.

Exosomes are extracellular vesicles that contain nucleic acids, lipids and metabolites, and play a critical role in health and disease as mediators of intercellular communication. The majority of extracellular vesicles in the blood are platelet-derived. Compared to adults, neonatal platelets are hyporeactive and show impaired granule release, associated with defects in Soluble N-ethylmaleimide-sensitive fusion Attachment protein REceptor (SNARE) proteins. Since these proteins participate in biogenesis of exosomes, we investigated the potential differences between newborn and adult plasma-derived exosomes. Plasma-derived exosomes were isolated by ultracentrifugation of umbilical cord blood from full-term neonates or peripheral blood from adults. Exosome characterization included size determination by transmission electron microscopy and quantitative proteomic analysis. Plasma-derived exosomes from neonates were significantly smaller and contained 65% less protein than those from adults. Remarkably, 131 proteins were found to be differentially expressed, 83 overexpressed and 48 underexpressed in neonatal (vs. adult) exosomes. Whereas the upregulated proteins in plasma exosomes from neonates are associated with platelet activation, coagulation and granule secretion, most of the underexpressed proteins are immunoglobulins. This is the first study showing that exosome size and content change with age. Our findings may contribute to elucidating the potential "developmental hemostatic mismatch risk" associated with transfusions containing plasma exosomes from adults.

[Prevalence of obstructive sleep apnea syndrome in Chilean adults. A sub-study of the national health survey, 2016/17]. / Estudio de prevalencia de síndrome de apneas obstructivas del sueño en la población adulta chilena. Subestudio de la Encuesta Nacional de Salud, 2016/17.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) affects approximately 10%-20% of adults and is associated with obesity, hypertension and metabolic syndrome. AIM: To assess the prevalence and risk factors associated with OSAS in Chilean adults. MATERIAL AND METHODS: A standardized sleep questionnaire and respiratory polygraphy at home were conducted on adults aged 18 years or more, residing in the Metropolitan Region and enrolled in the 2016/17 National Health Survey. RESULTS: Two-hundred and five people between 18 and 84 years old (46% men, mean age 50 years) underwent overnight respiratory polygraphy at home. The estimated obstructive sleep apnea prevalence was 49% (62% men, 31% women) considering an apnea-hypopnea index ≥ 5 respiratory events/hour, and 16% (21% men, 13% women) considering an apnea-hypopnea index ≥ 15 respiratory events/hour. The prevalence of obstructive sleep apnea continuously increased along with age for men and women, with a later onset for women. Age, gender, body mass index, cervical and waist circumference, snoring, reporting of apnea by proxies, self-reported cardiovascular and metabolic diseases such as hypertension, diabetes and dyslipidemia, were significantly associated with OSAS. No association was found with insomnia and daytime sleepiness. CONCLUSIONS: The prevalence and risk factors associated to obstructive sleep apnea syndrome were high among these adults.

Verb-mediated anticipatory eye movements in people with Down syndrome.

BACKGROUND: Children and adults with neurotypical development employ linguistic information to predict and anticipate information. Individuals with Down syndrome (DS) have weaknesses in language production and the domain of grammar but relative strengths in language comprehension and the domain of semantics. What is not clear is the extent to which they can use linguistic information, as it unfolds in real time, to anticipate upcoming information correctly. AIMS: To investigate whether children and young people with DS employ verb information to predict and anticipate upcoming linguistic information. METHODS & PROCEDURES: A preferential looking task was performed, using an eye-tracker, with children and teenagers with DS and a typically developing (TD) control group matched by sex and mental age (average = 5.48 years). In each of 10 trials, two images were presented, a target and a distractor, while participants heard a phrase that contained a semantically informative verb (e.g., 'eat') or an uninformative verb (e.g., 'see'). OUTCOMES & RESULTS: Both DS and TD control participants could anticipate the target upon hearing an informative verb, and prediction skills were positively correlated with mental age in those with DS. CONCLUSIONS & IMPLICATIONS: This work demonstrates for the first time that children and teenagers with DS can predict linguistic information based on semantic cues from verbs, and that sentence processing is driven by predictive relationships between verbs and arguments, as in children with typical development. Clinicians can take advantage of these prediction skills, using them in therapy to support weaker areas.

Effect of temperature increase on fertilization, embryonic development and larval survival of the sea urchin Toxopneustes roseus in the Mexican south Pacific.

Toxopneustes roseus performs a key role in the eastern tropical Pacific as a strategic herbivore and bioturbation promoter. We evaluated the effect of temperature on the fertilization success, embryonic development and larval survival of T. roseus under laboratory conditions, to understand how the increase in ocean temperature could affect it in a global warming. The highest percentage of fertilization occurred in gametes that were exposed to 30 °C, and a significant negative effect of 32 °C was evidenced by the lowest percentage. There was also a deleterious effect in embryos exposed to 32 °C, resulting in an abnormal development at all the time points. The highest percentage of larval survival occurred at 30 °C, while the lowest percentage occurred at 32 °C. The results suggest that T. roseus probably lives near its upper thermal limit, and future ocean warming could threaten the permanence of the species in the eastern tropical Pacific, or at least lead to contraction or fragmentation of its range limits. Therefore if sea temperature rises globally, it could cause the disappearance of these populations that are living at the edge of their thermal tolerance, but for other populations located in more temperate latitudes, it could propitiate favorable conditions for fertilization and survival of embryos and larvae.

[Performance of sleep questionnaires for the diagnosis of obstructive sleep apnea syndrome]. / Rendimiento de los cuestionarios de sueño en el diagnóstico de síndrome de apneas obstructivas del sueño en población chilena. Subestudio de la Encuesta Nacional de Salud, 2016/17.

Background The diagnosis of obstructive sleep apnea syndrome (OSAS) is based on nocturnal records: polysomnography or respiratory polygraphy. However, their high costs limit their use. Aim To examine the predictive value of three sleep questionnaires (STOP, STOP-Bang, Epworth Sleepiness Scale (ESS) in the screening of OSAS in Chilean adults. Material and Methods During the National Health Survey 2016/17, 205 adults aged 50.7 ± 15.0 years (46% males) living in the Metropolitan Region answered sleep questionnaires and underwent an ambulatory respiratory polygraphy. The sensitivity, specificity, positive and negative predictive values and receiver operating characteristic curves of sleep questionnaires were calculated. Results Fifty nine percent of participants had OSAS which was moderate to severe in 26%. The clinical variables associated with OSAS were age, male gender, hypertension, dyslipidemia, overweight, cervical and waist circumferences, history of regular snoring and witnessed apneas. Daytime somnolence, insomnia and unrefreshing sleep were not associated to OSAS risk. STOP, STOP-Bang and ESS questionnaires classified 64%, 71% and 12% of cases as high risk for OSAS, respectively. The STOP and STOP-Bang questionnaires had the highest sensitivity to predict OSAS (76% and 89%, respectively) while the ESS had the highest specificity (91%). Conclusions The sleep questionnaires allowed to identify the subjects at high risk for OSAS in this sample of adults from the Metropolitan Region.

First experimental in vivo model of enhanced dengue disease severity through maternally acquired heterotypic dengue antibodies.

Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved.

How Strong is the "Fake ID Effect?" An Examination Using Propensity Score Matching in Two Samples.

BACKGROUND: Underage college students who obtain and use false identification (fake ID) are at risk for negative outcomes. However, it is currently unclear how uniquely the fake ID itself serves as a vehicle to subsequent harm (i.e., the "fake ID effect") over and above general and trait-related risk factors (e.g., deviant peers, low self-control). METHODS: To investigate whether the "fake ID effect" would hold after accounting for phenotypic risk, we utilized propensity score matching (PSM) in a cross-sectional sample of 1,454 students, and a longitudinal replication sample of 3,720 undergraduates. Individuals with a fake ID were matched with individuals without a fake ID, in terms of a number of trait-based and social risk factors. These matched groups were then compared on 5 problematic outcomes (i.e., frequent binge drinking, alcohol-related problems, arrests, marijuana use, and hard drug use). RESULTS: Findings showed that "fake ID effects" were substantially-although not fully-diminished following PSM. The "fake ID effect" remained strongest for alcohol-related arrests. This may relate to issues of enforcement and students' willingness to engage in deviant behavior with a fake ID, or it may be a function of combined processes. CONCLUSIONS: Overall, the findings suggest that interventions should not only be aimed at reducing the fake ID-related alcohol access specifically, but should also be aimed more generally toward at-risk youths' access to alcohol. Future research might examine whether fake IDs have their strongest potency as moderators of the effects of risky traits-such as impulsiveness-on drinking outcomes.

A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.

BACKGROUND: Dihydrotestosterone is the main androgen causative of androgenetic alopecia, a psychologically and physically harmful condition warranting medical treatment. OBJECTIVE: We sought to compare the efficacy and safety of dutasteride (type 1 and 2 5-alpha reductase inhibitor) with finasteride (type 2 5-alpha reductase inhibitor) and placebo in men with androgenetic alopecia. METHODS: Men aged 20 to 50 years with androgenetic alopecia were randomized to receive dutasteride (0.02, 0.1, or 0.5 mg/d), finasteride (1 mg/d), or placebo for 24 weeks. The primary end point was hair count (2.54-cm diameter) at week 24. Other assessments included hair count (1.13-cm diameter) and width, photographic assessments (investigators and panel), change in stage, and health outcomes. RESULTS: In total, 917 men were randomized. Hair count and width increased dose dependently with dutasteride. Dutasteride 0.5 mg significantly increased hair count and width in a 2.54-cm diameter and improved hair growth (frontal view; panel photographic assessment) at week 24 compared with finasteride (P = .003, P = .004, and P = .002, respectively) and placebo (all P < .001). The number and severity of adverse events were similar among treatment groups. LIMITATIONS: The study was limited to 24 weeks. CONCLUSIONS: Dutasteride increased hair growth and restoration in men with androgenetic alopecia and was relatively well tolerated.

Use of Topical Corticosteroids in the Treatment of Noninfectious Inflammatory Dermatoses of the Scalp: A Survey of Practicing Dermatologists and Dermatology Residents Using Delphi Methodology.

Background: Noninfectious inflammatory dermatoses of the scalp are common, and their symptomsin particular, those affecting appearance, can have a psychological effect that may be disproportionate to their clinical severity. Effective, cosmetically acceptable treatments are important to manage these conditions. Topical corticosteroids form the cornerstone of acute treatment for many of these conditions. We surveyed practicing dermatologists and dermatology residents to determine the current clinical practice in prescribing topical corticosteroids for these disorders in their various preparation formats. Methods: A Delphi method was used, consisting of 2 questionnaire rounds. The first round contained 34 questions and was completed by 612 dermatologists and dermatology residents via email. The first round of responses was analyzed, and points that had > 70% agreement were used to form a second questionnaire of 21 statements. This second round was completed by 346 participants, and their responses were used to generate a final report. Participants were practicing in both public and private practices. Results: Clobetasol propionate 0.05% topical solution was considered to be the most appropriate treatment for noninfectious inflammatory scalp dermatoses in general, with 75.1% agreement in the second round of questionnaire. The main advantages of clobetasol propionate over other topical corticosteroids were reported as potency, effectiveness, and broad action spectrum (94.8% agreement). The preferred pharmaceutical format was the solution of clobetasol propionate. Conclusion: Clobetasol propionate was the preferred topical treatment for the management of scalp dermatoses, usually as first-line treatment; solution was the preferred preparation.