Role of the Binding Energy on Nondipole Effects in Single-Photon Ionization.

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

Tracing Photoinduced Hydrogen Migration in Alcohol Dications from Time-Resolved Molecular-Frame Photoelectron Angular Distributions.

The recent implementation of attosecond and few-femtosecond X-ray pump/X-ray probe schemes in large-scale free-electron laser facilities has opened the way to visualize fast nuclear dynamics in molecules with unprecedented temporal and spatial resolution. Here, we present the results of theoretical calculations showing how polarization-averaged molecular-frame photoelectron angular distributions (PA-MFPADs) can be used to visualize the dynamics of hydrogen migration in methanol, ethanol, propanol, and isopropyl alcohol dications generated by X-ray irradiation of the corresponding neutral species. We show that changes in the PA-MFPADs with the pump-probe delay as a result of intramolecular photoelectron diffraction carry information on the dynamics of hydrogen migration in real space. Although visualization of this dynamics is more straightforward in the smaller systems, methanol and ethanol, one can still recognize the signature of that motion in propanol and isopropyl alcohol and assign a tentative path to it. A possible pathway for a corresponding experiment requires an angularly resolved detection of photoelectrons in coincidence with molecular fragment ions used to define a molecular frame of reference. Such studies have become, in principle, possible since the first XFELs with sufficiently high repetition rates have emerged. To further support our findings, we provide experimental evidence of H migration in ethanol-OD from ion-ion coincidence measurements performed with synchrotron radiation.

Observation of Nondipole-Induced Asymmetry in the Angular Emission Distribution of Photoelectrons from Fixed-in-Space CO Molecules.

We investigate experimentally and theoretically the C and O 1s photoionization of fixed-in-space CO molecules at a photon energy of 905 eV. We find a significant dependence of the photoelectron angular distributions on the direction of propagation of the ionizing radiation. It results from an interplay of nondipole effects, on one hand, and molecular effects, on the other. The nondipole effects lead to an increase of the emission probability in the forward direction along the light propagation, and the photoelectron wave being scattered by the molecular potential gives rise to a strong peak in the direction of the atom neighboring the emitter site. These effects can either conspire or extenuate each other, depending on the photoelectron emission direction and molecular orientation in space.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c ), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.

Maternal peri-conceptional undernourishment perturbs offspring sperm methylome.

The genotype of an organism is stable throughout its life; however, its epigenome is dynamic and can be altered in response to environmental factors, such as diet. Inheritance of acquired epigenetic modifications by the next generation occurs through the germline, although the precise mechanisms remain to be elucidated. Here, we used a sheep model to evaluate if modification of the maternal diet (CTR; control, UND: undernutrition; FA: undernutrition and folic acid supplementation) during the peri-conceptional period affects the genome-wide methylation status of the gametes of male offspring. Sperm DNA methylation, measured by Reduced Representation Bisulfite Sequencing (RRBS), identified Differentially Methylated Regions (DMR) in offspring that experienced in utero undernutrition, both in UND (244) and FA (240), compared with CTR. Gene ontology (GO) analysis identified DMRs in categories related to sperm function, therefore we investigated whether the fertilizing capacity of the semen from the three groups differed in an in vitro fertilization assay. Spermatozoa from the undernourished groups showed lower motility and sperm chromatin structure abnormalities, represented by a higher percentage of DNA fragmentation and an increased number of immature cells, compared with CTR. While good quality blastocysts were obtained from all three groups, the proportion of embryos reaching the blastocyst stage was reduced in the UND vs CTR, an effect partially rescued by the FA treatment. The data reported here show that nutritional stress during early pregnancy leads to epigenetic modifications in the semen of the resulting offspring, the effects of which in next generation remain to be elucidated.

Recoil-Induced Asymmetry of Nondipole Molecular Frame Photoelectron Angular Distributions in the Hard X-ray Regime.

We investigate angular emission distributions of the 1s photoelectrons of N_{2} ionized by linearly polarized synchrotron radiation at hν=40 keV. As expected, nondipole contributions cause a very strong forward-backward asymmetry in the measured emission distributions. In addition, we observe an unexpected asymmetry with respect to the polarization direction, which depends on the direction of the molecular fragmentation. In particular, photoelectrons are predominantly emitted in the direction of the forward nitrogen atom. This observation cannot be explained via asymmetries introduced by the initial bound and final continuum electronic states of the oriented molecule. The present simulations assign this asymmetry to a novel nontrivial effect of the recoil imposed to the nuclei by the fast photoelectrons and high-energy photons, which results in a propensity for the ions to break up along the axis of the recoil momentum. The results are of particular importance for the interpretation of future experiments at x-ray free electron lasers operating in the few tens of keV regime, where such nondipole and recoil effects will be essential.

Photon-Momentum-Induced Molecular Dynamics in Photoionization of N_{2} at hν=40 keV.

We investigate K-shell ionization of N_{2} at 40 keV photon energy. Using a cold target recoil ion momentum spectroscopy reaction microscope, we determine the vector momenta of the photoelectron, the Auger electron, and both N^{+} fragments. These fully differential data show that the dissociation process of the N_{2}^{2+} ion is significantly modified not only by the recoil momentum of the photoelectron but also by the photon momentum and the momentum of the emitted Auger electron. We find that the recoil energy introduced by the photon and the photoelectron momentum is partitioned with a ratio of approximately 30∶70 between the Auger electron and fragment ion kinetic energies, respectively. We also observe that the photon momentum induces an additional rotation of the molecular ion.

A Storage-Dependent Platinum Functionalization with a Commercial Pre-Polymer Useful for Hydrogen Peroxide and Ascorbic Acid Detection.

A preliminary assessment of properties of the commercial product Chemiplus 2DS HB (BI-QEM Specialties SpA) is proposed. Cyclic voltammetry of this oligomer containing sulfate/sulfone groups shows a single oxidative peak at +0.866 V vs. Ag/AgCl, and its passivating process on Pt electrode suggests the formation of a non-conductive layer. Electrode modification was achieved by exploiting the constant potential amperometry setting potential at +0.900 V vs. Ag/AgCl. A substantial change in the oxidative currents from electroactive species H2O2 and ascorbic acid (AA) were observed on Pt/Chemiplus 2DS HB sensors compared to unmodified Pt. Furthermore, the influence of different storage conditions on modified sensors was examined. A storage solution containing AA concentration from 0.1 until 10 mM maintained effective AA rejection of Pt/Chemiplus 2DS HB after 7 days from construction; H2O2 oxidation capability was also retained. Sulfone and sulfonate groups of Chemiplus 2DS HB are likely responsible for the dimensionality of the film and the electrostatic interaction leading to a self-blocking/self-rejection of AA. The way Pt/Chemiplus can reveal the AA presence depends on the maintaining of AA rejection, and this peculiarity can distinguish it from other sensors or biosensors.

Direct Experimental Access to the Nonadiabatic Initial Momentum Offset upon Tunnel Ionization.

We report on the nonadiabatic offset of the initial electron momentum distribution in the plane of polarization upon single ionization of argon by strong field tunneling and show how to experimentally control the degree of nonadiabaticity. Two-color counter- and corotating fields (390 and 780 nm) are compared to show that the nonadiabatic offset strongly depends on the temporal evolution of the laser electric field. We introduce a simple method for the direct access to the nonadiabatic offset using two-color counter- and corotating fields. Further, for a single-color circularly polarized field at 780 nm, we show that the radius of the experimentally observed donutlike distribution increases for increasing momentum in the light propagation direction. Our observed initial momentum offsets are well reproduced by the strong-field approximation. A mechanistic picture is introduced that links the measured nonadiabatic offset to the magnetic quantum number of virtually populated intermediate states.

[A brief historical approach about the concept of paranoia]. / Un breve recorrido histórico acerca del concepto de paranoia.

From the ancient Greeks (V to III centuries BC), through Hippocrates to the Roman physician Aulo Cornelius Celso (I century), the term paranoia has been used as a manifestation of mental illness. After many centuries, Robert Burton in 1621 introduces the concept with a more modern meaning. Only with Heinroth (1818) the syndrome enters into the psychiatric nosology as a disorder of thought with unaltered perceptions. French and German psychiatry agree on the concept of paranoia as a partial psychosis with a maintained level of functioning and absence of deterioration. With this meaning the term is introduced in the modern psychiatry in Kahlbaum's work (1863). Jasper contributes with the introduction of paranoid development that can be influenced by the environment or previous experiences (1910). But to Kraepelin (1921) is owed the most precise description in a specifc essay based on his clinical experience. The German psychiatrist speaks of both a psychogenic and a more biological component. In modern psychiatric classifcations gradually the syndrome has disappeared and encompassed in the generic delusional disorder, clearly distinct from schizophrenia, and only if the delusions are understandable. The consequences of the absence of a diagnostic recognition implies that there is no specific research on this syndrome with difficulties in developing psychotherapeutic and pharmacological treatments.

Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study.

BACKGROUND: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM10 (both day-of and 14-day average exposures), personal PM2.5, black carbon (BC), and elemental components (potassium, sulfur, iron, silicon, aluminum, zinc, calcium, and titanium). For both PM10 measures, we obtained hourly ambient PM10 data for the study period from the Beijing Municipal Environmental Bureau's 27 representatively distributed monitoring stations. We then calculated a 24h average for each examination day and a moving average of ambient PM10 measured in the 14 days prior to each examination. Examinations measured global levels of H3 lysine 9 acetylation (H3K9ac), H3 lysine 9 tri-methylation (H3K9me3), H3 lysine 27 tri-methylation (H3K27me3), and H3 lysine 36 tri-methylation (H3K36me3) in blood leukocytes collected after work. We used adjusted linear mixed-effect models to examine percent changes in histone modifications per each µg/m3 increase in PM exposure. RESULTS: In all participants each µg/m3 increase in 14-day average ambient PM10 exposure was associated with lower H3K27me3 (ß=-1.1%, 95% CI: -1.6, -0.6) and H3K36me3 levels (ß=-0.8%, 95% CI: -1.4, -0.1). Occupation-stratified analyses showed associations between BC and both H3K9ac and H3K36me3 that were stronger in office workers (ß=4.6%, 95% CI: 0.9, 8.4; and ß=4.1%, 95% CI: 1.3; 7.0 respectively) than in truck drivers (ß=0.1%, 95% CI: -1.3, 1.5; and ß=0.9%, 95% CI: -0.9, 2.7, respectively; both pinteraction <0.05). Sex-stratified analyses showed associations between examination-day PM10 and H3K9ac, and between BC and H3K9me3, were stronger in women (ß=10.7%, 95% CI: 5.4, 16.2; and ß=7.5%, 95% CI: 1.2, 14.2, respectively) than in men (ß=1.4%, 95% CI: -0.9, 3.7; and ß=0.9%, 95% CI: -0.9, 2.7, respectively; both pinteraction <0.05). We observed no associations between personal PM2.5 or elemental components and histone modifications. CONCLUSIONS: Our results suggest a possible role of global histone H3 modifications in effects of traffic-derived PM exposures, particularly BC exposure. Future studies should assess the roles of these modifications in human diseases and as potential mediators of air pollution-induced disease, in particular BC exposure.

Diagnostic Efficacy of Digital Dermoscopy and Clinical Findings in Thin Melanoma of the Lower Limbs.

The introduction of dermoscopy has improved the accuracy of diagnosis of melanoma. However, early stage melanoma can be difficult to diagnose. Eighty-nine cases of thin melanoma with a Breslow thickness ≤1 mm located on the lower limb and diagnosed between 2008 and 2016 were assessed using 4 dermoscopic algorithms: (i) modified pattern analysis; (ii) ABCD rule of dermoscopy; (iii) 7-point checklist; and (iv) Menzies' method. Two groups of early stage melanomas of the legs were identified: "difficult to diagnose melanomas" (DDM) and "non-difficult to diagnose melanomas" (NDDM). In our series the dermoscopic features of DDM were difficult to differentiate from melanocytic naevi, and the reticular pattern was the most frequently observed. "Depigmentation" was the only specific criterion associated with DDM. The sensitivity of diagnostic systems for thin melanomas of the lower limbs was lower than in previous studies. This result could be related to the lower mean Breslow thickness of the invasive melanomas in our sample and the high number of melanomas in situ. In conclusion, early stage melanoma of the legs may be difficult to detect at clinical examination or with dermoscopic examination alone. Focusing on depigmentation in dermoscopy associated with anamnestic features could be a useful tool to detect difficult thin melanomas. In addition, sequential dermoscopy is recommended for high-risk patients with previous melanomas or atypical mole syndrome.

Psychopathology, quality of life and risk factors in children and adolescents with recent-onset epilepsy.

BACKGROUND: The aim of this study was to describe the distribution, timing, and risk factors for psychopathology and to further examine the quality of life (QoL) in an Italian sample of children with recent onset epilepsy. Sociodemographic and psychosocial variables, family factors, as well as illness-related factors themselves were examined in order to clarify the relationship among these variables, psychopathology and QoL. METHODS: For this purpose, 49 children and adolescents (4-18 years), consecutively referred to a Neurophysiology Service, were evaluated by a multidisciplinary team using dimensional as well as categorical instruments both self-administered (self-report and proxy-report) and interviewer administered. RESULTS: Forty-five percent of the patients exhibited one or more Axis I disorders (DSM-IV) when evaluated with K-SADS-PL interview. It's worth noting that preadolescent and adolescent patients tend to underestimate their problems compared to their parents'opinion, when answering self-administer questionnaires. Self-reported QoL appeared to be generally satisfactory. Social and family factor, as well as epilepsy related factors appeared to be linked both to the presence of psychopathology and to the QoL. Patients affected by psychiatric disorders exhibited the poorest QoL. CONCLUSIONS: Also after many years from the onset, childhood epilepsy frequently fosters negative consequences in terms of social life, work, psychopathology and life expectancy. The ability of health services and public health measures to prevent and treat psychiatric comorbidity may have a pivotal role in enhancing patients' QoL.

Primary breast cancer cell culture yields intra-tumor heterogeneous subpopulations expressing exclusive patterns of receptor tyrosine kinases.

BACKGROUND: It has become evident that intra-tumor heterogeneity of breast cancer impact on several biological processes such as proliferation, migration, cell death and also might contribute to chemotherapy resistance. The expression of Receptor Tyrosine Kinases (RTKs) has not been analyzed in the context of intra-tumor heterogeneity in a primary breast cancer cell culture. Several subpopulations were isolated from the MBCDF (M serial-breast cancer ductal F line) primary breast cancer cells and were successfully maintained in culture and divided in two groups according to their morphology and RTKs expression pattern, and correlated with biological processes like proliferation, migration, anchorage-independent cell growth, and resistance to cytotoxic chemotherapy drugs and tyrosine kinase inhibitors (TKIs). METHODS: Subpopulations were isolated from MBCDF primary breast cancer cell culture by limiting dilution. RTKs and hormone receptors were examined by Western blot. Proliferation was measure by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT assay). Cell viability was evaluated by Crystal Violet. Migration was assessed using Boyden chambers. Anchorage-independent cell growth was evaluated by colony formation in soft agar. RESULTS: Several subpopulations were isolated from the MBCDF breast cancer cells that were divided into two groups according to their morphology. Analysis of RTKs expression pattern showed that HER1, HER3, c-Met and VEGFR2 were expressed exclusively in cells from group 1, but not in cells from group 2. PDGFR was expressed only in cells from group 2, but not in cells from group 1. HER2, HER4, c-Kit, IGF1-R were expressed in all subpopulations. Biological processes correlated with the RTKs expression pattern. Group 2 subpopulations present the highest rate of cell proliferation, migration and anchorage-independent cell growth. Analysis of susceptibility to chemotherapy drugs and TKIs showed that only Paclitaxel and Imatinib behaved differently between groups. Group 1-cells were resistant to both Paclitaxel and Imatinib. CONCLUSIONS: We demonstrated that subpopulations from MBCDF primary cell culture could be divided into two groups according to their morphology and a RTKs excluding-expression pattern. The differences observed in RTKs expression correlate with the biological characteristics and chemoresistance of each group. These results suggest that intra-tumor heterogeneity contributes to generate groups of subpopulations with a more aggressive phenotype within the tumor.

Synergies between assisted reproduction technologies and functional genomics.

This review, is a synopsis of advanced reproductive technologies in farm animals, including the discussion of their limiting factors as revealed by the study of offspring derived from embryos produced in vitro and through cloning. These studies show that the problems of epigenetic mis-programming, which were reported in the initial stages of assisted reproduction, still persist. The importance of whole-genome analyses, including the methylome and transcriptome, in improving embryo biotechnologies in farm animals, are discussed. Genome editing approaches for the improvement of economically-relevant traits in farm animals are also described. Efficient farm animal embryo biotechnologies, including cloning and the most recent technologies such as genome editing, will effectively complement the latest strategies to accelerate genetic improvement of farm animals.

Sociodemographic characteristics, risk factors and psychobehavioral disorders associated to alcohol consumption in adolescents of Veneto.

BACKGROUND: This study aims to estimate the alcohol consumption in a large student population in Veneto (North Italy) and to identify possible psychosocial factors associated, with particular attention to the relationship between alcohol consumption and psychopathological vulnerability. METHODS: Two semi-structured questionnaires were administered: the Questionnaire for Adolescents' Saturday evening, ad hoc designed for the study, which investigates the habits and alcohol consumption patterns, and the Youth Self Report which assesses the possible presence of psychic and behavioral problems. We recruited 10,465 students attending secondary and high schools in two Venetian provinces (age range 11-19 years). Frequency and amount of alcohol consumption were analyzed in relation to socio-demographic characteristics, habits, and vulnerability to psycho-behavioral problems. RESULTS: Data confirmed the high occurrence of alcohol consumption among young people (36.5%), with a higher prevalence among males (58,0%); the frequency of consumption and the amount of alcohol in taking increase with age, in greater measure after the transition to higher education level (10.4% in secondary school, 36,% in first year till 50% in third year of high school). Alcohol misuse was associated with: pubs and clubs attendance, coming back home late, a greater availability of money and externalizing behavioral problems. CONCLUSIONS: Results from this study confirmed the worrying data about the prevalence of alcohol misuse among young people, pointing out some protective and risk factors to be taken into account in planning of preventive interventions.

Electropolymerized phenol derivatives as permselective polymers for biosensor applications.

Amperometric biosensors are often coated with a polymeric permselective film to avoid electroactive interference by reducing agents present in the target medium. Phenylenediamine and phenol monomers are commonly used to form these permselective films in the design of microsensors and biosensors. This paper aims to evaluate the permselectivity, stability and lifetime of polymers electrosynthesized using either constant potential amperometry (CPA) or cyclic voltammetry (CV) from naturally occurring phenylpropanoids in monomeric and dimeric forms (eugenol, isoeugenol, dehydrodieugenol and magnolol). Sensors were characterized by scanning electron microscopy and permselectivity analysis. Magnolol formed an electro-deposited polymer with a more defined three-dimensional texture in comparison with the other films. The phenol-derived films showed different permselectivity towards H2O2 over ascorbic acid and dopamine, likely to be related to the thickness and compactness of the polymer. The CV-derived films had a better permselectivity compared to the CPA-corresponding polymers. Based on these results, the permselectivity, stability and lifetime of a biosensor for glucose were studied when a magnolol coating was electro-deposited. The structural principles governing the permselectivity of the magnolol-derived film are suggested to be mainly related to the conformational flexibility of this monomer. Newly designed biosensors, coated with electropolymerized natural phenol derivatives, may represent promising analytical devices for different application fields.

Safety and efficacy of adapalene 0.1% / benzoyl peroxide 2.5% in the long-term treatment of predominantly moderate acne with or without concomitant medication - results from the non-interventional cohort study ELANG.

BACKGROUND: Acne is a chronic inflammatory disease requiring long-term treatment. The fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% (adapalene-BPO) is indicated for the once-daily topical treatment of Acne vulgaris when comedones, papules and pustules are present. OBJECTIVE: The main objectives of this non-interventional study were to assess long-term efficacy and safety of adapalene-BPO in moderate to severe acne with and without concomitant medication. METHODS: Patients with moderate to severe acne received adapalene-BPO alone or in combination with concomitant medication over a course of 9 months. The primary efficacy endpoint was changes in acne severity according to the Leeds Revised Acne Grading System; secondary endpoints included treatment success assessed by the patient and safety. RESULTS: In total, 5131 patients were eligible for efficacy and 5141 for safety evaluation. The majority of patients (78.8%) received adapalene-BPO alone. About 21.2% received adapalene-BPO in combination with another agent, mostly topical antibiotics (8.8%) or systemic antibiotics (8.7%). Mean (±SD) acne severity improved from 5.6 ± 1.5 at baseline to 3.3 ± 1.9 at month 3, and further to 1.9 ± 1.9 at month 9 (both P < 0.0001). The degree of improvement correlated significantly with the severity at baseline. After 3 and 9 months of treatment, the facial skin was cleared completely (no more visible acne lesions) in 420 (8.2%) and 1326 patients (25.8%), respectively. A therapeutic effect was noted by the patients after a median time of 3 weeks (range: from 1 day to 12 weeks). No serious adverse events were reported. Facial skin irritations, mostly mild to moderate, occurred in 49.5% of patients and led to discontinuation in only 1.7% of cases. CONCLUSION: In consistence with previous clinical findings, the use of adapalene-BPO in daily practice routine is safe and effective in the long-term management of patients with moderate to severe acne.

Effect of adapalene 0.1%/benzoyl peroxide 2.5% topical gel on quality of life and treatment adherence during long-term application in patients with predominantly moderate acne with or without concomitant medication - additional results from the non-interventional cohort study ELANG.

BACKGROUND: In addition to physical long-lasting effects such as permanent scarring and disfigurement, acne has acute and long-term psychosocial effects that affect the individual's quality of life. As with other chronic diseases, treatment success is often compromised by poor adherence. OBJECTIVE: Two main objectives of this non-interventional study were to assess the long-term effect of the fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% (adapalene-BPO gel) on quality of life and treatment adherence. METHODS: Patients with moderate to severe facial acne receiving adapalene-BPO alone or in combination with other drugs were enrolled in this non-interventional study. Data were documented at baseline and after 3 and 9 months of adapalene-BPO treatment. The secondary outcomes reported here include quality of life determined by the Cardiff Acne Disability Index (CADI), treatment adherence assessed by the ECOB (Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux) questionnaire, and patient satisfaction. RESULTS: In total, 5131 patients were included in the efficacy evaluation. After 9 months, mean (±SD) quality of life (CADI) improved significantly from 5.9 ± 3.0 to 2.4 ± 2.7 (P < 0.0001). Patients with more severe acne at baseline tended to achieve a greater improvement in quality of life. Long-term adherence was found to be good in 83.9% of patients. Adherence had a significant effect on efficacy and quality of life (P < 0.0001 respectively). The vast majority of patients (92.1%) reported subjective improvement at the interim analysis. Accordingly, most patients (84.8%) were satisfied or very satisfied with adapalene-BPO by the end of the observation period. CONCLUSION: The clinical improvement of the disease led to an increase in quality of life among acne patients. The treatment success may be a motivation factor for patients to stay adherent over the long-term treatment course, indicating the qualification of adapalene-BPO topical gel as an appropriate medication also in the long-term usage.