Miracle-dz/UniFAR-FTUs huggingface dataset:
Silver Nanoparticles Mediate Differential Responses in Keratinocytes and Fibroblasts during Skin Wound Healing

With advances in nanotechnology, pure silver has been recently engineered into nanometer‐sized particles (diameter <100 nm) for use in the treatment of wounds. In conjunction with other studies, we previously demonstrated that the topical application of silver nanoparticles (AgNPs) can promote wound healing through the modulation of cytokines. Nonetheless, the question as to whether AgNPs can affect various skin cell types—keratinocytes and fibroblasts—during the wound‐healing process still remains. Therefore, the aim of this study was to focus on the cellular response and events of dermal contraction and epidermal re‐epithelialization during wound healing under the influence of AgNPs; for this we used a full‐thickness excisional wound model in mice. The wounds were treated with either AgNPs or control with silver sulfadiazine, and the proliferation and biological events of keratinocytes and fibroblasts during healing were studied. Our results confirm that AgNPs can increase the rate of wound closure. On one hand, this was achieved through the promotion of proliferation and migration of keratinocytes. On the other hand, AgNPs can drive the differentiation of fibroblasts into myofibroblasts, thereby promoting wound contraction. These findings further extend our current knowledge of AgNPs in biological and cellular events and also have significant implications for the treatment of wounds in the clinical setting.
MULTIMODAL IMAGING OF WHITE AND DARK WITHOUT PRESSURE FUNDUS LESIONS

Purpose: To describe multimodal imaging findings in patients with dark or white without pressure lesions of the fundus. Methods: Retrospective observational case series of 10 patients with white or dark without pressure lesions. We analyzed multimodal imaging using spectral domain optical coherence tomography, color and near-infrared fundus photography, and fundus autofluorescence imaging to explore the findings associated with these lesions. Results: All patients had geographic dark or white lesions on clinical examination and color photography, which were either hyporeflective or hyperreflective on near-infrared reflectance imaging, respectively. On optical coherence tomography, these lesions correlated with an abrupt change of the photoreceptor reflectivity, with relative hyporeflectivity of photoreceptor zones (ellipsoid and interdigitation zones, as well as outer segments) within the dark, and relative hyperreflectivity within white lesions. Ten patients underwent fundus autofluorescence, which showed well-defined zones of relative hypo-autofluorescence within the lesion, compared with neighboring uninvolved regions, whether dark or white without pressure. In two patients who had a lesion combining white and dark without pressure, we observed the transition in photoreceptor reflectivity from the dark lesion (hyporeflective) to the white lesion (hyperreflective), relative to the surrounding retina. Conclusion: Both white and dark without pressure lesions are associated with changes in outer retinal reflectivity on optical coherence tomography, which occur in opposite directions compared with the surrounding unaffected areas. In the face of normal visual field testing to date, the clinical significance of this finding remains uncertain. Recognition of the optical coherence tomography appearance will help clinicians avoid unnecessary workup of these patients for outer retinal dystrophy or degeneration.
The Binding Mode of Side Chain‐ and C3‐Modified Epothilones to Tubulin

The tubulin‐binding mode of C3‐ and C15‐modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin‐bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3‐modified analogues investigated. In particular, 3‐deoxy‐ (compound 2) and 3‐deoxy‐2,3‐didehydro‐Epo A (3) were found to adopt similar conformations in the tubulin‐binding cleft as Epo A, thus indicating that the 3‐OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin–epothilone complex is able to fully recapitulate the differences in tubulin‐polymerizing activity and microtubule‐binding affinity between C20‐modified epothilones 6 (C20‐propyl), 7 (C20‐butyl), and 8 (C20‐hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline‐based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of β‐His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule‐binding data for 4, 5, and Epo B.
Characteristics of concatemeric GABAA receptors containing α4/δ subunits expressed in Xenopus oocytes

BACKGROUND AND PURPOSE GABAA receptors mediate both synaptic and extrasynaptic actions of GABA. In several neuronal populations, α4 and δ subunits are key components of extrasynaptic GABAA receptors that strongly influence neuronal excitability and could mediate the effects of neuroactive agents including neurosteroids and ethanol. However, these receptors can be difficult to study in native cells and recombinant δ subunits can be difficult to express in heterologous systems.
An Integrated Literature Review of the Knowledge Needs of Parents With Children With Special Health Care Needs and of Instruments to Assess These Needs

The purpose of this integrative (including both quantitative and qualitative studies) literature review was to identify knowledge needs of parents of a child with special health care needs and to evaluate instruments to assess these needs. The content analysis of 48 publications revealed a vast amount of knowledge needs that were categorized into 9 categories: (a) knowledge about the condition or illness, (b) support, (c) treatment, (d) everyday care of the child, (f) the future, (g) how to explain the illness to others, (h) equipment, (i) organizational issues, and (j) the effect of the illness on the family. Several instruments to assess these needs are described. There is evidence that parents have various knowledge needs at different times of their children's life and it is important that these needs are assessed systematically. Professionals have many possibilities to provide information and education as it is needed by these parents.
Psychiatric comorbidity in Wilson’s disease

Abstract Wilson’s disease (WD) is a relatively rare autosomal recessive inherited disorder causing copper accumulation in different organs, mainly the liver and brain. Psychiatric disturbances represent a diagnostic and therapeutic issue in WD. A search for relevant articles was carried out on PubMed/Medline, Scopus, and Google Scholar, for papers focused on psychiatric disorders in WD published between 1985–2016. Ninety-two articles were included in this review, showing the findings from 35 observational and case-control studies and 57 case reports. This study discussed the findings on the prevalence of psychiatric symptoms in WD, their impact on the life of those diagnosed, and the efficacy of available treatments on the psychiatric outcomes of WD. Psychiatric disorders are confirmed frequent in WD, with a high prevalence of mood disorders, and contribute to worse Quality-of-Life and psychosocial outcomes. Because specific therapies for WD lead to a good life expectancy, adherence to medicaments and clinical monitoring should be warranted by a multidisciplinary approach, including a hepathologic, neurologic, and psychiatric careful evaluation and education of those affected and their relatives.
PHASE II, RANDOMIZED, PLACEBO-CONTROLLED, 90-DAY STUDY OF EMIXUSTAT HYDROCHLORIDE IN GEOGRAPHIC ATROPHY ASSOCIATED WITH DRY AGE-RELATED MACULAR DEGENERATION

Purpose: This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy associated with dry age-related macular degeneration. Methods: Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity after a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events and ophthalmic examinations. Results: Seventy-two subjects (54 emixustat and 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14 and was reversible within 7 days to 14 days after drug cessation. Most systemic adverse events were not considered treatment related. Dose-related ocular adverse events (chromatopsia, 57% emixustat vs. 17% placebo and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate in severity, and the majority resolved on study or within 7 days to 14 days after study drug cessation. Reversibility of these adverse events with long-term administration, however, is undetermined. Conclusion: In this Phase II study, emixustat produced a dose-dependent reversible effect on rod function that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of geographic atrophy associated with dry age-related macular degeneration.
Hyperkeratosis of the nipple and areola: 2 years of remission with low‐dose acitretin and topical calcipotriol therapy

Hyperkeratosis of the nipple and areola is a rare disorder characterized by verrucous thickening and brown pigmentation of the nipple and areola with unknown etiology. Although it is a generally asymptomatic disorder, cosmetic disfiguring creates a real psychological problem for young women. Moreover, treatment regimens are not satisfactory. Surgical treatment has been suggested as an initial treatment in resistant and recurrent cases because of the relapses seen after medical treatment. We report a case who responded satisfactorily to low‐dose acitretin and topical calcipotriol treatment with no relapses during 2 years of follow‐up. Among all reported medical treatments and interventional approaches, including surgery, this is the first patient reported with 2 years of remission.
Adherence in dermatology

Abstract Non-adherence to treatment and medical recommendations is one of the leading causes of treatment failure, poor clinical outcomes, and increased healthcare utilization. Although non-adherence is observed across all medical specialties, adherence to treatment in dermatology deserves special attention given the multiple different routes of treatment. Adherence can be measured using subjective methods (patient reporting and questionnaires) or objective methods (pill counts, electronic chips, and pharmacy records). Adherence to dermatologic treatments varies based on the specific condition but is poor for systemic therapies and even worse with topical agents. Among the factors that influence adherence, duration of treatment, complexity of regimen, and access play a large role. Interventions to improve adherence can range from simplifying treatment regimens to scheduling more frequent office visits. Due to the profound effect on cost, healthcare outcomes, and mortality, understanding and improving adherence is equally as important as making the correct diagnosis and prescribing the correct treatment.
Treatment of hookworm-related cutaneous larva migrans with topical ivermectin

Oral ivermectin was first used in the treatment of hookwormrelated cutaneous larva migrans (HrCLM) in 1992 (1,2). The drug was mainly employed as single dose (1–5); however, in some cases, two or three courses have been necessary (4,6). In rare cases, ivermectin was ineffective (7,8). Percentage of complete remission ranges from 77% (4) to 81% (5) to 97% (4) to 100% (1,5). The time of response ranges from 24–48 h (1) to 3–7 days (4). Oral ivermectin was also successfully used in children (9). To our knowledge, topical ivermectin was never used for the treatment of HrCLM. In 14 Caucasian patients (eight adults (4 males and 4 females) and six children (5 males and 1 female)), with an age ranging from 4 to 55 years, a diagnosis of HrCLM was made by means of history and clinical picture. All patients had recently returned from a trip to Fortaleza (Brazil). Feet and/or ankles were involved in 12 patients; two children had tracks on the buttocks. Ten patients had one track, three patients two tracks and one patient three tracks. All patients were treated with 1% ivermectin cream (2 applications/ day with occlusive plaster for two weeks). All patients were followed up for at least three weeks after the end of the treatment. Complete remission was observed in one child. No clinical improvement was observed in the other patients. Significant reduction in pruritus was recorded in two adults. According to our observations, 1% ivermectin cream seems to be ineffective in the treatment of HrCLM.
OUTER RETINA CAPILLARY INVASION AND ELLIPSOID ZONE LOSS IN MACULAR TELANGIECTASIA TYPE 2 IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY

Purpose: Macular telangiectasia Type 2 (MacTel2) is a neurodegenerative and vascular disease limited to the macular area, resulting ultimately in Muller cell and photoreceptor loss and intra or subretinal proliferation. Optical coherence tomography angiography was used to correlate the proliferation of capillaries in the outer retina with the topography of the ellipsoid zone (EZ) loss. Methods: Thirty eyes of 15 patients with MacTel2 were examined using optical coherence tomography angiography. Images of the superficial and deep capillary plexus were analyzed and compared with en-face angio-flow images of the outer retina and en-face image of the EZ. Results: Twenty-one eyes were available for the study, including 12 with invasion of the outer retina capillary on optical coherence tomography angiography but without subretinal neovascularization. The outer retina capillary proliferation had a radial pattern in eight cases, formed loops in four, and was circumscribed to an area of EZ loss on en-face images. In nine cases, there was no outer capillary proliferation including two cases with foci of EZ loss. Conclusion: Optical coherence tomography angiography shows capillary proliferation in the outer retina corresponding to areas of EZ loss, which could be a useful marker to monitor the efficacy of possible treatments in MacTel2 disease.
Distinct endothelial pathways underlie sexual dimorphism in vascular auto‐regulation

BACKGROUND AND PURPOSE Pre‐menopausal females have a lower incidence of cardiovascular disease compared with age‐matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction in response to raised intraluminal pressure) is a major determinant of vascular resistance. Endothelium‐derived dilators, particularly NO, tonically moderate myogenic tone and, because the endothelium is an important target for female sex hormones, we investigated whether NO‐mediated moderation of myogenic tone differed between the sexes.
Treatment patterns in moderate-to-severe plaque psoriasis: results from a Belgian cross-sectional study (DISCOVER)

Abstract Purpose: The present study aimed to evaluate current treatment patterns and achievement of treatment goals in Belgian patients with moderate-to-severe plaque psoriasis. Materials and methods: This cross-sectional observational study (DISCOVER) was conducted in 2011 − 2012 in Belgian dermatology centers. Patient data were collected during a single visit and included information on psoriasis management and severity (PASI and DLQI). Treatment success was defined according to the current European consensus treatment goal algorithm. Results: Of the 556 patients included in the study, 38.1% reported no current treatment or only topicals, 34.2% were being treated with traditional systemics and/or phototherapy, and 29.5% with biologics. Methotrexate (11.7%) was the most commonly prescribed traditional systemic and adalimumab (14.2%) was the most commonly prescribed biologic agent at the time of the study. The percentage of patients achieving treatment goals was significantly higher in biologic-treated patients (73.1%) compared to those using traditional systemics (50.6%), phototherapy (41.1%), or no treatment/only topicals (20.9%; p < .001). Conclusions: Nearly 40% of Belgian patients with moderate-to-severe psoriasis in the DISCOVER study were undertreated despite the severity of their disease. Undertreatment of psoriasis remains a problem in Belgium and more effective educational strategies are needed to ensure the best treatment outcome for these patients.
District nurses’ documentation of patients with chronic pain conditions before and after the introduction of ‘pain advisers’

The aim of the present study was to review the district nurses’ documentation of patients suffering from chronic pain conditions and to investigate whether the documentation changed after the introduction of specifically educated, district nurses (‘pain advisers’) at the primary health care centres (PHCC). A study area with five PHCCs and a control area with seven PHCCs were selected. One ‘pain adviser’ was introduced at each PHCC in the study area. The district nurses in the study area and the control area were asked to register all the patients older than 16 years with chronic pain conditions with whom they were in contact. The records of all the registered patients were collected in two periods (before and after the introduction of the pain advisers) and a review of different aspects of the nursing documentation related to chronic pain was performed. The nurses’ documentation regarding the patients’ chronic pain conditions was found to be incomplete and minimal. After the introduction of ‘pain advisers’ into the study area, some improvements were found in both areas. Our results indicate that the introduction of ‘pain advisers’ to some extent improved the documentation in the study area, but that further interventions are needed in order to improve it further.
Secukinumab provides better relief from the impact of psoriasis on daily activities and personal relationships than etanercept: results of two phase 3 placebo-controlled randomized clinical trials in moderate-to-severe psoriasis

Abstract Background: Psoriasis can greatly impact patients’ lives, influencing what clothing they wear and impairing their sexual functioning. Objective: To provide a detailed comparison of the impact of secukinumab vs. etanercept on enabling patients with psoriasis to have more normal lives with respect to daily activities (DA) (e.g. choosing clothing) and personal relationships (PR) (e.g. sexual functioning). Methods: Baseline to Week 52 ERASURE and FIXTURE data for secukinumab 300 mg and etanercept were analyzed. Treatment differences in mean scores on the DA and PR subscales and items from the Dermatology Life Quality Index were compared. The proportions of subscale and item responders (score = 0) were compared. Results: Subjects receiving secukinumab (n = 572) achieved greater mean improvement in DA and items (q3 and q4) than subjects receiving etanercept (n = 326; all p < .01 through Week 52). Subjects receiving secukinumab achieved greater mean improvement in PR and items (q8 and q9) than subjects receiving etanercept (subscale: p < .05 at Weeks 8 and 12). Response rates were significantly higher for secukinumab than for etanercept for DA (all p < .0001) and PR (all p < .05 except Weeks 4 and 36). Conclusions: Secukinumab 300 mg provides greater improvements and more effective relief from psoriasis impact on DA and PR than etanercept.
Real-world outcomes in 2646 psoriasis patients: one in five has PASI ≥10 and/or DLQI ≥10 under ongoing systemic therapy

Abstract Background: Although biologics introduced a new era in psoriasis care when available a decade ago, it is unclear to what extent the available systemic treatments treat patients adequately. Objective: To analyse the clinical severity and quality of life of the psoriasis population in Sweden treated with systemics. Methods: Data included 2646 patients from the Swedish Registry for Systemic Treatment of Psoriasis. Average Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and EQ-5D were reported. A subgroup of persisting moderate-to-severe psoriasis as defined by PASI ≥10 and/or DLQI ≥10 after >12 weeks treatment was analysed. Results: Mean (SD) PASI, DLQI and EQ-5D were 4.12 (4.57), 4.11 (5.24) and 0.79 (0.22). Eighteen percent had persisting moderate-to-severe psoriasis (n = 472). These patients were younger, had higher BMI, had psoriasis arthritis and were smoking to a larger extent (p < 0.01) compared with lower-severity patients (n = 2174). Mean (SD) EQ-5D was also considerably lower 0.63 (0.29) vs. 0.82 (0.19) (p < 0.01). Conclusion: Almost one in every five patients had persisting moderate-to-severe psoriasis, despite ongoing systemic treatment. Both comorbidities and life style factors were associated with persisting moderate-to-severe psoriasis. The considerably lower generic quality of life in these patients demonstrates an unmet need. Subsequently, improved access to biologics and continuous drug development is needed in psoriasis.
Factors affecting the course and severity of adult acne. Observational cohort study

Abstract Objective: To identify factors improving symptoms and shortening duration of AA. Material and methods: The observational cohort study was performed in 111 patients with AA (>25 y.o.) in 2015–2016. Clinical manifestation, previous treatments, environmental risk factors and features of juvenile acne affecting AA were assessed. Results: The maximum severity of persistent acne was significantly lower after 25 years of age, as compared to adolescence (7.2 vs. 6.4; p = .0027). The number of acne therapies used in AA was twice as high as in juvenile acne (22 vs. 11). The severity of AA sufficient to leave scars was significantly lower than of juvenile acne (6.0 vs. 7.3; p = .0001) with 22% of patients developing scars only in adult life. Patients linked exacerbations to stress exposure (p = .09 and <.0001 for those reporting at least one stressor and all patients, respectively), finding lifestyle changes the most stressful (p = .046). Those using full-coverage foundations received significantly more acne treatments over lifetime (5.4 vs. 3.6; p = .0359) and for AA (4.4 vs. 2.8; p = .0043). Discontinuation of oral contraceptives or sensitive, erythema-prone skin also worsened the symptoms. Conclusion: Lifestyle change-related stress, sensitive skin, discontinuation of oral contraceptives and using full-coverage foundations increase severity of AA.