Dynamics of Plasma Cytokines in a Patient with Deficiency of Interleukin-36 Receptor Antagonist Successfully Treated with Anakinra

Generalized pustular psoriasis (GPP) is an autoinflammatory disease characterized by abrupt-onset episodes of erythematous skin plaques with countless pustules, fever, marked neutrophilia and increased acute phase reactants (APR).¹ Loss-of-function mutations in the IL36RN gene, encoding for interleukin (IL)-36 receptor antagonist (IL-36Ra), have been described in a significant proportion of GPP patients.^2,3 Previous studies have shown in vitro and ex vivo enhanced production of pro-inflammatory cytokines (IL-1, IL-6 and IL-8) and successful outcomes with anti-IL-1 drugs in patients carrying IL36RN mutations.^1,2 However, little is known about the correlation of plasma cytokines, inflammatory markers and clinical follow-up, before and after treatment with anti-IL-1 drugs.

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Comment on: A Visual Literacy Course for Dermatology Trainees

We would like to congratulate Griffin and colleagues on their report of an innovative training programme in visual literacy for dermatology registrars (residents).¹ Our experience of visual literacy training for registrars in South London resonates with that of the Manchester group, and we would like to add to this by describing our observation of some additional qualitative benefits which may be derived from such training. Training similar to that described by the Griffin et al was delivered to 10 dermatology registrars at the Dulwich Picture Gallery in London, England from September 2016 – January 2017 in 5 one hour sessions. Baseline and post-course assessments, scored on the unique accurate observations method described by Huang et al,² were carried out and demonstrated an increase in the number of unique accurate observations per image following the course compared to pre-course assessment.

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Halofuginone improves caustic-induced oxidative injury of esophagus in rats

Abstract

Background

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.

Materials and methods

Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.

Results

GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.

Conclusion

In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

Longitudinal melanonychia due to voriconazole therapy during treatment of chromoblastomycosis

A feasibility study for a triple-blind randomized controlled trial investigating the effects of oral isotretinoin on mood and quality of life in patients with acne vulgaris

Summary

Isotretinoin is used in the treatment of severe acne vulgaris (AV), but has controversially been associated with depression and suicide. Large prospective studies have failed to translate this clinically. We undertook a feasibility study to investigate the parameters of a triple-blind, randomized controlled trial (RCT) assessing the effect of oral isotretinoin on quality of life (QoL) and mood in patients with AV. Patients meeting the inclusion criteria were randomized for 2 weeks to isotretinoin or doxycycline. Participants completed verified depression and QoL screening questionnaires at baseline and week 2. In total, 194 patients with AV were screened, with 48 meeting the inclusion criteria and 13 of these being willing to participate. The follow-up rate was 92% and questionnaire response rate was 96%. To our knowledge, this is the first study to demonstrate a successful design for a triple-blind RCT investigating the effects of isotretinoin on mood in patients with AV.

Chromogranin A is not a biomarker of mastocytosis

Publication date: Available online 13 October 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Pahul Hanjra, Chyi-Chia R. Lee, Irina Maric, Melody Carter, Ana Olivera, Dean D. Metcalfe, Hirsh D. Komarow

Persistent tryptase elevation in a patient with Gaucher disease

Publication date: Available online 13 October 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Edith Schussler, Amy Yang, Jonathan J. Lyons, Joshua D. Milner, Julie Wang

Drug-Induced Paradoxical Vocal Fold Motion

Publication date: Available online 14 October 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Marlene Garcia-Neuer, Donna Marie Lynch, Kathleen Marquis, Jayme Dowdall, Mariana Castells, David Edward Sloane
Vocal cord dysfunction, also known as paradoxical vocal fold motion (PVFM), is a disorder characterized by abnormal vocal cord adduction during inspiration. PVFM is commonly misdiagnosed as asthma because of the similarity of symptoms: cough, wheezing, chest pain, and dyspnea. We present the clinical vignette of a 36-year-old woman with juvenile rheumatoid arthritis and multiple adverse drug reactions who presented with recurrent episodes of unrecognized PVFM during skin testing for drug allergy, omalizumab treatment, and tocilizumab desensitization. Before the diagnosis of PVFM, these episodes were treated as anaphylaxis, including the administration of epinephrine. Once diagnosed and treated for PVFM, the patient did not present any further events and continued treatment for drug allergy. PVFM may be underreported in hypersensitivity reactions because of the similarity to Type 1-mediated respiratory symptoms and comorbid asthma.

Epidemiology of skin cancer in the mature patient

Publication date: Available online 13 October 2017
Source:Clinics in Dermatology
Author(s): Vivien Lai, William Cranwell, Rodney Sinclair
Epidermal cancers include keratinocyte cancer, melanocyte cancer and Merkel cell carcinoma. These cancers account for the vast majority of new cancer diagnosed in Australia, North America and Europe. Keratinocyte cancer is the most common epidermal cancer and accounts for 7 out of 8 new cancers diagnosed in Australia. Melanoma and Merkel cell carcinoma are less common than keratinocyte carcinoma but are more important causes of mortality in Australia. Keratinocyte cancer has also been demonstrated to be a marker of cancer-prone phenotype. Risk factors for epidermal cancer include intrinsic and environmental factors, in particular exposure to ultraviolet radiation and advanced age. Actinic keratosis has an approximate prevalence of 79% of men and 68% of women between the ages of 60 to 69years, and has a low risk of malignant transformation into in squamous cell carcinoma. Basal cell carcinoma is the most common malignancy in Caucasians worldwide, with the incidence increasing by 2% per year in Australia. In 2010, the incidence of BCC in Australia was 1541 per 100,000 persons. Squamous cell carcinoma is the second most common epidermal cancer, with an incidence of approximately 1035 or 472 per 100,000 person years in males and females respectively. Primary risk factors for both BCC and SCC include light skin color, UV radiation exposure and chronic immunosuppression. Although the rate of melanoma is increasing, the mortality in Australia is reducing and is currently 9%. The overall incidence of melanoma in Australia is approximately 50 cases per 100,000 persons (62 for males and 40 for females). Keratinocyte carcinoma and melanoma are risk factors for developing further skin cancer and primary malignancy. This article reviews the incidence, prevalence and risk factors associated with the development of epidermal cancer and pre-malignant epidermal neoplasia.

Ethical Challenges with Treating Non-Adherent Patients in a Group Practice Setting

Omalizumab Response in Patients with Chronic Idiopathic Urticaria: Insights from the XTEND-CIU Study

Potential impact of global climate change on benthic deep-sea microbes

Abstract

Benthic deep-sea environments are the largest ecosystem on Earth, covering approximately 65% of the Earth surface. Microbes inhabiting this huge biome at all water depths represent the most abundant biological components and a relevant portion of the biomass of the biosphere, and play a crucial role in global biogeochemical cycles. Increasing evidence suggests that global climate changes are affecting also deep-sea ecosystems, both directly (causing shifts in bottom-water temperature, oxygen concentration and pH), and indirectly (through changes in surface oceans' productivity and in the consequent export of organic matter to the seafloor). However, the responses of the benthic deep-sea biota to such shifts remain largely unknown. This applies particularly to deep-sea microbes, which include bacteria, archaea, micro-eukaryotes and their viruses. Understanding the potential impacts of global change on the benthic deep-sea microbial assemblages and the consequences on the functioning of the ocean interior is a priority to better forecast the potential consequences at global scale. Here we explore the potential changes in the benthic deep-sea microbiology expected in the coming decades using case studies on specific systems used as test models.

The Role of Next-Generation Sequencing in Sarcomas: Evolution From Light Microscope to Molecular Microscope

Abstract

Purpose of Review

Sarcomas are rare, heterogeneous group of soft tissue and bone tumors. Precise diagnosis of specific subtypes is challenging using conventional methods. Herein, we review the role of next-generation sequencing (NGS) technology that is used for rapid sequencing of DNA and RNA.

Recent Findings

Recent sarcoma specific studies recommend that molecular genetic testing should be added at diagnosis for appropriate clinical management in addition to diagnosis by expert pathologists. NGS has already been used to identify potentially actionable mutations, copy number alterations, and gene fusions. Rationally, choosing a drug based on an individual patient profile aka: "precision oncology" has been so far limited to few case reports in sarcomas.

Summary

As we improve our ability to deliver personalized medicine using all modalities including conventional therapy, more patients may eventually benefit. As the cost and capacity of NGS outpace Moore's law, so does the probability of success.

Trichodysplasia spinulosa associated with HIV infection: clinical response to acitretin and valganciclovir

Stevens–Johnson syndrome induced by modafinil

N - tert -butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors

Abstract

The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A₁₆₅ with no effect on the activity of the non-heparin-binding VEGF-A₁₂₁ isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, and computer modeling indicate that BOC2 may interact with the heparin-binding domain of VEGF-A₁₆₅, thus competing for heparin interaction and preventing the binding of VEGF-A₁₆₅ to tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In addition, BOC2 inhibits the interaction of a variety of heparin-binding angiogenic growth factors with heparin, including fibroblast growth factor 2 (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2 suppresses the angiogenic potential of human tumor cell lines that co-express VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding growth factor antagonist. These findings caution about the interpretation of FPR-focusing experimental data obtained with this compound and set the basis for the design of novel BOC2-derived, FPR independent multi-target angiogenesis inhibitors.

Characterization of Adipose Tissue Product Quality Using Measurements of Oxygen Consumption Rate

Abstract

Background

Fat grafting is a common procedure in plastic surgery but associated with unpredictable graft retention. Adipose tissue (AT) "product" quality is affected by the methods used for harvest, processing and transfer, which vary widely amongst surgeons. Currently, there is no method available to accurately assess the quality of AT.

Objectives

In this study, we present a novel method for the assessment of AT product quality through direct measurements of oxygen consumption rate (OCR). OCR has exhibited potential in predicting outcomes following pancreatic islet transplant. Our study aim was to reapportion existing technology for its use with AT preparations and to confirm that these measurements are feasible.

Methods

OCR was successfully measured for en bloc and postprocessed AT using a stirred microchamber system. OCR was then normalized to DNA content (OCR/DNA), which represents the AT product quality.

Results

Mean (±SE) OCR/DNA values for fresh en bloc and post-processed AT were 149.8 (± 9.1) and 61.1 (± 6.1) nmol/min/mg DNA, respectively. These preliminary data suggest that: (1) OCR and OCR/DNA measurements of AT harvested using conventional protocol are feasible; and (2) standard AT processing results in a decrease in overall AT product quality.

Conclusions

OCR measurements of AT using existing technology can be done and enables accurate, real-time, quantitative assessment of the quality of AT product prior to transfer. The availability and further validation of this type of assay could enable optimization of fat grafting protocol by providing a tool for the more detailed study of procedural variables that affect AT product quality.

Non-Tuberculous Mycobacteria Infection Following Autologous Fat Grafting on the Face

Abstract

Autologous fat grafting (AFG) for facial augmentation has become more and more popular because of its biocompatibility and low donor site morbidity. The differential diagnoses of delayed nodule formation after the procedure include fat necrosis and atypical infection. In this study, we report on a female patient suffering from nontuberculous mycobacteria (NTM) infection after AFG for facial augmentation. Multiple flesh-colored and erythematous nodules and tumors developed on her face 6 weeks after the procedure. Tissue culture yielded Mycobacterium abscessus. The management of NTM infections is discussed and a reminder of the importance of standard aseptic surgical techniques is provided.

Level of Evidence: 5

Pure Mucinous (Colloid) Adenocarcinoma of the Conjunctiva

Mucinous carcinomas of the periorbital area are very rare malignant tumors and can be primary or secondary to metastasis. Primary mucinous carcinomas of the eyelid include, most commonly, primary cutaneous mucinous carcinoma with endocrine mucin-producing sweat gland carcinoma being a remote second.[1,2,3,4] To our knowledge, primary mucinous carcinomas of conjunctiva or lacrimal gland elements have not been described in the literature.[5,6] Metastatic carcinoma from visceral sites should also be considered in the differential diagnosis.

Lupus-like cutaneous reaction following pembrolizumab: an immune-related adverse event associated with anti-PD-1 therapy

PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignancies, are associated with development of immune-related adverse events in the skin. Such reactions include morbilliform eruptions, vitiligo, alopecia areata, and bullous pemphigoid. In this report, we describe a patient who developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy for metastatic melanoma, adding to the spectrum of reactions which may be observed in association with PD-1 inhibitor therapy.

Leukocytoclastic vasculitis presenting in association with Coxiella burnetii (Q fever); a case report

Q fever caused by Coxiella burnetii usually presents asymptomatically or as an undifferentiated febrile disease and rarely as rash or other cutaneous manifestations of the disease. Here we present a 41 year old male complaining of body aches, fevers, nausea, malaise, bilateral knee pain, and vomiting. Clinical examination revealed a notable erythematous blanching rash all over his body. Workup revealed positive serologic testing for C burnetii and skin biopsy of the rash revealed leukocytoclastic vasculitis.

The Warburg effect: persistence of stem cell metabolism in cancers as a failure of differentiation

Abstract

Background: Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive ('aerobic') glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate.Patients and Methods: Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we performed pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake.Results: We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters.Conclusions: Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We found that cancers cluster along the differentiation pathway into two groups, utilizing either glycolysis or oxidative phosphorylation. Our results have implications for multiple areas of clinical oncology.

Atypical ALK-positive Spitz tumors with 9p21 homozygous deletion: report of two cases and review of the literature

ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25 (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical behavior. Here we report two unique cases. Case 1 occurred in a 9-year-old male with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive Spitz tumor containing an irregular nodule of densely packed melanocytes with increased mitoses and loss of p16 immunoreactivity. FISH analysis showed homozygous deletion of 9p21 and gain of 6p25. Sentinel lymph node biopsy revealed small subcapsular foci of tumor. Case 2 occurred in a 7-year-old female with a 12-mm nodule on the anterior right ankle. Biopsy revealed an ALK-positive Spitz tumor containing an expansile nodule of pleomorphic epithelioid melanocytes with numerous mitoses and loss of p16 immunoreactivity. By FISH, the nodule showed homozygous deletion of 9p21 and gains of 6p25 and 11q13. Our cases demonstrate the transformation of tumors produced by an activating kinase fusion gene (ALK) through secondary genetic changes including loss of tumor suppressor activity (CDKN2A). Long-term follow-up will be important to further define the behavior of these unique Spitz tumors.

What does the character of medicine as a social practice imply for professional conscientious objection?

Abstract

The dispute over professional conscientious objection presumes a picture of medicine as a practice governed by rules. This rule-based conception of medical practice is identifiable with John Rawls's conception of social practices. This conception does not capture the character of medical practice as experienced by practitioners, for whom it is a sensibility or "form of life" rather than rules. Moreover, the sensibility of medical practice as experienced by physicians is at best neutral, and at worst hostile, to the demands of those who would override physician conscientious objection to the provision of currently contested services. That being so, calls for overriding physician conscientious objection are much more demanding of the medical profession than they appear in light of Rawls's view. As such overriding may entail the forcible transformation of medicine's form of life, the author contends that it would be more prudent to provide contested services by circumventing the medical profession than by compelling it.

Treatment of pediatric anogenital condyloma acuminata with sinecatechins ointment

Local hyperthermia therapy for refractory cutaneous Mycobacterium marinum infection

Co-inhibitory profile and cytotoxicity of CD57+PD-1- T-cells in end stage renal disease patients

Summary

Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection as compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28^- T-cells, which express CD57, are not susceptible to belatacept treatment. High number of CD4⁺CD57⁺PD-1^- T-cells pre transplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of FACS-sorted CD4⁺CD57⁺PD-1^- and CD8⁺CD57⁺PD-1^- T-cells, and their CD57^- control populations, after allo antigen stimulation. The effect of belatacept on the cytotoxic capacity of pre-transplantation peripheral blood mononuclear cells from 20 patients who received belatacept post-transplantation was also tested. Expression of co-inhibitory molecule CD223 increased by approximately 10-fold after allogeneic stimulation in all four T-cell subsets. Proliferation and upregulation of CD244 and PD-1 was observed for CD4⁺CD57^-PD-1^- T-cells after allogeneic stimulation, but no upregulation of these markers occurred on CD8⁺ T-cells or CD4⁺CD57⁺PD-1^- T-cells. However, CD4⁺CD57⁺ PD-1^- T-cells and, to a lesser extent, CD8⁺CD57⁺PD-1^- T-cells displayed higher cytotoxicity as indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential of CD4⁺CD57⁺PD-1^- T-cells (median of inhibition 31%, p<0.01) and CD8⁺CD57⁺PD-1^- T-cells (median of inhibition 10%, p<0.05).

In conclusion, alloantigen activated CD4⁺CD57⁺PD-1^- T-cells exhibited a less proliferative but more cytotoxic profile than their CD57^- counterparts. Their cytotoxic capacity can be partly inhibited by belatacept and was not associated with development of rejection after kidney transplantation. This article is protected by copyright. All rights reserved.

Generalized pustular psoriasis triggered by Zika virus infection

Summary

Zika virus is an emerging arbovirus, which is expanding in epidemic proportions through tropical and subtropical areas of the world. Although Zika is linked to a number of congenital and neurological complications, there is scarce knowledge on the impact of ZIKV infection in human skin. We report the case of a 68-year old woman who presented with generalized pustular psoriasis after a preceding and otherwise uneventful episode of ZIKV infection. Based on recent experimental data on the biology of ZIKV infection in the cutaneous environment, we speculate that ZIKV may have directly triggered the development of generalized pustular psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a polyfunctional T-cell driven immune reaction in the cutaneous milieu.

Lymphopenia and fumaric acid esters for psoriasis: a retrospective case series prompted by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommendations

Pemphigus vulgaris complicated by extensive keloid scarring

Characterization of two distinct lipomas: a comparative analysis from surgical perspective

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Iron’s fingerprint of deposits—iron speciation as a geochemical marker

Abstract

The article describes the studies of the iron speciation (the occurrence of Fe(II), Fe(III), and complexed iron) in acid leachable fraction of deposits. The speciation of iron was diverse for deposits of different origins and was the specific "fingerprint"—marker of deposition processes. The higher occurrence of Fe(II) may be connected with decantation which has been observed for lake sediments, the majority of Fe(III) with upper flow regime erosion-deposition processes, observed for river sediment deposition during flood episodes. As verification for this hypothesis, the explanation for the iron speciation in the different river sediment samples has been used.

Systemtherapie der Vitiligo

Zusammenfassung

Die systemische medikamentöse Behandlung der Vitiligo beschränkt sich derzeit vorwiegend auf adjuvante Maßnahmen zur Wirkungssteigerung einer UV-Licht-Therapie. In diesem Beitrag werden neue Ansätze für eine systemische Therapie der Vitiligo vorgestellt, die derzeit in klinischer Erprobung sind. Dazu gehören das α‑MSH-Analogon Afemelatonide sowie orale Immunsuppressiva, wie die Januskinasen(JAK)-Inhibitoren, die gezielt Interferon-α-abhängige autotoxische Entzündungsreaktionen hemmen. Im Jahr 2015 sind erste Publikationen über den erfolgreichen systemischen Einsatz von Januskinasen(JAK)-Inhibitoren Tofacitinib und Ruxolitinib bei Vitiligo erschienen, für deren Wirksamkeit Untersuchungen an Tiermodellen der Vitiligo sowie die Charakterisierung neuer Biomarker im Serum von Vitiligopatienten sprechen. Das Spektrum der systemischen Therapiemöglichkeiten bei Vitiligo wird sich dadurch möglicherweise erweitern. Die topische antientzündliche Therapie und Bestrahlungen mit UV-Licht bleiben aber die wichtigsten Komponenten der Vitiligobehandlung, die häufig kombiniert werden. Die entscheidenden Zielparameter für eine wirksame Therapie der Vitiligo sind Ausmaß und Dauer der Repigmentierung, Anhalten der Progression, Vermeidung von Nebenwirkungen und die Besserung der Lebensqualität der Patienten.

Use of carboxyhemoglobin as a biomarker of environmental CO exposure: critical evaluation of the literature

Abstract

Carbon monoxide (CO) poisoning is the primary cause for access to emergency department (ED) services for more than 50,000 persons in Europe and the USA every year. CO poisoning diagnosis is based on multiple factors and is usually confirmed by high carboxyhemoglobin (COHb) levels in the blood. We conducted a systematic evaluation of literature to investigate the usefulness of COHb as a biomarker of environmental CO exposure. We conducted an electronic search in Medline, Embase, and the Cochrane Library databases. We selected studies reporting high or low environmental CO concentrations, as well as COHb levels in exposed subjects presenting in ED or staying at home. We included 19 studies, but only 7 studies reported environmental CO concentration and proved a correlation between COHb and CO exposure in healthy and non-smoker subjects only. However, confounding factors were often incompletely assessed. The main symptoms reported were headache, nausea, vertigo and vomiting. COHb data stored in healthcare databases were used in six studies and provided useful information about symptoms, CO sources and patient characteristics. Most studies were classified at risk of bias. This review indicates that COHb is the most commonly used biomarker to assess CO exposure and seems to be useful. Further studies are needed to establish the reliability of COHb as a biomarker and/or explore other possible biomarkers. Surveillance systems of the general population, correlated with geographical locations and other confounding factors, could be important for CO exposure monitoring and the development of focused prevention programs.

Changes in circulating cell-free DNA and nucleosomes in patients with exacerbated psoriasis

Abstract

Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6. The range of PASI score in psoriatic patients was 10–34 (median 19). In the patients, we found significantly elevated levels (p < 0.001) of cfDNA, nucleosomes, TNF-α, CRP, and IL-6. We did not find any significant relationship between the analyzed parameters in either group (i.e., experimental or control). Elevated levels of the biomarkers of inflammation (TNF-α, CRP, and IL-6) and the indicators of apoptosis (cfDNA, circulating nucleosomes) proved that exacerbated psoriasis vulgaris is associated with a high degree of systemic inflammatory responses and dysregulated apoptotic pathways.

Animal morality: What is the debate about?

Abstract

Empirical studies of the social lives of non-human primates, cetaceans, and other social animals have prompted scientists and philosophers to debate the question of whether morality and moral cognition exists in non-human animals. Some researchers have argued that morality does exist in several animal species, others that these species may possess various evolutionary building blocks or precursors to morality, but not quite the genuine article, while some have argued that nothing remotely resembling morality can be found in any non-human species. However, these different positions on animal morality generally appear to be motivated more by different conceptions of how the term "morality" is to be defined than by empirical disagreements about animal social behaviour and psychology. After delving deeper into the goals and methodologies of various of the protagonists, I argue that, despite appearances, there are actually two importantly distinct debates over animal morality going on, corresponding to two quite different ways of thinking about what it is to define "morality", "moral cognition", and associated notions. Several apparent skirmishes in the literature are thus cases of researchers simply talking past each other. I then focus on what I take to be the core debate over animal morality, which is concerned with understanding the nature and phylogenetic distribution of morality conceived as a psychological natural kind. I argue that this debate is in fact largely terminological and non-substantive. Finally, I reflect on how this core debate might best be re-framed.

Epistemic justification and the ignorance excuse

Abstract

One of the most common excuses is ignorance. Ignorance does not always excuse, however, for sometimes ignorance is culpable. One of the most natural ways to think of the difference between exculpating and culpable ignorance is in terms of justification; that is, one's ignorance is exculpating only if it is justified and one's ignorance is culpable only if it not justified (call this the justification thesis). Rosen (J Phil 105(10):591–610, 2008) explores this idea by first offering a brief account of justification, and then two cases that he claims are counter examples to the justification thesis. The aim of this paper is to defend the justification thesis against Rosen's two cases. The argument will proceed in the following way. First, I clarify a few things about the nature of culpable ignorance generally and why the justification thesis is so intuitive. I then present Rosen's purported counterexamples. Once this is done, I argue that Rosen misses an important view of justification in the epistemology literature that I call the pragmatic view. I present a general picture of the pragmatic view, and explain how it fits naturally with our practices of criticizing people's beliefs, including claims of culpable ignorance. Finally, I address Rosen's cases arguing that, if the pragmatic view is right, then Rosen's cases are not counterexamples to the justification thesis.

Dysosmia-Associated Changes in Eating Behavior

Abstract

Introduction

Olfaction is a highly emotionally charged sense and contributes to our quality of life, which olfactory impairment or dysosmia thus strongly impacts. The aim of the present study was to examine how olfactory deficits alter eating behavior, which is a pillar of health and well-being.

Methods

Patients with quantitative smell impairment and control participants were asked to perform a series of chemosensory tasks: odor identification and ratings of odor intensity, pleasantness, familiarity, irritation, and edibility. They also filled out a detailed food questionnaire.

Results

Results showed significant decrease in olfactory function in smell-impaired patients. Although no significant consequences of dysosmia were found for most aspects of food preferences and culinary habits, the patients were less attracted than controls by novel foods and tended to experience less pleasure when eating. They also used significantly more condiments such as sugar, mayonnaise, or sour cream to make their dishes tasty.

Conclusions

Olfactory impairment has a clear effect on certain aspects of eating behavior.

Implications

These findings highlight the compensatory mechanisms that go along with dysosmia. This also reflects the patients' attempts to restore part of the lost flavor and its hedonic component through non-olfactory cues.

The Ethical Conundrum of Supervising Physician Assistants at a Distant Site

The Emboldened Medical Student:Ethical Dilemmas in a University Clinic

A systematic review of safety and efficacy of systemic corticosteroids in atopic dermatitis

Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies assessed the safety and efficacy of systemic corticosteroids in AD.

“Arrow” Mark for Orientation in Paramedian Forehead Flap

Reply to Lee and Howden

To the Editor—We thank Dr Lee and Prof Howden for their letter and for giving us an opportunity to better articulate our interpretation of findings, especially with respect to transmission of Mycobacterium tuberculosis among patients within 2 southern Indian districts. Based on analysis of single nucleotide polymorphism (SNP) differences between 223 M. tuberculosis strains from 196 patients within the Thiruvallur and Madurai districts of Tamil Nadu, we report recent intradistrict, but no recent interdistrict, transmission of strains among patients. In drawing these conclusions, we limited our interpretation to the data available to us, which showed that the closest SNP distance between M. tuberculosis isolated from patients in different districts was 85 SNPs, which is substantially higher than the very small numbers of SNPs (as few as 0) observed when comparing isolates from patients treated in the same district and treatment center.

The Critical Importance of Sampling Fraction to Inferences of Mycobacterium tuberculosis Transmission

To the Editor—In the study by Manson et al [1], whole-genome sequencing was performed on 223 Mycobacterium tuberculosis isolates from the Tiruvallur and Madurai districts of India. They subsequently examined local strain diversity and mutations associated with phenotypic drug resistance in these regions. In this important study, the authors show that lists of published resistance mutations (including [2–4]) have lower positive predictive values for phenotypic resistance in this context; lineages 1 and 3 predominate in India [1], but these published mutations were largely identified using strains from different M. tuberculosis lineages. This highlights a key obstacle to the implementation of genomics for resistance prediction in India and potentially other endemic regions with diverse lineages of M. tuberculosis. By extension, this study emphasizes the critical need to collect strains and categorize the mutations circulating in these regions to better inform such predictions.

Let us talk about eggs! Professional resistance to elective egg vitrification and gendered medical paternalism

Abstract

In this paper, by applying a feminist bioethical perspective, we identify a new form of medical paternalism that still shapes contemporary legal policies on human egg cryopreservation performed without medical reasons. The fear of negligent, careless women who opt to delay their pregnancy for mere convenience is a widely known gender biased stereotype. Nevertheless, the opinions and judgments of medical professionals on this issue have not yet been sufficiently explored by in-depth research. In this essay, therefore, first we look at the broader bioethical, legal, and social aspects of human egg cryopreservation. In the second part of the paper we discuss a unique qualitative study conducted with professionals working at Hungarian IVF clinics. We argue, based on a bioethical analysis of the collected data, that when new reproduction technologies provide opportunities for women to widen their range of reproductive choices, the traditional forms of medical paternalism can be reinforced by gendered paternalism, as well. We identify several elements of gendered paternalism that characterized the attitudes of the IVF staff and discuss the professionals' resistance to elective egg freezing and vitrification of eggs for the future. We conclude by suggesting directions for future policy. Although we focus on the Hungarian case in this paper, we are aware that similar attitudes can be observed in some other countries where this technology has become available and requested by women, but where they also face difficulties in their access to it.