An Enlarging Lung Nodule in an Immunocompromised Host

(See pages 978–9 for the Answer to the Photo Quiz)

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An Enlarging Lung Nodule in an Immunocompromised Host

(See page 977 for the Photo Quiz.)

Assessing Viral Transfer During Doffing of Ebola-Level Personal Protective Equipment in a Biocontainment Unit

Abstract

Background

Personal protective equipment (PPE) protects healthcare workers (HCWs) caring for patients with Ebola virus disease (EVD), and PPE doffing is a critical point for preventing viral self-contamination. We assessed contamination of skin, gloves, and scrubs after doffing Ebola-level PPE contaminated with surrogate viruses: bacteriophages MS2 and Φ6.

Methods

In a medical biocontainment unit, HCWs (n = 10) experienced in EVD care donned and doffed PPE following unit protocols that incorporate trained observer guidance and alcohol-based hand rub (ABHR). A mixture of Φ6 (enveloped), MS2 (nonenveloped), and fluorescent marker was applied to 4 PPE sites, approximating body fluid viral load (Φ6, 10⁵; MS2, 10⁶). They performed a patient care task, then doffed. Inner gloves, face, hands, and scrubs were sampled for virus, as were environmental sites with visible fluorescent marker.

Results

Among 10 HCWs there was no Φ6 transfer to inner gloves, hands, or face; 1 participant had Φ6 on scrubs at low levels (1.4 × 10²). MS2 transfer (range, 10¹–10⁶) was observed to scrubs (n = 2), hands (n = 1), and inner gloves (n = 7), where it was highest. Most (n = 8) had only 1 positive site. Environmental samples with visible fluorescent marker (n = 21) were negative.

Conclusions

Among experienced HCWs, structured, observed doffing using ABHR protected against hand contamination with enveloped virus. Nonenveloped virus was infrequent on hands and scrubs but common on inner gloves, suggesting that inner gloves, but not necessarily ABHR, protect against hand contamination. Optimizing doffing protocols to protect against all types of viruses may require reinforcing careful handling of scrubs and good glove/hand hygiene with effective agents.

Human Factors Risk Analyses of a Doffing Protocol for Ebola-Level Personal Protective Equipment: Mapping Errors to Contamination

Abstract

Background

Doffing protocols for personal protective equipment (PPE) are critical for keeping healthcare workers (HCWs) safe during care of patients with Ebola virus disease. We assessed the relationship between errors and self-contamination during doffing.

Methods

Eleven HCWs experienced with doffing Ebola-level PPE participated in simulations in which HCWs donned PPE marked with surrogate viruses (ɸ6 and MS2), completed a clinical task, and were assessed for contamination after doffing. Simulations were video recorded, and a failure modes and effects analysis and fault tree analyses were performed to identify errors during doffing, quantify their risk (risk index), and predict contamination data.

Results

Fifty-one types of errors were identified, many having the potential to spread contamination. Hand hygiene and removing the powered air purifying respirator (PAPR) hood had the highest total risk indexes (111 and 70, respectively) and number of types of errors (9 and 13, respectively). ɸ6 was detected on 10% of scrubs and the fault tree predicted a 10.4% contamination rate, likely occurring when the PAPR hood inadvertently contacted scrubs during removal. MS2 was detected on 10% of hands, 20% of scrubs, and 70% of inner gloves and the predicted rates were 7.3%, 19.4%, 73.4%, respectively. Fault trees for MS2 and ɸ6 contamination suggested similar pathways.

Conclusions

Ebola-level PPE can both protect and put HCWs at risk for self-contamination throughout the doffing process, even among experienced HCWs doffing with a trained observer. Human factors methodologies can identify error-prone steps, delineate the relationship between errors and self-contamination, and suggest remediation strategies.

Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs

Abstract

Background

Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively).

Methods

We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts.

Results

A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed.

Conclusions

Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

Erratum

An error appeared in the 15 October 2016 issue of the journal [Hanna DB, Ramaswamy C, Kaplan RC, et al. Trends in Cardiovascular Disease Mortality Among Persons with HIV in New York City, 2001–2012. Clin Infect Dis 2016; 63(8):1122–9]. The financial support section is missing information. It should read:

Erratum

An error appeared in the 15 March 2016 issue of the journal [Polizzotto MN, Uldrick TS, Wyvill KM, et al. Clinical Features and Outcomes of Patients with Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS). Clin Infect Dis 2016; 62: 730–8]. The units for C reactive protein were improperly listed as g/dL, when they should be mg/L. This error appears in number 2 of Table 1, the "C-reactive protein" in Table 4, panel E in Figure 1, the upper right panel in Figure 2, and at the end of the first sentence under the heading "Systemic Inflammation in KICS Subjects."

Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower- and Middle-Income Countries

Abstract

Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to the development of antibiotic resistance that can disseminate globally. Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but simultaneously improve antibiotic access, have been proposed. However, most approaches to date have not considered the growing impact of animal and environmental reservoirs of antibiotic resistance, which threaten to exacerbate the antibiotic resistance crisis in LMICs. In particular, current strategies do not prioritize the impacts of increased antibiotic use for terrestrial food-animal and aquaculture production, inadequate food safety, and widespread environmental pollution. Here, we propose new approaches that address emerging, One Health challenges.

Infectious Diseases, Weather, and Climate

infectionclimate changeweatherrisk factors

The Human Immunodeficiency Virus Care Continuum in China: 1985–2015

Abstract

Background

Human immunodeficiency virus (HIV) care continuum attrition is a major global public health challenge. Few studies have examined this problem in resource-limited settings. We aimed to assess cumulative, current, and historical achievement along China's HIV continuum of care.

Methods

A nationwide, serial cross-sectional study of all individuals with HIV infection diagnosed in China between 1 January 1985 and 31 December 2015 was conducted using data from China's HIV/AIDS information systems. Biennial estimates of the number of persons living with HIV were also used. We defined 7 steps in HIV care continuum as infected (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral therapy (ART), and virally suppressed. Cumulative, 30-year performance, and biennial performance during the most recent 10 years were examined.

Results

A total of 573529 persons diagnosed with HIV infection were included. Cumulatively, 94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART, and 44% were suppressed. Greatest attrition was observed for adolescents, minorities, and those who reported injecting drug use as their route of infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68% among those infected were diagnosed, 67% among diagnosed were receiving ART, and 65% among those receiving ART were virally suppressed. After adjusting for those without viral load testing, the proportion suppressed increased to 89%.

Conclusions

Despite dramatic improvements, China faces serious challenges in achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets, because of substantial attrition along its continuum of HIV care.

Reply to Raoult

To the Editor—We thank Professor Raoult for his interest in our study and for his remarks, which underline the role of patients' oral status and dental hygiene in the genesis of streptococcal infective endocarditis [1, 2]. He suggests that we analyze our data to assess antibiotic prophylaxis efficacy, which we purposely did not perform for the following reasons:

Endocarditis Prophylaxis

To the Editor—The work by Duval and colleagues [1] is interesting because it shows that patients' oral health and dental hygiene play an important role in the etiology of streptococcal endocarditis. It is also likely that the continuous improvement of the dental condition of modern populations explains the very significant decrease of endocarditis with streptococci of buccal origin [2]. However, the careful reanalysis of their data does not support the conclusion that antibiotic prophylaxis before dental care plays a role, which is currently the most debated subject [3]. In fact, the analysis of their data, obtained from supplementary material online, makes it possible to confirm or not whether antibiotic prophylaxis could prevent streptococcal endocarditis in a patient with underlying valvulopathy. Indeed, among the 12 patients with oral streptococcal endocarditis, 3 had no known valvulopathy, and the one who had known valvulopathy received antibiotic prophylaxis. These 4 are outside the purpose of this study. Therefore, only 8 patients among a cohort of 73 patients with oral streptococcal endocarditis could be analyzed vs 11 patients with endocarditis due to another microorganism in a cohort of 192 patients. This difference is not significant. Following this analysis, this work confirms that there is no evidence in the literature showing an even slight effect of prophylaxis of oral streptococcal endocarditis by the use of antibiotic prophylaxis before dental care.

Management of an Outbreak of Exophiala dermatitidis Bloodstream Infections at an Outpatient Oncology Clinic

Abstract

We report the presentation and management of 17 cases of Exophiala dermatitidis and Rhodotorula mucilaginosa bloodstream infections caused by a compounded parenteral medication at an oncology clinic. Twelve patients were asymptomatic. All central venous catheters were removed and antifungal therapy, primarily voriconazole, was administered to patients. Three patients died.

Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals

Abstract

Background

Recent evidence suggests that hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centers that have implemented sustained infection control programs. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals.

Methods

A cross-sectional observational study was performed in 2 National Health Service hospital groups and a general district hospital in Southeast London. All MRSA patients identified at inpatient, outpatient, and community settings between 1 November 2011 and 29 February 2012 were included. We identified genetically defined MRSA transmission clusters in individual hospitals and across the healthcare network, and examined genetic differentiation of sequence type (ST) 22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single-nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates.

Results

Two hundred forty-eight of 610 (40.7%) MRSA patients were linked in 90 transmission clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26 of 32 patients (81.3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient, or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (P ≤ .01).

Conclusions

There is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA status data between hospitals.

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

Abstract

Background

Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.

Methods

We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.

Results

Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)–based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59–29.13] and 10.92 [1.15–104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03–838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2–84 months), led to minor adverse effects.

Conclusion

L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients.

High Human Immunodeficiency Virus Incidence and Prevalence and Associated Factors Among Adolescent Sexual Minority Males—3 Cities, 2015

Abstract

Background

Much has been written about the impact of human immunodeficiency virus (HIV) among young (13–24) sexual minority men (SMM). Evidence for concern is substantial for emerging adult (18–24 years) SMM. Data documenting the burden and associated risk factors of HIV among adolescent SMM (<18 years) remain limited.

Methods

Adolescent SMM aged 13–18 years were recruited in 3 cities (Chicago, New York City, and Philadelphia) for interview and HIV testing. We used χ² tests for percentages of binary variables and 1-way analysis of variance for means of continuous variables to assess differences by race/ethnicity in behaviors. We calculated estimated annual HIV incidence density (number of HIV infections per 100 person-years [PY] at risk). We computed Fisher's exact tests to determine differences in HIV prevalence by selected characteristics.

Results

Of 415 sexually active adolescent SMM with a valid HIV test result, 25 (6%) had a positive test. Estimated annual HIV incidence density was 3.4/100 PY; incidence density was highest for blacks, followed by Hispanics, then whites (4.1, 3.2, and 1.1/100 PY, respectively). Factors associated with higher HIV prevalence included black race; ≥4 male partners, condomless anal sex, and exchange sex in the past 12 months; and a recent partner who was older, black, HIV-infected, or had ever been in jail or prison (P < .05).

Conclusions

HIV-related risk behaviors, prevalence, and estimated incidence density for adolescent SMM were high, especially for minority SMM. Our findings suggest that initiating intervention efforts early may be helpful in combating these trends.

Vancomycin Is Ineffective in Eliminating Methicillin-Resistant Staphylococcus aureus Colonization of Respiratory Secretions in Ventilated Intensive Care Unit Patients: A Clinical and Pharmacokinetic Perspective

To the Editor—We read Stulik and colleagues' article with much interest, and some aspects deserve comment [1]. In intubated adults in the intensive care unit (ICU), airway colonization is common, with aerobic gram-negative bacilli (GNB) or Staphylococcus aureus often persisting for prolonged periods without progression to ventilator-associated pneumonia (VAP) [2].

Phytotoxicity and cytogenotoxicity of hydroalcoholic extracts from Solanum muricatum Ait. and Solanum betaceum Cav. (Solanaceae) in the plant model Lactuca sativa

Abstract

Plants are rich in biologically active compounds. They can be explored for the production of bioherbicides. In this context, the present work aimed to evaluate the allelopathic effect of hydroalcoholic extracts from two Solanaceae species: Solanum muricatum Ait. and Solanum betaceum Cav. For this end, we conducted phytochemical screening and biological assays, determining the effects of the extracts on germination, early development, cell cycle, and DNA fragmentation in plantlets and meristematic cells of the plant model Lactuca sativa L. (lettuce). The percentage of seeds germinated under effect of S. muricatum extract did not differ from the control, but plantlet growth was reduced at the highest concentrations. For S. betaceum extract, dose dependence was observed for both germination and plantlet development, with the highest concentrations inhibiting germination. The growth curves revealed the concentrations of 2.06 and 1.93 g/L for S. muricatum and S. betaceum extracts, respectively, as those reducing 50% of root growth (RG). At these concentrations, both extracts presented mitodepressive effect, besides inducing significant increase in the frequency of condensed nuclei, associated to DNA fragmentation and cytoplasmic shrinkage. The frequency of chromosome alterations was not significant. We further discuss the mechanisms of action related to the chemical composition of the extracts, which presented organic acids, reducing sugars, proteins, amino acids, and tannins, besides catechins and flavonoids, only found in the extract of S. betaceum.

Correction to: Risk exposure assessment of per- and polyfluoroalkyl substances (PFASs) in drinking water and atmosphere in central eastern China

Abstract

The original publication of this paper contains a mistake.

The effect of mesenchymal stem cells combined with platelet-rich plasma on skin wound healing

Summary

Introduction

Mesenchymal stem cells (MSCs) are multipotent stem cells that have the potential of proliferation, high self-renewal, and the potential of multilineage differentiation. The differentiation potential of the MSCs in vivo and in vitro has caused these cells to be regarded as potentially appropriate tools for wound healing. After the burn, trauma or removal of the tumor of wide wounds is developed. Although standard treatment for skin wounds is primary healing or skin grafting, they are not always practical mainly because of limited autologous skin grafting.

Evidence Acquisitions

Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science have been searched.

Evidence Synthesis

For clinical use of the MSCs in wound healing, two key issues should be taken into account: First, engineering biocompatible scaffolds clinical use of which leads to the least amount of side effects without any immunologic response and secondly, use of stem cells secretions with the least amount of clinical complications despite their high capability of healing damage.

Conclusion

In light of the MSCs' high capability of proliferation and multilineage differentiation as well as their significant role in modulating immunity, these cells can be used in combination with tissue engineering techniques. Moreover, the MSCs' secretions can be used in cell therapy to heal many types of wounds. The combination of MSCs and PRP aids wound healing which could potentially be used to promote wound healing.

Cytokine profile (IL-2, IL-6, IL-17, IL-22, and TNF-α) in vitiligo—New insight into pathogenesis of disease

Summary

Background

Vitiligo is an autoimmune disease associated with alteration in levels of various cytokines. However, there are very few studies in this regard.

Objectives

To assess the serum levels of cytokines secreted by Th1 (IL-2, TNF-α), Th2 (IL-6), and Th17 cells (IL-17, IL-22) in patients with localized vitiligo and generalized vitiligo and to correlate their levels with the extent, duration, and activity of disease.

Material and Methods

Sixty patients of vitiligo (30 each of localized and generalized) and 30 controls were recruited in the study. Serum IL-2, -6, -17, -22, and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA) in all patients and healthy controls, and their levels were correlated with the extent, duration, and activity of vitiligo.

Results

We observed significantly raised levels of IL-2, -6, -17, -22, and TNF-α in both localized vitiligo and generalized vitiligo (P < .05). IL-2 was significantly raised (P = .028) in localized vitiligo, whereas IL-17 and IL-22 were significantly raised in generalized vitiligo (P = .00 and P = .019, respectively). Activity of disease showed positive correlation with serum TNF-α levels (P = .015) in localized vitiligo. Positive correlation of IL-17 (R = .238) with body surface area (BSA) was observed in patients with generalized vitiligo.

Conclusions

Our study shows that cytokines secreted by Th17 cells play an important role in maintenance and spread of vitiligo as they increase in line with extent of disease. Also TNF-α increases in proportion with activity of disease, hence may act as biomarker for identifying patient with aggressive disease.

Effect of hyperbaric oxygen on the process of hypertrophic scar formation in rabbit ears

Summary

Objective

To explore the influence of hyperbaric oxygen on scar formation in rabbit ears.

Methods

A total of 20 New Zealand rabbits were selected to establish the hypertrophic scar model on the ears. The rabbits were randomly divided into control group and experimental group (7d, 14d, 21d, and 28d group according to different HBO treatment days),each experimental group received hyperbaric oxygen treatment after the operation at the same time everyday for 1 hour. After the day 29, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining, and transmission electrical microscope. The expression of bax, bcl-2, and the cell apoptosis rate was detected by immunohistochemical method.

Results

(i) Both number of fibroblast and amount of collagen fibrils in experimental group were significantly reduced compared with those in control group. In Masson staining, arrangement of collagen fibrils in experimental group was much more irregular and coarse than control groups. (ii) HI value can be found much smaller in the experimental groups than the control (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05). (iii) Expression of Bax could be detected up-regulated in experimental group (P < .05). While the expression of Bcl-2 is detected significantly down-regulated in experimental group than that in control group (P < .05). Compared with the 7d group, the expression of Bax and Bcl-2 has significant difference in 14d group (P < .05), and the expression of this two factors in 21d group has significant difference comparing with 14d group(P < .05),but there is no significant difference between 28d group and 21d group(P > .05). (iv) Significant difference of cell apoptosis rate can be detected between the experimental groups and the control group (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05).

Conclusion

The hyperbaric oxygen can up-regulate bax/bcl-2 value, increase the cell apoptosis rate, and inhibit the early hypertrophic scar in rabbit ears.

A single-center clinical trial to evaluate the efficacy of a tripeptide/hexapeptide antiaging regimen

Summary

Introduction

An antiaging regimen that aids in clearing the matrix of waste products and stimulating neocollagenesis and neoelastogenesis was tested among a group of subjects over the course of 12 weeks to assess its efficacy in women with mild to moderate wrinkles and skin sagging on the face.

Materials and methods

The efficacy of the product regimen was tested in 22 subjects using investigator clinical grading measurements, raking light imaging, 3D imaging, biopsies, and self-assessment questionnaires at baseline and weeks 4, 8, and 12.

Results

Clinical grading indicated that use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters; the raking light image analysis demonstrated a statistically significant improvement in values for length, width, and area of wrinkles when compared with baseline values as did 3D imaging. Biopsy results in the 5 patients tested showed improvement in solar elastosis, collagen stimulation, and improvement in cornified layers in all 5 patients. Elastin stimulation was evident in 3 of 5 patients. Results from the self-assessment questionnaire analysis indicated favorable responses in a statistically significant proportion of subjects after 12 weeks of use for all inquiries.

Conclusion

Use of this facial antiaging regimen was effective in improving visual facial photoaging conditions and well-perceived when used by women with mild to moderate wrinkles and skin sagging on the face under the conditions of this study.

A systematic review of associations of physical activity and sedentary time with asthma outcomes

Publication date: Available online 3 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Laura Cordova-Rivera, Peter G. Gibson, Paul A. Gardiner, Vanessa M. McDonald
BackgroundPhysical inactivity and high sedentary time are associated with adverse health outcomes in several diseases. However, their impact in asthma is less clear.ObjectiveWe aimed to synthesise the literature characterising physical activity and sedentary time in adults with asthma, to estimate activity levels using meta-analysis, and to evaluate associations between physical activity and sedentary time and the clinical and physiological characteristics of asthma.MethodsArticles written in English and addressing the measurement of physical activity or sedentary time in adults ≥18 years old with asthma were identified using four electronic databases. Meta-analysis was used to estimate steps/day in applicable studies.ResultsThere were 42 studies that met the inclusion criteria. Physical activity in asthma was lower compared to controls. The pooled mean (95%CI) steps/day for people with asthma was 8390 (7361, 9419). Physical activity tended to be lower in females compared with males, and in older people with asthma compared with their younger counterparts. Higher levels of physical activity were associated with better measures of lung function, disease control, health status, and health care use. Measures of sedentary time were scarce, and indicated a similar engagement in this behavior between asthma participants and controls. High sedentary time was associated with higher health care use, and poorer lung function, asthma control and exercise capacity.ConclusionsPeople with asthma engage in lower levels of physical activity compared to controls. Higher levels of physical activity may positively impact on asthma clinical outcomes. Sedentary time should be more widely assessed.

Theophylline as a precision therapy in a young girl with PIK3R1-immunodeficiency

Publication date: Available online 3 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Erica Valencic, Antonio Giacomo Grasso, Ester Conversano, Marianna Lucafò, Elisa Piscianz, Massimo Gregori, Francesca Conti, Caterina Cancrini, Alberto Tommasini

Coca-Cola allergy identified as fructose-induced anaphylaxis

Publication date: Available online 3 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Chang-Gyu Jung, Eun-Mi Yang, Ji-Ho Lee, Seung-Hyun Kim, Hae-Sim Park, Yoo Seob Shin

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

Abstract

Psoriasis is a common chronic inflammatory skin disease with a significant socio-economic impact that can greatly affect the patients' quality of life. The prevailing dogma in the aetiology and pathophysiology of this complex disease is that skin cells, immune cells as wells as environmental factors contribute to psoriatic skin inflammation. For a better understanding of the disease pathogenesis, models are required that mimic the disease and which can be used to develop therapeutics. Over the last decades, in vitro human reconstructed skin models have been widely used in dermatological research and have also been developed to mimic psoriatic skin. This viewpoint summarizes the most commonly used in vitro models and the latest accomplishments for the combination of the dermal and epidermal compartments with other cell types and factors that are important players in the psoriatic skin environment. We aim to critically list the most complete and best validated models that include major psoriasis hallmarks with regard to gene and protein expression profile and epidermal morphology, but also discuss the shortcoming of the current models. This viewpoint intends to guide the development of in vitro 3D skin models that faithfully mimics all features of psoriatic skin. Such model will enable fundamental biological studies for a better understanding of the aetiology and pathophysiology of psoriasis and aid in novel therapeutic target identification and drug development studies.

This article is protected by copyright. All rights reserved.

The Teaching Instinct

Abstract

Teaching allows human culture to exist and to develop. Despite its significance, it has not been studied in depth by the cognitive neurosciences. Here we propose two hypotheses to boost the claim that teaching is a human instinct, and to expand our understanding of how teaching occurs as a dynamic bi-directional relation within the teacher-learner dyad. First, we explore how children naturally use ostensive communication when teaching; allowing them to be set in the emitter side of natural pedagogy. Then, we hypothesize that the capacity to teach may precede to even have a mature metacognition and, we argue that a teacher will benefit from the interaction with her student, improving her understanding on both contents of knowledge: her own and her student's. Thus, we propose that teaching may be the driving force of metacognitive development and may be occurring as an instinct from very early ages.

On Deflationary Accounts of Human Action Understanding

Abstract

A common deflationary tendency has emerged recently in both philosophical accounts and comparative animal studies concerned with how subjects understand the actions of others. The suggestion emerging from both arenas is that the default mechanism for understanding action involves only a sensitivity to the observable, behavioural (non-mental) features of a situation. This kind of 'smart behaviour reading' thus suggests that, typically, predicting or explaining the behaviour of conspecifics does not require seeing the other through the lens of mental state attribution. This paper aims to explore and assess this deflationary move. In §1 I clarify what might be involved in a smart behaviour reading account via looking at some concrete examples. Then in §2 I critically assess the deflationary move, arguing that, at least in the human case, it would in fact be a mistake to assume that our default method of action understanding proceeds without appeal to mental state attribution. Finally in §3 I consider briefly how the positive view proposed here relates to discussions about standard two-system models of cognition.

First-Person Experiments: A Characterisation and Defence

Abstract

While first-person methods are essential for a science of consciousness, it is controversial what form these methods should take and whether any such methods are reliable. I propose that first-person experiments are a reliable method for investigating conscious experience. I outline the history of these methods and describe their characteristics. In particular, a first-person experiment is an intervention on a subject's experience in which independent variables are manipulated, extraneous variables are held fixed, and in which the subject makes a phenomenal judgement about the target experience of the investigation. I examine historical and contemporary examples of first-person experiments: Mariotte's demonstration of the visual blind spot, Kanizsa's subjective contours, the Tse Illusion, and investigations of the non-uniform resolution of the visual field. I discuss the role that phenomenal contrast plays in these methods, and how they overcome typical introspective errors. I argue that their intersubjective repeatability is an important factor in their scientific status, however, it is not the only factor. That they control for extraneous factors and confounds is another factor which sets them apart from pseudoscience (e.g., the perception of auras), and hence another reason for classifying them as genuine experiments. Furthermore, by systematically mapping out the structure of visual experience, these methods make scientific progress. Praises of such first-person experimental approaches may not always be sung by philosophers and psychologists, but they continue to flourish as respectable scientific methods nevertheless.

Interacting with Fictions: The Role of Pretend Play in Theory of Mind Acquisition

Abstract

Pretend play is generally considered to be a developmental landmark in Theory of Mind acquisition. The aim of the present paper is to offer a new account of the role of pretend play in Theory of Mind development. To this end I combine Hutto and Gallagher's account of social cognition development with Matravers' recent argument that the cognitive processes involved in engagement with narratives are neutral regarding fictionality. The key contribution of my account is an analysis of pretend play as interaction with fictions. I argue that my account offers a better explanation of existing empirical data on the development of children's pretend play and Theory of Mind than the competing theories from Leslie, Perner and Harris.

Rethinking the Negativity Bias

Abstract

The negativity bias is a broad psychological principle according to which the negative is more causally efficacious than the positive. Bad, as it is often put, is stronger than good. The principle is widely accepted and often serves as a constraint in affective science. If true, it has significant implications for everyday life and philosophical inquiry. In this article, I submit the negativity bias to its first dose of philosophical scrutiny and argue that it should be rejected. I conclude by offering some alternative hedonic hypotheses that survive the offered arguments and may prove fruitful.

Branched poly (lactic acid) microparticles for enhancing the 5-aminolevulinic acid phototoxicity

Publication date: Available online 3 March 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Antonio Di Martino, Marina E. Trusova, Pavel S. Postnikov, Vladimir Sedlarik
An innovative microcarrier based on a carboxy-enriched and branched polylactic acid derivative was developed to enhance the in vitro phototoxicity of the photosensitizer and prodrug 5-aminolevulinic. Microparticles, prepared by double emulsion technique and loaded with the prodrug were carefully characterized and the effect of the polymer structure on the chemical, physical and biological properties of the final product was evaluated. Results showed that microparticles have a spherical shape and ability to allocate up to 30 μg of the photosensitizer per mg of carrier despite their difference in solubility. Release studies performed in various simulated physiological conditions demonstrate the influence of the branched structure and the presence of the additional carboxylic groups on the release rate and the possibility to modulate it. In vitro assays conducted on human epithelial adenocarcinoma cells proved the not cytotoxicity of the carriers in a wide range of concentrations. The hemocompatibility and surface proteins adsorption were evaluated at different microparticles concentrations to evaluate the safety and estimate the possible microparticles residential time in the bloodstream. The advantages, of loading 5-aminolevulinic acid in the prepared carrier has been deeply described in terms of enhanced phototoxicity, compared to the free 5-aminolevulinic acid formulation after irradiation with light at 635 nm. The obtained results demonstrate the advantages of the prepared derivative compared to the linear polylactide for future application in photodynamic therapy based on the photosensitizer 5-aminolevulinic acid.

Biopsy-Proven Metastatic Merkel Cell Carcinoma to the Orbit: Case Report and Review of Literature

Merkel cell carcinoma is a rare neuroendocrine tumor of subspecialized dermal mechanoreceptors, associated with immunosuppression. The usual ophthalmic presentation is an eyelid lesion. The authors present a case of biopsy-proven orbital metastatic Merkel cell carcinoma in the absence of any eyelid lesion, in an immunosuppressed patient with a history of multiple cancers. There are to the authors' knowledge only 2 other case reports of presumed metastatic Merkel cell carcinoma to the orbit, though neither were biopsied. Despite its rarity, metastatic Merkel cell carcinoma should be included in the differential of a metastatic orbital lesion, in the patient with a known or suspected cutaneous primary. The patient has had an excellent response to combined radiotherapy and programmed death-1 inhibitor pembrolizumab, and this case highlights the potential benefit of an exciting new biologic therapy. Accepted for publication December 15, 2017. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Dean R. Cugley, M.B.B.S.(Hons), B.Med.Sci., Royal Victorian Eye & Ear Hospital, 32 Gisborne Street, East Melbourne, VIC 3002, Australia. E-mail: dean.cugley@eyeandear.org.au © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Bilateral Limbal Keratin-Associated Amyloidosis

Conjunctival amyloid is usually of the immunoglobulin light chain (AL) variety. The authors report an exceptional case of bilateral limbal amyloid deposits that were identified by mass spectrometry as keratin-related specifically regarding to basal keratinocyte keratins 5 and 14. Cytokeratin-related amyloid has been described by immunohistochemical analysis of formalin-fixed cutaneous and mucous membrane lesions but not ocular tissues. The conjunctival lesion in the right eye contained intraepithelial dyskeratotic cells that extended to the surface, causing a lacy leukoplakia on clinical examination. The authors excluded the diagnosis of hereditary benign intraepithelial dyskeratosis in this patient. Collection of patient data and all protected patient health information was compliant with the Health Insurance Portability and Accountability Act. Accepted for publication January 12, 2018. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. Address correspondence and reprint requests to Norman C. Charles, M.D., NYU Langone Medical Center, 550 First Avenue, New York, NY 10016. E-mail: norman.charles@nyumc.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Nasal Glioma: A Rare Cause of Congenital Inner Canthal Swelling

Nasal glioma, encephalocele, and ectopic brain are rare congenital anomalies. The terminology applied to these entities has been historically confusing. In many cases, the terms overlap and may be employed synonymously although some authors emphasize their differences. The authors describe herein a child with an inner canthal mass of brain-like tissue that they interpret as nasal glioma, a variety of encephalocele that has lost its connection to the intracranial contents. This research was conducted in conformity with the Helsinki Declaration and Health Insurance Portability and Accountability Act regulations. Accepted for publication January 17, 2018. The authors report no conflicts of interest. The authors alone are responsible for the content. Address correspondence and reprint requests to Norman C. Charles, M.D., NYU Langone Medical Center, 550 First Avenue, New York, NY 10016. E-mail: norman.charles@nyumc.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Measurement of Medial Wall Bowing and Clinical Associations in Thyroid Eye Disease

Purpose: To propose and validate a measure of medial wall bowing in thyroid eye disease (TED) and to assess the clinical correlates of bowing in TED. Methods: In this cross-sectional cohort study, all patients affected with TED seen by a single specialist over a 2-year period were screened for study entry. Eligible participants were adults with clinical evidence of TED and either CT or MRI of the orbits. Exclusion criteria included prior history of decompression surgery and/or medical or other ophthalmic conditions that could alter the orbital anatomy. The primary outcome measure was prevalence of medial wall bowing. Secondary outcomes included the associations between medial wall bowing and exophthalmometry, diplopia, rectus muscle restriction, dysthyroid optic neuropathy (DON), strabismus, and quality of life. Medial wall bowing was defined as medial divergence of the medial wall from a straight line drawn between the anterior lacrimal crest and the middle of the optic canal and measured radiographically using axial images of the orbits. Volumetric analysis of bowing was performed on a sample of orbits with and without bowing. Volumetric and axial single slice measurements were compared. Bivariate statistics were performed. Results: The final sample included 112 orbital images from 56 patients with TED. Medial wall bowing was found to be evident in 11.6% (n = 13/112) of orbits. Medial wall bowing was significantly associated with greater Hertel measurements, horizontal and vertical muscle restriction, ocular surface symptoms and Clinical Activity Score, as well as lower quality of life scores. Patients with demonstrable medial wall bowing were more likely to be affected by optic neuropathy, diplopia (Gorman score ≥ 1), strabismus, or horizontal muscle restriction. Analysis of the volume for medial wall bowing demonstrated that the height of the arc at the peak of bowing on an axial image of a 2-dimensional CT scan correlated highly with the total volume of bowing (r = 0.90, p

Xanthomonas oryzae pv. oryzae type III effector PthXo3JXOV suppresses innate immunity and induces susceptibility and binds to multiple targets in rice

Abstract

Transcription activator-like (TAL) effectors encoded by tal genes were recognized as a key virulence strategy used by Xanthomonas oryzae pv. oryzae (Xoo) to cause bacterial leaf blight of rice. TAL effector PthXo3 is a major virulence factor identified in a Philippine Xoo strain PXO61, and it can induce the expression of susceptibility gene OsSWEET14 by binding to the effector-binding element (EBE) in the promoter region. In this study, pthXo3 homologous genes were also identified and isolated from Xoo Chinese strain OS198 and Japanese strain JXOV, which were named as PthXo3_OS198 and PthXo3_JXOV respectively. When pthXo3JXOV was delivered into PXO99^A, the resulting strain PXO99^A/pthXo3JXOV had significantly increased virulence in 18 out of 23 rice varieties tested, with the most prominent increase in lesion length and bacteria propagation in rice IRBB13. PthXo3_JXOV suppresses the plant innate immunity by inhibiting HR and callose deposition. The Agrobacterium tumefaciens-mediated transient expression assays showed that, besides OsSWEET14, PthXo3_JXOV also interacts with other targets by binding to the EBEs in their promoter regions. Our results suggest that PthXo3_JXOV may interact with multiple targets to execute its virulence functions.

Chromium resistance genetic element flanked by XerC/XerD recombination sites and its distribution in environmental and clinical Acinetobacter strains

Abstract

A novel mobile genetic element has been identified in small plasmids isolated from permafrost strains of Acinetobacter lwoffii. This element, designated the chrAB dif module, contains the chromium resistance genes chrA and chrB, functionally active both in the original host strains and after transfer into Acinetobacter baylyi. The 3011 bp chrAB dif module is flanked by XerC/XerD recombination sites highly homologous to those of the site-specific recombination system dif/Xer. Analysis of public databases revealed almost identical variants of the chrAB dif module in different plasmids in strains of various Acinetobacter species predominantly inhabiting the environment (A. lwoffii, A. indicus, A. idrijaensis, A. shindleri and A. nosocomialis). Together with previously described Acinetobacter antibiotic resistance elements, the chrAB dif module defines a new group of mobile elements that rely on the dif/Xer system for their mobility. Our observations suggest an ancient origin of the mobile elements flanked by dif sites and their participation in the mobilization of plasmid genes bearing adaptive functions.

Characteristics and optimized fermentation of a novel magnetotactic bacterium, Magnetospirillum sp. ME-1

Abstract

Magnetotactic bacteria (MTB) can biosynthesize magnetosomes, which have great potential for applications. A new MTB strain, Magnetospirillum sp. ME-1, was isolated and cultivated from freshwater sediments of East Lake (Wuhan, China) using the limiting dilution method. ME-1 had a chain of 17 ± 4 magnetosomes in the form of cubooctahedral crystals with a shape factor of 0.89. ME-1 was closest to Magnetospirillum sp. XM-1 according to 16S rRNA gene sequence similarity. Compared with XM-1, ME-1 possessed additional copy of mamPA and a larger mamO in magnetosome-specific genes. ME-1 had an intact citric acid cycle, and complete pathway models of ammonium assimilation and dissimilatory nitrate reduction. Potential carbon and nitrogen sources in these pathways were confirmed to be used in ME-1. Adipate was determined to be used in the fermentation medium as a new kind of dicarboxylic acid. The optimized fermentation medium was determined by orthogonal tests. The large-scale production of magnetosomes was achieved and the magnetosome yield (wet weight) reached 120 mg/L by fed-batch cultivation of ME-1 at 49 h in a 10-L fermenter with the optimized fermentation medium. This study may provide insights into the isolation and cultivation of other new MTB strains and the production of magnetosomes.