ResearchPad - skin https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Evidence of recombination of vaccine strains of lumpy skin disease virus with field strains, causing disease]]> https://www.researchpad.co/article/elastic_article_14489 Vaccination against lumpy skin disease (LSD) is crucial for maintaining the health of animals and the economic sustainability of farming. Either homologous vaccines consisting of live attenuated LSD virus (LSDV) or heterologous vaccines consisting of live attenuated sheeppox or goatpox virus (SPPV/GPPV) can be used for control of LSDV. Although SPPV/GTPV-based vaccines exhibit slightly lower efficacy than live attenuated LSDV vaccines, they do not cause vaccine-induced viremia, fever, and clinical symptoms of the disease following vaccination, caused by the replication capacity of live attenuated LSDVs. Recombination of capripoxviruses in the field was a long-standing hypothesis until a naturally occurring recombinant LSDV vaccine isolate was detected in Russia, where the sheeppox vaccine alone is used. This occurred after the initiation of vaccination campaigns using LSDV vaccines in the neighboring countries in 2017, when the first cases of presumed vaccine-like isolate circulation were documented with concurrent detection of a recombinant vaccine isolate in the field. The follow-up findings presented herein show that during the period from 2015 to 2018, the molecular epidemiology of LSDV in Russia split into two independent waves. The 2015–2016 epidemic was attributable to the field isolate. Whereas the 2017 epidemic and, in particular, the 2018 epidemic represented novel disease importations that were not genetically linked to the 2015–2016 field-type incursions. This demonstrated a new emergence rather than the continuation of the field-type epidemic. Since recombinant vaccine-like LSDV isolates appear to have entrenched across the country’s border, the policy of using certain live vaccines requires revision in the context of the biosafety threat it presents.

]]>
<![CDATA[Investigating barriers and challenges to the integrated management of neglected tropical skin diseases in an endemic setting in Nigeria]]> https://www.researchpad.co/article/elastic_article_13828 Community perceptions of causation of neglected tropical diseases (NTDs) of the skin may play an important role in access to or utilization of health services. The World Health Organization (WHO) has recommended empowerment of populations affected by or at risk of NTDs in control interventions. Furthermore, the WHO recommends that social mobilisation needs to be maintained in order to create demand for integrated management of skin NTDs and to address specific community aspects and concerns related to the diseases. There are no studies on community knowledge, attitudes and practices (KAP) on skin NTDs co-occurring in the same community in Nigeria. We surveyed community members and health workers and also held group discussions with community members, health workers and individuals with lymphatic filariasis and Buruli ulcer in order to assess their understanding of the causes, treatment and effects of the skin NTDs (leprosy, Buruli ulcer and lymphatic filariasis) which were all occurring in the study communities. There was a shared understanding that these NTDs were caused by germ/infection or through witchcraft/curse/poison. Also, a substantial proportion of the community believed that these conditions are not amenable to treatment. The focus group discussions reinforced these findings.

]]>
<![CDATA[Microbeam X-ray diffraction study of lipid structure in stratum corneum of human skin]]> https://www.researchpad.co/article/elastic_article_7631 Human skin, not previously frozen, was studied by small-angle X-ray diffraction. The samples were folded so that a 6μm X-ray beam passed through the top layer of skin, stratum corneum. Diffraction patterns recorded with this method consisted of peaks at about q = 0.5, 1.0 and 1.4 nm-1 in the direction perpendicular to the skin surface more clearly than in previous studies. These peaks are interpreted to arise from lipids between corneocytes. A simple unit of a linear electron density profile with three minima was used to account for the observed intensity profiles. Combinations of calculated diffraction from models with one, two and three units accounted for the major part of the observed diffraction pattern, showing the diversity in the structure of the intercellular lipids.

]]>
<![CDATA[In vitro and in vivo evaluation of a moisture treatment cream containing three critical elements of natural skin moisturization]]> https://www.researchpad.co/article/elastic_article_7086 To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin.MethodsIn an epidermal skin model, tissues (n = 5/group) were topically treated with 25 µL of TRMT, 25 µL of a market‐leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice‐daily application of TRMT, assessing changes in fine lines/wrinkles, brightness, texture, erythema, and tolerability from baseline through week 8. Hydration was measured using electrical impedance.ResultsTRMT and MLM demonstrated significant increases in hydration vs untreated tissue at each timepoint (P < .005), with greater hydration effects observed for TRMT vs MLM. TRMT‐treated tissues demonstrated greater expression of CLD, AQP, and HA, and reduced expression of HYAL vs untreated and MLM‐treated tissues. Twice‐daily application of TRMT demonstrated significant improvements at 2 weeks in fine lines/wrinkles (P < .001), brightness (P < .0001), texture (P < .0004), and hydration (P < .004). At 8 weeks, statistically significant improvements were achieved in all categories.ConclusionIn an epidermal skin model, TRMT demonstrated significant increases in hydration, greater hydration effects, and expression of key markers associated with skin barrier and hydration vs a MLM. Twice‐daily application of TRMT was well tolerated and resulted in early, significant improvements in hydration and visible improvements in skin brightness, texture, fine lines/wrinkles, and erythema at 8 weeks. ]]> <![CDATA[Interleukin 31 in insect bite hypersensitivity—Alleviating clinical symptoms by active vaccination against itch]]> https://www.researchpad.co/article/elastic_article_6918 Equine IL‐31 is detectable in insect bite hypersensitivity (IBH) skin lesions upon insect bites and mediates pruritus by targeting peripheral nerves. IL‐31 is absent in skin biopsies from nonlesional or healthy skin. eIL‐31‐CuMVTT vaccine successfully induces autoantibodies against IL‐31 and reduces lesion scores in horses.

]]>
<![CDATA[Topical antifungals for seborrhoeic dermatitis]]> https://www.researchpad.co/article/Nfc71b64a-3351-42f6-962d-7c7d1405796f

Abstract

Background

Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy.

Objectives

To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.

A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS.

Search methods

We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials.

Selection criteria

Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life.

Data collection and analysis

Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed‐effect meta‐analysis for studies with low statistical heterogeneity and used a random‐effects model when heterogeneity was high.

Main results

We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.

Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another.

Ketoconazole

Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low‐quality evidence) at four weeks of follow‐up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.

Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low‐quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate‐quality evidence).

Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low‐quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects.

Ciclopirox

Ciclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow‐up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate‐quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate‐quality evidence).

Other antifungals

Clotrimazole and miconazole efficacies were comparable with those of steroids on short‐term assessment in single studies.

Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.

Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash‐free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar.

Authors' conclusions

Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.

]]>
<![CDATA[Investigating the potential use of an ionic liquid (1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide) as an anti-fungal treatment against the amphibian chytrid fungus, Batrachochytrium dendrobatidis]]> https://www.researchpad.co/article/N5c2fa054-4262-4dfe-83a3-c606a06f5241

The disease chytridiomycosis, caused by the pathogenic chytrid fungus, Batrachochytrium dendrobatidis (Bd), has contributed to global amphibian declines. Bd infects the keratinized epidermal tissue in amphibians and causes hyperkeratosis and excessive skin shedding. In individuals of susceptible species, the regulatory function of the amphibian’s skin is disrupted resulting in an electrolyte depletion, osmotic imbalance, and eventually death. Safe and effective treatments for chytridiomycosis are urgently needed to control chytrid fungal infections and stabilize populations of endangered amphibian species in captivity and in the wild. Currently, the most widely used anti-Bd treatment is itraconazole. Preparations of itraconazole formulated for amphibian use has proved effective, but treatment involves short baths over seven to ten days, a process which is logistically challenging, stressful, and causes long-term health effects. Here, we explore a novel anti-fungal therapeutic using a single application of the ionic liquid, 1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-NTf2), for the treatment of chytridiomycosis. BMP-NTf2 was found be effective at killing Bd in vitro at low concentrations (1:1000 dilution). We tested BMP-NTf2 in vivo on two amphibian species, one that is relatively tolerant of chytridiomycosis (Pseudacris regilla) and one that is highly susceptible (Dendrobates tinctorius). A toxicity trial revealed a surprising interaction between Bd infection status and the impact of BMP-NTf2 on D. tinctorius survival. Uninfected D. tinctorius tolerated BMP-NTf2 (mean ± SE; 96.01 ± 9.00 μl/g), such that only 1 out of 30 frogs died following treatment (at a dose of 156.95 μL/g), whereas, a lower dose (mean ± SE; 97.45 ± 3.52 μL/g) was not tolerated by Bd-infected D. tinctorius, where 15 of 23 frogs died shortly upon BMP-NTf2 application. Those that tolerated the BMP-NTf2 application did not exhibit Bd clearance. Thus, BMP-NTf2 application, under the conditions tested here, is not a suitable option for clearing Bd infection in D. tinctorius. However, different results were obtained for P. regilla. Two topical applications of BMP-NTf2 on Bd-infected P. regilla (using a lower BMP-NTf2 dose than on D. tinctorius, mean ± SE; 9.42 ± 1.43 μL/g) reduced Bd growth, although the effect was lower than that obtained by daily doses of itracanozole (50% frogs exhibited complete clearance on day 16 vs. 100% for itracanozole). Our findings suggest that BMP-NTf2 has the potential to treat Bd infection, however the effect depends on several parameters. Further optimization of dose and schedule are needed before BMP-NTf2 can be considered as a safe and effective alternative to more conventional antifungal agents, such as itraconazole.

]]>
<![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/article/N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

]]>
<![CDATA[A randomized double‐blind trial evaluating the efficacy and tolerability of topical body treatment with TriHex Technology® combined with abdomen cryolipolysis or radiofrequency procedures]]> https://www.researchpad.co/article/N5f31a437-4a00-4a0f-81e9-cf63001edc81

Abstract

Background

Nonsurgical fat reduction procedures using cryolipolysis and radiofrequency are among the most popular noninvasive aesthetic procedures. In a previous study, TransFORM Body Treatment (TFB) with TriHex Technology® (ALASTIN® Skincare) improved the contour and reduced skin laxity following cryolipolysis of the arms. This product is formulated using a combination of peptides and other active ingredients designed to stimulate the autophagic breakdown of lipid droplets and expedite the apoptotic process after fat reduction procedures.

Aims

To assess the changes in abdominal volume after application of TFB for 12 weeks following cryolipolysis and radiofrequency procedures.

Methods

Following abdominal cryolipolysis or radiofrequency therapy, the subjects (N = 15) received TFB product and placebo and were randomly assigned to apply to the right or left sides of the abdomen for 12 weeks. Using 3‐dimensional digital imaging analysis, subjects were evaluated at 4, 8, and 12 weeks posttreatment.

Results

Topical TFB resulted in increased volume loss, which was greater than that for placebo at weeks 4 (P = .0511), 8 (P = .0238), and 12 (P = .0078), respectively, and statistically significant at weeks 8 and 12. There were no reported adverse events.

Conclusion

In this study, Topical application of TFB significantly increased adipose volume loss and improved clinical outcomes of nonsurgical fat reduction procedures.

]]>
<![CDATA[Well‐aging: A new strategy for skin homeostasis under multi‐stressed conditions]]> https://www.researchpad.co/article/N2bc6a0b1-8cc7-42a8-8a25-13fff38de784

Abstract

Background

Several studies evidenced significant increase of cortisol is the consequence of UV or emotional stress and leads to various deleterious effects in the skin.

Aim

The well‐aging, a new concept of lifestyle, procures an alternative to the anti‐aging strategy. We demonstrated that Tephrosia purpurea extract is able to stimulate well‐being hormones while reducing cortisol release. Furthermore, we hypothesized that the extract could positively influence the global skin homeostasis.

Method

We evaluated the impact of the extract on cortisol, β‐endorphin, and dopamine, released by normal human epidermal keratinocytes (NHEKs). A gene expression study was realized on NHEKs and NHDFs. The protein over‐expression of HMOX1 and NQO1 was evidenced at cellular and tissue level. Finally, we conducted a clinical study on 21 women living in a polluted environment in order to observe the impact of the active on global skin improvement.

Results

The extract is able to reduce significantly the cortisol release while inducing the production of β‐endorphin and dopamine. The gene expression study revealed that Tephrosia purpurea extract up‐regulated the genes involved in antioxidant response and skin renewal. Moreover, the induction of HMOX and NQO1 expression was confirmed on NHDFs, NHEKs and in RHE. We clinically demonstrated that the extract improved significantly the skin by reducing dark circles, represented by an improvement of L*, a*, and ITA parameters.

Conclusion

Tephrosia purpurea extract has beneficial effects on skin homeostasis through control of the well‐being state and antioxidant defenses leading to an improvement of dark circles, a clinical features particularly impacted by emotional and environmental stress.

]]>
<![CDATA[A novel moisturizer with high sun protection factor improves cutaneous barrier function and the visible appearance of rosacea‐prone skin]]> https://www.researchpad.co/article/N538a8be2-438f-4170-af47-f4552bad99bd

Summary

Background

Consensus guidelines advocate general skincare for rosacea patients.

Objectives

Two independent studies were performed to assess whether a tinted daily SPF‐30 facial moisturizer (DFM30) improves barrier function of dry skin and the efficacy and tolerability of DFM30 on rosacea‐prone skin.

Methods

In study 1, electrical capacitance (EC) and transepidermal water loss (TEWL) were measured at baseline, 2, 4, 8, and 24 hours after a single application of DFM30 and on a control site in 21 healthy females with dry skin. Study 2 evaluated 33 females with mild to moderate rosacea and nontransient erythema. Efficacy and tolerability after once‐daily DFM30 were assessed using a chromameter, image analysis of photographs, and trained rater and patient evaluations up to day 22.

Results

In study 1, EC showed statistically significant increases at 2, 4, and 8 hours, and TEWL showed statistically significant decreases 2, 4, 8, and 24 hours after DFM30 application to healthy females compared to baseline. In study 2, covering skin redness improved significantly after DFM30 application on day 1; 33.3% showed improved covering skin redness compared to baseline. Patients reported significantly less redness on day 8 than day 3. Feelings of dryness and tightness/tension were lower 30 minutes after first application. Feeling of dryness was lower than baseline after 3 days, 1 and 3 weeks. Image analysis suggested redness was significantly lower on day 22 compared to baseline. Chromameter readings showed significantly lower erythema on the cheek compared to baseline. All patients stated that DFM30 relieves and neutralizes visible redness who also indicated that they would purchase DFM30, and the product was well tolerated.

Conclusions

These studies show that DFM30 is suitable as part of the skincare regimens advocated by ROSacea COnsensus (ROSCO) for rosacea patients. DFM30 is an effective moisturizer that improves cutaneous barrier function and the appearance of rosacea‐prone skin.

]]>
<![CDATA[Is there a fundamental flaw in Canada’s post-arrival immigrant surveillance system for tuberculosis?]]> https://www.researchpad.co/article/5c8c1957d5eed0c484b4d464

Background

New immigrants to Canada with a history of tuberculosis or evidence of old healed tuberculosis on chest radiograph are referred to public health authorities for medical surveillance. This ostensible public health protection measure identifies a subgroup of patients (referrals) who are at very low risk (compared to non-referrals) of transmission.

Methods

To assess whether earlier diagnosis or a different phenotypic expression of disease explains this difference, we systematically reconstructed the immigration and transmission histories from a well-defined cohort of recently-arrived referral and non-referral pulmonary tuberculosis cases in Canada. Incident case chest radiographs in all cases and sequential past radiographs in referrals were re-read by three experts. Change in disease severity from pre-immigration radiograph to incident radiograph was the primary, and transmission of tuberculosis, the secondary, outcome.

Results

There were 174 cohort cases; 61 (35.1%) referrals and 113 (64.9%) non-referrals. Compared to non-referrals, referrals were less likely to be symptomatic (26% vs. 80%), smear-positive (15% vs. 50%), or to have cavitation (0% vs. 35%) or extensive disease (15% vs. 59%) on chest radiograph. After adjustment for referral status, time between films, country-of-birth, age and co-morbidities, referrals were less likely to have substantial changes on chest radiograph; OR 0.058 (95% CI 0.018–0.199). All secondary cases and 82% of tuberculin skin test conversions occurred in contacts of non-referrals.

Conclusions

Phenotypically different disease, and not earlier diagnosis, explains the difference in transmission risk between referrals and non-referrals. Screening, and treating high-risk non-referrals for latent tuberculosis is necessary to eliminate tuberculosis in Canada.

]]>
<![CDATA[Identification of Merkel cells associated with neurons in engineered skin substitutes after grafting to full thickness wounds]]> https://www.researchpad.co/article/5c8823d9d5eed0c484639153

Engineered skin substitutes (ESS), prepared using primary human fibroblasts and keratinocytes with a biopolymer scaffold, were shown to provide stable closure of excised burns, but relatively little is known about innervation of ESS after grafting. This study investigated innervation of ESS and, specifically, whether Merkel cells are present in healed grafts. Merkel cells are specialized neuroendocrine cells required for fine touch sensation in skin. We discovered cells positive for keratin 20 (KRT20), a general marker for Merkel cells, in the basal epidermis of ESS after transplantation to mice, suggesting the presence of Merkel cells. Cells expressing KRT20 were not observed in ESS in vitro. However, widely separated KRT20-positive cells were observed in basal epidermis of ESS by 2 weeks after grafting. By 4 weeks, these cells increased in number and expressed keratins 18 and 19, additional Merkel cells markers. Putative Merkel cell numbers increased further between weeks 6 and 14; their densities varied widely and no specific pattern of organization was observed, similar to Merkel cell localization in human skin. KRT20-positive cells co-expressed epidermal markers E-cadherin and keratin 15, suggesting derivation from the epidermal lineage, and neuroendocrine markers synaptophysin and chromogranin A, consistent with their identification as Merkel cells. By 4 weeks after grafting, some Merkel cells in engineered skin were associated with immature afferents expressing neurofilament-medium. By 8 weeks, Merkel cells were complexed with more mature neurons expressing neurofilament-heavy. Positive staining for human leukocyte antigen demonstrated that the Merkel cells in ESS were derived from grafted human cells. The results identify, for the first time, Merkel cell-neurite complexes in engineered skin in vivo. This suggests that fine touch sensation may be restored in ESS after grafting, although this must be confirmed with future functional studies.

]]>
<![CDATA[Increasing atmospheric CO2 and canopy temperature induces anatomical and physiological changes in leaves of the C4 forage species Panicum maximum]]> https://www.researchpad.co/article/5c75ac6cd5eed0c484d08750

Changes in leaf anatomy and ultrastructure are associated with physiological performance in the context of plant adaptations to climate change. In this study, we investigated the isolated and combined effects of elevated atmospheric CO2 concentration ([CO2]) up to 600 μmol mol-1 (eC) and elevated temperature (eT) to 2°C more than the ambient canopy temperature on the ultrastructure, leaf anatomy, and physiology of Panicum maximum Jacq. grown under field conditions using combined free-air carbon dioxide enrichment (FACE) and temperature free-air controlled enhancement (T-FACE) systems. Plants grown under eC showed reduced stomatal density, stomatal index, stomatal conductance (gs), and leaf transpiration rate (E), increased soil-water content (SWC) conservation and adaxial epidermis thickness were also observed. The net photosynthesis rate (A) and intrinsic water-use efficiency (iWUE) were enhanced by 25% and 71%, respectively, with a concomitant increase in the size of starch grains in bundle sheath cells. Under air warming, we observed an increase in the thickness of the adaxial cuticle and a decrease in the leaf thickness, size of vascular bundles and bulliform cells, and starch content. Under eCeT, air warming offset the eC effects on SWC and E, and no interactions between [CO2] and temperature for leaf anatomy were observed. Elevated [CO2] exerted more effects on external characteristics, such as the epidermis anatomy and leaf gas exchange, while air warming affected mainly the leaf structure. We conclude that differential anatomical and physiological adjustments contributed to the acclimation of P. maximum growing under elevated [CO2] and air warming, improving the leaf biomass production under these conditions.

]]>
<![CDATA[Sensitivity and specificity of computer vision classification of eyelid photographs for programmatic trachoma assessment]]> https://www.researchpad.co/article/5c6b2655d5eed0c48428986e

Background/aims

Trachoma programs base treatment decisions on the community prevalence of the clinical signs of trachoma, assessed by direct examination of the conjunctiva. Automated assessment could be more standardized and more cost-effective. We tested the hypothesis that an automated algorithm could classify eyelid photographs better than chance.

Methods

A total of 1,656 field-collected conjunctival images were obtained from clinical trial participants in Niger and Ethiopia. Images were scored for trachomatous inflammation—follicular (TF) and trachomatous inflammation—intense (TI) according to the simplified World Health Organization grading system by expert raters. We developed an automated procedure for image enhancement followed by application of a convolutional neural net classifier for TF and separately for TI. One hundred images were selected for testing TF and TI, and these images were not used for training.

Results

The agreement score for TF and TI tasks for the automated algorithm relative to expert graders was κ = 0.44 (95% CI: 0.26 to 0.62, P < 0.001) and κ = 0.69 (95% CI: 0.55 to 0.84, P < 0.001), respectively.

Discussion

For assessing the clinical signs of trachoma, a convolutional neural net performed well above chance when tested against expert consensus. Further improvements in specificity may render this method suitable for field use.

]]>
<![CDATA[Heme peroxidase HPX-2 protects Caenorhabditis elegans from pathogens]]> https://www.researchpad.co/article/5c59fefdd5eed0c484135895

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. Caenorhabditis elegans encodes for several heme peroxidases, and in a previous study we identified the ShkT-containing peroxidase, SKPO-1, as necessary for pathogen resistance. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific RNA interference (RNAi) revealed that HPX-2 functionally localizes to the hypodermis of the worm. In congruence with this observation, hpx-2 mutant animals possessed a weaker cuticle structure, indicated by higher permeability to a DNA dye, but exhibited no obvious morphological defects. In addition, fluorescent labeling of HPX-2 revealed its expression in the pharynx, an organ in which BLI-3 is also present. Interestingly, loss of HPX-2 increased intestinal colonization of E. faecalis, suggesting its role in the pharynx may limit intestinal colonization. Moreover, disruption of a catalytic residue in the peroxidase domain of HPX-2 resulted in decreased survival on E. faecalis, indicating its peroxidase activity is required for pathogen resistance. Finally, RNA-seq analysis of an hpx-2 mutant revealed changes in genes encoding for cuticle structural components under the non-pathogenic conditions. Under pathogenic conditions, genes involved in infection response were differentially regulated to a greater degree, likely due to increased microbial burden. In conclusion, the characterization of the heme-peroxidase, HPX-2, revealed that it contributes to C. elegans pathogen resistance through a role in generating cuticle material in the hypodermis and pharynx.

]]>
<![CDATA[Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study]]> https://www.researchpad.co/article/5c5ca31cd5eed0c48441f191

Background

Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.

Methods and findings

Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI.

Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02–1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13–1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03–1.04; P = 1.73 × 10−60). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06–1.12) per 1 kg/m2; P = 4.67 × 10−9). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (−0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.

Conclusions

Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.

]]>
<![CDATA[3D images as a field grader training tool for trachomatous trichiasis: A diagnostic accuracy study in Ethiopia]]> https://www.researchpad.co/article/5c536bc1d5eed0c484a49190

Background

Trachomatous trichiasis (TT) will continue to develop among those people who have had repeated infections after active trachoma is controlled. Detecting and treating affected individuals will remain necessary for years; a long “tail” of incident cases is anticipated. As the prevalence of TT declines, there will be fewer cases available for training trachoma graders (TG), necessitating alternative methods.

Methodology/Principal findings

Prospective, diagnostic accuracy study assessing sensitivity and specificity of 3D and 2D photography as a tool for training TG to detect TT. Individuals with TT in Ethiopia were examined, and 2D and 3D clinical images taken. Images were independently graded by four graders for presence or absence of trichiasis and compared to field grading. We recruited 153 participants. Clinical assessments and images were available for 306 eyes. Trichiasis was identified in 204 eyes by field grading. Image grading was performed on a selection of 262 eyes (131 with trichiasis). Most eyes with trichiasis had minor trichiasis (94/131). Pooled sensitivity was 88.3% (3D) and 98.0% (2D); pooled specificity was 59.8% (3D) and 26.8% (2D). 3D photo grading was 33.0% more specific than the 2D photo grading (p = 0.0002). The overall Kappa scores were 0.48 (3D) and 0.25 (2D). We trained 26 novice TG in Ethiopia using 3D images. They were tested on a 3D images set and had 71.4% agreement (kappa 0.46), relative to an expert. They were then tested examining 50 people, and had 86.8% agreement (kappa 0.75). We also tested 27 experienced TG on the same cases (86.4% agreement, kappa 0.75). There was no difference in performance between groups (p = 0.76). All participants preferred 3D over 2D images for training.

Conclusions/Significance

The slightly higher sensitivity of 2D photos comes at considerable cost in specificity. Training with 3D images enabled novice TG to identify cases as well as experienced TG. 3D were preferred to conventional 2D photos for training. Standardized 3D images of TT could be a useful tool for training TG, in settings where there are now few TT cases.

]]>
<![CDATA[Orf virus (ORFV) infection in a three-dimensional human skin model: Characteristic cellular alterations and interference with keratinocyte differentiation]]> https://www.researchpad.co/article/5c5b523fd5eed0c4842bc547

ORF virus (ORFV) is the causative agent of contagious ecthyma, a pustular dermatitis of small ruminants and humans. Even though the development of lesions caused by ORFV was extensively studied in animals, only limited knowledge exists about the lesion development in human skin. The aim of the present study was to evaluate a three-dimensional (3D) organotypic culture (OTC) as a human skin model for ORFV infection considering lesion development, replication of the virus, viral gene transcription and modulation of differentiation of human keratinocytes by ORFV. ORFV infection of OTC was performed using the ORFV isolate B029 derived from a human patient. The OTC sections showed a similar structure of stratified epidermal keratinocytes as human foreskin and a similar expression profile of the differentiation markers keratin 1 (K1), K10, and loricrin. Upon ORFV infection, OTCs exhibited histological cytopathic changes including hyperkeratosis and ballooning degeneration of the keratinocytes. ORFV persisted for 10 days and was located in keratinocytes of the outer epidermal layers. ORFV-specific early, intermediate and late genes were transcribed, but limited viral spread and restricted cell infection were noticed. ORFV infection resulted in downregulation of K1, K10, and loricrin at the transcriptional level without affecting proliferation as shown by PCNA or Ki-67 expression. In conclusion, OTC provides a suitable model to study the interaction of virus with human keratinocytes in a similar structural setting as human skin and reveals that ORFV infection downregulates several differentiation markers in the epidermis of the human skin, a hitherto unknown feature of dermal ORFV infection in man.

]]>
<![CDATA[Skin marks in bottlenose dolphins (Tursiops truncatus) interacting with artisanal fishery in the central Mediterranean Sea]]> https://www.researchpad.co/article/5c633968d5eed0c484ae664b

Skin marks occur frequently in many cetacean species across the globe revealing a broad spectrum of causes, including social interactions, infectious diseases and injuries produced by anthropogenic factors. The current study used photo-id data from 2005–2014 to estimate the skin mark pattern on resident bottlenose dolphins (Tursiops truncatus) from the Aeolian Archipelago (Italy). Thirteen skin mark types were identified and their origin, prevalence and permanence time were examined. The pattern of skin marks was assessed for the abundance, richness, distribution and severity in six body regions and compared among age classes, sex and degree of dolphins’ interaction with trammel nets (DIN). Our results showed higher prevalence, abundance, richness and distribution of skin marks in adults than in the younger age classes, with the exception of black marks and white ring lesions. The prevalence and abundance of skin marks were higher in males than females, with the exception of scratches and white patches. Moreover, gunshot wounds, mutilations and irregular dorsal fin edges were found only on adult males. Since males showed higher DIN than females and, in dolphins with higher DIN, skin marks were more abundant and frequently distributed in different body regions, the skin mark pattern in regard to DIN seems to be sex-related. The more severe marks were observed on adults, males and dolphins with higher DIN, namely skin disorder, tooth rake marks, small shallow indentations, deep indentations and mutilations. On the contrary, the severity of scratches, white patches and dark ring lesions was higher in females than males, but not significantly related to DIN and age of the individuals. Our results showed that photo-id data provide an efficient and cost-effective approach to document the occurrence of skin marks in free-ranging bottlenose dolphin populations, a critical step toward understanding the cause and supporting the conservation strategies.

]]>