Microplastics in a freshwater mussel (Anodonta anatina) in Northern Europe.

Alarming amounts of microplastics have recently been shown to accumulate in the environment. Recent focus has been on synthetic material contaminating the marine environment, while effects on freshwater habitats and organisms have received less attention. We here confirm and analyse occurrence of microplastics in the duck mussel, Anodonta anatina, in a Swedish river. All analysed mussels contained microplastics, and the number of microplastic debris found in the mussels increased with mussel size. In addition, we demonstrate higher concentrations of microplastics downstream urban areas with wastewater treatment plants compared to a rural upstream location. Both fibres and particles were found in the mussels, indicating that the emissions of these pollutants may have varying origin. Our study indicates that microplastics can be suspended in the water column in streams and that concentrations are higher downstream anthropogenic activity. We discuss our results in light of potential pathways in rural versus surrounding arable land, and highlight a number of required research directions in the aquatic system.

Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome.

BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. Pregnant dams were exposed to nano-titanium dioxide (nano-TiO2) aerosols (10 ± 0.5 mg/m3) for 7-8 days (calculated, cumulative lung deposition = 217 ± 1 µg) and on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. RESULTS: The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO2 exposed progeny. The most notable alterations in major biologic systems included immune adaptation and organismal growth. Changes in normal physiology were linked with other tissues, including liver and kidneys. CONCLUSIONS: These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

What can aquatic gastropods tell us about phenotypic plasticity? A review and meta-analysis.

There have been few attempts to synthesise the growing body of literature on phenotypic plasticity to reveal patterns and generalities about the extent and magnitude of plastic responses. Here, we conduct a review and meta-analysis of published literature on phenotypic plasticity in aquatic (marine and freshwater) gastropods, a common system for studying plasticity. We identified 96 studies, using pre-determined search terms, published between 1985 and November 2013. The literature was dominated by studies of predator-induced shell form, snail growth rates and life history parameters of a few model taxa, accounting for 67% of all studies reviewed. Meta-analyses indicated average plastic responses in shell thickness, shell shape, and growth and fecundity of freshwater species was at least three times larger than in marine species. Within marine gastropods, species with planktonic development had similar average plastic responses to species with benthic development. We discuss these findings in the context of the role of costs and limits of phenotypic plasticity and environmental heterogeneity as important constraints on the evolution of plasticity. We also consider potential publication biases and discuss areas for future research, indicating well-studied areas and important knowledge gaps.

Selection on outlier loci and their association with adaptive phenotypes in Littorina saxatilis contact zones.

A fundamental issue in speciation research is to evaluate phenotypic variation and the genomics driving the evolution of reproductive isolation between sister taxa. Above all, hybrid zones are excellent study systems for researchers to examine the association of genetic differentiation, phenotypic variation and the strength of selection. We investigated two contact zones in the marine gastropod Littorina saxatilis and utilized landmark-based geometric morphometric analysis together with amplified fragment length polymorphism (AFLP) markers to assess phenotypic and genomic divergence between ecotypes under divergent selection. From genetic markers, we calculated the cline width, linkage disequilibrium and the average effective selection on a locus. Additionally, we conducted an association analysis linking the outlier loci and phenotypic variation between ecotypes and show that a proportion of outlier loci are associated with key adaptive phenotypic traits.

Support for the hypoxia theory in the pathogenesis of infantile haemangioma.

BACKGROUND: The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. AIM: To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. METHODS: IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. RESULTS: Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. CONCLUSIONS: Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.

Genital divergence in sympatric sister snails.

A pattern of greater divergence in mating traits between sister-species pairs with overlapping ranges than between allopatric species pairs is expected if reinforcement commonly contributes to speciation. Few large-scale comparative analyses have addressed this prediction, especially for genital form. Here, we show that penial morphology follows the predicted pattern in 40 robustly identified sister-species pairs in the marine gastropod subfamily Littorininae. Further work is needed to exclude other processes that may contribute to genital divergence between sympatric species, but the clear pattern we observe strongly suggests a role for genital form in reproductive isolation in this large clade.

Use of highly active antiretroviral therapy is associated with lower prevalence of anal intraepithelial neoplastic lesions and lower prevalence of human papillomavirus in HIV-infected men who have sex with men.

BACKGROUND: The incidence of anal intraepithelial neoplasia (AIN) and anal cancer is increased in HIV-positive men who have sex with men (MSM). Persistent high-risk human papillomavirus (HPV) infection is an important etiologic agent. METHODS: In this study, a group of 250 HIV-positive MSM was included to determine the prevalence of AIN and to investigate the role of highly active antiretroviral therapy (HAART), high-risk HPV, and other risk factors possibly associated with this prevalence. RESULTS: Among patients included, 108 (43.2%) had lesions suspicious for AIN. Histologic analyses showed AIN 1 in 24 patients (22.2%), AIN 2 in 6 patients (5.6%), and AIN 3 in 10 patients (9.3%). In multivariable analyses, the use of HAART was associated with the absence of AIN (P = 0.045). In MSM without HAART, HPV infection was detected significantly more often compared with those who used HAART (P = 0.010). AIN was associated with HPV types 16 and 6. CONCLUSIONS: In this cross-sectional study in 250 HIV-positive MSM, the use of HAART was associated with lower prevalence of AIN and a significantly lower prevalence of HPV. This association between the prevalence of AIN and the absence of HAART may contribute to the current debate on when to start HAART in HIV-infected individuals.

Marked bilateral lower eyelid ectropion in cutis laxa: a paraneoplastic process in multiple myeloma.

PURPOSE: To describe a bilateral involutional lower eyelid ectropion in a patient with cutis laxa, a paraneoplastic process in multiple myeloma. DESIGN: Case report. RESULTS: A 60-year-old male presented with a marked involutional left lower eyelid ectropion. Systemic history included cutis laxa, a paraneoplastic feature of multiple myeloma. After surgical treatment, the ectropion recurred; furthermore, a right lower eyelid ectropion developed. In addition, a distinct dermatochalasis of both upper eyelids was present. CONCLUSIONS: This case is the first description of a marked bilateral involutional ectropion in cutis laxa acquisita.

Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions.

BACKGROUND: Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary. OBJECTIVES: To identify histological alterations and leucocyte subsets in normal-appearing perilesional skin, and early and chronic HS lesions. METHODS: In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining. RESULTS: Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low-grade influx of tryptase-positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation. CONCLUSIONS: Psoriasiform hyperplasia, follicular plugging and low-grade leucocytic infiltration are already present in normal-appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in 'pseudo' follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin.

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Use of skin substitute dressings in the treatment of staphylococcal scalded skin syndrome in neonates and young infants.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a rare toxin-mediated skin disease caused by Staphylococcus aureus and seen in infants and children younger than 5 years. OBJECTIVES: The supportive role of skin substitutes in SSSS is stressed as a new and relatively unknown method. METHODS: Retrospective observational case-series study, in neonates and young infants diagnosed with SSSS. RESULTS: Seven infants with SSSS, treatment with antibiotics, skin substitutes, strict pain relief strategy and prognosis were described. One of them was severely affected and deceased. CONCLUSION: This study describes 7 infants with SSSS and stresses the important role of skin substitutes as Omiderm® and Suprathel® as valuable adjuvant treatment modality.

Case studies and mathematical models of ecological speciation. 3: Ecotype formation in a Swedish snail.

Formation of partially reproductively isolated ecotypes in the rough periwinkle, Littorina saxatilis, may be a case of incipient nonallopatric ecological speciation. To better understand the dynamics of ecotype formation, its timescale, driving forces and evolutionary consequences, we developed a spatially explicit, individual-based model incorporating relevant ecological, spatial and mate selection data for Swedish L. saxatilis. We explore the impact of bounded hybrid superiority, ecological scenarios and mate selection systems on ecotype formation, gene flow and the evolution of prezygotic isolation. Our model shows that ecotypes are expected to form rapidly in parapatry under conditions applicable to Swedish L. saxatilis and may proceed to speciation. However, evolution of nonrandom mating had complex behaviour. Ecotype evolution was inhibited by pre-existing mating preferences, but facilitated by the evolution of novel preferences. While in many scenarios positive assortative mating reduced gene flow between ecotypes, in others negative assortative mating arose, preferences were lost after ecotype formation, preferences were confined to one ecotype or the ancestral ecotype became extinct through sexual selection. Bounded hybrid superiority (as observed in nature) enhanced ecotype formation but increased gene flow. Our results highlight that ecotype formation and speciation are distinct processes: factors that contribute to ecotype formation can be detrimental to speciation and vice versa. The complex interactions observed between local adaptation and nonrandom mating imply that generalization from data is unreliable without quantitative theory for speciation.

Complete lack of mitochondrial divergence between two species of NE Atlantic marine intertidal gastropods.

Some mitochondrial introgression is common between closely related species, but distinct species rarely show substantial introgression in their entire distribution range. In this study, however, we report a complete lack of mitochondrial divergence between two sympatric species of flat periwinkles (Littorina fabalis and Littorina obtusata) which, based on previous allozyme studies, diverged approximately 1 Ma. We re-examined their species status using both morphology (morphometric analysis) and neutral genetic markers (microsatellites) and our results confirmed that these species are well separated. Despite this, the two species shared all common cytochrome-b haplotypes throughout their NE Atlantic distribution and no deep split between typical L. fabalis and L. obtusata haplotypes could be found. We suggest that incomplete lineage sorting explains most of the lack of mitochondrial divergence between these species. However, coalescent-based analyses and the sympatric sharing of unique haplotypes suggest that introgressive hybridization also has occurred.

Unusual late nodular presentation of secondary syphilis.

A 20-year-old man presented with a five-week history of an eruption of papules and nodules disseminated over his body and face. We propose that this patient has a late form of secondary syphilis with a nodular, granulomatous inflammation in urgent need of treatment. Otherwise late irreversible sequelae could develop and unwanted possible further sexual transmission could take place.