Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen.

The spatial organization of eukaryotic genomes is linked to their biological functions, although it is not clear how this impacts the overall evolution of a genome. Here, we uncover the three-dimensional (3D) genome organization of the phytopathogen Verticillium dahliae, known to possess distinct genomic regions, designated adaptive genomic regions (AGRs), enriched in transposable elements and genes that mediate host infection. Short-range DNA interactions form clear topologically associating domains (TADs) with gene-rich boundaries that show reduced levels of gene expression and reduced genomic variation. Intriguingly, TADs are less clearly insulated in AGRs than in the core genome. At a global scale, the genome contains bipartite long-range interactions, particularly enriched for AGRs and more generally containing segmental duplications. Notably, the patterns observed for V. dahliae are also present in other Verticillium species. Thus, our analysis links 3D genome organization to evolutionary features conserved throughout the Verticillium genus.

The 2020 to 2021 California megafires and their impacts on wildlife habitat.

Fire activity during 2020 to 2021 in California, USA, was unprecedented in the modern record. More than 19,000 km2 of forest vegetation burned (10× more than the historical average), potentially affecting the habitat of 508 vertebrate species. Of the >9,000 km2 that burned at high severity, 89% occurred in large patches that exceeded historical estimates of maximum high-severity patch size. In this 2-y period, 100 vertebrate species experienced fire across >10% of their geographic range, 16 of which were species of conservation concern. These 100 species experienced high-severity fire across 5 to 14% of their ranges, underscoring potentially important changes to habitat structure. Species in this region are not adapted to high-severity megafires. Management actions, such as prescribed fires and mechanical thinning, can curb severe fire behavior and reduce the potential negative impacts of uncharacteristic fires on wildlife.

Rising wildfire risk to houses in the United States, especially in grasslands and shrublands.

Wildfire risks to homes are increasing, especially in the wildland-urban interface (WUI), where wildland vegetation and houses are in close proximity. Notably, we found that more houses are exposed to and destroyed by grassland and shrubland fires than by forest fires in the United States. Destruction was more likely in forest fires, but they burned less WUI. The number of houses within wildfire perimeters has doubled since the 1990s because of both housing growth (47% of additionally exposed houses) and more burned area (53%). Most exposed houses were in the WUI, which grew substantially during the 2010s (2.6 million new WUI houses), albeit not as rapidly as before. Any WUI growth increases wildfire risk to houses though, and more fires increase the risk to existing WUI houses.

Epigenetic regulation of nuclear processes in fungal plant pathogens.

Through the association of protein complexes to DNA, the eukaryotic nuclear genome is broadly organized into open euchromatin that is accessible for enzymes acting on DNA and condensed heterochromatin that is inaccessible. Chemical and physical alterations to chromatin may impact its organization and functionality and are therefore important regulators of nuclear processes. Studies in various fungal plant pathogens have uncovered an association between chromatin organization and expression of in planta-induced genes that are important for pathogenicity. This review discusses chromatin-based regulation mechanisms as determined in the fungal plant pathogen Verticillium dahliae and relates the importance of epigenetic transcriptional regulation and other nuclear processes more broadly in fungal plant pathogens.

The Interspecific Fungal Hybrid Verticillium longisporum Displays Subgenome-Specific Gene Expression.

Hybridization is an important evolutionary mechanism that can enable organisms to adapt to environmental challenges. It has previously been shown that the fungal allodiploid species Verticillium longisporum, the causal agent of verticillium stem striping in rapeseed, originated from at least three independent hybridization events between two haploid Verticillium species. To reveal the impact of genome duplication as a consequence of hybridization, we studied the genome and transcriptome dynamics upon two independent V. longisporum hybridization events, represented by the hybrid lineages "A1/D1" and "A1/D3." We show that V. longisporum genomes are characterized by extensive chromosomal rearrangements, including between parental chromosomal sets. V. longisporum hybrids display signs of evolutionary dynamics that are typically associated with the aftermath of allodiploidization, such as haploidization and more relaxed gene evolution. The expression patterns of the two subgenomes within the two hybrid lineages are more similar than those of the shared A1 parent between the two lineages, showing that the expression patterns of the parental genomes homogenized within a lineage. However, as genes that display differential parental expression in planta do not typically display the same pattern in vitro, we conclude that subgenome-specific responses occur in both lineages. Overall, our study uncovers genomic and transcriptomic plasticity during the evolution of the filamentous fungal hybrid V. longisporum and illustrates its adaptive potential. IMPORTANCEVerticillium is a genus of plant-associated fungi that includes a few plant pathogens that collectively affect a wide range of hosts. On several occasions, haploid Verticillium species hybridized into the stable allodiploid species Verticillium longisporum, which is, in contrast to haploid Verticillium species, a Brassicaceae specialist. Here, we studied the evolutionary genome and transcriptome dynamics of V. longisporum and the impact of the hybridization. V. longisporum genomes display a mosaic structure due to genomic rearrangements between the parental chromosome sets. Similar to other allopolyploid hybrids, V. longisporum displays an ongoing loss of heterozygosity and more relaxed gene evolution. Also, differential parental gene expression is observed, with enrichment for genes that encode secreted proteins. Intriguingly, the majority of these genes display subgenome-specific responses under differential growth conditions. In conclusion, hybridization has incited the genomic and transcriptomic plasticity that enables adaptation to environmental changes in a parental allele-specific fashion.

Three putative DNA methyltransferases of Verticillium dahliae differentially contribute to DNA methylation that is dispensable for growth, development and virulence.

BACKGROUND: DNA methylation is an important epigenetic control mechanism that in many fungi is restricted to genomic regions containing transposable elements (TEs). Two DNA methyltransferases, Dim2 and Dnmt5, are known to perform methylation at cytosines in fungi. While most ascomycete fungi encode both Dim2 and Dnmt5, only few functional studies have been performed in species containing both. METHODS: In this study, we report functional analysis of both Dim2 and Dnmt5 in the plant pathogenic fungus Verticillium dahliae. RESULTS: Our results show that Dim2, but not Dnmt5 or the putative sexual-cycle-related DNA methyltransferase Rid, is responsible for the majority of DNA methylation under the tested conditions. Single or double DNA methyltransferase mutants did not show altered development, virulence, or transcription of genes or TEs. In contrast, Hp1 and Dim5 mutants that are impacted in chromatin-associated processes upstream of DNA methylation are severely affected in development and virulence and display transcriptional reprogramming in specific hypervariable genomic regions (so-called adaptive genomic regions) that contain genes associated with host colonization. As these adaptive genomic regions are largely devoid of DNA methylation and of Hp1- and Dim5-associated heterochromatin, the differential transcription is likely caused by pleiotropic effects rather than by differential DNA methylation. CONCLUSION: Overall, our study suggests that Dim2 is the main DNA methyltransferase in V. dahliae and, in conjunction with work on other fungi, is likely the main active DNMT in ascomycetes, irrespective of Dnmt5 presence. We speculate that Dnmt5 and Rid act under specific, presently enigmatic, conditions or, alternatively, act in DNA-associated processes other than DNA methylation.

A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.

Local Rather than Global H3K27me3 Dynamics Are Associated with Differential Gene Expression in Verticillium dahliae.

Differential growth conditions typically trigger global transcriptional responses in filamentous fungi. Such fungal responses to environmental cues involve epigenetic regulation, including chemical histone modifications. It has been proposed that conditionally expressed genes, such as those that encode secondary metabolites but also effectors in pathogenic species, are often associated with a specific histone modification, lysine27 methylation of H3 (H3K27me3). However, thus far, no analyses on the global H3K27me3 profiles have been reported under differential growth conditions in order to assess if H3K27me3 dynamics govern differential transcription. Using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing data from the plant-pathogenic fungus Verticillium dahliae grown in three in vitro cultivation media, we now show that a substantial number of the identified H3K27me3 domains globally display stable profiles among these growth conditions. However, we observe local quantitative differences in H3K27me3 ChIP-seq signals that are associated with a subset of differentially transcribed genes between media. Comparing the in vitro results to expression during plant infection suggests that in planta-induced genes may require chromatin remodeling to achieve expression. Overall, our results demonstrate that some loci display H3K27me3 dynamics associated with concomitant transcriptional variation, but many differentially expressed genes are associated with stable H3K27me3 domains. Thus, we conclude that while H3K27me3 is required for transcriptional repression, it does not appear that transcriptional activation requires the global erasure of H3K27me3. We propose that the H3K27me3 domains that do not undergo dynamic methylation may contribute to transcription through other mechanisms or may serve additional genomic regulatory functions. IMPORTANCE In many organisms, including filamentous fungi, epigenetic mechanisms that involve chemical and physical modifications of DNA without changing the genetic sequence have been implicated in transcriptional responses upon developmental or environmental cues. In fungi, facultative heterochromatin that can decondense to allow transcription in response to developmental changes or environmental stimuli is characterized by the trimethylation of lysine 27 on histone H3 (H3K27me3), and H3K27me3 has been implicated in transcriptional regulation, although the precise mechanisms and functions remain enigmatic. Based on ChIP and RNA sequencing data, we show for the soilborne broad-host-range vascular wilt plant-pathogenic fungus Verticillium dahliae that although some loci display H3K27me3 dynamics that can contribute to transcriptional variation, other loci do not show such a dependence. Thus, although we recognize that H3K27me3 is required for transcriptional repression, we also conclude that this mark is not a conditionally responsive global regulator of differential transcription upon responses to environmental cues.

A unique chromatin profile defines adaptive genomic regions in a fungal plant pathogen.

Genomes store information at scales beyond the linear nucleotide sequence, which impacts genome function at the level of an individual, while influences on populations and long-term genome function remains unclear. Here, we addressed how physical and chemical DNA characteristics influence genome evolution in the plant pathogenic fungus Verticillium dahliae. We identified incomplete DNA methylation of repetitive elements, associated with specific genomic compartments originally defined as Lineage-Specific (LS) regions that contain genes involved in host adaptation. Further chromatin characterization revealed associations with features such as H3 Lys-27 methylated histones (H3K27me3) and accessible DNA. Machine learning trained on chromatin data identified twice as much LS DNA as previously recognized, which was validated through orthogonal analysis, and we propose to refer to this DNA as adaptive genomic regions. Our results provide evidence that specific chromatin profiles define adaptive genomic regions, and highlight how different epigenetic factors contribute to the organization of these regions.

The exploration of aza-quinolines as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors with low brain exposure.

GlaxoSmithKline and Astex Pharmaceuticals recently disclosed the discovery of the potent H-PGDS inhibitor GSK2894631A 1a (IC50 = 9.9 nM) as part of a fragment-based drug discovery collaboration with Astex Pharmaceuticals. This molecule exhibited good murine pharmacokinetics, allowing it to be utilized to explore H-PGDS pharmacology in vivo. Yet, with prolonged dosing at higher concentrations, 1a induced CNS toxicity. Looking to attenuate brain penetration in this series, aza-quinolines, were prepared with the intent of increasing polar surface area. Nitrogen substitutions at the 6- and 8-positions of the quinoline were discovered to be tolerated by the enzyme. Subsequent structure activity studies in these aza-quinoline scaffolds led to the identification of 1,8-naphthyridine 1y (IC50 = 9.4 nM) as a potent peripherally restricted H-PGDS inhibitor. Compound 1y is efficacious in four in vivo inflammatory models and exhibits no CNS toxicity.

Complementary NAD+ replacement strategies fail to functionally protect dystrophin-deficient muscle.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder stemming from a loss of functional dystrophin. Current therapeutic options for DMD are limited, as small molecule modalities remain largely unable to decrease the incidence or mitigate the consequences of repetitive mechanical insults to the muscle during eccentric contractions (ECCs). METHODS: Using a metabolomics-based approach, we observed distinct and transient molecular phenotypes in muscles of dystrophin-deficient MDX mice subjected to ECCs. Among the most chronically depleted metabolites was nicotinamide adenine dinucleotide (NAD), an essential metabolic cofactor suggested to protect muscle from structural and metabolic degeneration over time. We tested whether the MDX muscle NAD pool can be expanded for therapeutic benefit using two complementary small molecule strategies: provision of a biosynthetic precursor, nicotinamide riboside, or specific inhibition of the NAD-degrading ADP-ribosyl cyclase, CD38. RESULTS: Administering a novel, potent, and orally available CD38 antagonist to MDX mice successfully reverted a majority of the muscle metabolome toward the wildtype state, with a pronounced impact on intermediates of the pentose phosphate pathway, while supplementing nicotinamide riboside did not significantly affect the molecular phenotype of the muscle. However, neither strategy sustainably increased the bulk tissue NAD pool, lessened muscle damage markers, nor improved maximal hindlimb strength following repeated rounds of eccentric challenge and recovery. CONCLUSIONS: In the absence of dystrophin, eccentric injury contributes to chronic intramuscular NAD depletion with broad pleiotropic effects on the molecular phenotype of the tissue. These molecular consequences can be more effectively overcome by inhibiting the enzymatic activity of CD38 than by supplementing nicotinamide riboside. However, we found no evidence that either small molecule strategy is sufficient to restore muscle contractile function or confer protection from eccentric injury, undermining the modulation of NAD metabolism as a therapeutic approach for DMD.

Repetitive Elements Contribute to the Diversity and Evolution of Centromeres in the Fungal Genus Verticillium.

Centromeres are chromosomal regions that are crucial for chromosome segregation during mitosis and meiosis, and failed centromere formation can contribute to chromosomal anomalies. Despite this conserved function, centromeres differ significantly between and even within species. Thus far, systematic studies into the organization and evolution of fungal centromeres remain scarce. In this study, we identified the centromeres in each of the 10 species of the fungal genus Verticillium and characterized their organization and evolution. Chromatin immunoprecipitation of the centromere-specific histone CenH3 (ChIP-seq) and chromatin conformation capture (Hi-C) followed by high-throughput sequencing identified eight conserved, large (∼150-kb), AT-, and repeat-rich regional centromeres that are embedded in heterochromatin in the plant pathogen Verticillium dahliae Using Hi-C, we similarly identified repeat-rich centromeres in the other Verticillium species. Strikingly, a single degenerated long terminal repeat (LTR) retrotransposon is strongly associated with centromeric regions in some but not all Verticillium species. Extensive chromosomal rearrangements occurred during Verticillium evolution, of which some could be linked to centromeres, suggesting that centromeres contributed to chromosomal evolution. The size and organization of centromeres differ considerably between species, and centromere size was found to correlate with the genome-wide repeat content. Overall, our study highlights the contribution of repetitive elements to the diversity and rapid evolution of centromeres within the fungal genus VerticilliumIMPORTANCE The genus Verticillium contains 10 species of plant-associated fungi, some of which are notorious pathogens. Verticillium species evolved by frequent chromosomal rearrangements that contribute to genome plasticity. Centromeres are instrumental for separation of chromosomes during mitosis and meiosis, and failed centromere functionality can lead to chromosomal anomalies. Here, we used a combination of experimental techniques to identify and characterize centromeres in each of the Verticillium species. Intriguingly, we could strongly associate a single repetitive element to the centromeres of some of the Verticillium species. The presence of this element in the centromeres coincides with increased centromere sizes and genome-wide repeat expansions. Collectively, our findings signify a role of repetitive elements in the function, organization, and rapid evolution of centromeres in a set of closely related fungal species.

Sustained elevation of MG53 in the bloodstream increases tissue regenerative capacity without compromising metabolic function.

MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body.

The discovery of quinoline-3-carboxamides as hematopoietic prostaglandin D synthase (H-PGDS) inhibitors.

With the goal of discovering more selective anti-inflammatory drugs, than COX inhibitors, to attenuate prostaglandin signaling, a fragment-based screen of hematopoietic prostaglandin D synthase was performed. The 76 crystallographic hits were sorted into similar groups, with the 3-cyano-quinoline 1a (FP IC50 = 220,000 nM, LE = 0.43) being a potent member of the 6,6-fused heterocyclic cluster. Employing SAR insights gained from structural comparisons of other H-PGDS fragment binding mode clusters, the initial hit 1a was converted into the 70-fold more potent quinoline 1d (IC50 = 3,100 nM, LE = 0.49). A systematic substitution of the amine moiety of 1d, utilizing structural information and array chemistry, with modifications to improve inhibitor stability, resulted in the identification of the 300-fold more active H-PGDS inhibitor tool compound 1bv (IC50 = 9.9 nM, LE = 0.42). This selective inhibitor exhibited good murine pharmacokinetics, dose-dependently attenuated PGD2 production in a mast cell degranulation assay and should be suitable to further explore H-PGDS biology.

Tinea nigra: Report of three pediatrics cases. / Tiña negra: reporte de tres casos pediátricos.

INTRODUCTION: Tinea nigra is a superficial mycosis caused by Hortaea werneckii. Its clinical characte ristic is the appearance of a blackish brown macula of rapid growth, caused by the pigment produced by the fungus itself. The presence of a dark, fast growing, acral pigmentary lesion causes concern among patients and their treating physician about the possibility of a malignant pigmentary lesion. OBJECTIVE: To present a series of three clinical cases in pediatric patients with this pathology and to show the tools that help to make a differential diagnosis. CLINICAL CASES: Three patients between three and five years of age, which present a macular pigmented lesion on palms or soles, whose parents reported a rapid growth over a short period of time. Two of the patients reported previous trips to the Caribbean. Clinical and dermatoscopy suspicion of tinea nigra lead to a direct mycological exa mination, which confirmed the diagnosis. In all three cases, treatment with topical antifungals led to complete healing of the lesions. CONCLUSIONS: Although tinea nigra is rare in a dry climate, increasing travel of patients to tropical countries will increase the number of cases. Dermatoscopy and direct mycological examination are the tools that allow performing a correct diagnosis and avoiding unne cessary biopsies and/or surgeries.

Tiña negra: reporte de tres casos pediátricos / Tinea nigra: report of three pediatrics cases

Resumen: Introducción: La tiña negra es una micosis superficial causada por Hortaea werneckii. Su caracte rística clínica es la aparición de una mácula café negruzca de rápido crecimiento, producto del pig mento sintetizado por el mismo hongo. Sus características pigmentarias y de rápido crecimiento, de localización preferentemente acral, genera preocupación en los pacientes y en sus médicos tratantes por la sospecha de una lesion névica en evolución. Objetivos: Presentar 3 casos clínicos de pacientes pediátricos con esta patología y dar a conocer las herramientas para su diagnóstico diferencial. Casos clínicos: Tres pacientes, edades 3 y 5 años, con lesión macular pigmentada en palmas o plantas, cuyos padres referían habían crecido en forma rápida en poco tiempo. Dos de los casos tenían antecedentes de viajes previos al Caribe. Ante la sospecha clínica y dermatoscópica de una tiña negra, se realizó exámen micológico que confirmó el diagnóstico. En todos los casos, el tratamiento con antimicóticos tópicos llevó a la resolución completa de las lesiones. Conclusión: Aunque la tiña negra es rara en un clima seco, los viajes cada vez más frecuentes de los pacientes a países tropicales, probablemente aumentarán el número de casos. La dermatoscopía y el examen micológico son las herramientas que permiten realizar un correcto diagnóstico, evitando biopsias y/o cirugías innecesarias.

Abstract: Introduction: Tinea nigra is a superficial mycosis caused by Hortaea werneckii. Its clinical characte ristic is the appearance of a blackish brown macula of rapid growth, caused by the pigment produced by the fungus itself. The presence of a dark, fast growing, acral pigmentary lesion causes concern among patients and their treating physician about the possibility of a malignant pigmentary lesion. Objective: To present a series of three clinical cases in pediatric patients with this pathology and to show the tools that help to make a differential diagnosis. Clinical cases: Three patients between three and five years of age, which present a macular pigmented lesion on palms or soles, whose parents reported a rapid growth over a short period of time. Two of the patients reported previous trips to the Caribbean. Clinical and dermatoscopy suspicion of tinea nigra lead to a direct mycological exa mination, which confirmed the diagnosis. In all three cases, treatment with topical antifungals led to complete healing of the lesions. Conclusions: Although tinea nigra is rare in a dry climate, increasing travel of patients to tropical countries will increase the number of cases. Dermatoscopy and direct mycological examination are the tools that allow performing a correct diagnosis and avoiding unne cessary biopsies and/or surgeries.

[Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents]. / Onicomadesis secundaria a enfermedad pie-mano-boca: una manifestación frecuente y motivo de preocupación de los padres.

INTRODUCTION: Nail alterations in children are an important cause of parent anxiety and derive in multiple and unnecessary consultations. The onychomadesis corresponds to the complete and pain less detachment of the nail plate from the proximal fold. This self-resolving nail finding has been described as a late complication of hand-foot-mouth disease, a frequent viral exanthema in the pedia tric age. OBJECTIVE: To describe a classic pediatric case of hand-foot-mouth disease with subsequent onychomadesis. CLINICAL CASE: A 3-years-old male patient with an acute presentation of acute erythe matous perioral papulovesicles, which extend to upper extremities and hands, buttocks, thighs and feet, asymptomatic, and without compromising general condition. Skin lesions resolve completely, but after one month, he develops detachment of the nails, with subsequent complete recovery. Con clusions: The recognition of this association will allow primary care physicians to guide the parents about a benign and self-resolving process that may occur as part of the evolution of hand-foot-mouth disease, thus avoiding unnecessary anxiety, referral and treatments.

Onicomadesis secundaria a enfermedad pie-mano-boca: una manifestación frecuente y motivo de preocupación de los padres / Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents

INTRODUCCIÓN: Las alteraciones ungueales en niños provocan gran ansiedad en los padres y múltiples consultas en su mayoría innecesarias. La onicomadesis corresponde al despegamiento completo e indoloro de la lámina ungueal desde el pliegue proximal. Este hallazgo ungueal autoresolutivo se ha descrito como una complicación tardía de la enfermedad pie-mano-boca, exantema viral frecuente en la edad pediátrica. OBJETIVO: Reportar un caso pediátrico clásico de enfermedad pie-mano-boca que evolucionó con onicomadesis y revisión de la literatura. CASO CLÍNICO: Paciente masculino de 3 años de edad, con cuadro agudo de microampollas eritematosas, peribucales en un comienzo, luego brazos y manos, glúteos, muslo y pies, asintomático y sin compromiso del estado general. Se reali za diagnóstico clínico de enfermedad pie-mano-boca. Evoluciona con resolución total de lesiones cutáneas , pero al mes, desprendimiento completo de uñas, las que se recuperan con posterioridad. CONCLUSIÓN: El reconocimiento de la asociación entre enfermedad pie-mano-boca con onicomadesis nos permite orientar a los padres sobre un fenómeno benigno y transitorio que puede ocurrir como parte de la evolución de esta virosis, evitando así la ansiedad, derivación y tratamientos innecesarios.

INTRODUCTION: Nail alterations in children are an important cause of parent anxiety and derive in multiple and unnecessary consultations. The onychomadesis corresponds to the complete and pain less detachment of the nail plate from the proximal fold. This self-resolving nail finding has been described as a late complication of hand-foot-mouth disease, a frequent viral exanthema in the pedia tric age. OBJECTIVE: To describe a classic pediatric case of hand-foot-mouth disease with subsequent onychomadesis. CLINICAL CASE: A 3-years-old male patient with an acute presentation of acute erythe matous perioral papulovesicles, which extend to upper extremities and hands, buttocks, thighs and feet, asymptomatic, and without compromising general condition. Skin lesions resolve completely, but after one month, he develops detachment of the nails, with subsequent complete recovery. CONCLUSIONS: The recognition of this association will allow primary care physicians to guide the parents about a benign and self-resolving process that may occur as part of the evolution of hand-foot-mouth disease, thus avoiding unnecessary anxiety, referral and treatments.

Longitudinal Deformation of the Right Ventricle in Hypoplastic Left Heart Syndrome: A Comparative Study of 2D-Feature Tracking Magnetic Resonance Imaging and 2D-Speckle Tracking Echocardiography.

In hypoplastic left heart syndrome (HLHS), long-term outcome is closely related to right ventricular function. Echocardiography and magnetic resonance imaging (MRI) are routinely used for functional assessment. MRI 2D-tissue feature tracking (2D-FT) allows quantification of myocardial deformation but has not yet been applied to HLHS patients. We sought to investigate the feasibility of this technique and to compare the results to 2D-speckle tracking echocardiography (2D-STE). In routine MRI 2D anatomical four chamber view, cine images were recorded in 55 HLHS patients (median age 4.9 years [1.6, 17.0]). Regional and global peak systolic longitudinal strain (LS) and strain rate (LSR) were determined using 2D-FT software. Echocardiographic four chamber view was analyzed with 2D-STE. Visualization of all myocardial segments with MRI was excellent, regional, and global LS and LSR could be assessed in all data sets. In 2D-STE, 28% of apical segments could not be analyzed due to poor image quality. Agreement of 2D-FT MRI and 2D-STE was acceptable for global LS, but poor for global LSR. In MRI, regional LS was lower in the septal segments, while LSR was not different between the segments. GLS and GLSR correlated with ejection fraction (GLS: r = - 0.45 and r < 0.001, GLSR: r = - 0.34 and p = 0.01). With new post-processing options, the assessment of regional and global LS and LSR is feasible in routine MRI of HLHS patients. For LS, results were comparable with 2D-STE. The agreement was poor for LSR, which might relate to differences in temporal resolution between the two imaging modalities.

[Is there also a gynecologist for men? : A randomised controlled trial of ÄGGF information sessions in schools as a bridge to the urologist's consultations with boys]. / Gibt's auch 'nen Frauenarzt für Männer? : Eine randomisiert kontrollierte Studie der ÄGGF-Präventionsveranstaltungen in Schulen als Brücke zur Jungensprechstunde beim Urologen.

BACKGROUND: There are hardly any prevention programmes for health education and communication for boys in Germany. Boys seldom know when, how and to whom to turn to for questions or problems in the field of sexual and reproductive health. METHODS: From 2014-2016 the Medical Society for Health Promotion carried out a unique project for gender-sensitive medical health promotion for boys of all school types at 130 Bavarian schools. In 2015, 15 Bavarian schools took part in the evaluation (6th, 8th, 9th and 11th grade). At school level, similar schools have been randomised to trial and control groups. In the experimental group, three waves were conducted in panel design and two interviews were conducted in the control group using paper questionnaires. The number of cases in the panel is 599 (358 intervention group, 241 waiting control group). RESULTS: In all school types and grade levels, a highly significant increase in knowledge can be demonstrated. There is an average of 28% of the intervention group's overall knowledge improvement compared to the control group. More than 50% of the participants consider themselves to be very well informed before the intervention, although the objectively available knowledge does not justify this (e. g. average proportion of correctly answered questions on male anatomy and physiology 0.7 out of 6). The participants rate the medical information sessions and the fact that they are conducted by doctors with 1.7 or 1.6 (1: very good, to 5: poor). DISCUSSION: Boys urgently need proper knowledge transfer in the field of sexual health. They benefit regardless of the types of school from these health information sessions. The gender-sensitive and socially compensatory medical information sessions are highly accepted, effective and serve as a bridge to the general practitioners. A nationwide establishment of the intervention seems thus absolutely necessary.