A novel Ca2+ double cone vector system to treat compromised skin.

BACKGROUND: Stressed, damaged or very aged skin is predominantly characterized by a malfunctioning skin barrier. Underlying skin barrier malfunction is a reduced or defective calcium gradient in the epidermis. Consequently, replenishing the compromised skin's calcium stores with topical calcium could be a potential therapeutic approach. METHODS: We investigated the effect of our novel Ca2+ double cone vector system on improving the differentiation and barrier function of reconstructed human epidermis (RHE), cultured at low basal calcium (0.3 mM) to represent very aged skin. Furthermore, in a randomized placebo-controlled clinical study the skin barrier of 20 healthy volunteers was challenged with 2% sodium lauryl sulphate (SLS) for 24 h under occlusion, following and/or prior to treatment with a gel containing 2% of our calcium vector system. RESULTS: Culture in reduced basal calcium conditions (0.3 mM) strongly impeded the formation of a dense stratified epidermis. The apical treatment with 1.1 mM CaCl2 was not able to restore a functional differentiation. Treatment with 0.1% of the Ca2+ delivery system rescued the differentiation process and resulted in a normal stratified epidermis. Clinically, application of the Ca2+ vector system prior to and following SLS stress prevented increases in skin irritation and transepidermal water loss (TEWL) compared to placebo controls. Importantly, the treatment also significantly accelerated the recovery time following SLS stress. CONCLUSION: With our novel Ca2+ vector system, we highlight the delivery of bioavailable Ca2+ ions into the skin as a new and successful approach to treat a damaged barrier present in stressed, aged or atopic skin.

CONTEXTE: Les peaux stressées, lésées ou très âgées se caractérisent principalement par un dysfonctionnement de la barrière cutanée. Le dysfonctionnement de la barrière cutanée est sous­tendu par un gradient de calcium réduit ou défectueux dans l'épiderme. Par conséquent, la reconstitution des réserves de calcium de la peau fragilisées à l'aide de calcium topique pourrait constituer une approche thérapeutique potentielle. MÉTHODES: Nous avons étudié l'effet de notre nouveau système de vecteur à double cône Ca2+ sur l'amélioration de la différenciation et de la fonction de barrière de l'épiderme humain reconstitué (EHR), cultivé à un faible niveau de calcium basal (0,3 mM) pour représenter une peau très âgée. En outre, dans une étude clinique randomisée, contrôlée par placebo, la barrière cutanée de 20 volontaires en bonne santé a été exposée à 2 % de laurylsulfate de sodium (SLS) pendant 24 heures sous occlusion, après et/ou avant le traitement avec un gel contenant 2 % de notre système de vecteur de calcium. RÉSULTATS: La culture dans des conditions de calcium basal réduit (0,3 mM) a fortement empêché la formation d'un épiderme stratifié dense. Le traitement apical avec 1,1 mM de CaCl2 n'a pas permis de rétablir une différenciation fonctionnelle. Le traitement avec 0,1 % du système de libération de Ca2+ a permis de rétablir le processus de différenciation et d'obtenir un épiderme stratifié normal. Sur le plan clinique, l'application du système de vecteur Ca2+ avant et après l'exposition au SLS a empêché l'augmentation de l'irritation cutanée et de la perte d'eau transépidermique (Transepidermal Water Loss, TEWL) par rapport aux témoins sous placebo. Il est important de noter que le traitement a également accéléré de manière significative le temps de récupération après l'exposition au SLS. CONCLUSION: Grâce à notre nouveau système de vecteurs Ca2+, nous mettons en évidence l'apport d'ions Ca2+ biodisponibles dans la peau comme une approche nouvelle et efficace pour traiter la barrière endommagée présente dans une peau stressée, âgée ou atopique.

Self-control and performance while working from home.

This study explores the role of trait self-control in individuals' changes in performance and well-being when working from home (WFH). In a three-wave longitudinal study with UK workers in the midst of the COVID-19 pandemic, we find that low self-control workers experienced a significant positive adjustment to WFH over time: The number of reported work distractions decreased, and self-assessed performance increased over the period of four months. In contrast, high self-control individuals did not show a similar upward trajectory. Despite the positive adjustment of low self-control individuals over time, on average, self-control was still positively associated with performance and negatively associated with work distractions. However, trait self-control was not consistently associated with changes in well-being. These findings provide a more nuanced view on trait self-control, suggesting that low self-control individuals can improve initial performance over time when working from home.

Exploring the health and well-being of a national sample of U.K. treatment-seeking veterans.

OBJECTIVE: Military veterans experience a higher prevalence of mental health difficulties compared with the general population. Research has highlighted veterans who experience mental health difficulties have poorer treatment outcomes. Understanding veteran needs may help improve veteran mental health services and treatment outcomes. The aim of this study was to explore the complexity of health and well-being needs among a national clinical sample of veterans. METHOD: In total, 989 veterans from a U.K. veterans mental health charity were invited to complete a questionnaire about their sociodemographic characteristics, military experiences, physical and mental health, and well-being. RESULTS: Of the invitees, 428 veterans (43.3%) completed the questionnaire. Common mental disorders, such as anxiety and depression, were the most frequently reported mental health difficulty (80.7%), followed by loneliness (79.1%) and perceived low social support (72.2%). Rates of PTSD were also high (68.7% any PTSD), with most participants experiencing complex PTSD (CPTSD; 62.5%) compared with PTSD (6.2%). Veterans with co-occurring CPTSD symptoms have poorer health due to a higher number of comorbidities, for instance between CPTSD and moral injury. CONCLUSIONS: Comorbidity appeared to be the norm rather than the exception within treatment-seeking veterans. As such, it seems important for veteran mental health services to take a holistic approach when supporting veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A closer look reveals hidden diversity in the intertidal Caribbean Fortuyniidae (Acari, Oribatida).

A molecular genetic and morphometric investigation revealed the supposedly widespread Caribbean and Western Atlantic intertidal oribatid mite species Fortuynia atlantica to comprise at least two different species. Although there are no distinct morphological differences separating these taxa, COI and 18S sequence divergence data, as well as different species delimitation analyses, clearly identify the two species. Fortuynia atlantica is distributed in the northern Caribbean and the Western Atlantic and the new Fortuynia antillea sp. nov. is presently endemic to Barbados. Vicariance is supposed to be responsible for their genetic diversification and stabilizing selection caused by the extreme intertidal environment is suggested to be the reason for the found morphological stasis. The genetic structure of Fortuynia atlantica indicates that Bermudian populations are derived from the northern Caribbean and thus support the theory of dispersal by drifting on the Gulf Stream. Haplotype network data suggest that Bermudian and Bahamian populations were largely shaped by colonization, expansion and extinction events caused by dramatic sea level changes during the Pleistocene. A preliminary phylogenetic analysis based on 18S gene sequences indicates that the globally distributed genus Fortuynia may be a monophyletic group, whereas Caribbean and Western Atlantic members are distinctly separated from the Indo-Pacific and Western Pacific species.

Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo.

BACKGROUND: Ways to prevent disease-induced vascular modifications that accelerate brain damage remain largely elusive. Improved understanding of perivascular cell signalling could provide unparalleled insight as these cells impact vascular stability and functionality of the neurovascular unit as a whole. Identifying key drivers of astrocyte and pericyte responses that modify cell-cell interactions and crosstalk during injury is key. At the cellular level, injury-induced outcomes are closely entwined with activation of the hypoxia-inducible factor-1 (HIF-1) pathway. Studies clearly suggest that endothelial HIF-1 signalling increases blood-brain barrier permeability but the influence of perivascular HIF-1 induction on outcome is unknown. Using novel mouse lines with astrocyte and pericyte targeted HIF-1 loss of function, we herein show that vascular stability in vivo is differentially impacted by perivascular hypoxia-induced HIF-1 stabilization. METHODS: To facilitate HIF-1 deletion in adult mice without developmental complications, novel Cre-inducible astrocyte-targeted (GFAP-CreERT2; HIF-1αfl/fl and GLAST-CreERT2; HIF-1αfl/fl) and pericyte-targeted (SMMHC-CreERT2; HIF-1αfl/fl) transgenic animals were generated. Mice in their home cages were exposed to either normoxia (21% O2) or hypoxia (8% O2) for 96 h in an oxygen-controlled humidified glove box. All lines were similarly responsive to hypoxic challenge and post-Cre activation showed significantly reduced HIF-1 target gene levels in the individual cells as predicted. RESULTS: Unexpectedly, hypoxia-induced vascular remodelling was unaffected by HIF-1 loss of function in the two astrocyte lines but effectively blocked in the pericyte line. In correlation, hypoxia-induced barrier permeability and water accumulation were abrogated only in pericyte targeted HIF-1 loss of function mice. In contrast to expectation, brain and serum levels of hypoxia-induced VEGF, TGF-ß and MMPs (genes known to mediate vascular remodelling) were unaffected by HIF-1 deletion in all lines. However, in agreement with the permeability data, immunofluorescence and electron microscopy showed clear prevention of hypoxia-induced tight junction disruption in the pericyte loss of function line. CONCLUSION: This study shows that pericyte but not astrocyte HIF-1 stabilization modulates endothelial tight junction functionality and thereby plays a pivotal role in hypoxia-induced vascular dysfunction. Whether the cells respond similarly or differentially to other injury stimuli will be of significant relevance.

Cryptic diversity within the Poecilochirus carabi mite species complex phoretic on Nicrophorus burying beetles: Phylogeny, biogeography, and host specificity.

Coevolution is often considered a major driver of speciation, but evidence for this claim is not always found because diversity might be cryptic. When morphological divergence is low, molecular data are needed to uncover diversity. This is often the case in mites, which are known for their extensive and often cryptic diversity. We studied mites of the genus Poecilochirus that are phoretic on burying beetles (Silphidae: Nicrophorus). Poecilochirus taxonomy is poorly understood. Most studies on this genus focus on the evolutionary ecology of Poecilochirus carabi sensu lato, a complex of at least two biological species. Based on molecular data of 230 specimens from 43 locations worldwide, we identified 24 genetic clusters that may represent species. We estimate that these mites began to diversify during the Paleogene, when the clade containing P. subterraneus branched off and the remaining mites diverged into two further clades. One clade resembles P. monospinosus. The other clade contains 17 genetic clusters resembling P. carabi s.l.. Among these are P. carabi sensu stricto, P. necrophori, and potentially many additional cryptic species. Our analyses suggest that these clades were formed in the Miocene by large-scale geographic separation; co-speciation of mites with the host beetles can be largely ruled out. Diversification also seems to have happened on a smaller scale, potentially due to adaptation to specific hosts or local abiotic conditions, causing some clusters to specialize on certain beetle species. Our results suggest that biodiversity in this genus was generated by multiple interacting forces shaping the tangled webs of life.

The impact of the COVID-19 pandemic on treatment-seeking veterans in the United Kingdom with preexisting mental health difficulties: A longitudinal study.

Individuals with preexisting psychological difficulties are at risk of further deterioration of their mental well-being during the COVID-19 pandemic. This longitudinal study, conducted during the period between two national lockdowns, aimed to investigate the impact of the COVID-19 pandemic on veterans in the United Kingdom with preexisting mental health difficulties. Treatment-seeking veterans with preexisting mental health difficulties (N = 95) were surveyed in two waves. Wave 1 was conducted at the end of the first lockdown (June 2020-July 2020), and Wave 2 took place during the second lockdown (November 2020). Participants completed measures to assess symptoms of posttraumatic stress disorder (PTSD); common mental health difficulties (CMDs), including anxiety and depression; anger; and alcohol use. Initial analyses revealed no significant changes in symptoms of PTSD, CMDs, anger, or alcohol use between the lockdowns, ps = .247-.986. However, veterans who experienced more COVID-19-related stressors were more likely to experience increases in PTSD, odds ratio (OR) = 6.30, p = .002, and CMD symptoms, OR = 4.32, p = .025. Participants with lower levels of social support during the second lockdown were more likely to experience increased anger difficulties, OR = 0.91, p = .025. The findings suggest that although mental health among veterans in the United Kingdom may have remained relatively stable between the two lockdowns, those who reported more COVID-related stressors and lower levels of social support may have been particularly vulnerable to symptom exacerbation. Such findings hold important implications for tailoring support for veterans during the COVID-19 pandemic.

A taxonomist's nightmare - Cryptic diversity in Caribbean intertidal arthropods (Arachnida, Acari, Oribatida).

There has been a long controversy about what defines a species and how to delimitate them which resulted in the existence of more than two dozen different species concepts. Recent research on so-called "cryptic species" heated up this debate as some scientists argue that these cryptic species are only a result of incompatible species concepts. While this may be true, we should keep in mind that all concepts are nothing more than human constructs and that the phenomenon of high phenotypic similarity despite reproductive isolation is real. To investigate and understand this phenomenon it is important to classify and name cryptic species as it allows to communicate them with other fields of science that use Linnaean binomials. To provide a common framework for the description of cryptic species, we propose a possible protocol of how to formally name and describe these taxa in practice. The most important point of this protocol is to explain which species concept was used to delimitate the cryptic taxon. As a model, we present the case of the allegedly widespread Caribbean intertidal mite Thalassozetes barbara, which in fact consists of seven phenotypically very similar but genetically distinct species. All species are island or short-range endemics with poor dispersal abilities that have evolved in geographic isolation. Stabilizing selection caused by the extreme conditions of the intertidal environment is suggested to be responsible for the morphological stasis of this cryptic species complex.

Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.

Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability. Since pericytes are critical for barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity and injury severity in a mouse model of ischemic stroke. We show that pericyte HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing pericyte death thereby maintaining vessel coverage and junctional protein organization, and suppressing vascular remodeling. Importantly, considerable improvements in sensorimotor function were observed in HIF-1 LoF mice indicating that better vascular functionality post stroke improves outcome. Thus, boosting vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing pericyte survival may be a lucrative option to accelerate recovery after severe brain injury.

Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro.

BACKGROUND: Astrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment. Hypoxia-inducible factor-1 (HIF-1) has long been assumed to be a culprit for barrier dysfunction as a number of its target genes are potent angiogenic factors. Indeed AC themselves, reservoirs of an array of different growth factors and molecules, are frequently assumed to be the source of such molecules although direct supporting evidence is yet to be published. Being well known reservoirs of HIF-1 dependent angiogenic molecules, we asked if AC HIF-1 dependent paracrine signaling drives brain EC disturbance during hypoxia. METHODS: First we collected conditioned media from control and siRNA-mediated HIF-1 knockdown primary rat AC that had been exposed to normoxic or hypoxic conditions. The conditioned media was then used to culture normoxic and hypoxic (1% O2) rat brain microvascular EC (RBE4) for 6 and 24 h. Various activation parameters including migration, proliferation and cell cycling were assessed and compared to untreated controls. In addition, tight junction localization and barrier stability per se (via permeability assay) was evaluated. RESULTS: AC conditioned media maintained both normoxic and hypoxic EC in a quiescent state by suppressing EC metabolic activity and proliferation. By FACs we observed reduced cell cycling with an increased number of cells in G0 phase and reduced cell numbers in M phase compared to controls. EC migration was also blocked by AC conditioned media and in correlation hypoxic tight junction organization and barrier functionality was improved. Surprisingly however, AC HIF-1 deletion did not impact EC responses or barrier stability during hypoxia. CONCLUSIONS: This study demonstrates that AC HIF-1 dependent paracrine signaling does not contribute to AC modulation of EC barrier function under normoxic or hypoxic conditions. Thus other cell types likely mediate EC permeability in stress scenarios. Our data does however highlight the continuous protective effect of AC on the barrier endothelium. Exploring these protective mechanisms in more detail will provide essential insight into ways to prevent barrier disturbance during injury and disease.

Patterns of intraspecific morphological variability in soil mites reflect their dispersal ability.

The ability to disperse is one of the most important factors influencing the biogeography of species and speciation processes. Highly mobile species have been shown to lack geographic population structures, whereas less mobile species show genetically strongly subdivided populations which are expected to also display at least subtle phenotypic differences. Geometric morphometric methods (GMM) were now used to analyze morphological differences between European populations of a presumed non-phoretic, little mobile mite species in comparison to a highly mobile, phoretic species. The non-phoretic species Scutacarus carinthiacus showed a phenotypic population structure, whereas the phoretic species S. acarorum displayed homogeneity. These different patterns most probably can be explained by different levels of gene flow due to different dispersal abilities of the two species. GMM proved to be a sensitive tool that is especially recommendable for the analysis of (old) museum material and/or specimens in microscopic slides, which are not suitable for molecular genetic analysis.

The Caribbean enigma: the presence of unusual cryptic diversity in intertidal mites (Arachnida, Acari, Oribatida).

The definition, as well as the existence of cryptic species, is still a subject of controversial debates. Some scientists claim that cryptic diversity is a real phenomenon that should be extensively studied while others argue that cryptic species do not exist as they are nothing more than an incompatibility of species concepts. We investigated the enigmatic case of two widely distributed Caribbean intertidal oribatid mites, Carinozetes bermudensis and Carinozetes mangrovi, consisting of five distinct genetic lineages. Morphological features allowing to clearly distinguish between these lineages are absent, and despite certain congruence with genetic data, comprehensive morphometric analyses also do not show clear separation. Species delimitation analyses based on COI sequence data, on the other hand, suggest five distinct genetic species. Despite the lack of diagnostic characters for these suggested species, the lineages can be classified at least into two morphological groups, the bermudensis and the mangrovi group which can only be distinguished by the arrangement of cuticular ventral carinae. Specimens within a group show nearly identical phenotypes, impeding morphological identification and hence rendering the found diversity cryptic. Stabilizing selection caused by the extreme conditions of the intertidal environment is suggested to be responsible for the found morphological stasis. The genetic lineages show more or less clear geographic patterns; in C. mangrovi, there is a northern, an Antillean, and a Pacific lineage, whereas in C. bermudensis, there is a Bermudian and a Caribbean lineage. In a few places, e.g., the Bahamas and Panama, distributions may overlap. Neither the found biogeographic pattern nor the observed ecological needs could explain the reason for the genetic diversification of Caribbean Carinozetes.

The intertidal genus Indopacifica (Acari, Oribatida, Selenoribatidae): new species, juvenile morphology and distribution.

Two new intertidal oribatid mite species from the Indo-pacific region are described. Indopacifica iohanna sp. n. was found on the coasts of the Philippines and can be distinguished from its congeners by the lack of a ventral tooth on the claws. The larva and nymphs of this species show the same type of plication and setation typical for juveniles of other selenoribatid mites. Indopacifica mauritiana sp. n. was discovered on the coast of Mauritius and can be separated from its congeners by possessing only vestigial lamellar setae. A morphometric comparison of these two species and Indopacifica pantai from Thailand and Malaysia showed a clear separation between the three species. The known distribution of the genus Indopacifica stretches now from Mauritius in the West to the Philippines in the East and further occurrences within this area should be expected.

Furin inhibition prevents hypoxic and TGFß-mediated blood-brain barrier disruption.

Hypoxic blood-brain barrier (BBB) dysfunction is a common feature of CNS diseases however mechanisms underlying barrier disturbance are still largely unknown. This study investigated the role of transforming growth factor ß (TGFß), a cytokine known to induce expression of the proprotein convertase Furin, in hypoxia-mediated barrier compromise. We show that exposure of brain endothelial cells (ECs) to hypoxia (1% O2) rapidly stimulates their migration. Additional exogenous TGFß (0.4 nM) exposure potentiated this effect and increased Furin expression in a TGFß type I receptor activin-like kinase 5 (ALK5) - dependent manner (prevented by 10 µM SB431542). Furin inhibition prevented hypoxia-induced EC migration and blocked TGFß-induced potentiation suggesting existence of a feedback loop. TGFß and Furin were also critical for hypoxia-induced BBB dysfunction. TGFß treatment aggravated hypoxia-induced BBB permeability but ALK5 or Furin blockade reversed injury-induced permeability changes. Thus during insult Furin compromises endothelial integrity by mediating the effects of TGFß. Targeting the Furin or ALK5 pathway may offer novel therapeutic strategies for improving BBB stability and CNS function during disease.

New and cryptic species of intertidal mites (Acari, Oribatida) from the Western Caribbean - an integrative approach.

The present study highlights the distribution, systematics, morphology, genetics, and ecology of two newly discovered intertidal oribatid mites from the Western Caribbean. The fortuyniid Litoribates floridae sp. nov. represents a cryptic species as it looks nearly identical to L. bonairensis. The two species can be distinguished only by subtle morphological and morphometric characteristics, whereas cytochrome oxidase subunit I gene sequences clearly separate the two taxa. The absence of morphological divergence in these disjunct species may have resulted from stabilizing selection due to the extreme intertidal environment. Litoribates floridae sp. nov. is presently known from the Florida Keys, primarily in mangrove leaf litter. The selenoribatid Thalassozetes balboa sp. nov. can be distinguished from all known congeners by a unique cuticular notogastral pattern, the presence of only two pairs of adanal setae, and two ventral teeth on each leg claw. It is morphologically most similar to T. barbara from the Eastern Caribbean. Thalassozetes balboa sp. nov. was found in Panama and Florida. This species usually occurs on rocky substrate and feeds on the intertidal alga Bostrychia. Litoribates floridaehttp://www.zoobank.org/urn:lsid:zoobank.org:act:A4B830FC-A03F-405D-9DE4-DE4C39DB6211 Thalassozetes balboahttp://www.zoobank.org/urn:lsid:zoobank.org:act:EBF8C435-5C07-4B0E-8279-2101DC9E2CD4.

18F-FDG PET Response of Skeletal (Bone Marrow and Bone) Involvement After Induction Chemotherapy in Pediatric Hodgkin Lymphoma: Are Specific Response Criteria Required?

To determine whether the current 18F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: The initial PET scans of 1,068 pediatric HL patients from the EuroNet-PHL-C1 trial were evaluated for skeletal involvement by central review. Three types of skeletal lesions were distinguished: PET-only lesions (those detected on PET only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response for skeletal and nodal involvement on PET-2 were compared. Results: Of the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM, and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET-2-negative in the skeleton and 94 (68%) became PET-2-negative in the lymph nodes. The highest number of PET-2-negative scans in the skeleton was 42 (95%) in the 44 PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients and 37 (59%) in the 63 bone patients. Lesions that became PET-2-negative showed a lower initial median qPET (2.74) and MTV (2 cm3) than lesions that remained PET-2-positive (3.84 and 7 cm3, respectively). Conclusion: In this study with pediatric HL patients, the complete response rate for skeletal involvement on PET-2 was similar to that for nodal involvement. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion-comparison with the local skeletal background-is well suited. The initial qPET and MTV of skeletal lesions were predictive of the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response.

Consecutive antibiotic treatment with doxycycline and marbofloxacin clears bacteremia in Mycoplasma haemofelis-infected cats.

Mycoplasma haemofelis is the most pathogenic feline hemoplasma species and a causative agent of infectious hemolytic anemia in cats. Current treatment protocols are effective in reducing M. haemofelis blood loads and clinical signs but consistent bacteremia clearance is rarely achieved. The aim of this study was to develop an antibiotic treatment protocol capable of clearing M. haemofelis bacteremia. Doxycycline and marbofloxacin treatment protocols were evaluated in chronically M. haemofelis infected cats in two pre-experiments and a controlled treatment study (main experiment) using five treated and four untreated cats. The blood bacterial loads in the main experiment were monitored weekly by real-time PCR for 203 days. Cats were treated with doxycycline (5 mg/kg bid orally) for 28 days. Cats that remained M. haemofelis PCR-positive or became positive again (all 5 cats in the main experiment) were switched to marbofloxacin treatment (2 mg/kg sid orally) for 14 days; then, all cats were PCR-negative. Immunosuppression after the antibiotic treatment did not lead to reactivation of bacteremia. Fine needle aspirates of different organs and bone marrow collected before and after immunosuppression were PCR-negative. Overall, 5 cats cleared bacteremia with doxycycline alone (showing lower bacterial loads at the treatment start), while 10 cats needed to be switched to marbofloxacin. Based on our results, we recommend doxycycline treatment (10 mg/kg up to 28 days) for clearance of M. haemofelis infection and monitoring bacterial loads by real-time PCR. Only if bacteremia persists or reoccurs, antibiotic treatment should be switched to marbofloxacin (2 mg/kg sid for 14 days).

Pharmacotherapeutic Management of Pediatric Lymphoma.

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) comprise approximately 15% of all childhood malignancies. Cure rates for both lymphoma entities have evolved tremendously during the last couple of decades, raising the 5-year survival rates to almost 100% for HL and to 85% for NHL. The mainstay therapy for both malignancies is still chemotherapy-with different regimens recommended for different types of disease. In HL, combined modality treatment, i.e., chemotherapy followed by radiotherapy, has long been the standard regimen. In order to reduce long-term side effects, such as second malignancies, most major pediatric HL consortia have studied response-based radiotherapy reduction strategies over the last 3 decades. For recurrent disease, high-dose chemotherapy followed by an autologous or an allogeneic hematopoietic stem-cell transplant is an option. No targeted agents have yet gained regulatory approval for use in pediatric patients with lymphoma. For adult lymphoma patients, the CD20 antibody rituximab and the CD30 antibody-drug conjugate brentuximab vedotin are targeted agents used regularly in first- and second-line treatment regimens. More recently, immune checkpoint inhibitors, phosphatidyl-inositol-3-kinase inhibitors, and Bruton's tyrosine kinase inhibitors appear to be very promising new treatment options in adult lymphoma. Here, we discuss the current experience with these types of agents in pediatric lymphoma patients.

Morphological diversification among island populations of intertidal mites (Acari, Oribatida, Fortuyniidae) from the Galápagos archipelago.

The intertidal oribatid mite species Alismobates galapagoensis and Litoribates caelestis occur on the archipelago of Galápagos. To test for morphological variation between populations of different islands, a comprehensive morphometric study was performed. Four A. galapagoensis populations from the islands Bartolomé, Isabela, Santa Cruz and San Cristobal, as well as two L. caelestis populations from Bartolomé and Santa Cruz were investigated. The L. caelestis populations did not show any significant differences whereas the A. galapagoensis populations exhibited clear divergences indicating speciation. Differences in overall size of A. galapagoensis apparently followed a gradient from East to West, with specimens from San Cristóbal being the largest and individuals from Bartolomé and Isabela being the smallest. Apart from size, significant shape differences were found in the epimeral region and females showed stronger variation among islands than males. The degree of morphological divergence seems to correlate with geographic distance, i.e. populations from islands located closer to each other showed fewer differences than populations from distant islands. Based on this correlation we suggest that transport between islands has happened mainly by drifting on ocean currents.

Support for the underrepresented sex: new descriptions of scutacarid males (Acari, Heterostigmatina).

Based on males gained from laboratory cultures, nine new descriptions and one redescription of scutacarid males are given: the respective species are Heterodispus foveatus Jagersbacher-Baumann and Ebermann 2012, Imparipes dispar Rack, 1964, Lamnacarus ornatus Balogh and Mahunka, 1963, Scutacarus acarorum (Goeze, 1780), S. deserticolus Mahunka, 1969, S. ellipticus Karafiat, 1959, S. longipes Rack, 1975, S. longitarsus (Berlese, 1905), S. tackei Willmann, 1942 and S. tyrrhenicus Ebermann, 1986. The taxonomic relevance of male morphology is evaluated. It reveals a strong potential for differentiating between species, and possible characters diagnostic for scutacarid genera are discussed. Within Heterostigmatina, males of Scutacaridae show the most derived characters.