Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).

Similar long-term outcomes for venous, bovine pericardial, and polyester patches for primary carotid endarterectomy.

BACKGROUND: Currently, the type of patch used for carotid endarterectomy closure depends on the preference of the operating surgeon. Various materials are available, including autologous venous patches, bovine pericardial patches (BPP), and synthetic patches. The purpose of this study was to compare the long-term outcomes. METHODS: All patients who underwent primary carotid endarterectomy with patch angioplasty using a venous, bovine, or polyester patch between 2010 and 2020 at two high-volume medical centers were included in this retrospective analysis on largely prospectively collected data. Study endpoints included long-term ipsilateral transient ischemic attack or cerebrovascular accident, restenosis, reintervention, and all-cause mortality. Cox proportional hazard models were fitted to assess the effect of patch type to each outcome. RESULTS: In total, 1481 CEAs were performed with a follow-up of 32 (13-65) months. Venous patch was used in 309 patients (20.9%), BPP in 1000 patients (67.5%), and polyester patch in 172 patients (11.6%). A preoperative symptomatic carotid artery stenosis of >50% was observed in 91.9% (n = 284) of the patients who received a venous patch, 92.1% (n = 921) of the patients who received BPP, and 90.7% (n = 156) of the patients who received a polyester patch (p = 0.799). Only in selected patients with an asymptomatic stenosis of >70% surgery was considered. Multivariable analyses showed no significant differences between the three patch types regarding long-term outcomes after adjusting for confounders. CONCLUSIONS: In patients undergoing primary carotid endarterectomy, the use of venous, bovine pericardial, or polyester patches seems equally safe and durable in terms of comparability in long-term outcomes.

An Integrated Approach for Synonymization of Rotylenchus rhomboides with R. goodeyi (Nematoda: Hoplolaimidae) Reveals High Intraspecific Mitogenomic Variation.

Rotylenchus is a widely distributed, economically important plant-parasitic nematode group whose species-level identification relies largely on limited morphological characters, including character-based tabular keys and molecular data of ribosomal and mitochondrial genes. In this study, a combined morphological and molecular analysis of three populations of Rotylenchus goodeyi from Belgium, Poland, and the Netherlands revealed important character variations of this species, leading to synonymization of R. rhomboides with R. goodeyi and a high nucleotide variation within cox1 gene sequences in these populations. Additional Illumina sequencing of DNA from individuals of the Dutch population revealed two variants of mitogenomes, each approximately 23 Kb in size, differing by approximately 9% and containing 11 protein-coding genes, 2 ribosomal RNA genes, and as many as 29 transfer RNA genes. In addition to the first representative whole-genome shotgun sequence datasets of the genus Rotylenchus, this study also provides the full-length mitogenome and the ribosomal DNA sequences of R. goodeyi.

H/ACA snoRNA levels are regulated during stem cell differentiation.

H/ACA small nucleolar RNAs (snoRNAs) guide pseudouridylation as part of a small nucleolar ribonucleoprotein complex (snoRNP). Disruption of H/ACA snoRNA levels in stem cells impairs pluripotency, yet it remains unclear how H/ACA snoRNAs contribute to differentiation. To determine if H/ACA snoRNA levels are dynamic during differentiation, we comprehensively profiled H/ACA snoRNA abundance in multiple murine cell types and during differentiation in three cellular models, including mouse embryonic stem cells and mouse myoblasts. We determined that the profiles of H/ACA snoRNA abundance are cell-type specific, and we identified a subset of snoRNAs that are specifically regulated during differentiation. Additionally, we demonstrated that a decrease in Snora27 abundance upon differentiation corresponds to a decrease in pseudouridylation of its target site within the E-site transfer RNA (tRNA) binding region of the 28S ribosomal RNA (rRNA) in the large ribosomal subunit. Together, these data point toward a potential model in which H/ACA snoRNAs are specifically regulated during differentiation to alter pseudouridylation and fine tune ribosome function.

The Synchytrium endobioticum AvrSen1 Triggers a Hypersensitive Response in Sen1 Potatoes While Natural Variants Evade Detection.

Synchytrium endobioticum is an obligate biotrophic fungus of division Chytridiomycota. It causes potato wart disease, has a worldwide quarantine status and is included on the Health and Human Services and United States Department of Agriculture Select Agent list. S. endobioticum isolates are grouped in pathotypes based on their ability to evade host resistance in a set of differential potato varieties. Thus far, 39 pathotypes are reported. A single dominant gene (Sen1) governs pathotype 1 (D1) resistance and we anticipated that the underlying molecular model would involve a pathogen effector (AvrSen1) that is recognized by the host. The S. endobioticum-specific secretome of 14 isolates representing six different pathotypes was screened for effectors specifically present in pathotype 1 (D1) isolates but absent in others. We identified a single AvrSen1 candidate. Expression of this candidate in potato Sen1 plants showed a specific hypersensitive response (HR), which cosegregated with the Sen1 resistance in potato populations. No HR was obtained with truncated genes found in pathotypes that evaded recognition by Sen1. These findings established that our candidate gene was indeed Avrsen1. The S. endobioticum AvrSen1 is a single-copy gene and encodes a 376-amino-acid protein without predicted function or functional domains, and is the first effector gene identified in Chytridiomycota, an extremely diverse yet underrepresented basal lineage of fungi.

The linear mitochondrial genome of the quarantine chytrid Synchytrium endobioticum; insights into the evolution and recent history of an obligate biotrophic plant pathogen.

BACKGROUND: Chytridiomycota species (chytrids) belong to a basal lineage in the fungal kingdom. Inhabiting terrestrial and aquatic environments, most are free-living saprophytes but several species cause important diseases: e.g. Batrachochytrium dendrobatidis, responsible for worldwide amphibian decline; and Synchytrium endobioticum, causing potato wart disease. S. endobioticum has an obligate biotrophic lifestyle and isolates can be further characterized as pathotypes based on their virulence on a differential set of potato cultivars. Quarantine measures have been implemented globally to control the disease and prevent its spread. We used a comparative approach using chytrid mitogenomes to determine taxonomical relationships and to gain insights into the evolution and recent history of introductions of this plant pathogen. RESULTS: We assembled and annotated the complete mitochondrial genome of 30 S. endobioticum isolates and generated mitochondrial genomes for five additional chytrid species. The mitochondrial genome of S. endobioticum is linear with terminal inverted repeats which was validated by tailing and PCR amplifying the telomeric ends. Surprisingly, no conservation in organisation and orientation of mitochondrial genes was observed among the Chytridiomycota except for S. endobioticum and its sister species Synchytrium microbalum. However, the mitochondrial genome of S. microbalum is circular and comprises only a third of the 72.9 Kbp found for S. endobioticum suggesting recent linearization and expansion. Four mitochondrial lineages were identified in the S. endobioticum mitochondrial genomes. Several pathotypes occur in different lineages, suggesting that these have emerged independently. In addition, variations for polymorphic sites in the mitochondrial genome of individual isolates were observed demonstrating that S. endobioticum isolates represent a community of different genotypes. Such communities were shown to be complex and stable over time, but we also demonstrate that the use of semi-resistant potato cultivars triggers a rapid shift in the mitochondrial haplotype associated with increased virulence. CONCLUSIONS: Mitochondrial genomic variation shows that S. endobioticum has been introduced into Europe multiple times, that several pathotypes emerged multiple times, and that isolates represent communities of different genotypes. Our study represents the most comprehensive dataset of chytrid mitogenomes, which provides new insights into the extraordinary dynamics and evolution of mitochondrial genomes involving linearization, expansion and reshuffling.

The Environmental Behavior of Methylene-4,4'-dianiline.

Methylene-4,4'-dianiline (MDA, CAS-No. 101-77-9) is a high production volume intermediate that is mainly processed to diisocyanates and finally polyurethanes. This review summarizes available data concerning the environmental behavior. When released into the environment, MDA distributes into water and subsequently sediment and soil compartments; the air is of little relevance, owed to the low vapor pressure and short atmospheric half-life, which renders MDA non-critical for long-range transport. Biodegradation data present a diverged picture; in some tests, MDA is not readily biodegradable or even not inherent biodegradable; in other tests, MDA turned out to be readily biodegradable (but failing the 10-d window). The history and composition of the inoculum used for testing seem to play an important role, which is underlined by good test results with adapted inoculum. In soil, initially a rapid mineralization is observed, which slows down within the first days due to competitive chemical absorption. The latter results in degradation rates comparable to that of natural organic matter. Under anaerobic conditions, mineralization is poor. Irreversible chemisorption occurs unless soils/sediments are highly reduced. Half-lives due to primary decay do not indicate MDA to be persistent according to the regulatory guidance used in then EU, Canada, or the USA; in Japan, however, due to test results in MITI degradation tests, MDA would be regarded as persistent. The identification of microbial MDA metabolites deserves further research. MDA is not bioaccumulative, but it is toxic to aquatic organisms and mammals. MDA in pore water of soils is rapidly adsorbed on the surface of plant roots. Test runs were too short to draw a final conclusion with regards to transport to stem, leaves, and fruits. Data from structurally similar compounds indicate that such transport would account for less than 1% of the root-adsorbed material.

The transition from stem cell to progenitor spermatogonia and male fertility requires the SHP2 protein tyrosine phosphatase.

SHP2 is a widely expressed protein tyrosine phosphatase required for signal transduction from multiple cell surface receptors. Gain and loss of function SHP2 mutations in humans are known to cause Noonan and LEOPARD syndromes, respectively, that are characterized by numerous pathological conditions including male infertility. Using conditional gene targeting in the mouse, we found that SHP2 is required for maintaining spermatogonial stem cells (SSCs) and the production of germ cells required for male fertility. After deleting SHP2, spermatogenesis was halted at the initial step during which transit-amplifying undifferentiated spermatogonia are produced from SSCs. In the absence of SHP2, proliferation of SSCs and undifferentiated spermatogonia was inhibited, thus germ cells cannot be replenished and SSCs cannot undergo renewal. However, germ cells beyond the undifferentiated spermatogonia stage of development at the time of SHP2 knockout were able to complete their maturation to become sperm. In cultures of SSCs and their progeny, inhibition of SHP2 activity reduced growth factor-mediated intracellular signaling that regulates SSC proliferation and cell fate. Inhibition of SHP2 also decreased the number of SSCs present in culture and caused SSCs to detach from supporting cells. Injection of mice with an SHP2 inhibitor blocked the production of germ cells from SSCs. Together, our studies show that SHP2 is essential for SSCs to maintain fertility and indicates that the pathogenesis of infertility in humans with SHP2 mutations is due to compromised SSC functions that block spermatogenesis.

Blood donor to inactive donor transition in the Basel region between 1996 and 2011: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: For the prevention of blood shortages, it is essential for blood banks to design and implement donor recruitment and donor retention strategies that take into account the determinants of donor return. MATERIAL AND METHODS: We studied the behaviour of first-time blood donors in the region of Basel, Switzerland, between 1996 and 2011 and described factors associated with transition from active to inactive donor in two successive first-time donor cohorts (1996-2002, 2003-2008). RESULTS: The risk of becoming an inactive donor was associated with being younger and female, not being a 0-negative donor and living in an urban area. Over time, hazards of becoming an inactive donor were converging for individuals living in non-urban and urban areas as were those of younger and older donors. After their first donation, 73.6% and 67.5% of males in the 1996-2002 and 2003-2008 cohorts, respectively, donated at least once in the following 24 months. The proportion of returning female donors was 71.8% and 65.4%, respectively. CONCLUSIONS: The increased volatility of first-time blood donors suggests that marketing actions and strategies aimed at increasing return rates should be reinforced, especially for younger and female blood donors.

Phytophthora terminalis sp. nov. and Phytophthora occultans sp. nov., two invasive pathogens of ornamental plants in Europe.

In the past decade several Phytophthora strains were isolated from diseased Pachysandra terminalis plants suffering stem base and root rot, originating from the Netherlands and Belgium. All isolates were homothallic and had a felt-like colony pattern, produced semi-papillate sporangia, globose oogonia and had a maximum growth at ~ 27 C. Several additional Phytophthora strains were isolated from diseased Buxus sempervirens plants, originating from the Netherlands and Belgium, which had sustained stem base and root rot; similar strains also were isolated from Acer palmatum, Choisya ternata and Taxus in the United Kingdom. All isolates were homothallic and had a stellate colony pattern, produced larger semi-papillate sporangia and smaller globose oogonia than the isolates from Pa. terminalis and had a maximum growth temperature of ~ 30 C. Phylogenetic analyses of both species using the internal transcribed spacer region of the nuc rDNA (ITS), mt cytochrome oxidases subunit I gene (CoxI) and nuc translation elongation factor 1-α gene (TEF1α) revealed that all sequences of each species were identical at each locus and unique to that species, forming two distinct clusters in subclade 2a. Sequence analysis of partial ß-tubulin genes showed that both taxa share an identical sequence that is identical to that of Ph. himalsilva, a species originating from Asia, suggesting a common Asian origin. Pathogenicity trials demonstrated disease symptoms on their respective hosts, and re-isolation and re-identification of the inoculated pathogens confirmed Koch's postulates.

A target enrichment approach for enhanced recovery of Synchytrium endobioticum nuclear genome sequences.

Potato wart disease is caused by the obligate fungal pathogen Synchytrium endobioticum. DNA extraction from compost, purified spores and crude wart tissue derived from tuber galls of infected potatoes often results in low S. endobioticum DNA concentration or highly contaminated with DNA coming from other microorganisms and the potato host. Therefore, Illumina sequencing of these samples generally results in suboptimal recovery of the nuclear genome sequences of S. endobioticum. A hybridization-based target enrichment protocol was developed to strongly enhance the recovery of S. endobioticum DNA while off-target organisms DNA remains uncaptured. The design strategy involved creating a set of 180,000 molecular baits targeting both gene and non-gene regions of S. endobioticum. The baits were applied to whole genome amplified DNA samples of various S. endobioticum pathotypes (races) in compost, from purified spores and crude wart tissue samples. This was followed by Illumina sequencing and bioinformatic analyses. Compared to non-enriched samples, target enriched samples: 1) showed a significant increase in the proportion of sequenced bases mapped to the S. endobioticum nuclear genome, especially for crude wart tissue samples; 2) yielded sequencing data with higher and better nuclear genome coverage; 3) biased genome assembly towards S. endobioticum sequences, yielding smaller assembly sizes but higher representation of putative S. endobioticum contigs; 4) showed an increase in the number of S. endobioticum genes detected in the genome assemblies. Our hybridization-based target enrichment protocol offers a valuable tool for enhancing genome sequencing and NGS-based molecular detection of S. endobioticum, especially in difficult samples.

Building an Equity-Centered Ecosystem: University of Utah Health as a Microcosm.

Academic medicine, and medicine in general, are less diverse than the general patient population. Family Medicine, while still lagging behind the general population, has the most diversity in leadership and in the specialty in general, and continues to lead in this effort, with 16.7% of chairs identifying as underrepresented in medicine. Historical and current systematic marginalization of Black or African American, Latina/e/o/x, Hispanic or of Spanish Origin (LHS), American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and Southeast Asian individuals has created severe underrepresentation within health sciences professions. Over the last 30 years, the percentage of faculty from these groups has increased from 7 to 9% in allopathic academic medicine, with similar increases in Osteopathic Medicine, Dentistry, and Pharmacy, but all lag behind age-adjusted population means. Traditionally, diversity efforts have focused on increasing pathway programs to address this widening disparity. While pathway programs are a good start, they are only a portion of what is needed to create lasting change in the diversity of the medical profession as well as the career trajectory and success of underrepresented in medicine (URiM) health professionals toward self-actualization and positions of leadership. This article elucidates all parts of an ecosystem necessary to ensure that equity, diversity, and inclusion outcomes can improve.

[The history of electroconvulsive therapy in the Netherlands]. / Psychiatrie onder hoogspanning.

Electroconvulsive therapy (ECT) has a tumultuous history in the Netherlands. It was found to have particularly favorable results in patients with severe depression or catatonia. Inconvenient side effects such as fractures, muscle tears and memory loss, however, became apparent. Due to technical developments and application of anesthesia, these side effects decreased considerably. In the 1960s, the use of ECT decreased due to the rise of psychopharmaceuticals and the emergence of the antipsychiatry movement. The procedure regained popularity in the 1980s, following the favorable, yet cautious recommendations of the Dutch Health Council. Nevertheless, the use of ECT still remains limited today. The public outcry over the treatment has left its mark, leaving the sometimes life-saving treatment with a poor image. An overview of the historical development of ECT in the Netherlands may help to understand the significant stigma and fear of side effects patients continue to experience today.

Analysis of Thaumatotibia leucotreta (Lepidoptera: Tortricidae: Olethreutinae) mitochondrial genomes in the context of a recent host range expansion.

BACKGROUND: The false codling moth (FCM), Thaumatotibia leucotreta (Meyrick, 1913), is a significant pest of various important economic crops and is a EU quarantine pest. In the last decade the pest has been reported on Rosa spp. In this study we determined whether this shift occurred within specific FCM populations across seven eastern sub-Saharan countries or whether the species opportunistically switches to this novel host as it presents itself. To achieve this, we assessed the genetic diversity of complete mitogenomes of T. leucotreta specimens intercepted at import and analysed potential linkages with the geographical origin and host species. RESULTS: Genomic, geographical and host information were integrated into a T. leucotreta Nextstrain build which contains 95 complete mitogenomes generated from material intercepted at import between January 2013 and December 2018. Samples represented seven sub-Saharan countries and mitogenomic sequences grouped in six main clades. DISCUSSION: If host strains of FCM would exist, specialization from a single haplotype towards the novel host is expected. Instead, we find specimens intercepted on Rosa spp. in all six clades. The absence of linkage between genotype and host suggests opportunistic expansion to the new host plant. This underlines risks of introducing new plant species to an area as the effect of pests already present on the new plant might be unpredictable with current knowledge.

The Nijmegen ultra-sensitive Bethesda Assay detects very low-titer factor VIII inhibitors in patients with congenital and acquired hemophilia A.

BACKGROUND: An inhibitor can develop in congenital hemophilia A (HA) patients against exogenous infused factor (F)VIII, whereas in acquired HA (AHA) inhibitors initially develop against endogenous FVIII. Inhibitors can be detected with the Nijmegen Bethesda Assay (NBA), which has an international cut-off level of 0.60 Nijmegen Bethesda Units/mL (NBU/mL). Thereby, very low-titer inhibitors may remain undetected. AIM: To describe the design and validation of the Nijmegen ultra-sensitive Bethesda Assay (NusBA) for the detection of very low-titer inhibitors. METHODS: The NusBA is a modification of the NBA in which the ratio of patient plasma to normal pooled plasma is changed from 1:1 to 9:1. Analytical validation was performed according to the CLSI EP10 guideline in order to determine trueness and reproducibility. Clinical validation was performed in two cohorts of congenital HA patients (82 adults) with pharmacokinetic data and four AHA patients. The limit of quantitation (LOQ) was determined by measuring plasma samples spiked with inhibitor levels in the low range (0.05-0.80 NBU/mL). RESULTS: The LOQ for the NusBA was 0.10 NusBU/mL, with a coefficient of variation of 24.2 %. Seven (8.5 %) congenital HA patients had a positive NusBA result, of which only one was detected with the NBA. There was no correlation between NusBA and FVIII half-life. In three of the AHA patients the NusBA remained positive, when the NBA became negative. DISCUSSION: The NusBA is able to detect very low-titer FVIII inhibitors of ≥0.10 NBU/mL. Thereby, it may have added value in early inhibitor detection and therapy adjustments in patients with congenital HA and AHA.

The distribution of the prostaglandin E receptor type 2 (EP2) in the detrusor of the guinea pig.

OBJECTIVE: To explore the distribution of prostaglandin E receptor type 2 (EP2) in the bladder muscle layers and its spatial relationship to cyclo-oxygenase type 1 (COX I). MATERIALS AND METHODS: Twelve male guinea pigs were killed by cervical dislocation, the bladders removed and fixed in 4% paraformaldehyde in PBS. Frozen sections of 10 µm were cut and stained with antibodies to EP2, COX I and vimentin. RESULTS: EP2 receptor immunoreactivity is located on the smooth muscle cells as well as on vimentin positive surface muscle and intramuscular interstitial cells. EP2 expression on interstitial cells is highly localized. Discrete regions of intense staining were observed on the interstitial cell processes. COX I is expressed in the muscle interstitial cells and was found to be located on discrete regions of the cell and cell processes. Double staining with EP2 and COX I suggests that the regions of a cell expressing EP2 are different from those expressing COX I. CONCLUSIONS: The presence of COX I, prostaglandin E receptor type 2 (EP2) immune-reactivity in the network of interstitial cells suggests a role of this network in the propagation of signals. Due to a cAMP coupling of the EP2 receptor in many other tissues and a lower dissociation constant of EP2, it is suggested that a rise in PG levels may gradually push the balance from a relaxant EP2 effect towards a contractile effect. Hence, PG could have a modulatory role on the non-voiding bladder contractions by changing the threshold level for excitability of the interstitial cell network.

Kruppel-like factor 2 regulates thymocyte and T-cell migration.

Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool, suggesting KLF2 regulates T-cell quiescence and survival. Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2-/-) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P1, CD62L and beta7 integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P1--a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.

A randomized controlled trial of fractional laser therapy and dermabrasion for scar resurfacing.

BACKGROUND: Dermabrasion has been the standard resurfacing procedure for postsurgical scars, but recovery can be long. Fractionated carbon dioxide (CO2 ) laser is a safe, effective tissue resurfacing modality, but no prospective trial has compared its safety or efficacy with that of dermabrasion for postsurgical scar resurfacing. OBJECTIVE: To compare the safety and efficacy of single-treatment fractional photothermolysis with that of single-treatment dermabrasion for postsurgical scar resurfacing on the face. METHODS AND MATERIALS: A split-scar method was used to compare fractionated CO2 laser and diamond fraise dermabrasion on postsurgical scars of the face. Primary endpoint was safety at day 0, 1 week, and 1 month. Secondary endpoint was efficacy at 3 months as measured by blinded evaluation of standardized photographs. RESULTS: Safety data revealed that there was less erythema (p = .001) and bleeding (p = .001) at day 0, less erythema (p = .01) and edema (p = .046) at 1 week, and a trend toward less erythema at 1 month (p = .06) with fractionated CO2 . Efficacy data at 3 months revealed equivalent scar improvements (p = .77). CONCLUSION: Fractionated CO2 laser therapy should be considered a safe alternative for surgical scar resurfacing on the face. The safety profile exceeds that of dermabrasion, and it has a quicker clinical recovery and equivalent cosmetic efficacy.

Synchytrium endobioticum, the potato wart disease pathogen.

Potato wart disease is considered one of the most important quarantine pests for cultivated potato and is caused by the obligate biotrophic chytrid fungus Synchytrium endobioticum. This review integrates observations from early potato wart research and recent molecular, genetic, and genomic studies of the pathogen and its host potato. Taxonomy, epidemiology, pathology, and formation of new pathotypes are discussed, and a model for molecular S. endobioticum-potato interaction is proposed. TAXONOMY: Currently classified as kingdom: Fungi, phylum: Chytridiomycota, class: Chytridiomycetes, order: Chytridiales, family: Synchytriaceae, genus: Synchytrium, species: Synchytrium endobioticum, there is strong molecular support for Synchytriaceae to be transferred to the order Synchytriales. HOSTS AND DISEASE SYMPTOMS: Solanum tuberosum is the main host for S. endobioticum but other solanaceous species have been reported as alternative hosts. It is not known if these alternative hosts play a role in the survival of the pathogen in (borders of) infested fields. Disease symptoms on potato tubers are characterized by the warty cauliflower-like malformations that are the result of cell enlargement and cell multiplication induced by the pathogen. Meristematic tissue on tubers, stolons, eyes, sprouts, and inflorescences can be infected while the potato root system seems to be immune. PATHOTYPES: For S. endobioticum over 40 pathotypes, which are defined as groups of isolates with a similar response to a set of differential potato varieties, are described. Pathotypes 1(D1), 2(G1), 6(O1), and 18(T1) are currently regarded to be most widespread. However, with the current differential set other pathogen diversity largely remains undetected. PATHOGEN-HOST INTERACTION: A single effector has been described for S. endobioticum (AvrSen1), which is recognized by the potato Sen1 resistance gene product. This is also the first effector that has been described in Chytridiomycota, showing that in this fungal division resistance also fits the gene-for-gene concept. Although significant progress was made in the last decade in mapping wart disease resistance loci, not all resistances present in potato breeding germplasm could be identified. The use of resistant varieties plays an essential role in disease management.

DenseUNets with feedback non-local attention for the segmentation of specular microscopy images of the corneal endothelium with guttae.

Corneal guttae, which are the abnormal growth of extracellular matrix in the corneal endothelium, are observed in specular images as black droplets that occlude the endothelial cells. To estimate the corneal parameters (endothelial cell density [ECD], coefficient of variation [CV], and hexagonality [HEX]), we propose a new deep learning method that includes a novel attention mechanism (named fNLA), which helps to infer the cell edges in the occluded areas. The approach first derives the cell edges, then infers the well-detected cells, and finally employs a postprocessing method to fix mistakes. This results in a binary segmentation from which the corneal parameters are estimated. We analyzed 1203 images (500 contained guttae) obtained with a Topcon SP-1P microscope. To generate the ground truth, we performed manual segmentation in all images. Several networks were evaluated (UNet, ResUNeXt, DenseUNets, UNet++, etc.) and we found that DenseUNets with fNLA provided the lowest error: a mean absolute error of 23.16 [cells/mm[Formula: see text]] in ECD, 1.28 [%] in CV, and 3.13 [%] in HEX. Compared with Topcon's built-in software, our error was 3-6 times smaller. Overall, our approach handled notably well the cells affected by guttae, detecting cell edges partially occluded by small guttae and discarding large areas covered by extensive guttae.