Epidemiology of a major honey bee pathogen, deformed wing virus: potential worldwide replacement of genotype A by genotype B.

The western honey bee (Apis mellifera) is of major economic and ecological importance, with elevated rates of colony losses in temperate regions over the last two decades thought to be largely caused by the exotic ectoparasitic mite Varroa destructor and deformed wing virus (DWV), which the mite transmits. DWV currently exists as two main genotypes: the formerly widespread DWV-A and the more recently described and rapidly expanding DWV-B. It is an excellent system to understand viral evolution and the replacement of one viral variant by another. Here we synthesise published results on the distribution and prevalence of DWV-A and -B over the period 2008-2021 and present novel data for Germany, Italy and the UK to suggest that (i) DWV-B has rapidly expanded worldwide since its first description in 2004 and (ii) that it is potentially replacing DWV-A. Both genotypes are also found in wild bee species. Based on a simple mathematical model, we suggest that interference between viral genotypes when co-infecting the same host is key to understanding their epidemiology. We finally discuss the consequences of genotype replacement for beekeeping and for wild pollinator species.

Safety with Innovation in Colon and Rectal Robotic Surgery.

Robotic colorectal surgery has been touted as a possible way to overcome the limitations of laparoscopic surgery and has shown promise in rectal resections, thus shifting traditional open surgeons to a minimally invasive approach. The safety, efficacy, and learning curve have been established for most colorectal applications. With this and a robust sales and marketing model, utilization of the robot for colorectal surgery continues to grow steadily. However, this disruptive technology still requires standards for training, privileging and credentialing, and safe implementation into clinical practice.

The Two Prevalent Genotypes of an Emerging Infectious Disease, Deformed Wing Virus, Cause Equally Low Pupal Mortality and Equally High Wing Deformities in Host Honey Bees.

Deformed wing virus (DWV) is an emerging infectious disease of the honey bee (Apis mellifera) that is considered a major cause of elevated losses of honey bee colonies. DWV comprises two widespread genotypes: the originally described genotype A, and genotype B. In adult honey bees, DWV-B has been shown to be more virulent than DWV-A. However, their comparative effects on earlier host developmental stages are unknown. Here, we experimentally inoculated honey bee pupae and tested for the relative impact of DWV-A versus DWV-B on mortality and wing deformities in eclosing adults. DWV-A and DWV-B caused similar, and only slightly elevated, pupal mortality (mean 18% greater mortality than control). Both genotypes caused similarly high wing deformities in eclosing adults (mean 60% greater wing deformities than control). Viral titer was high in all of the experimentally inoculated eclosing adults, and was independent of wing deformities, suggesting that the phenotype 'deformed wings' is not directly related to viral titer or viral genotype. These viral traits favor the emergence of both genotypes of DWV by not limiting the reproduction of its vector, the ectoparasitic Varroa destructor mite, in infected pupae, and thereby facilitating the spread of DWV in honey bees infested by the mite.

Restoration of Dendritic Complexity, Functional Connectivity, and Diversity of Regenerated Retinal Bipolar Neurons in Adult Zebrafish.

Adult zebrafish (Danio rerio) are capable of regenerating retinal neurons that have been lost due to mechanical, chemical, or light damage. In the case of chemical damage, there is evidence that visually mediated behaviors are restored after regeneration, consistent with recovery of retinal function. However, the extent to which regenerated retinal neurons attain appropriate morphologies and circuitry after such tissue-disrupting lesions has not been investigated. Adult zebrafish of both sexes were subjected to intravitreal injections of ouabain, which destroys the inner retina. After retinal regeneration, cell-selective markers, confocal microscopy, morphometrics, and electrophysiology were used to examine dendritic and axonal morphologies, connectivities, and the diversities of each, as well as retinal function, for a subpopulation of regenerated bipolar neurons (BPs). Although regenerated BPs were reduced in numbers, BP dendritic spreads, dendritic tree morphologies, and cone-bipolar connectivity patterns were restored in regenerated retinas, suggesting that regenerated BPs recover accurate input pathways from surviving cone photoreceptors. Morphological measurements of bipolar axons found that numbers and types of stratifications were also restored; however, the thickness of the inner plexiform layer and one measure of axon branching were slightly reduced after regeneration, suggesting some minor differences in the recovery of output pathways to downstream partners. Furthermore, ERG traces from regenerated retinas displayed waveforms matching those of controls, but with reduced b-wave amplitudes. These results support the hypothesis that regenerated neurons of the adult zebrafish retina are capable of restoring complex morphologies and circuitry, suggesting that complex visual functions may also be restored.SIGNIFICANCE STATEMENT Adult zebrafish generate new retinal neurons after a tissue-disrupting lesion. Existing research does not address whether regenerated neurons of adults successfully reconnect with surrounding neurons and establish complex morphologies and functions. We report that, after a chemical lesion that ablates inner retinal neurons, regenerated retinal bipolar neurons (BPs), although reduced in numbers, reconnected to undamaged cone photoreceptors with correct wiring patterns. Regenerated BPs had complex morphologies similar to those within undamaged retina and a physiological measure of photoreceptor-BP connectivity, the ERG, was restored to a normal waveform. This new understanding of neural connectivity, morphology, and physiology suggests that complex functional processing is possible within regenerated adult retina and offers a system for the future study of synaptogenesis during adult retinal regeneration.

Identifying coevolving loci using interspecific genetic correlations.

Evaluating the importance of coevolution for a wide range of evolutionary questions, such as the role parasites play in the evolution of sexual reproduction, requires that we understand the genetic basis of coevolutionary interactions. Despite its importance, little progress has been made identifying the genetic basis of coevolution, largely because we lack tools designed specifically for this purpose. Instead, coevolutionary studies are often forced to re-purpose single species techniques. Here, we propose a novel approach for identifying the genes mediating locally adapted coevolutionary interactions that relies on spatial correlations between genetic marker frequencies in the interacting species. Using individual-based multi-locus simulations, we quantify the performance of our approach across a range of coevolutionary genetic models. Our results show that when one species is strongly locally adapted to the other and a sufficient number of populations can be sampled, our approach accurately identifies functionally coupled host and parasite genes. Although not a panacea, the approach we outline here could help to focus the search for coevolving genes in a wide variety of well-studied systems for which substantial local adaptation has been demonstrated.

Outcomes for concomitant common iliac artery aneurysms after endovascular abdominal aortic aneurysm repair.

OBJECTIVE: This study evaluated the morbidity of endovascular abdominal aortic aneurysm repair (EVAR) in patients with concomitant common iliac artery aneurysm (CCIAA). METHODS: This was a retrospective review of all patients who underwent elective EVAR from June 2006 through June 2012 at a single institution. Demographics, comorbidities, preoperative presentation, intraoperative details, and postoperative complications were tabulated. Patients with CCIAA were categorized into three groups according to the distal extent of their iliac limb: iliac limb extension into the external iliac artery with internal iliac artery coil embolization (EE); flared iliac limb ≥20 mm in diameter to the iliac bifurcation (FL); and iliac limb ≤20 mm ending proximal to the CCIAA (no-FL). RESULTS: During this period, 627 consecutive patients underwent elective EVAR and preoperative computed tomographic angiograms were available for 523 patients to evaluate the presence of CCIAA. Of these, 211 patients (40.2%) had a CCIAA in at least one common iliac artery, with a total of 307 aneurysmal arteries. Of these 307 aneurysmal arteries, 62 (20.2%) were treated with EE, 132 (43.0%) were treated with FL, and 113 (36.8%) had a sufficient landing zone in the proximal common iliac artery to use an iliac limb ≤20 mm in diameter (no-FL). The overall reintervention rate was 12.4% of patients, with a higher reintervention rate between patients with CCIAA compared with those without (15.2% vs 10.9%; P = .039). There were no significant differences in reintervention rates between the EE, FL, and no-FL techniques (4.5% vs 4.8% vs 6.2%; P = .802) over a mean 59.8 months follow-up. The FL and EE techniques had a lower risk of distal endoleak than the no-FL technique, but the difference was not statistically significant (3.2% vs 2.3% vs 5.3% compared with 4.23% in the entire cohort). CONCLUSIONS: Patients with CCIAA had a higher reintervention rate after EVAR for abdominal aortic aneurysm compared with non-CCIAA patients. Of the techniques studied (EE, FL, and no-FL), there was no significant difference in reintervention rates between the three. All three techniques remain viable options for the endovascular repair of CCIAA.

Predictors of readmission in nonagenarians: analysis of the American College of Surgeons National Surgical Quality Improvement Project dataset.

BACKGROUND: Increased longevity has led to more nonagenarians undergoing elective surgery. Development of predictive models for hospital readmission may identify patients who benefit from preoperative optimization and postoperative transition of care intervention. Our goal was to identify significant predictors of 30-d readmission in nonagenarians undergoing elective surgery. METHODS: Nonagenarians undergoing elective surgery from January 2011 to December 2012 were identified using the American College of Surgeons National Surgical Quality Improvement Project participant use data files. This population was randomly divided into a 70% derivation cohort for model development and 30% validation cohort. Using multivariate step-down regression, predictive models were developed for 30-d readmission. RESULTS: Of 7092 nonagenarians undergoing elective surgery, 798 (11.3%) were readmitted within 30 d. Factors significant in univariate analysis were used to develop predictive models for 30-d readmissions. Diabetes (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.24-1.84), dialysis dependence (OR: 2.97, CI: 1.77-4.99), functional status (OR: 1.52, CI: 1.29-1.79), American Society of Anesthesiologists class II or higher (American Society of Anesthesiologist physical status classification system; OR: 1.80, CI: 1.42-2.28), operative time (OR: 1.05, CI: 1.02-1.08), myocardial infarction (OR: 5.17, CI: 3.38-7.90), organ space surgical site infection (OR: 8.63, CI: 4.04-18.4), wound disruption (OR: 14.3, CI: 4.80-42.9), pneumonia (OR: 8.59, CI: 6.17-12.0), urinary tract infection (OR: 3.88, CI: 3.02-4.99), stroke (OR: 6.37, CI: 3.47-11.7), deep venous thrombosis (OR: 5.96, CI: 3.70-9.60), pulmonary embolism (OR: 20.3, CI: 9.7-42.5), and sepsis (OR: 13.1, CI: 8.57-20.1), septic shock (OR: 43.8, CI: 18.2-105.0), were included in the final model. This model had a c-statistic of 0.73, indicating a fair association of predicted probabilities with observed outcomes. However, when applied to the validation cohort, the c-statistic dropped to 0.69, and six variables lost significance. CONCLUSIONS: A reliable predictive model for readmission in nonagenarians undergoing elective surgery remains elusive. Investigation into other determinants of surgical outcomes, including social factors and access to skilled home care, might improve model predictability, identify areas for intervention to prevent readmission, and improve quality of care.

Aneurysmal Degeneration in Patients with Type B Aortic Dissection.

BACKGROUND: The optimal management of type B aortic dissection (TBAD) remains controversial in the era of endovascular therapies. This study reports the outcomes and complication rates of different treatment paradigms for TBAD. METHODS: A retrospective review was undertaken of all patients with TBAD from June 2006 to June 2012. Demographics, hospital course, and follow-up visits were analyzed. Patients who underwent surgical interventions were compared to those with medical therapy. Survival rates and predictors of outcome were determined using the Kaplan-Meier method with Cox proportional hazards. RESULTS: Of 261 consecutive patients who were hospitalized during this period with a confirmed thoracic dissection, 134 (51%) had TBAD. Sixty-two (46%) were women, and the mean age was 66.4 ± 14.9. Median follow-up was 22.4 (0, 184) months. Thirty-five patients underwent surgical intervention with 20 thoracic endovascular aortic repair (TEVAR) and open surgery in 15. The overall 30-day mortality was 7%, and cumulative survival rates at 1, 3, and 5 years were 85% (95% confidence interval [CI], 79-91), 68% (95% CI, 59-78), and 57% (95% CI, 47-69) with no difference between medical versus surgical groups (P = 0.8) and TEVAR versus open surgery group (P = 1.0). Sixty-six (50%) patients developed aneurysmal expansion, which required surgical intervention in 26 (hazard ratios [HR], 0.99; P = 0.96). Malperfusion and rupture only occurred in 5 (HR, 1.57; P = 0.54) and 5 (HR, 3.64; P = 0.01) patients, respectively. Multivariate analysis for overall survival found renal insufficiency (HR, 2.6; P = 0.004) and age (HR, 1.06; P < 0.0001) and rupture (HR 3.3, P = 0.04) were independent predictors of mortality. Intramural hematoma was not a significant predictor of survival (HR, 0.49; P = 0.11). CONCLUSIONS: Medical therapy remains the mainstay of treating TBAD with low morbidity. Surgical interventions are indicated in selected patients with malperfusion or aneurysmal expansion with comparable survival rates.

Novel Educational Module for Subclavian Central Venous Catheter Insertion Using Real-Time Ultrasound Guidance.

OBJECTIVE: Given increasing evidence supporting a real-time ultrasound (US)-guided approach for subclavian vein (SCV) central venous catheter (CVC) insertion as compared with the traditional landmark approach, we sought to develop a standardized curriculum to offer healthcare providers a means to attain increased competency and confidence in US-guided SCV CVC insertion. DESIGN: Retrospective review of prospectively collected data. SETTING: Single institution's American College of Surgeons Level 1 Accredited Education Institute within an academic tertiary care center. SUBJECTS: A total of 77 residents and midlevel providers working in our surgical intensive care unit. INTERVENTIONS: Providers participated in a tiered educational module designed to teach safe US-guided SCV CVC insertion. The education consisted of a multimedia didactic presentation and a hands-on simulation session, including US anatomy on live subjects and anatomical model-based SCV CVC insertion. MEASUREMENTS AND MAIN RESULTS: Assessment of the effect of education included a written examination and confidence survey, administered pre- and postintervention, and videotaped simulation session graded by blinded expert evaluators. Of the 77 participants, 70 participants completed a posttest with a median 5-point increase in score compared with that of the pretest score (p < 0.0001). Confidence ratings based on a 5-point Likert scale demonstrated an increase in confidence in SCV CVC insertion (p < 0.0001), using the landmark approach (p < 0.0001), using US-guided approach (p < 0.0001), and in use of US to image the SCV (p < 0.0001). Postgraduate year-1 residents had lower mean global rating score (p = 0.010) than any other participants. CONCLUSIONS: This comprehensive hands-on teaching module-based curriculum enhanced learner knowledge of and confidence in US-guided SCV CVC insertion. This module can be implemented in simulation centers for teaching safe and successful SCV CVC insertion.

Identifying the molecular basis of host-parasite coevolution: merging models and mechanisms.

Mathematical models of the coevolutionary process have uncovered consequences of host-parasite interactions that go well beyond the traditional realm of the Red Queen, potentially explaining several important evolutionary transitions. However, these models also demonstrate that the specific consequences of coevolution are sensitive to the structure of the infection matrix, which is embedded in models to describe the likelihood of infection in encounters between specific host and parasite genotypes. Traditional cross-infection approaches to estimating infection matrices might be unreliable because evolutionary dynamics and experimental sampling lead to missing genotypes. Consequently, our goal is to identify the likely structure of infection matrices by synthesizing molecular mechanisms of host immune defense and parasite counterdefense with coevolutionary models. This synthesis reveals that the molecular mechanisms of immune reactions, although complex and diverse, conform to two basic models commonly used within coevolutionary theory: matching infection and targeted recognition. Our synthesis also overturns conventional wisdom, revealing that the general models are not taxonomically restricted but are applicable to plants, invertebrates, and vertebrates. Finally, our synthesis identifies several important areas for future research that should improve the explanatory power of coevolutionary models. The most important among these include empirical studies to identify the molecular hotspots of genotypic specificity and theoretical studies examining the consequences of matrices that more accurately represent multistep infection processes and quantitative defenses.

Foreign gene recruitment to the fatty acid biosynthesis pathway in diatoms.

Diatoms are highly successful marine and freshwater algae that contribute up to 20% of global carbon fixation. These species are leading candidates for biofuel production owing to ease of culturing and high fatty acid content. To assist in strain improvement and downstream applications for potential use as a biofuel, it is important to understand the evolution of lipid biosynthesis in diatoms. The evolutionary history of diatoms is however complicated by likely multiple endosymbioses involving the capture of foreign cells and horizontal gene transfer into the host genome. Using a phylogenomic approach, we assessed the evolutionary history of 12 diatom genes putatively encoding functions related to lipid biosynthesis. We found evidence of gene transfer likely from a green algal source for seven of these genes, with the remaining showing either vertical inheritance or evolutionary histories too complicated to interpret given current genome data. The functions of horizontally transferred genes encompass all aspects of lipid biosynthesis (initiation, biosynthesis, and desaturation of fatty acids) as well as fatty acid elongation, and are not restricted to plastid-targeted proteins. Our findings demonstrate that the transfer, duplication, and subfunctionalization of genes were key steps in the evolution of lipid biosynthesis in diatoms and other photosynthetic eukaryotes. This target pathway for biofuel research is highly chimeric and surprisingly, our results suggest that research done on related genes in green algae may have application to diatom models.

Expression of a human cytomegalovirus latency-associated homolog of interleukin-10 during the productive phase of infection.

The human cytomegalovirus UL111A region is active during both productive and latent phases of infection. During productive infection, the virus expresses ORF79, a protein with oncogenic properties, and cmvIL-10, a functional homolog of human IL-10. During latent infection of myeloid progenitor cells, an alternately spliced variant of cmvIL-10, termed latency-associated (LA) cmvIL-10 has previously been identified. To determine whether LAcmvIL-10 transcription occurs during productive infection, we performed 5' and 3' RACE to map UL111A-region transcripts in productively infected human foreskin fibroblasts (HFFs). This analysis revealed the presence of a singly spliced UL111A-region transcript predicted to encode LAcmvIL-10. This transcript was expressed in HFFs with early (beta) kinetics, a temporal class that differs from that of ORF79 (alpha kinetics) and cmvIL-10 (gamma kinetics). These data identify and map a transcript encoding a latency-associated homolog of IL-10 which is expressed by the virus during the productive phase of infection.

A novel viral transcript with homology to human interleukin-10 is expressed during latent human cytomegalovirus infection.

Human cytomegalovirus (CMV) establishes latent infections in hematopoietic cells such as granulocyte-macrophage progenitors (GM-Ps). During latency the virus is sequestered in a nonreplicating state, although limited transcriptional activity has been previously reported. In this study we sought to further examine viral gene expression during the latent phase of infection. Using an experimental model of latency, primary human GM-Ps were latently infected with CMV strain Toledo and extracted RNA subjected to reverse transcription-PCR by using CMV gene-specific primers. Using this approach, we detected transcription from the UL111.5A region of the viral genome. This transcription was also detected in GM-Ps latently infected with AD169 and Towne strains, indicating that expression was CMV strain independent. Significantly, we detected UL111.5A-region transcripts in mononuclear cells from healthy bone marrow and mobilized peripheral blood allograft donors, demonstrating expression during natural latent infection. Mapping experiments with RNA extracted from latently infected GM-Ps revealed the expression of a novel UL111.5A region transcript with a splicing pattern that differed from that reported during productive infection of permissive cells. This UL111.5A region transcript expressed during latent infection is predicted to encode a 139-amino-acid protein with homology to the potent immunosuppressor interleukin-10 (IL-10) and to the viral IL-10 homolog that is expressed during productive CMV infection. Expression of a latency-associated cmvIL-10 may confer upon the virus an ability to avoid immune recognition and clearance during the latent phase of infection.