Fertility costs of cryptic viral infections in a model social insect.

Declining insect populations emphasize the importance of understanding the drivers underlying reductions in insect fitness. Here, we investigated viruses as a threat to social insect reproduction, using honey bees as a model species. We report that in two independent surveys (N = 93 and N = 54, respectively) of honey bee (Apis mellifera) queens taken from a total of ten beekeeping operations across British Columbia, high levels of natural viral infection are associated with decreased ovary mass. Failed (poor quality) queens displayed higher levels of viral infection, reduced sperm viability, smaller ovaries, and altered ovary protein composition compared to healthy queens. We experimentally infected queens with Israeli acute paralysis virus (IAPV) and found that the ovary masses of IAPV-injected queens were significantly smaller than control queens, demonstrating a causal relationship between viral infection and ovary size. Queens injected with IAPV also had significantly lower expression of vitellogenin, the main source of nutrition deposited into developing oocytes, and higher levels of heat-shock proteins, which are part of the honey bee's antiviral response. This work together shows that viral infections occurring naturally in the field are compromising queen reproductive success.

Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswax.

Honey bee queen health is crucial for colony health and productivity, and pesticides have been previously associated with queen loss and premature supersedure. Prior research has investigated the effects of indirect pesticide exposure on queens via workers, as well as direct effects on queens during development. However, as adults, queens are in constant contact with wax as they walk on comb and lay eggs; therefore, direct pesticide contact with adult queens is a relevant but seldom investigated exposure route. Here, we conducted laboratory and field experiments to investigate the impacts of topical pesticide exposure on adult queens. We tested six pesticides commonly found in wax: coumaphos, tau-fluvalinate, atrazine, 2,4-DMPF, chlorpyriphos, chlorothalonil, and a cocktail of all six, each administered at 1, 4, 8, 16, and 32 times the concentrations typically found in wax. We found no effect of any treatment on queen mass, sperm viability, or fat body protein expression. In a field trial testing queen topical exposure of a pesticide cocktail, we found no impact on egg-laying pattern, queen mass, emergence mass of daughter workers, and no proteins in the spermathecal fluid were differentially expressed. These experiments consistently show that pesticides commonly found in wax have no direct impact on queen performance, reproduction, or quality metrics at the doses tested. We suggest that previously reported associations between high levels of pesticide residues in wax and queen failure are most likely driven by indirect effects of worker exposure (either through wax or other hive products) on queen care or queen perception.

Survey-derived best management practices for backyard beekeepers improve colony health and reduce mortality.

Honey bee colony losses in the US have exceeded acceptable levels for at least a decade, leaving beekeepers in need of management practices to improve colony health and survival. Here, an empirical Best Management Practice (BMP) regimen was tested, comprised of the top four management practices associated with reduced colony mortality in backyard beekeeping operations according to Bee Informed Partnership Loss and Management survey results. Seven study locations were established across the US, and each location consisted of ten colonies treated according to empirical BMPs and ten according to average beekeeping practice. After 3 years, colonies treated according to empirical BMPs experienced reduced Varroa infestation, viral infection, and mortality compared to colonies managed with Average practices. In addition, BMP colonies produced more new colonies via splits. The colonies under Average practices were given chemical Varroa treatments only once per year, and thus spent more months above economic threshold of 3.0 mites/100 bees. Increased time spent above the economic threshold was significantly correlated to both increased viral infection and colony mortality. This study demonstrates the cumulative effects of management and colony health stressors over months and years, especially the dire importance of regular Varroa monitoring and management.

The Pathogen Profile of a Honey Bee Queen Does Not Reflect That of Her Workers.

Throughout a honey bee queen's lifetime, she is tended to by her worker daughters, who feed and groom her. Such interactions provide possible horizontal transmission routes for pathogens from the workers to the queen, and as such a queen's pathogen profile may be representative of the workers within a colony. To explore this further, we investigated known honey bee pathogen co-occurrence, as well as pathogen transmission from workers to queens. Queens from 42 colonies were removed from their source hives and exchanged into a second, unrelated foster colony. Worker samples were taken from the source colony on the day of queen exchange and the queens were collected 24 days after introduction. All samples were screened for Nosema spp., Trypanosome spp., acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), Israeli acute paralysis virus (IAPV), Lake Sinai virus (LSV), and deformed wing virus master variants (DWV-A, B, and C) using RT-qPCR. The data show that LSV, Nosema, and DWV-B were the most abundant pathogens in colonies. All workers (n = 42) were LSV-positive, 88% were Nosema-positive, whilst pathogen loads were low (<1 × 106 genome equivalents per pooled worker sample). All queens (n = 39) were negative for both LSV and Nosema. We found no evidence of DWV transmission occurring from worker to queen when comparing queens to foster colonies, despite DWV being present in both queens and workers. Honey bee pathogen presence and diversity in queens cannot be revealed from screening workers, nor were pathogens successfully transmitted to the queen.

Is the Brood Pattern within a Honey Bee Colony a Reliable Indicator of Queen Quality?

Failure of the queen is often identified as a leading cause of honey bee colony mortality. However, the factors that can contribute to "queen failure" are poorly defined and often misunderstood. We studied one specific sign attributed to queen failure: poor brood pattern. In 2016 and 2017, we identified pairs of colonies with "good" and "poor" brood patterns in commercial beekeeping operations and used standard metrics to assess queen and colony health. We found no queen quality measures reliably associated with poor-brood colonies. In the second year (2017), we exchanged queens between colony pairs (n = 21): a queen from a poor-brood colony was introduced into a good-brood colony and vice versa. We observed that brood patterns of queens originally from poor-brood colonies significantly improved after placement into a good-brood colony after 21 days, suggesting factors other than the queen contributed to brood pattern. Our study challenges the notion that brood pattern alone is sufficient to judge queen quality. Our results emphasize the challenges in determining the root source for problems related to the queen when assessing honey bee colony health.

Forebrain Control of Behaviorally Driven Social Orienting in Zebrafish.

Deficits in social engagement are diagnostic of multiple neurodevelopmental disorders, including autism and schizophrenia [1]. Genetically tractable animal models like zebrafish (Danio rerio) could provide valuable insight into developmental factors underlying these social impairments, but this approach is predicated on the ability to accurately and reliably quantify subtle behavioral changes. Similarly, characterizing local molecular and morphological phenotypes requires knowledge of the neuroanatomical correlates of social behavior. We leveraged behavioral and genetic tools in zebrafish to both refine our understanding of social behavior and identify brain regions important for driving it. We characterized visual social interactions between pairs of adult zebrafish and discovered that they perform a stereotyped orienting behavior that reflects social attention [2]. Furthermore, in pairs of fish, the orienting behavior of one individual is the primary factor driving the same behavior in the other individual. We used manual and genetic lesions to investigate the forebrain contribution to this behavior and identified a population of neurons in the ventral telencephalon whose ablation suppresses social interactions, while sparing other locomotor and visual behaviors. These neurons are cholinergic and express the gene encoding the transcription factor Lhx8a, which is required for development of cholinergic neurons in the mouse forebrain [3]. The neuronal population identified in zebrafish lies in a region homologous to mammalian forebrain regions implicated in social behavior such as the lateral septum [4]. Our data suggest that an evolutionarily conserved population of neurons controls social orienting in zebrafish.

Assessing Auditory Processing Abilities in Typically Developing School-Aged Children.

BACKGROUND: Large discrepancies exist in the literature regarding definition, diagnostic criteria, and appropriate assessment for auditory processing disorder (APD). Therefore, a battery of tests with normative data is needed. PURPOSE: The purpose of this study is to collect normative data on a variety of tests for APD on children aged 7-12 yr, and to examine effects of outside factors on test performance. RESEARCH DESIGN: Children aged 7-12 yr with normal hearing, speech and language abilities, cognition, and attention were recruited for participation in this normative data collection. STUDY SAMPLE: One hundred and forty-seven children were recruited using flyers and word of mouth. Of the participants recruited, 137 children qualified for the study. Participants attended schools located in areas that varied in terms of socioeconomic status, and resided in six different states. DATA COLLECTION AND ANALYSIS: Audiological testing included a hearing screening (15 dB HL from 250 to 8000 Hz), word recognition testing, tympanometry, ipsilateral and contralateral reflexes, and transient-evoked otoacoustic emissions. The language, nonverbal IQ, phonological processing, and attention skills of each participant were screened using the Clinical Evaluation of Language Fundamentals-4 Screener, Test of Nonverbal Intelligence, Comprehensive Test of Phonological Processing, and Integrated Visual and Auditory-Continuous Performance Test, respectively. The behavioral APD battery included the following tests: Dichotic Digits Test, Frequency Pattern Test, Duration Pattern Test, Random Gap Detection Test, Compressed and Reverberated Words Test, Auditory Figure Ground (signal-to-noise ratio of +8 and +0), and Listening in Spatialized Noise-Sentences Test. Mean scores and standard deviations of each test were calculated, and analysis of variance tests were used to determine effects of factors such as gender, handedness, and birth history on each test. RESULTS: Normative data tables for the test battery were created for the following age groups: 7- and 8-yr-olds (n = 49), 9- and 10-yr-olds (n = 40), and 11- and 12-yr-olds (n = 48). No significant effects were seen for gender or handedness on any of the measures. CONCLUSIONS: The data collected in this study are appropriate for use in clinical diagnosis of APD. Use of a low-linguistically loaded core battery with the addition of more language-based tests, when language abilities are known, can provide a well-rounded picture of a child's auditory processing abilities. Screening for language, phonological processing, attention, and cognitive level can provide more information regarding a diagnosis of APD, determine appropriateness of the test battery for the individual child, and may assist with making recommendations or referrals. It is important to use a multidisciplinary approach in the diagnosis and treatment of APD due to the high likelihood of comorbidity with other language, learning, or attention deficits. Although children with other diagnoses may be tested for APD, it is important to establish previously made diagnoses before testing to aid in appropriate test selection and recommendations.

Outcomes of pregnancies fathered by solid-organ transplant recipients exposed to mycophenolic acid products.

CONTEXT-In women, exposure to mycophenolic acid products during pregnancy results in an increase in both miscarriages and birth defects in the live born. OBJECTIVE-To describe the outcomes of pregnancies fathered by transplant recipients who were being maintained on mycophenolic acid products at the estimated time of conception and compare these pregnancies with pregnancies in the general population. METHODS- Data were collected by the National Transplantation Pregnancy Registry via questionnaires, telephone interviews, and medical records. RESULTS -One hundred fifty-two male transplant recipients with exposure to mycophenolic acid products fathered 205 pregnancies (208 outcomes, including 3 pairs of twins). Pregnancy outcomes included 194 live births with a prematurity rate of 10.8%, 14 spontaneous abortions, and no therapeutic abortions or stillbirths. Among the live births, 6 malformations were reported, for an incidence of 3.1%. No pattern of malformations was identified. CONCLUSION-The outcomes of pregnancies fathered by transplant recipients treated with mycophenolic acid products appear similar to outcomes in the general population.

The AIM2 inflammasome is critical for innate immunity to Francisella tularensis.

Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens.

Impact of video review on surgical procedure determination for patients with cerebral palsy.

PURPOSE: Evaluation of patients with cerebral palsy is complex and variable. Several examinations, including video analysis, are necessary as part of the surgical planning process. Videotaped evaluation of the upper extremity in children with cerebral palsy has been used as an objective assessment of functional ability and deformity. The effect of review of these videotaped evaluations on altering the initially proposed surgical plan has not been evaluated. METHODS: This is a retrospective study completed through a chart review. Inclusion criteria were all patients with cerebral palsy having upper extremity surgical consultation with the primary investigator (M.G.C.) between 1995 and 2005, having at least 2 presurgical consultations, completing a videotaped evaluation, and proceeding to surgery. Of 167 new patients, 94 patients, having 430 procedures, were eligible for the study. Five distinct anatomical areas (elbow, forearm, wrist, digit, and thumb) were delineated. RESULTS: Changes to the initial surgical plan based on a review of the videotaped evaluation were made for 77 patients (138 procedures) and carried through to surgery for 68 patients (108 procedures). Those procedure changes that carried through to surgery most often involved the thumb, wrist, and digit, as compared to the elbow and forearm. CONCLUSIONS: Videotaping evaluations allows for more precise understanding of ability and improves diagnosis. Changes to the initial presurgical plan were made in 77 patients (72%) after videotaped evaluation, most commonly for procedures addressing the wrist, digit, and thumb.

Four-corner arthrodesis using a circular plate and distal radius bone grafting: a consecutive case series.

PURPOSE: Four-corner arthrodesis with scaphoid excision has been shown to be an acceptable method for treating wrist degenerative changes. Some recent studies have identified higher complication rates when circular plates are used. This study examined a consecutive case series with defined technique for outcome and complications. METHODS: A retrospective assessment was performed in a consecutive cohort of 28 patients who underwent a standardized 4-corner arthrodesis with a 2nd-generation circular plate and distal radius bone grafting for a diagnosis of scapholunate advanced collapse, scaphoid nonunion advanced collapse, or midcarpal arthrosis. Complete data were obtained for 26 of the patients and partial data for the other 2. Follow-up examination included visual analog scale and activity scores, work status, posteroanterior and lateral radiographs, bone union status, grip strength, range of motion, and complications. RESULTS: Average follow-up was 46 months. Range of motion averaged 45% of the uninjured side (average extension, 35 degrees; average flexion, 26 degrees). Grip strength averaged 82% of the uninjured side. The mean visual analog scale pain and activity scores were 2.3/10 and 2.4/10. Only 1 patient required job modification because of wrist impairment. Radiographs demonstrated union of the primary capitolunate fusion mass in all of the cases. There was 1 case of probable but not certain peritriquetral nonunion and 1 case of asymptomatic loss of radiolunate joint space; in terms of hardware, there was screw back-out (of 1 screw) in 1 case the plate broke in 1 case. Two patients underwent reoperation, one for radial styloid impingement pain and the other for lack of flexion. CONCLUSIONS: Despite recent reports indicating a high nonunion rate with plate fixation, standardized 4-corner arthrodesis using a recessed, dorsal circular plate and distal radius bone grafting produced excellent and reproducible results in this consecutive series. Notably, there was no development of secondary arthritic changes at the radiolunate joint, indicating a reasonable durability to the procedure. Optimal results require exacting technique with quality bone graft.

Glomus tumors.

Glomus tumors are rare vascular tumors that are found most commonly in the hand. Although the tumors are benign, they can cause intense focal pain. Patients often go undiagnosed or misdiagnosed for many years because the tumors are small, usually not palpable, and have varying presentations. A combination of magnetic resonance imaging and clinical examination is used to support the diagnosis. Surgical excision normally provides complete pain relief. An awareness of the diagnosis is critical to preventing an unnecessary delay in treatment.