Uncertainty in the mating strategy of honeybees causes bias and unreliability in the estimates of genetic parameters.

BACKGROUND: Breeding queens may be mated with drones that are produced by a single drone-producing queen (DPQ), or a group of sister-DPQs, but often only the dam of the DPQ(s) is reported in the pedigree. Furthermore, datasets may include colony phenotypes from DPQs that were open-mated at different locations, and thus to a heterogeneous drone population. METHODS: Simulation was used to investigate the impact of the mating strategy and its modelling on the estimates of genetic parameters and genetic trends when the DPQs are treated in different ways in the statistical evaluation model. We quantified the bias and standard error of the estimates when breeding queens were mated to one DPQ or a group of DPQs, assuming that this information was known or not. We also investigated four alternative strategies to accommodate the phenotypes of open-mated DPQs in the genetic evaluation: excluding their phenotypes, adding a dummy pseudo-sire in the pedigree, or adding a non-genetic (fixed or random) effect to the statistical evaluation model to account for the origin of the mates. RESULTS: The most precise estimates of genetic parameters and genetic trends were obtained when breeding queens were mated with drones of single DPQs that are correctly assigned in the pedigree. However, when they were mated with drones from one or a group of DPQs, and this information was not known, erroneous assumptions led to considerable bias in these estimates. Furthermore, genetic variances were considerably overestimated when phenotypes of colonies from open-mated DPQs were adjusted for their mates by adding a dummy pseudo-sire in the pedigree for each subpopulation of open-mating drones. On the contrary, correcting for the heterogeneous drone population by adding a non-genetic effect in the evaluation model produced unbiased estimates. CONCLUSIONS: Knowing only the dam of the DPQ(s) used in each mating may lead to erroneous assumptions on how DPQs were used and severely bias the estimates of genetic parameters and trends. Thus, we recommend keeping track of DPQs in the pedigree, and not only of the dams of DPQ(s). Records from DPQ colonies with queens open-mated to a heterogeneous drone population can be integrated by adding non-genetic effects to the statistical evaluation model.

[Early hospital discharge for patients with COVID-19: evaluation of the transmural healthcare program in Amsterdam]. / Vervroegd ontslag van patiënten met covid-19.

OBJECTIVE: Evaluation of an early discharge program for COVID-19-patients who still required additional oxygen support, supervised by their own general practitioner (GP) in a home setting. We evaluated safety and gathered experiences from patients, caregivers and GPs. DESIGN: Cohort study (prospective and retrospective inclusion) METHOD: Adult COVID-19-patients admitted to one of the three Amsterdam hospitals, the Netherlands, were eligible when clinically stable for at least 48 hours, with a minimum oxygen saturation of 94% and a maximum of 3 l/min oxygen support. Patients were included from 23-10-2020 to 26-03-2021. RESULTS: We included 113 patients, of whom 40 retrospectively . Median age was 58 years and median length of hospital stay 8 days. Four patients (3.7%) were readmitted within 14 days after discharge. Median duration of oxygen support at home was 8 days. Almost no home visits were conducted by GPs, but contact by telephone was regular (median 6 times in 2 weeks). All stakeholders reported feeling safe, able and confident while delivering the necessary (self) care. The program was graded by patients and GPs with an 8 (on a scale of 1 to 10). CONCLUSION: Early discharge for COVID-19-patients with a necessity for oxygen support, under supervision of the GP, is safe and was positively evaluated by all stakeholders involved.

Exploring Two Honey Bee Traits for Improving Resistance Against Varroa destructor: Development and Genetic Evaluation.

For the development of novel selection traits in honey bees, applicability under field conditions is crucial. We thus evaluated two novel traits intended to provide resistance against the ectoparasitic mite Varroa destructor and to allow for their straightforward implementation in honey bee selection. These traits are new field estimates of already-described colony traits: brood recapping rate ('Recapping') and solidness ('Solidness'). 'Recapping' refers to a specific worker characteristic wherein they reseal a capped and partly opened cell containing a pupa, whilst 'Solidness' assesses the percentage of capped brood in a predefined area. According to the literature and beekeepers' experiences, a higher recapping rate and higher solidness could be related to resistance to V. destructor. During a four-year field trial in Switzerland, the two resistance traits were assessed in a total of 121 colonies of Apis mellifera mellifera. We estimated the repeatability and the heritability of the two traits and determined their phenotypic correlations with commonly applied selection traits, including other putative resistance traits. Both traits showed low repeatability between different measurements within each year. 'Recapping' had a low heritability (h2 = 0.04 to 0.05, depending on the selected model) and a negative phenotypic correlation to non-removal of pin-killed brood (r = -0.23). The heritability of 'Solidness' was moderate (h2 = 0.24 to 0.25) and did not significantly correlate with resistance traits. The two traits did not show an association with V. destructor infestation levels. Further research is needed to confirm the results, as only a small number of colonies was evaluated.

Heritability estimates of the novel trait 'suppressed in ovo virus infection' in honey bees (Apis mellifera).

Honey bees are under pressure due to abnormal high colony death rates, especially during the winter. The infestation by the Varroa destructor mite and the viruses that this ectoparasite transmits are generally considered as the bees' most important biological threats. Almost all efforts to remedy this dual infection have so far focused on the control of the Varroa mite alone and not on the viruses it transmits. In the present study, the sanitary control of breeding queens was conducted on eggs taken from drone brood for 4 consecutive years (2015-2018). The screening was performed on the sideline of an ongoing breeding program, which allowed us to estimate the heritabilities of the virus status of the eggs. We used the term 'suppressed in ovo virus infection' (SOV) for this novel trait and found moderate heritabilities for the presence of several viruses simultaneously and for the presence of single viral species. Colonies that expressed the SOV trait seemed to be more resilient to virus infections as a whole with fewer and less severe Deformed wing virus infections in most developmental stages, especially in the male caste. The implementation of this novel trait into breeding programs is recommended.

Evaluation of Traits for the Selection of Apis Mellifera for Resistance against Varroa Destructor.

Infestation with Varroa destructor is a serious cause of bee colony (Apis mellifera) losses on a global level. However, the presence of untreated survivor populations in many different regions supports the idea that selection for resistance can be successful. As colony survival is difficult or impossible to measure, differences in mite infestation levels and tests for specific behavioral traits are used for selective breeding for Varroa resistance. In this paper we looked into different definitions of mite infestation and linked these with brood hygiene (pin test), brood recapping and suppressed mite reproduction. We based our analyses on datasets of Apis mellifera carnica from three countries: Austria (147 records), Croatia (135) and Germany (207). We concluded that bee infestation in summer, adjusted for the level of natural mite fall in spring, is a suitable trait in the breeding objective, and also suggested including brood infestation rate and the increase rate of bee infestation in summer. Repeatability for bee infestation rate was about 0.55, for cells opened in pin test about 0.33, for recapping 0.35 and for suppressed mite reproduction (SMR) virtually zero. Although in most cases we observed correlations with the expected sign between infestation parameters and behavioral traits, the values were generally low (<0.2) and often not significantly different from zero.

A note on genetic parameters and accuracy of estimated breeding values in honey bees.

BACKGROUND: In honey bees, observations are usually made on colonies. The phenotype of a colony is affected by the average breeding value for the worker effect of the thousands of workers in the colony (the worker group) and by the breeding value for the queen effect of the queen of the colony. Because the worker group consists of multiple individuals, interpretation of the variance components and heritabilities of phenotypes observed on the colony and of the accuracy of selection is not straightforward. The additive genetic variance among worker groups depends on the additive genetic relationship between the drone-producing queens (DPQ) that produce the drones that mate with the queen. RESULTS: Here, we clarify how the relatedness between DPQ affects phenotypic variance, heritability and accuracy of the estimated breeding values of replacement queens. Second, we use simulation to investigate the effect of assumptions about the relatedness between DPQ in the base population on estimates of genetic parameters. Relatedness between DPQ in the base generation may differ considerably between populations because of their history. CONCLUSIONS: Our results show that estimates of (co)variance components and derived genetic parameters were seriously biased (25% too high or too low) when assumptions on the relationship between DPQ in the statistical analysis did not agree with reality.

Methods to estimate breeding values in honey bees.

BACKGROUND: Efficient methodologies based on animal models are widely used to estimate breeding values in farm animals. These methods are not applicable in honey bees because of their mode of reproduction. Observations are recorded on colonies, which consist of a single queen and thousands of workers that descended from the queen mated to 10 to 20 drones. Drones are haploid and sperms are copies of a drone's genotype. As a consequence, Mendelian sampling terms of full-sibs are correlated, such that the covariance matrix of Mendelian sampling terms is not diagonal. RESULTS: In this paper, we show how the numerator relationship matrix and its inverse can be obtained for honey bee populations. We present algorithms to derive the covariance matrix of Mendelian sampling terms that accounts for correlated terms. The resulting matrix is a block-diagonal matrix, with a small block for each full-sib family, and is easy to invert numerically. The method allows incorporating the within-colony distribution of progeny from drone-producing queens and drones, such that estimates of breeding values weigh information from relatives appropriately. Simulation shows that the resulting estimated breeding values are unbiased predictors of true breeding values. Benefits for response to selection, compared to an existing approximate method, appear to be limited (~5%). Benefits may however be greater when estimating genetic parameters. CONCLUSIONS: This work shows how the relationship matrix and its inverse can be developed for honey bee populations, and used to estimate breeding values and variance components.

The effects of conventional extracorporeal circulation versus miniaturized extracorporeal circulation on microcirculation during cardiopulmonary bypass-assisted coronary artery bypass graft surgery.

OBJECTIVES To reduce the complications associated with cardiopulmonary bypass (CPB) during cardiac surgery, many modifications have been made to conventional extracorporeal circulation systems. This trend has led to the development of miniaturized extracorporeal circulation systems. Cardiac surgery using conventional extracorporeal circulation systems has been associated with significantly reduced microcirculatory perfusion, but it remains unknown whether this could be prevented by an mECC system. Here, we aimed to test the hypothesis that microcirculatory perfusion decreases with the use of a conventional extracorporeal circulation system and would be preserved with the use of an miniaturized extracorporeal circulation system. METHODS Microcirculatory density and perfusion were assessed using sublingual side stream dark-field imaging in patients undergoing on-pump coronary artery bypass graft (CABG) surgery before, during and after the use of either a conventional extracorporeal circulation system (n = 10) or a miniaturized extracorporeal circulation system (n = 10). In addition, plasma neutrophil gelatinase-associated lipocalin and creatinine levels and creatinine clearance were assessed up to 5 days post-surgery to monitor renal function. RESULTS At the end of the CPB, one patient in the miniaturized extracorporeal circulation-treated group and five patients in the conventional extracorporeal circulation-treated group received one bag of packed red blood cells (300 ml). During the CPB, the haematocrit and haemoglobin levels were slightly higher in the miniaturized extracorporeal circulation-treated patients compared with the conventional extracorporeal circulation-treated patients (27.7 ± 3.3 vs 24.7 ± 2.0%; P = 0.03; and 6.42 ± 0.75 vs 5.41 ± 0.64 mmol/l; P < 0.01). The density of perfused vessels with a diameter <25 µm (i.e. perfused vessel density) decreased slightly in the conventional extracorporeal circulation-treated group from 16.4 ± 3.8 to 12.8 ± 3.3 mm/mm(2) (P < 0.01) and remained stable in the miniaturized extracorporeal circulation-treated group (16.3 ± 2.7 and 15.2 ± 2.9 mm/mm(2) before and during the pump, respectively). Plasma neutrophil gelatinase-associated lipocalin levels were increased following the use of extracorporeal circulation in both groups, and no differences were observed between the groups. Plasma creatinine levels and creatinine clearance were not affected by CABG surgery or CPB. CONCLUSIONS The results from this relatively small study suggest that the use of the miniaturized extracorporeal circulation system is associated with a statistically significant (but clinically insignificant) reduction in haemodilution and microcirculatory hypoperfusion compared with the use of the conventional extracorporeal circulation system.

The influence of dental caries on body growth in prepubertal children.

Dental decay and dental treatment are suggested to be related to body growth in children. The aim of this study was first to assess the relation between dental caries and body proportions cross-sectionally in a Suriname caries child population and secondly to investigate whether dental treatment had a significant influence on body growth of these children in a randomised controlled trial using different treatment strategies. Three hundred eighty 6-year-old children with untreated dental decay participated in the study. Caries prevalence and presence of dentogenic infections were recorded. All children were randomly assigned to four different treatment groups ranging from full dental treatment to no invasive treatment at all. Body growth was evaluated by children's height, weight and body mass index. Participants were evaluated after 6 months and 1, 2 and 3 years. Cross-sectionally, negative correlations were observed between anthropometric measures and the number of untreated carious surfaces and caries experience of the children. Next, no significant differences in growth pattern between the treatment groups were observed. Based on these results, it is suggested that caries activity is a negative predictor for body growth in children and dental intervention does not show significant improvement within 3 years.

Reverse breeding: a novel breeding approach based on engineered meiosis.

Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on reducing genetic recombination in the selected heterozygote by eliminating meiotic crossing over. Male or female spores obtained from such plants contain combinations of non-recombinant parental chromosomes which can be cultured in vitro to generate homozygous doubled haploid plants (DHs). From these DHs, complementary parents can be selected and used to reconstitute the heterozygote in perpetuity. Since the fixation of unknown heterozygous genotypes is impossible in traditional plant breeding, RB could fundamentally change future plant breeding. In this review, we discuss various other applications of RB, including breeding per chromosome.

Safety and feasibility of elective high-risk percutaneous coronary intervention procedures with left ventricular support of the Impella Recover LP 2.5.

Currently, the most used left ventricular (LV) support device is intra-aortic balloon counterpulsation. The percutaneous implantable Impella Recover LP 2.5 system is a novel LV (unloading) assist device. We studied the feasibility and safety of LV support with the percutaneous implantable Impella Recover LP 2.5 system in 19 consecutive high-risk patients with percutaneous coronary intervention. Procedural success using the device and percutaneous coronary intervention was achieved in all 19 patients, who were very poor candidates for surgery. The patients were elderly (84% were >60 years of age), 74% had previous myocardial infarction, 63% had LV ejection fractions of < or =25%, and all had LV ejection fractions of < or =40%. There were no procedural deaths and 2 device-unrelated in-hospital late deaths. Mean decrease in hemoglobin level was 0.7 +/- 0.4 mmol/L. The device did not induce or increase aortic valve regurgitation. There were no important device-related adverse events during LV support with the Impella Recover LP 2.5 system. However, these encouraging findings must be confirmed by larger studies, longer assist times, and in other patient categories.

Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.

The East Flanders Prospective Twin Survey (EFPTS).

The East Flanders Prospective Twin Survey (EFPTS) is a prospective, population-based registry of multiple births in the province of East Flanders, Belgium. EFPTS has several unique features: it is population based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are ascertained at birth; basic perinatal data recorded; chorion type and zygosity established; and since 1969 placental biopsies have been taken and frozen at -20 degrees C for later determination of genetic markers. The EFPTS is the only large register that includes placental data and allows differentiation of 3 subtypes of monozygotic (MZ) twins based on the time of the initial zygotic division: the dichorionic-diamnionic pairs (early, before the 4th day after fertilization), the monochorionic-diamnionic pairs (intermediate, between the 4th and the 7th day post fertilization), and the monochorionic-monoamnionic pairs (late, after the 8-day post fertilization). This added a new dimension to didymology (the science of twins; didymos is the Greek word for twin): the timing of MZ twinning. Studies can be initiated taking into account primary biases, those originating in utero. Such studies could throw new light on the controversy over the validity of the classic twin method, the consequences of early embryological events (before and just after implantation of the embryo), the origin of congenital malformations, the sex proportion of multiples, the gene-environment interactions as far as intrauterine environment is concerned, to name but a few.

An unusual presentation of idiopathic thrombocytopenic purpura in pregnancy.

A 35-year-old, 39-week pregnant woman underwent an uneventful emergent cesarean delivery for suspected placental abruption or uterine dehiscence. Given the urgency of the situation and the unremarkable airway anatomy, general anesthesia was the chosen technique. Four hours after her surgery, she returned to the operating room for persistent vaginal bleeding. Hematology tests performed before the cesarean delivery revealed severe thrombocytopenia. This was later diagnosed as idiopathic thrombocytopenia, which was treated successfully with steroid therapy.

New pattern of brain MRI lesions in isolated complex I deficiency.

We describe a boy presenting at the end of the first year of life with severely delayed motor development and only mild mental retardation. Neurological examination revealed axial hypotonia, mild ataxia and pyramidal signs. Elevated lactate and protein in cerebrospinal fluid were the most prominent laboratory abnormalities. Brain MRI showed severe supratentorial white matter changes. Cerebellar white matter appeared normal whereas the signal of the atrophic cerebellar cortex was markedly increased. In vivo 1H-magnetic resonance spectroscopy of the parietooccipital white matter region showed a distinct resonance of lactate. By means of biochemical analysis of respiratory chain enzymes in fibroblasts, the diagnosis of an isolated complex I deficiency could be established in our patient.

[Glycogen storage disease type I with normal in vitro activity of glucose-6-phosphatase (author's transl)]. / Glykogenose Typ I mit normaler Aktivität der Glucose-6-Phosphatase in vitro.

A 4.5 months old girl was suspected to have Glycogenosis type I because of hepatomegalie and recurrent hypoglycemia. Liverbiopsy revealed a normal glycogen content and a normal in vitro activity of glucose-6-phosphatase. We then examined the carbohydrate metabolism and could demonstrate that in vitro the transfer of glucose-6-phosphate to glucose was blocked. We therefore conclude that a normal in vitro activity of glucose-6-phosphatase does not rule out the diagnosis of Glycogenosis type I. Evaluation of carbohydrate metabolism is an important tool in marking the diagnosis. We suggest to use the term Glycogenosis type I B, which some institutions already use for this disorder.

[Hypothyreosis--screening in newborn (author's transl)]. / Hypothyreose-Screening beim Neugeborenen.

Summing up, we can say that, basing on the hypothyreosis screening results obtained in the Federal Republic of Germany, a rate of 100 to 160 new hypothyreosis patients must be expected annually for every 500.000 births. Of these more than half is recognized at a time only at which irreparable damage of the central nervous system has already occurred. With the help of TSH screening, a large proportion of these patients can be saved from several mental retardation and damage, with all its severe social consequences, by enabling early institution of appropriate therapeutics measures. Hence, it would be desirable to achieve, throughout the territory of the Federal Republic, comprehensive hypothyreosis screening in combination with already introduced programme of screening in respect of metabolism, covering without exceptions all newborn and comprising responsible, rapid and efficient co-operation without "red tape", between obstetricians or midwives on the one hand and screening centers on the other.