Recombinant inbred lines derived from wide crosses in Pisum.

Genomic resources are becoming available for Pisum but to link these to phenotypic diversity requires well marked populations segregating for relevant traits. Here we describe two such resources. Two recombinant inbred populations, derived from wide crosses in Pisum are described. One high resolution mapping population involves cv Caméor, for which the first pea whole genome assembly was obtained, crossed to JI0281, a basally divergent P. sativum sativum landrace from Ethiopia. The other is an inter sub-specific cross between P. s. sativum and the independently domesticated P. s. abyssinicum. The corresponding genetic maps provide information on chromosome level sequence assemblies and identify structural differences between the genomes of these two Pisum subspecies. In order to visualise chromosomal translocations that distinguish the mapping parents, we created a simplified version of Threadmapper to optimise it for interactive 3-dimensional display of multiple linkage groups. The genetic mapping of traits affecting seed coat roughness and colour, plant height, axil ring pigmentation, leaflet number and leaflet indentation enabled the definition of their corresponding genomic regions. The consequence of structural rearrangement for trait analysis is illustrated by leaf serration. These analyses pave the way for identification of the underlying genes and illustrate the utility of these publicly available resources. Segregating inbred populations derived from wide crosses in Pisum, together with the associated marker data, are made publicly available for trait dissection. Genetic analysis of these populations is informative about chromosome scale assemblies, structural diversity in the pea genome and has been useful for the fine mapping of several discrete and quantitative traits.

[Genetic risk of mental illness: what do we know and how do we communicate this?] / Genetisch risico van psychiatrische ziekten: wat weten we en hoe communiceren we dat?

BACKGROUND: Insights from psychiatric genetics research and large international psychiatric genetics consortia are promising but still remain outside the realm of clinical practice.
AIM: To provide an overview of developments in the field of psychiatric genetics; and to offer guidance for health professionals how to assess and manage clinical implications of these developments.
METHOD: In this review, we address: recent developments in psychiatric genetics, with a focus on polygenic risk scores (PRS); ethical dilemmas associated with clinical application of PRS; and basic principles of genetic counseling for psychiatric disorders.
RESULTS: PRS are not yet ready for implementation in clinical practice because of limited predictive value and poor generalizability. In addition, it is still unclear how genetic risk and PRS can be communicated clearly to patients and families.
CONCLUSION: Advances in psychiatric genetics and increased availability of genetic risk scores may lead to questions from patients and families coping with psychiatric illness. These questions may be best addressed using psychiatric genetic counseling techniques. We recommend that psychiatrists have some basic knowledge of psychiatric genetics and know how to refer their patients to a clinical geneticist. Implementing a psychiatric genetics theme in training and education may be helpful.
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Outcomes of ulna shortening osteotomy: a cohort analysis of 106 patients.

BACKGROUND: Ulna shortening osteotomy (USO) for ulnar impaction syndrome (UIS) aims to improve pain and function by unloading the ulnar carpus. Previous studies often lack validated patient-reported outcomes or have small sample sizes. The primary objective of this study was to investigate patient-reported pain and hand function at 12 months after USO for UIS. Secondary objectives were to investigate the active range of motion, grip strength, complications, and whether outcomes differed based on etiology. MATERIALS AND METHODS: We report on 106 patients with UIS who received USO between 2012 and 2019. In 44 of these patients, USO was performed secondary to distal radius fracture. Pain and function were measured with the Patient Rated Wrist/Hand Evaluation (PRWHE) before surgery and at 3 and 12 months after surgery. Active range of motion and grip strength were measured before surgery and at 3 and 12 months after surgery. Complications were scored using the International Consortium for Health Outcome Measurement Complications in Hand and Wrist conditions (ICHAW) tool. RESULTS: The PRWHE total score improved from a mean of 64 (SD = 18) before surgery to 40 (22) at 3 months and 32 (23) at 12 months after surgery (P < 0.001; effect size Cohen's d = -1.4). There was no difference in the improvement in PRWHE total score (P = 0.99) based on etiology. Also, no clinically relevant changes in the active range of motion were measured. Independent of etiology, mean grip strength improved from 24 (11) before surgery to 30 (12) at 12 months (P = 0.001). Sixty-four percent of patients experienced at least one complication, ranging from minor to severe. Of the 80 complications in total, 50 patients (47%) had complaints of hardware irritation, of which 34 (32%) had their hardware removed. Six patients (6%) needed refixation because of nonunion. CONCLUSION: We found beneficial outcomes in patients with UIS that underwent USO, although there was a large variance in the outcome and a relatively high number of complications (which includes plate removals). Results of this study may be used in preoperative counseling and shared decision-making when considering USO. LEVEL OF EVIDENCE: Therapeutic III.

The prevalence, incidence, and progression of radiographic thumb base osteoarthritis in a population-based cohort: the Rotterdam Study.

OBJECTIVE: To describe the prevalence, incidence, and progression of radiographic thumb carpometacarpal (CMC-1) and trapezioscaphoid (TS) radiographic osteoarthritis (ROA) in the general Dutch population aged ≥55y. DESIGN: Data were from the first and second cohort of the Rotterdam Study (1990-2005, 4-12 years follow-up, age 55+). Participants underwent bilateral radiographs at baseline (N = 7792) and follow-up (N = 3804), read for Kellgren-Lawrence (K-L) grade. ROA was defined on the joint level as K-L grade ≥2. The prevalence was assessed at baseline, incidence at follow-up in those free of ROA at baseline, and progression in those with ROA. Differences based on sex and age were evaluated using logistic regression models. RESULTS: At baseline, 1977 (25.3%) had CMC-1 ROA and 1133 (14.5%) TS ROA. The prevalence was higher in females for CMC-1 (aOR = 1.98 95%CI [1.77-2.21]) and TS ROA (aOR = 2.00 [1.74-2.29]) and increased for every year of age (CMC-1 ROA 1.08 [1.07-1.08]) (TS ROA 1.06 [1.05-1.07]). Most (437/512; 85.4%) incident cases of CMC-1 ROA (2994 at risk) were mild (K-L = 2), whereas most (145/167; 86,8%) incident cases of TS ROA (3311 at risk) were moderate to severe (K-L = 3/4). CMC-1 ROA progression was mostly (88/100; 88.0%) seen in the K-L 2 group at baseline, whereas that was (4/17; 23.5%) for TS ROA. CONCLUSION: CMC-1 ROA and TS ROA are prevalent in the general Dutch population. While incident CMC-1 ROA was primarily mild, incident TS ROA was more often moderate to severe. CMC-1 ROA was a strong predictor for incident TS ROA.

The prevalence of radiographic thumb base osteoarthritis: a meta-analysis.

INTRODUCTION: Osteoarthritis (OA) affects millions of people worldwide. In hand OA, the thumb base is the most affected single joint. The reported radiographic prevalence ranges from 0 to 100%, making the true radiographic prevalence unclear. Hence, we conducted a meta-analysis on the age and sex-specific prevalence of radiographic thumb base OA. METHODS: We performed a search in Embase, Medline Ovid, Web of Science Core Collection, Cochrane Central Register of Trials, and Google Scholar. We included studies of the general population that reported thumb base OA for males and females separately based on a hand radiograph and reported the age of these groups. Using meta-regression, we estimated the odds ratio (OR) of having radiographic thumb base OA for age and sex, while adjusting for within-study correlation. RESULTS: The initial search yielded 4,278 articles; we finally included 16 studies that reported the age- and sex-stratified prevalence. Taken together, there were 104 age and gender specific-prevalence rates that could be derived from the 16 studies. The prevalence of radiographic OA for the 50-year-old male and female participants was 5.8% and 7.3%, respectively, while the respective prevalence for 80-year-old male and female participants was 33.1% and 39.0%. We found an OR for having radiographic OA of 1.06 (95%CI [1.055-1.065], p < 0.001) per increasing year of age, and 1.30 (95%CI: 1.05-1.61], p = 0.014) for females. CONCLUSION: In the general population, radiographic thumb base OA is more prevalent in females and is strongly associated with age.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

If it ain't broke don't fix it? Ethics of splinting deformed newborn ears.

Neonatal ear splinting is a proven and safe method to mold deformed ears into a more common shape. Based on our earlier studies, splinting is recommended only before the age of six weeks and preferably within the first week after birth. This can be done by initiating a system in which this intervention is actively proposed to parents. In this paper, we ethically evaluate such a system. By molding perfectly healthy newborn ears, we reach the boundary between treatment and enhancement. A key question is, therefore, whether we could classify neonatal ear splinting as a therapy. On the level of the individual, the advantages outweigh the drawbacks, but on the level of society, it is more complicated. Making ear deformities a part of official national screening programs fails to meet WHO criteria. Moreover, by systematically offering ear molding, professionals may be promoting guilt or fear of missing the opportunity. Additionally, it could affect societal attitudes toward cosmetic deformities. However, if we argue that on the individual level infants may benefit from ear splinting, then active detection of ear deformities allows parents to choose in a timely way from the full range of options, including splinting and a wait-and-see approach. We are inclined to optimally inform parents without setting up a full-blown public health program. The extent to which it is possible to timely offer splints to parents of newborns depends on the infrastructure of health care systems. The key will be for everyone involved, public or commercial, to responsibly educate and facilitate.

Transient thyroiditis after parathyroidectomy for tertiary hyperparathyroidism.

Thyrotoxicosis due to thyroiditis is predominantly caused by infection or autoimmune disease of the thyroid. Parathyroid surgery however, is a lesser known cause of thyroiditis, due to thyroid manipulation. We treated a patient who developed transient symptomatic thyroiditis following parathyroid surgery for tertiary hyperparathyroidism. Therefore, the differential diagnosis for patients with symptoms after parathyroid surgery should include transient thyroiditis.

Determinants of in-hospital antibiotic prescription behaviour: a systematic review and formation of a comprehensive framework.

BACKGROUND: Knowledge of determinants that influence antibiotic prescription behaviour (APB) is essential for the successful implementation of antimicrobial stewardship interventions. The theory of planned behaviour (TPB) is an established model that describes how cognitions drive human behaviour. OBJECTIVES: The objective of this study was to identify the sociocultural and behavioural determinants that affect APB and to construct a TPB framework of behavioural intent. METHODS: The following online databases were searched: PubMed, Medline, Embase, Web of Science, Cochrane Library and Central. Studies published between July 2010 and July 2017 in European countries, the United States, Canada, New Zealand or Australia were included if they identified one or more determinants of physicians' APB. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the TPB, determinants were categorized in behavioural, normative and control beliefs, thus shaping a conceptual framework for APB. RESULTS: Nine studies were eligible for inclusion, and 16 determinants were identified. Determinants relating to fear of adverse outcome (5/9), tolerance of risk and uncertainty (5/9), hierarchy (6/9), and determinants concerning normative beliefs-particularly social team dynamics (6/9)-were most frequently reported. Beliefs about antimicrobial resistance and potential negative consequences of antibiotic use were rarely mentioned. CONCLUSIONS: Behavioural, normative and control beliefs are all relevant in APB. There is a need for quantitative studies to assess the weight of the individual determinants to be able to efficiently design and implement future stewardship interventions. The constructed framework enables a comprehensive approach towards understanding and altering APB.

Managing unsolicited findings in genomics: A qualitative interview study with cancer patients.

OBJECTIVE: Next-generation sequencing (NGS) is increasingly being employed in the context of personalized cancer treatment. Anticipating unsolicited findings that may arise during a NGS procedure is a key consideration; however, little is known about cancer patients' intentions, needs, and preferences concerning the return of unsolicited findings. METHODS: A qualitative design using individual semi-structured interviews with 24 cancer patients was utilized to explore patients' decisions on whether to receive unsolicited findings from NGS. These interviews were subsequently analyzed using the constant comparative method to develop codes and themes. RESULTS: We identified 4 interrelated themes that emerged in the context of the return of unsolicited findings. First, we describe how cancer patients expressed a strong need to control their lives. Second, we show the importance of family dynamics. Third, the NGS procedure regarding unsolicited findings is perceived as cognitively complex, and fourth, the procedure is also considered emotionally complex. CONCLUSIONS: The results of our study contribute to a better understanding of what cancer patients consider important and what may motivate and influence them when making decisions on the disclosure of unsolicited findings following NGS. We show how Joel Feinberg's classification of autonomy may help clinicians to better understand cancer patients' desire for autonomous decision making while also acknowledging the emotional and cognitive difficulties regarding the disclosure of unsolicited findings. These insights could be helpful for clinicians to guide patients through this complex process.

[Hypocortisolism associated with nephrotic syndrome]. / Hypocortisolisme bij het nefrotisch syndroom.

BACKGROUND: With nephrotic syndrome, cortisol levels may be falsely lowered by loss of cortisol-binding globulin (CBG) in the urine. An incorrect diagnosis of adrenal insufficiency could therefore be made. CASE DESCRIPTION: We describe the case of a 52-year-old female with nephrotic syndrome that did not sufficiently respond to medication. Treatment management was complicated by symptomatic hypotension, which was thought to be caused by adrenal insufficiency. The cortisol levels in the blood were low and a clinical cause could not be identified. However, free cortisol in the saliva appeared normal and serum CBG levels were low; this therefore precluded adrenal insufficiency. After complete remission of the nephrotic syndrome, cortisol levels normalised. CONCLUSION: The reduced cortisol level in this patient was caused by the reduced CBG level due to loss associated with nephrotic syndrome. First and foremost it is important to indicate an abnormal laboratory result within an existing disease, before making a new diagnosis of concomitant disease.

Persistence and transgenerational effect of plant-mediated RNAi in aphids.

Plant-mediated RNA interference (RNAi) has been successfully used as a tool to study gene function in aphids. The persistence and transgenerational effects of plant-mediated RNAi in the green peach aphid (GPA) Myzus persicae were investigated, with a focus on three genes with different functions in the aphid. Rack1 is a key component of various cellular processes inside aphids, while candidate effector genes MpC002 and MpPIntO2 (Mp2) modulate aphid-plant interactions. The gene sequences and functions did not affect RNAi-mediated down-regulation and persistence levels in the aphids. Maximal reduction of gene expression was ~70% and this was achieved at between 4 d and 8 d of exposure of the aphids to double-stranded RNA (dsRNA)-producing transgenic Arabidopsis thaliana. Moreover, gene expression levels returned to wild-type levels within ~6 d after removal of the aphids from the transgenic plants, indicating that a continuous supply of dsRNA is required to maintain the RNAi effect. Target genes were also down-regulated in nymphs born from mothers exposed to dsRNA-producing transgenic plants, and the RNAi effect lasted twice as long (12-14 d) in these nymphs. Investigations of the impact of RNAi over three generations of aphids revealed that aphids reared on dsMpC002 transgenic plants experienced a 60% decline in aphid reproduction levels compared with a 40% decline of aphids reared on dsRack1 and dsMpPIntO2 plants. In a field setting, a reduction of the aphid reproduction by 40-60% would dramatically decrease aphid population growth, contributing to a substantial reduction in agricultural losses.

Hypocitraturia: a common but not well-known cause of nephrolithiasis.

Nephrolithiasis is a frequent problem that can cause serious morbidity. When associated with an underlying metabolic disorder the recurrence rate is higher. Hypocitraturia is estimated to be present in 20-60% of cases. Several secondary causes are known. Potassium citrate is the primary treatment. In the case we present here we emphasise the need for metabolic screening, focussing on hypocitraturia, a less well-known cause of nephrolithiasis.

Selective ambulatory management of imported falciparum malaria: a 5-year prospective study.

The ambulatory management of imported Plasmodium falciparum malaria is controversial because criteria for safe selection of patients are imprecise. The aim of the present study was to investigate the evolution and outcome of patients diagnosed with Plasmodium falciparum malaria at a Belgian referral institute in order to assess the safety of the institute's current selective ambulatory management protocol. From 2000 to 2005, all patients diagnosed with P. falciparum infection at the Institute of Tropical Medicine and the University Hospital of Antwerp were enrolled prospectively. Ambulatory treatment was offered to nonvomiting patients if they exhibited none of the 2000 World Health Organization criteria of severity and had parasitemia below 1% at the initial assessment. The treatment of choice was quinine (plus doxycycline or clindamycin) for inpatients and atovaquone-proguanil for outpatients. P. falciparum malaria was diagnosed in 387 patients, of whom 246 (64%) were Western travelers or expatriates and 117 (30%) were already on antimalarial therapy. At diagnosis, 60 (15%) patients had severe malaria. Vital organ dysfunction was initially seen in 34 and developed later in five others. Five patients died. Of the 327 patients initially assessed as having uncomplicated malaria, 113 (35%) were admitted immediately; of these, 4 developed parasitemia >/=5% at a later stage but without any clinical consequence. None of the 214 individuals initially treated as outpatients experienced any malaria-related complications, including 10 who were admitted later. Vital organ dysfunction was observed in only 2 of the 214 patients with initial parasitemia <1% who had not taken antimalarial agents (both patients had impaired consciousness at presentation). Ambulatory treatment is safe in treatment-naive malaria patients with parasitemia <1% who do not vomit and who do not exhibit any criteria of severe malaria.

[Hypoglycaemic coma due to falsely elevated glucose values in a patient with diabetes mellitus and peritoneal dialysis]. / Hypoglykemisch coma als gevolg van foutiefverhoogde glucosewaarden bij een patiënte met diabetes mellitus en peritoneale dialyse.

A 45-year-old female diabetes-mellitus patient on peritoneal dialysis was admitted because of vertigo. During her stay in hospital she developed a comatose condition with abnormal head posture and deviation ofthe eyes to the left. Capillary blood from the fingertip showed a glucose value of 15.4 mmol/l. However, the automatically obtained glucose value delivered with a blood-gas analysis was found to be 1.2 mmol/l. The neurological state of the patient normalised fully after intravenous glucose administration. The glucose values were falsely elevated because the patient used a peritoneal dialysis fluid at night which contained icodextrin as an osmotic agent. Metabolites of icodextrin can influence blood-glucose measurements taken using analyzers that depend on the enzyme glucose dehydrogenase. To prevent potentially life-threatening situations, the use of an adequate glucose meter is of paramount importance.