Pair bonding and disruption impact lung transcriptome in monogamous Peromyscus californicus.

Social interactions affect physiological and pathological processes, yet their direct impact in peripheral tissues remains elusive. Recently we showed that disruption of pair bonds in monogamous Peromyscus californicus promotes lung tumorigenesis, pointing to a direct effect of bonding status in the periphery (Naderi et al., 2021). Here we show that lung transcriptomes of tumor-free Peromyscus are altered in a manner that depends on pair bonding and superseding the impact of genetic relevance between siblings. Pathways affected involve response to hypoxia and heart development. These effects are consistent with the profile of the serum proteome of bonded and bond-disrupted Peromyscus and were extended to lung cancer cells cultured in vitro, with sera from animals that differ in bonding experiences. In this setting, the species' origin of serum (deer mouse vs FBS) is the most potent discriminator of RNA expression profiles, followed by bonding status. By analyzing the transcriptomes of lung cancer cells exposed to deer mouse sera, an expression signature was developed that discriminates cells according to the history of social interactions and possesses prognostic significance when applied to primary human lung cancers. The results suggest that present and past social experiences modulate the expression profile of peripheral tissues such as the lungs, in a manner that impacts physiological processes and may affect disease outcomes. Furthermore, they show that besides the direct effects of the hormones that regulate bonding behavior, physiological changes influencing oxygen metabolism may contribute to the adverse effects of bond disruption.

Longitudinal associations between depression and diabetes complications: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of longitudinal studies assessing the bi-directional association between depression and diabetes macrovascular and microvascular complications. Embase, Medline and PsycINFO databases were searched from inception through 27 November 2017. A total of 4592 abstracts were screened for eligibility. Meta-analyses used multilevel random/mixed-effects models. Quality was assessed using the Newcastle-Ottawa scale. Twenty-two studies were included in the systematic review. Sixteen studies examined the relationship between baseline depression and incident diabetes complications, of which nine studies involving over one million participants were suitable for meta-analysis. Depression was associated with an increased risk of incident macrovascular (HR = 1.38; 95% CI: 1.30-1.47) and microvascular disease (HR = 1.33; 95% CI: 1.25-1.41). Six studies examined the association between baseline diabetes complications and subsequent depression, of which two studies involving over 230 000 participants were suitable for meta-analysis. The results showed that diabetes complications increased the risk of incident depressive disorder (HR = 1.14; 95% CI: 1.07-1.21). The quality analysis showed increased risk of bias notably in the representativeness of selected cohorts and ascertainment of exposure and outcome. Depression in people with diabetes is associated with an increased risk of incident macrovascular and microvascular complications. The relationship between depression and diabetes complications appears bi-directional. However, the risk of developing diabetes complications in depressed people is higher than the risk of developing depression in people with diabetes complications. The underlying mechanisms warrant further research.

Selenium levels in patients with autoimmune thyroiditis and controls in lower Austria.

Autoimmune thyroiditis (AIT) is one of the most common autoimmune diseases; genetic as well as environmental factors contribute to its pathogenesis. The thyroid is the organ with the highest selenium content per unit weight. Selenium status appears to have an impact on the development of thyroid pathologies. We investigated a possible difference of selenium serum levels as a marker of nutritional selenium supply between patients with AIT in central Lower Austria and a matched group of healthy persons living in the same region. Selenium serum levels in the patients with AIT were 98.0 ± 15.6 µg/l. A significant difference to the matched group of normal persons, whose selenium serum levels were 103.2 ± 12.4 µg/l, could not be detected by the t-test (p>0.05). We considered the serum selenium levels to be indicators of selenium supply (by alimentation). A serum level of 120-160 µg/l of selenium represents the normal range. According to this, most patients and control persons showed mild to moderate selenium deficiency (80-120 µg/l selenium). Although our data present slightly higher selenium levels in normal persons than in patients with AIT, this weak and statistically insignificant trend is not sufficient to support the conclusion of a link between inadequate selenium supply and autoimmune thyroid disease.

Pancreatitis, pregestational diabetes and hyperchylomicronia in a pregnant woman with COVID-19.

A 37-year-old pregnant woman, was diagnosed with acute pancreatitis whilst being infected with COVID-19. Additionally, she had a hyperchylomicronemia and an uncontrolled (most probably, pre-gestational) type 2 diabetes. The coronavirus is able to enter the pancreatic cells through ACE-2 receptors. On the pancreatic level, ACE- 2 receptor expression is present but not as abundant as on pulmonary level. However, with inflammation (due to hyperchylomicronemia), the ACE-2 receptor expression may change and hypothetically make the pancreas more susceptible for a Covid-19 surinfection. Here it is difficult to conclude whether the COVID-19 infection contributed substantially to the development of pancreatitis. Late term pregnancy, uncontrolled glycaemia and the heterozygote mutation in the GPIHBP1 gene (c.523G>C p; Gly175Arg), all contribute to increased TG levels, a principal factor in the development of pancreatitis. This case shows a rare but serious clinical presentation late in pregnancy that could have interesting consequences postpartum.

Genetic diversity of SARS-CoV-2 infections in Ghana from 2020-2021.

The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.

Burnout, psychosomatic symptoms and job satisfaction among Dutch nurse anaesthetists: a survey.

BACKGROUND: To meet the increasing demand for healthcare providers, it is crucial to recruit and retain more nurse anaesthetists (NAs). The majority of NAs in the Netherlands are >45 years old, and retaining them in their jobs is very important. This study investigates the relationships among burnout, physical health and job satisfaction among Dutch NAs. METHODS: Two thousand NAs working in Dutch hospitals were invited to participate in this online questionnaire. We tested the relationships among burnout, psychosomatic symptoms, sickness absence, perceived general health and job satisfaction. RESULTS: Nine hundred and twenty-three questionnaires were completed and analysed (46% response rate). Burnout and psychosomatic symptoms were negatively associated with job satisfaction, and predicted 27% of job satisfaction. Perceived general health was positively and sickness absence was negatively related to job satisfaction. Older NAs had a higher incidence of burnout than their younger counterparts. CONCLUSIONS: The results confirmed the importance of a healthy psychosocial work environment for promoting job satisfaction. To prevent burnout, further research is necessary to determine the factors causing stress. These findings may also apply to anaesthesiologists who share many tasks and work in close cooperation with NAs.

Personality dimensions and their relationship with job satisfaction amongst Dutch nurse anaesthetists.

AIM: This study investigates the relationship between personality dimensions and job satisfaction. BACKGROUND: The shortage of nurses, and those voluntarily leaving their jobs, continues to be a problem affecting the delivery of healthcare all over the world, including anaesthesia. If it is found that nurse anaesthetists with certain personality types have high levels of job satisfaction, the information may be helpful for the retention of nurse anaesthetists. METHODS: A questionnaire was distributed amongst Dutch nurse anaesthetists. Factor and multiple regression analyses were performed to reveal personality dimensions and their impact on job satisfaction. RESULTS: Nine hundred and twenty-three questionnaires were completed and analysed (46% response rate). Two personality dimensions -'easy going' and 'orderly'- explained 3.5% of the variance in job satisfaction. CONCLUSION: Personality dimensions as measured with the Myers-Briggs Type Indicator (MBTI) are only minimally relevant in predicting job satisfaction amongst Dutch nurse anaesthetists. IMPLICATIONS FOR NURSING MANAGEMENT: Before using personality traits as a selection tool for retaining employees, it is important to understand the relationship of particular personalities to job satisfaction; it is also important to know which combination of personality traits is likely to create a highly cohesive work group.

Job satisfaction amongst Dutch nurse anaesthetists: the influence of emotions on events.

BACKGROUND: An ageing population, combined with a shortage of health-care professionals, can result in a decrease in the capacity of health-care systems. Therefore, it is important to explore possible solutions for this problem. By finding methods to increase job satisfaction, it may be possible to retain employees within their profession. In this study, we examined events, their influence on emotions and, consequently, the effect of these emotions on job satisfaction. We attempted to answer the question: Which events and emotions influence job satisfaction? METHODS: We collected data on events and emotions, and their effects on job satisfaction, amongst Dutch nurse anaesthetists. Participants (n = 314) were asked to complete two questionnaires about events, emotions and job satisfaction at two different times during an average working day. RESULTS: One hundred thirty-two nurse anaesthetists from 24 Dutch hospitals participated. Both positive and negative events were significant in the development of positive and negative emotions at the end of the working day. Positive emotions at the end of the working day contributed significantly to job satisfaction. Negative emotions did not have a significant effect on job satisfaction. CONCLUSIONS: The mediating role of positive emotions in relation to positive and negative events should be taken into account in managing job satisfaction amongst Dutch nurse anaesthetists. Further research is necessary to determine whether the relationship between events and emotions provides a foundation for developing a more positive working atmosphere, and also to explore how hospitals can trigger positive emotions to increase job satisfaction.

Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study.

AIMS: To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. METHODS: People with type 2 diabetes treated in out-patient settings aged 18-65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of 'upset') between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. RESULTS: In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. CONCLUSION: This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

Overtrained horses alter their resting pulsatile growth hormone secretion.

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

[Treatment planning in patients with a severe reduced dentition]. / Behandeling van een sterk gemutileerde dentitie.

Because loss of teeth many people have a reduced maxillary and mandibular dentition. The appropriate prosthetic rehabilitation is dependent on whether or not a standard mutilation of the dentition can be achieved. In this article, the focus is on treatment of a remaining mandibular dentition combined with an edentulous maxilla, whether or not with a reduced residual alveolar ridge. In the literature, there is no consensus on the appropriate prosthetic treatment if implant-supported overdentures are not applicable. The amount of bone loss in already during some time edentulous maxillary and mandibular alveolar ridge segments as well as the available vertical space for the removable (partial) denture are important decision-making factors.

The danger of metabolic pathways with turbo design.

Many catabolic pathways begin with an ATP-requiring activation step, after which further metabolism yields a surplus of ATP. Such a 'turbo' principle is useful but also contains an inherent risk. This is illustrated by a detailed kinetic analysis of a paradoxical Saccharomyces cerevisiae mutant; the mutant fails to grow on glucose because of overactive initial enzymes of glycolysis, but is defective only in an enzyme (trehalose 6-phosphate synthase) that appears to have little relevance to glycolysis. The ubiquity of pathways that possess an initial activation step, suggests that there might be many more genes that, when deleted, cause rather paradoxical regulation phenotypes (i.e. growth defects caused by enhanced utilization of growth substrate).

Discriminating work context factors in the working environment of Dutch nurse anesthetists.

With an ever increasing number of patients and more demanding health care system it is important to keep nurse anesthetists as mentally and physically fit as possible. Especially with a shortage of nurse anesthetists it is important to know which work context factors are important for maintaining a healthy balance between the nurse anesthetist and his work environment. This study is the first to determine which work context factors of nurse anesthetists are most relevant for a healthy work environment. A questionnaire survey, containing work related items, was distributed among all nurse anesthetists working in Dutch hospitals. All together 882 questionnaires (response rate 44%) were completed and analyzed, including factor analysis for the discriminating work context factors. Four discriminating work context factors (career/rewards, relation with supervisor, task contents and social environment) were found to be relevant, explaining 48% of the variance in work context. All four work context factors are considered to be job resources, although not hospital related. Supervisors (head nurses) interpret these work context factors differently from nurse anesthetists, which can result in dissatisfaction of the latter group. Nurse anesthetists participate more in sub-functions and activities in larger peripheral and academic anesthesia departments. Smaller anesthesia departments require nurse anesthetists to be more flexible and perform many different functions within the anesthesia domain.

Experiences of adults who as children lived with a parent experiencing mental illness in a small-scale society : A Qualitative study.

WHAT IS KNOWN ON THE SUBJECT?: Children of parent with severe mental illness are often carrying a caring burden; they keep the illness in the family, are documented to be stigmatized, bullied and to take special attention to their mentally ill parent's health and well-being. Little is however known about these children's experiences when growing up in a small-scale society. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE?: Children's experiences of living with a parent with severe mental illness in the small-scale society (Faroe Islands) are paradoxical, life is often unreasonable and evidently contradictory but anyway connected. The results show that "everybody knows everybody" which refers to that, in the small-scale society, it is difficult to be anonymous. The children were familiar with that people talked and had a prejudiced attitude; this resulted that the participants were constantly reminded of their mental ill parent's difference, and they were feeling less worthy than their pals. Children of parents with severe mental illness in a small-scale society need to support from the close family as well as mental healthcare professionals. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The study adds knowledge about the challenges that children of mental ill parents have to go through. Dialogue among mental healthcare colleagues not only about caring for the sick parent but also about modes of caring for the children and the family at large would deepen the staff's knowing of the need for family-centred care within mental health care. ABSTRACT: Introduction An estimated 23% of children worldwide live with a parent experiencing mental illness. These children are exposed to emotional and psychosocial challenges. Little is known about these children when living in small-scale societies. Aim To explore how adults, who as children lived with parents experiencing mental illness in a small-scale society, recalled their childhood life. Method Individual interviews with 11 adults were analysed using content analysis. Results Living as a child with a parent experiencing mental illness in a small-scale society was described as "living in a paradox" which emerged from three categories: "intergenerational help and caring," "barriers understanding parental illness" and "everybody knows everybody". The children received little or no support from family members, nor from health and education professionals. Discussion In a small-scale society, stigma surrounding mental illness is notable. Families often attempt to conceal mental illness from outsiders with negative or adverse effects on children. Implications for practice Mental healthcare professionals need to consider the needs of children who have parents experiencing mental illness. It is imperative for the well-being of the patients' children to support them in understanding what is happening, turn gossiping in a positive direction and address stigma in the communities.

Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident.

In order to maintain a stable karyotype, the eukaryotic cell cycle is coordinated such that only one round of S phase precedes each mitosis, and mitosis is not initiated until DNA replication is completed. Several checkpoints and regulatory proteins have been defined in lower eukaryotes that govern this coordination, but little is known about the proteins that are involved in mammalian cells. Previously, we have shown that the winged-helix transcription factor Trident - also known as HFH-11, FKL16 and WIN [1] [2] [3] - is exclusively expressed in cycling cells and is phosphorylated during mitosis [1] [4]. The cellular function of Trident has yet to be described, however. Here, we have shown that disruption of the Trident gene in mice resulted in postnatal death, most probably because of circulatory failure. Histological analysis of Trident -/- embryos from embryonic day 10 (E10) onwards revealed a specific, characteristic defect in the developing myocardium. The orientation of the myocytes was highly irregular and the nuclei of these disorganized cardiomyocytes were clearly polyploid with up to a 50-fold increase in DNA content. Polyploidy was also observed in embryonic hepatocytes. Our results indicate that expression of Trident is required to prevent multiple rounds of S phase in the heart and the liver. Trident therefore appears to have a role in preventing DNA re-replication during the G2 and M phases.

A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations.

A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent, " that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY-an abbreviation for functional analysis by co-responses in yeast.

Association of bacteriorhodopsin with lipid-impregnated filters. Evidence for fusion of bacteriorhodopsin-containing vesicles with the lipid phase of the filter.

Bacteriorhodopsin vesicles were associated with cellulose-nitrate filters impregnated with a solution of phospholipids in hexadecane. The generation of (photo)potentials upon illumination of the filter was studied in the absence and presence of ionophores, phospholipase A2, EDTA or polyene antibiotics. From these experiments the following conclusions are drawn. 1. Upon illumination of the filter, bacteriorhodopsin pumps protons into aqueous compartments located in the filter. 2. These aqueous compartments possibly do not originate from the compartments enclosed by the bacteriorhodopsin vesicles. Evidence is obtained that aqueous compartments are present in the surface layers of the lipid-impregnated filters. 3. The results are explained most easily by a mechanism, whereby fusion occurs between the vesicles and the lipids of the filter.

On the stoichiometry between uncouplers of oxidative phosphorylation and respiratory chains. The catalytic action of SF 6847 (3,5-di-tert-butyl-4-hydroxy-benzylidenemalononitrile).

Titration of State 4 rat-liver mitochondria at pH 7.2 with the uncoupler 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847) at various concentrations of mitochondria and using various substrates indicates that under optimal conditions less than 0.2 molecule of 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile per respiratory chain is sufficient to induce complete uncoupling. This result suggests that there is not a stoichiometric relationship between uncoupler molecules and cytochrome c oxidase, involved in oxidative phosphorylation, or between the former and phosphorylation assemblies. Experiments on the release by 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile of azide-inhibited respiration of State 3 mitochondria and titrations with 5-chloro-3-tert-butyl-2'-chloro-4'-nitrosalicylanilide (S13) of State 4 mitochondria at various mitochondrial concentrations confirm this conclusion.

Effect of concentration of substrates and products on the growth of Klebsiella pneumoniae in chemostat cultures.

Non-equilibrium thermodynamics (NET) can be used to describe microbial growth. In this description, the concentrations of products contribute to the driving forces of the metabolic processes (anabolism and catabolism). Thus, in contrast to the model of bacterial growth of Monod (Recherches sur la Croissance les Cultures Bactériennes (1942) Herman et Cie, Paris), it is predicted that the growth rate of a bacterial chemostat culture is, in principle, dependent on the concentration of the catabolic product (for instance HCO3-) during catabolite limitation and on the concentration of the anabolic product (for instance biomass) during anabolite limitation. In order to test this prediction, Klebsiella pneumoniae was grown in aerobic citrate-limited, glucose-limited or ammonia-limited chemostat cultures. Ammonia-limited cultures were considered to be essentially anabolite-limited, whereas citrate limitation was used as a representative for catabolite limitation. In ammonia-limited or in glucose-limited cultures it was found that the growth rate was independent of the biomass concentration present. In the NET description this means that the 'back' reaction (i.e., in the direction from biomass to substrates) is saturated with respect to biomass. On the other hand, in citrate-limited cultures, the steady-state concentration of citrate increased with the concentration of the catabolic product HCO3-. At relatively low concentrations of HCO3-, 'thermodynamic back-pressure' of growth (i.e., increase in product concentration was compensated by an increase in substrate concentration so that the driving force for growth remained almost constant) was demonstrated as predicted by the NET model. At concentrations above 40 mM, a kinetic (allosteric) effect of HCO3- was detected. This was concluded from a reduced growth yield on citrate, and from a significant decrease in the maximal growth rate and the maximal oxygen consumption rate after relief of the citrate limitation.

Uncoupler-inhibitor titrations of ATP-driven reverse electron transfer in isolated rat-liver mitochondria.

Uncoupler-inhibitor titrations of ATP-driven reverse electron transfer across the first site of the respiratory chain were performed in isolated rat-liver mitochondria, and the experimental results were compared with the predictions of a simple delocalized chemiosmotic mechanism. The rates of ATP hydrolysis (Jp) and reverse electron transfer (-J0) were measured at different uncoupler (S-13) concentrations, either in the absence or in the presence of rotenone. When the rates -J0 and Jp measured at different uncoupler concentrations were expressed as percentages of the activity at zero uncoupler concentration, it was found that the efficiency of S-13 to uncouple the reverse electron transfer and to stimulate ATP hydrolysis was not significantly changed upon partial inhibition with rotenone. These results are in contrast with data from a study of uncoupler-inhibitor titrations in submitochondrial particles published previously, in which a higher effectiveness of several uncouplers to inhibit ATP-driven reverse electron transfer was observed in the presence of rotenone.