Environmental factors shaping the gut microbiome in a Dutch population.

The gut microbiome is associated with diverse diseases1-3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

[(Self)-compassion as an antidote for psychopathology]. / (Zelf)compassie als antidotum voor psychische stoornissen.

BACKGROUND: The prevalence of psychopathology did not decrease in prosperous countries, despite evidence-based treatment, focus on prevention and long prosperity. AIM: To investigate if the eastern concept of self-compassion can help to decrease the prevalence of psychopathology. METHOD: Literature review and interviews with experts. RESULTS: Health is defined as a state of complete wellbeing. This seems like a maintainable goal in prosperous countries. Setbacks are, however, an unavoidable part of life and therefore resilience is important. Normalizing a state of complete wellbeing comes at the expense of resilience because it increases stress after setbacks. Stress is an important precursor to psychopathology because it leads to suffering and dysfunction. The concept of self-compassion and compassion in a broader sense, refer to the capacity to be mild when setbacks occur. (Self)-compassion helps to regulate stress and can therefore improve resilience and contribute to decrease the prevalence of psychopathology. CONCLUSION: In prosperous countries, there is little attention to resilience. The concept of (self)-compassion can contribute to mental resilience and can help to decrease the prevalence of psychopathology. Therefore, it deserves a place in the diagnostics and treatment of psychiatric disorders.

[Transdiagnostic psychiatry: work in progress]. / Transdiagnostische psychiatrie: concept in ontwikkeling.

BACKGROUND: There is an increasing awareness that the current approach to clinical thought and work in psychiatry in relation to psychiatric diagnosis, treatment and research has its limitations. This necessitates a process to reform both the clinical practice and future scientific research. One way to reform this is the transdiagnostic approach. AIM: To clarify the psychological, biological and therapeutic aspects of a transdiagnostic approach in psychiatry. METHOD: An analysis of new approaches based on recent findings from the recent literature. RESULTS: Transdiagnostic psychiatry is a relatively new concept which is still under development. The examples extracted from the reviewed literature on developmental psychology, neurobiology and treatment demonstrate that this approach may lead to improvements in clinical care and generate new etiological insights. CONCLUSION: A transdiagnostic approach in psychiatry may lead to new insights that are relevant for clinical practice and future scientific research.

Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands.

BACKGROUND: Management of insulin administration for intake of carbohydrates and physical activity can be burdensome for people with type 1 diabetes on hybrid closed-loop systems. Bihormonal fully closed-loop (FCL) systems could help reduce this burden. In this trial, we assessed the long-term performance and safety of a bihormonal FCL system. METHODS: The FCL system (Inreda AP; Inreda Diabetic, Goor, Netherlands) that uses two hormones (insulin and glucagon) was assessed in a 1 year, multicentre, prospective, single-arm intervention trial in adults with type 1 diabetes. Participants were recruited in eight outpatient clinics in the Netherlands. We included adults with type 1 diabetes aged 18-75 years who had been using flash glucose monitoring or continuous glucose monitors for at least 3 months. Study visits were integrated into standard care, usually every three months, to evaluate glycaemic control, adverse events, and person-reported outcomes. The primary endpoint was time in range (TIR; glucose concentration 3·9-10·0 mmol/L) after 1 year. The study is registered in the Dutch Trial Register, NL9578. FINDINGS: Between June 1, 2021, and March 2, 2022, we screened 90 individuals and enrolled 82 participants; 78 were included in the analyses. 79 started the intervention and 71 were included in the 12 month analysis. Mean age was 47.7 (SD 12·4) years and 38 (49%) were female participants. The mean preintervention TIR of participants was 55·5% (SD 17·2). After 1 year of FCL treatment, mean TIR was 80·3% (SD 5·4) and median time below range was 1·36% (IQR 0·80-2·11). Questionnaire scores improved on Problem Areas in Diabetes (PAID) from 30·0 (IQR 18·8-41·3) preintervention to 10·0 (IQR 3·8-21·3; p<0·0001) at 12 months and on World Health Organization-Five Well-Being Index (WHO-5) from 60·0 (IQR 44·0-72·0) preintervention to 76·0 (IQR 60·0-80·0; p<0·0001) at 12 months. Five serious adverse events were reported (one cerebellar stroke, two severe hypoglycaemic, and two hyperglycaemic events). INTERPRETATION: Real-world data obtained in this trial demonstrate that use of the bihormonal FCL system was associated with good glycaemic control in patients who completed 1 year of treatment, and could help relieve these individuals with type 1 diabetes from making treatment decisions and the burden of carbohydrate counting. FUNDING: Inreda Diabetic.

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome.

The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

[Quality of life and oral health in children]. / Levenskwaliteit en mondgezondheid van kinderen.

In recent years, research on the influence of oral health on quality of life among children has become increasingly popular Half of the children and adolescents will have had moments of diminished oral health and that can lead to functional problems, pain and decreased quality of life. While measuring oral health-related quality of life of children, reports of parents are frequently used as a proxy. Diminished oral health not only has an impact on the child's quality of life, but also on that of his family members. Results from studies on oral health-related quality of life in children may be used as the basis for useful guidance for parents and children on improving oral health and quality of life.

Interpersonal differences in the friction response of skin relate to FTIR measures for skin lipids and hydration.

Understanding the mechanical response of skin to contact is of importance when developing products that interact with the skin. The shear forces that arise due to friction in the interface are a key aspect of skin interactions, because shear is known to contribute to discomfort and tissue injury. However, the frictional response of skin shows large variations between people. It has been hypothesised that these variations relate to differences between people in the physiological properties of their skin, but the underlying mechanisms are not well understood. In order to gain new insights into these interpersonal differences in friction behaviour, in vivo FTIR measurements and in vivo friction measurements were performed on the same patch of skin. Quantitative analysis of the various peaks in the FTIR spectra provided information on the moisture content of the stratum corneum and the amount and mechanical properties of the lipids on the skin. The lipid viscosity, as characterised by the width of the 2920 cm-1 peak, correlates with the friction, whilst, interestingly, no relationship was found between the quantity of lipids on the skin surface and the coefficient of friction. Additionally, and as expected, a fairly strong correlation was obtained between the moisture content, as characterised by the height of the Amide I peak and the coefficient of friction. The presented results show that spectroscopy techniques can be used in as a non-invasive method to identify people who may show elevated levels of friction and thus are at increased risk of developing shear induced tissue injury.

[A patient with a prolonged untreated psychosis]. / Een patiënt met een langdurig onbehandelde psychose.

A 30-year-old male was treated with antipsychotic medication because he had developed psychotic symptoms associated with schizophrenia. It became apparent that the symptoms had been present for many years, but, unfortunately, remained untreated. In the literature there is some evidence of a link between an untreated psychosis of long duration and a poor prognosis. Several early intervention programmes are based on this link. In this case report we illustrate that treatment of a psychosis that has lasted for many years can yield amazingly rapid results.

Friction in the contact between skin and a soft counter material: Effects of hardness and surface finish.

The interaction behaviour of skin with a counter surface depends strongly on the surface roughness of the counter surface. For relatively hard surfaces this effect is described in various literature, but for soft, or compliant, materials this is much less studied. Inside the contact, the protuberances on the surface will deform substantially. In order to gain insights into the effect of surface roughness and hardness on the frictional behaviour between skin and a soft counter surface a range of experiments were performed using artificial skin and various silicone compounds which are commonly used in medical devices that interact with the human skin. Using these results, a 'friction map' was created that shows the friction behaviour as a function of the elastic modulus and the surface roughness. When the surface roughness is increased the friction coefficient decreases due to the reduction in the real area of contact, which weakens the adhesion between the two surfaces. A minimum coefficient of friction was observed at a surface roughness of approximately 4 µm. For the softest compounds tested there was minimal effect of surface roughness on friction because the roughness protuberances inside the contact will be flattened. Silicone compounds with increased hardness showed a larger sensitivity of the friction to the surface roughness, because these harder surface roughness protuberances are more resistant against deformation. The friction map provides a tool when designing products that require certain frictional properties: for products that are required to adhere to skin a smooth and soft material is recommended, whereas for products that require a low coefficient of friction a harder compound with a surface roughness of approximately 4 µm is recommended.

[Is there any point in detecting high risk factors prior to a first psychosis?]. / Wanneer heeft detectie van hoogrisicofactoren voor een eerste psychose zin?

BACKGROUND: If schizophrenia and related disorders are diagnosed and treated early, symptoms will be less severe and the prognosis will be more favourable. There is little point in screening for schizophrenia in the general population because the illness has such a low incidence. However, we do need to find out whether it is meaningful to screen genetically impaired individuals (high risk group) and specific groups of psychiatric patients (ultra high risk group). AIM: To survey the research into the (high and ultra high) risk factors for developing a first psychosis and to find out whether it makes good sense to screen certain groups of persons. METHOD: We conducted extensive desk-research and a wide-ranging search of the literature from 1990 to 2004. The key words we used in our search were 'prodrome', 'high risk', 'ultra high risk', in conjunction with 'psychosis' and 'schizophrenia'. RESULTS: In the genetically impaired group risk factors for developing schizophrenia seem to be transient psychiatric problems in childhood, schizotypical traits, anxiety, behavioural problems in adolescence, being brought up in an unstable environment and producing deviant results in neurocognitive tests. Among the patients referred to a psychiatrist it is possible to identify a special group of patients with an ultra high risk of developing a psychosis. Within ayear 40% of patients who had mild or short-term psychotic symptoms or who were genetically impaired adolescents with decreased functioning had developed a psychosis. CONCLUSION: Screening all genetically vulnerable persons in the general population has no consequencesfor treatment. Early diagnosis by psychiatrists is certainly advisable. However, larger groups and longer studies are needed in order to demonstrate conclusively the preventive effect of interventions prior to a first psychosis.

Avian influenza in Australia: a summary of 5 years of wild bird surveillance.

BACKGROUND: Avian influenza viruses (AIVs) are found worldwide in numerous bird species, causing significant disease in gallinaceous poultry and occasionally other species. Surveillance of wild bird reservoirs provides an opportunity to add to the understanding of the epidemiology of AIVs. METHODS: This study examined key findings from the National Avian Influenza Wild Bird Surveillance Program over a 5-year period (July 2007-June 2012), the main source of information on AIVs circulating in Australia. RESULTS: The overall proportion of birds that tested positive for influenza A via PCR was 1.9 ± 0.1%, with evidence of widespread exposure of Australian wild birds to most low pathogenic avian influenza (LPAI) subtypes (H1-13, H16). LPAI H5 subtypes were found to be dominant and widespread during this 5-year period. CONCLUSION: Given Australia's isolation, both geographically and ecologically, it is important for Australia not to assume that the epidemiology of AIV from other geographic regions applies here. Despite all previous highly pathogenic avian influenza outbreaks in Australian poultry being attributed to H7 subtypes, widespread detection of H5 subtypes in wild birds may represent an ongoing risk to the Australian poultry industry.

Control of an epidemic spread of a multi-resistant strain of Acinetobacter calcoaceticus in a hospital.

The spread of a multi-resistant glucose-acidifying Acinetobacter calcoaceticus strain in a community hospital was studied. After admission of a colonized patient to the hospital the strain was found in clinical specimens from ICU patients and subsequently from several of these patients after transfer to medical wards. Environmental specimens from the ICU and medical wards were analysed in order to investigate the mode of spread of the strain. Isolates of A. calcoaceticus were screened by their antibiotic resistance pattern. In addition, the cell envelope protein electrophoretic profiles were used as epidemiological markers. The multi-resistant acinetobacters all had the same protein profile. To prevent spread of the epidemic strain strict hygienic measures were enforced, e.g. scrupulous cleaning of the room after discharge of any colonized patient and increased attention to the hand hygiene of the medical and nursing staff. Furthermore, the use of antibiotics was restricted. Although this strain was only eradicated with difficulty in the affected patients, it did not spread throughout the hospital. Colonization of patients with the multi-resistant micro-organism was predominantly localized to the ICU.

Metabolic constraints on long-distance migration in birds

The flight range of migrating birds depends crucially on the amount of fuel stored by the bird prior to migration or taken up en route at stop-over sites. However, an increase in body mass is associated with an increase in energetic costs, counteracting the benefit of fuel stores. Water imbalance, occurring when water loss exceeds metabolic water production, may constitute another less well recognised problem limiting flight range. The main route of water loss during flight is via the lungs; the rate of loss depends on ambient temperature, relative humidity and ventilatory flow and increases with altitude. Metabolite production results in an increased plasma osmolality, also endangering the proper functioning of the organism during flight. Energetic constraints and water-balance problems may interact in determining several aspects of flight behaviour, such as altitude of flight, mode of flight, lap distance and stop-over duration. To circumvent energetic and water-balance problems, a bird could migrate in short hops instead of long leaps if crossing of large ecological barriers can be avoided. However, although necessitating larger fuel stores and being more expensive, migration by long leaps may sometimes be faster than by short hops. Time constraints are also an important factor in explaining why soaring, which conserves energy and water, occurs exclusively in very large species: small birds can soar at low speeds only. Good navigational skills involving accurate orientation and assessment of altitude and air and ground speed assist in avoiding physiological stress during migration.

Wingbeat frequency and the body drag anomaly: wind-tunnel observations on a thrush nightingale (Luscinia luscinia) and a teal (Anas crecca)

A teal (Anas crecca) and a thrush nightingale (Luscinia luscinia) were trained to fly in the Lund wind tunnel for periods of up to 3 and 16 h respectively. Both birds flew in steady flapping flight, with such regularity that their wingbeat frequencies could be determined by viewing them through a shutter stroboscope. When flying at a constant air speed, the teal's wingbeat frequency varied with the 0.364 power of the body mass and the thrush nightingale's varied with the 0.430 power. Both exponents differed from zero, but neither differed from the predicted value (0.5) at the 1 % level of significance. The teal continued to flap steadily as the tunnel tilt angle was varied from -1 ° (climb) to +6 ° (descent), while the wingbeat frequency declined progressively by about 11 %. In both birds, the plot of wingbeat frequency against air speed in level flight was U-shaped, with small but statistically significant curvature. We identified the minima of these curves with the minimum power speed (Vmp) and found that the values predicted for Vmp, using previously published default values for the required variables, were only about two-thirds of the observed minimum-frequency speeds. The discrepancy could be resolved if the body drag coefficients (CDb) of both birds were near 0.08, rather than near 0.40 as previously assumed. The previously published high values for body drag coefficients were derived from wind-tunnel measurements on frozen bird bodies, from which the wings had been removed, and had long been regarded as anomalous, as values below 0.01 are given in the engineering literature for streamlined bodies. We suggest that birds of any size that have well-streamlined bodies can achieve minimum body drag coefficients of around 0.05 if the feet can be fully retracted under the flank feathers. In such birds, field observations of flight speeds may need to be reinterpreted in the light of higher estimates of Vmp. Estimates of the effective lift:drag ratio and range can also be revised upwards. Birds that have large feet or trailing legs may have higher body drag coefficients. The original estimates of around CDb=0.4 could be correct for species, such as pelicans and large herons, that also have prominent heads. We see no evidence for any progressive reduction of body drag coefficient in the Reynolds number range covered by our experiments, that is 21 600­215 000 on the basis of body cross-sectional diameter.

Heterotopic ossification after severe burns: a report of three cases and review of the literature.

Heterotopic ossification (HO) is a rare complication of head and spinal injuries, polio, orthopaedic surgery and burns. Three patients are reported, who developed severe HO following major, life-threatening burn injury. The aetiology, diagnosis and treatment of this condition are discussed. Particular attention is given to measures which may help reduce morbidity.

Predicting dental anxiety. The clinical value of anxiety questionnaires: an explorative study.

AIM: This was to explore the usefulness of the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS) and the Child Behaviour Checklist (CBCL), used prior to treatment, in relation to the actual behaviour displayed during treatment. METHODS: The study group was 26 children, referred to a special dental care clinic for behaviour management problems, mostly caused by dental fear. Questionnaires used were the parent versions of the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS) and the Child Behaviour Checklist (CBCL). Behaviour was registered on videotape and scored by independent observers using the modified Venham scale. Treatment consisted of a familiarization visit and two restorative sessions. RESULTS: There was a significant reduction in fear, based on pre and post treatment CFSS-DS scores, and also the child's fearful behaviour during the two restorative sessions appeared to be related. But no correlation was found between the CFSS-DS and the CBCL, nor between the CFSS-DS and the behaviour displayed during the treatment sessions. CONCLUSION: The child's anxious behaviour during actual restorative dental treatment is not so much related to its own anticipatory dental anxiety or the anxiety of the mother. Results support the role of a multifactorial model.

Referring children to a Special Dental Care Centre in the Netherlands: parents' experiences and expectations.

AIM: The aim of the present study was to assess the relation between treatment at the family dentist versus referral and different aspects of treatment at a Special Dental Care Centre (SDCC), including the choice to return to their family dentist or not. The same study was performed for a group of patients recently referred to and still treated at a Special Dental Care Centre ( SDCC). METHODS: A questionnaire was sent to the parents of 852 children for whom complete dental records were available. Treatment was completed for 111 children (study 1) and 170 children were recently referred and had just started treatment (study 2). RESULTS/STATISTIC: In total 281 questionnaires were returned and filled out. Parents of children who returned to their general dental practitioner (GDP) were more satisfied with their GDP treatment than parents of children who did not return to their GDP (study 1: Z=- 3.65, p<0.001; study 2: Z=-2.86, p=0.004). CONCLUSION: The decision to return to the family dentist or not after treatment at a SDCC centre was based on their satisfaction with their treatment.