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Objectives: Long-term care facilities (LTCFs) have been disproportionately impacted by COVID-19. Yet, the reasons why certain LTCFs are affected more by outbreaks are poorly understood. This study aimed to identify the facility-and ward-level factors associated with SARS-CoV-2 outbreaks among LTCF residents. Methods: We conducted a retrospective cohort study of multiple Dutch LTCFs (N = 60; with 298 wards providing care for similar to 5600 residents) from September 2020 to June 2021. A dataset was constructed linking SARS-CoV-2 cases among LTCF residents to facility-and ward-level factors. Multilevel logistic regression analyses examined the associations between these factors and the likelihood of a SARS-CoV-2 outbreak among residents.Results: During periods of the Classic variant, the mechanical recirculation of air was associated with significantly increased odds of a SARS-CoV-2 outbreak. During periods of the Alpha variant, the factors associated with significantly increased odds included large ward size ( >= 21 beds), wards providing psy-chogeriatric care, fewer restrictions on staff movement between wards and facilities, and a greater num-ber of cases among staff ( > 10 cases).Conclusion: Policy and protocols on reducing resident density, staff movement, and mechanical recircu-lation of air in buildings are recommended to enhance outbreak preparedness in LTCFs. The implemen- tation of low-threshold preventive measures among psychogeriatric residents is important because they appear as a particularly vulnerable group.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Aims/hypothesis Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex. Methods In a population-based cohort study (n=7639; age 40–75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRI-derived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status. Results Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W–M] mean difference [95% CI]: 15.0 cm2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W–M mean difference [95% CI]: −14.8 cm2 [−26.4, −3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men. Conclusions/interpretation This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study. Graphical abstract

Introduction Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle-aged individuals. Methods A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors. Results More atrophic and vascular brain damage was associated with worse cognition scores. Increasing connectivity moderated the negative association between damage and cognition (chi(2) = 8.64, df = 3, p

BACKGROUND: The efficacy of an indicated prevention strategy for long-term absence due to sickness has been demonstrated and is implemented in multinational companies. Such a strategy may also be beneficial for small and medium-sized enterprises (SMEs). However, due to the different contexts, adaption, and implementation of this strategy in SMEs may be quite different.OBJECTIVE: This study aims to investigate the opportunities, barriers, and facilitators for adoption and implementation of this preventive strategy, as anticipated by employers and employees of SMEs.METHODS: A qualitative needs assessment was conducted using semi-structured interviews with higher managers (n = 15) and a focus group with employees (n = 8). Purposive sampling was used, and data were analyzed using content analysis.RESULTS: Employers had positive expectations concerning the gains of the preventive strategy, whereas employees had more reservations. Anticipated gains and intentions to implement the preventive strategy were rooted in underlying conceptions of the causes of sickness absence and the responsibilities of stakeholders. One key barrier shared across employers and employees concerned the potential lack of confidentiality. For employees, the role of the occupational health professional in the prevention of sickness absence was perceived as uncommon. Employers stressed lack of capacity and resources as a barrier, whereas employees stressed lack of follow-up by the employer as a barrier.CONCLUSIONS: SMEs are considerably receptive to the implementation of an indicated prevention strategy for long-term absence. Insight into the barriers and facilitators gives clues for wider and optimal implementation across a wider range of organizational settings.

Objectives Antimicrobial resistance poses a major public health threat. Despite Indian retail sector antibiotic consumption per capita increasing by approximately 22% between 2008 and 2016, empirical studies that examine policy or behavioural interventions addressing antibiotic misuse in primary healthcare are scarce. Our study aimed to assess perceptions of interventions and gaps in policy and practice with respect to outpatient antibiotic misuse in India. Methods We conducted 23 semi-structured, in-depth interviews with a variety of key informants with diverse backgrounds in academia, non-government organisations, policy, advocacy, pharmacy, medicine and others. Data were charted into a framework matrix and analysed using a hybrid, inductive and deductive thematic analysis. Themes were analysed and organised according to the socio-ecological model at various levels ranging from the individual to the enabling environment. Results Key informants largely focused on the importance of adopting a structural perspective to addressing socio-ecological drivers of antibiotic misuse. There was a recognition that educational interventions targeting individual or interpersonal interactions were largely ineffective, and policy interventions should incorporate behavioural nudge interventions, improve the healthcare infrastructure and embrace task shifting to rectify staffing disparities in rural areas. Conclusions Prescription behaviour is perceived to be governed by structural issues of access and limitations in public health infrastructure that create an enabling environment for antibiotic overuse. Interventions should move beyond a clinical and individual focus on behaviour change with respect to antimicrobial resistance and aim for structural alignment between existing disease specific programs and between the informal and formal sector of healthcare delivery in India.

Objective: To determine the association between early post-endovascular treatment (EVT) contrast extravasation (CE) on dual-energy CT (DECT) and stroke outcomes. Methods: EVT records in 2010–2019 were screened. Exclusion criteria included the occurrence of immediate post-procedural intracranial haemorrhage (ICH). Hyperdense areas on iodine overlay maps were scored according to the Alberta Stroke Programme Early CT Score (ASPECTS), thus forming a CE-ASPECTS. Maximum parenchymal iodine concentration and maximum iodine concentration relative to the torcula were recorded. Follow-up imaging was reviewed for ICH. The primary outcome measure was the modified Rankin Scale (mRS) at 90 days. Results: Out of 651 records, 402 patients were included. CE was found in 318 patients (79%). Thirty-five patients developed ICH on follow-up imaging. Fourteen ICHs were symptomatic. Stroke progression occurred in 59 patients. Multivariable regression showed a significant association between decreasing CE-ASPECTS and the mRS at 90 days (adjusted (a)cOR: 1.10, 95% CI: 1.03–1.18), NIHSS at 24–48 h (aβ: 0.57, 95% CI: 0.29–0.84), stroke progression (aOR: 1.14, 95% CI: 1.03–1.26) and ICH (aOR: 1.21, 95% CI: 1.06–1.39), but not symptomatic ICH (aOR 1.19, 95% CI: 0.95–1.38). Iodine concentration was significantly associated with the mRS (acOR: 1.18, 95% CI: 1.06–1.32), NIHSS (aβ: 0.68, 95% CI: 0.30–1.06), ICH (aOR: 1.37, 95% CI: 1.04–1.81) and symptomatic ICH (aOR: 1.19, 95% CI: 1.02–1.38), but not stroke progression (aOR: 0.99, 95% CI: 0.86–1.15). Results of the analyses with relative iodine concentration were similar and did not improve prediction. Conclusions: CE-ASPECTS and iodine concentration are both associated with short- and long-term stroke outcomes. CE-ASPECTS is likely a better predictor for stroke progression.

IntroductionThe study of crisis events provides important lessons to prepare for upcoming events. The Great Recession’s impact on perinatal health in Europe can provide relevant insights into the healthcare and social protection systems’ response to the protection of the health of the most vulnerable groups.ObjectiveTo assess time trends and international disparities in perinatal mortality rates (PMR) and infant mortality rates (IMR), following the Great Recession, and their association with socioeconomic indicators in Portugal, Greece, Italy and Spain.MethodsAssociations were assessed through generalised linear models for all four countries. A Poisson joinpoint regression model was applied to explore PMR and IMR trend changes between 2000 and 2018. Country disparities were analysed using mixed-effects multilevel models.ResultsIMR and PMR have decreased overall in the four selected countries between 2000 and 2018. Still, whereas in Spain, Italy and Portugal the decreasing pace was attenuated after 2009, in Greece a positive trend was found after the 2008 crisis. IMR and PMR were significantly associated with socioeconomic indicators in all four countries. National disparities in the evolution of IMR and PMR were significantly associated with most socioeconomic indicators between 2000 and 2018.ConclusionOur results confirm the impact of the Great Recession on PMR and IMR trends in all four countries, taking recurring associations between macroeconomic cycles, variations in mortality trends, macroeconomic volatility and stagnation of IMR and PMR into account. The association with socioeconomic indicators stresses the need to strengthen social protection and healthcare systems to better protect the population’s health from the earliest days.

In this paper I use normative analysis to explore the curious and seemingly singular phenomenon whereby some dog owners deny the physical and moral facts about a situation where it is claimed their dog harmed or irritated others. I define these as epistemic and ethical denial, respectively, and offer a tentative exploration of their implications in terms of relational autonomy and responsible behaviour in public spaces.

BackgroundMycoplasma genitalium (MG) is associated with urethritis in men and weakly associated with pelvic inflammatory disease in women. Mycoplasma genitalium coinfections with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are commonly reported; however, little is known about their interaction. One study suggested that MG/NG coinfections might increase the bacterial load of NG, which has been shown to have a higher transmission potential. As even less is known about the impact of a simultaneous MG/CT infection, we assessed whether patients with urogenital MG/CT coinfections have a higher bacterial load than patients with a single infection.MethodsThere were 1673 urogenital samples from patients from a population-based chlamydia study, and our sexually transmitted infection clinic tested for both CT and MG. When positive, the load was quantified. Nonparametric tests compared the CT and MG load, and linear regression analyses tested the association of the CT and MG load within a patient.ResultsIn 60 MG-positive patients, MG load ranged from 1.7 to 6.0 log10 copies/ml, similar to the CT load distribution. Only 6 patients were MG-positive and CT-negative, but the MG load distribution was similar to that of CT-positive patients (n.s.). The MG and CT load was unrelated in coinfected persons (n.s.).ConclusionsWe found no correlation between the CT and MG load in urogenital samples, and the MG load distribution was similar in CT-positive and CT-negative patients. These results could have implications for the transmission risk of these infections.

Background Social networks, i.e., all social relationships that people have, contribute to well-being and health. Governmental measures against COVID-19 were explicitly aimed to decrease physical social contact. We evaluated ego-centric social network structure and function, and changes therein, among various sociodemographic subgroups before and during the COVID-19 pandemic. Methods Independently living Dutch adults aged 40 years and older participating in the SaNAE longitudinal cohort study filled in online questionnaires in 2019 and 2020. Changes in network size (network structure) and social supporters (network function) were assessed. Associations with risk for changes (versus stable) were assessed for sociodemographic subgroups (sex, age, educational level, and urbanization level) using multivariable regression analyses, adjusted for confounders. Results Of 3,344 respondents 55% were men with a mean age of 65 years (age range 41–95 in 2020). In all assessed sociodemographic subgroups, decreases were observed in mean network size (total population: 11.4 to 9.8), the number of emotional supporters (7.2 to 6.1), and practical supporters (2.2 to 1.8), and an increase in the number of informational supporters (4.1 to 4.7). In all subgroups, the networks changed to being more family oriented. Some individuals increased their network size or number of supporters; they were more often women, higher-educated, or living in rural areas. Conclusion The COVID-19 pandemic impacted social networks of people aged 40 years and older, as they increased informational support and reduced the number of their social relationships, mainly in terms of emotional and practical supporters. Notably, some individuals did not show such unfavorable trends and managed to reorganize their networks to attribute social support roles more centrally.

This study aims to compare the accelerometer-measured daily patterns of PA and sedentary behaviour among participants with and without prevalent/incident depressive symptoms. We used data from 5,582 individuals in The Maastricht Study (59.9 ± 8.6 years, 50.3% women). Daily patterns of sedentary time, light-intensity physical activity (LiPA), moderate-to-vigorous physical activity (MVPA), and sit-to-stand transitions were objectively measured at baseline with the activPAL3 activity monitor. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire, both at baseline and annually (median follow-up: 5.1 years). General linear models were used to compare patterns of physical activity and sedentary behaviour between those with and without prevalent/incident depressive symptoms. Participants with prevalent depressive symptoms had significantly more sedentary time (18.6 min/day) and lower LiPA (26.8 min/day) and MVPA (4.8 min/day) than participants without depressive symptoms. Considering the daily patterns, participants with prevalent depressive symptoms had significantly more sedentary time early in the afternoon (12:00-18:00), early evening (18:00-21:00), and during the night (00:00-03:00), less time in LiPA in all periods between 09:00-21.00 and less MVPA in the morning (09:00:12:00), early afternoon (12:00-15:00), and evening (18:00-21:00), then those without. Similar differences in activity and sedentary behaviour patterns between those and without incident depressive symptoms were observed albeit the differences were smaller Overall, we did not find specific time slots particularly associated with both prevalent and incident depressive symptoms. These findings may indicate that less sedentary time and more intense PA can be important targets for the prevention of depression irrespective of the timing of the day.

UNLABELLED: Healthcare costs in the Netherlands are rising and vary considerably among regions. Explaining regional differences in healthcare costs can help policymakers in targeting appropriate interventions in order to restrain costs. Factors usually taken into account when analyzing regional differences in healthcare costs are demographic structure and socioeconomic status (SES). However, health, lifestyle, loneliness and mastery have also been linked to healthcare costs. Therefore, this study analyzes the contribution of health, lifestyle factors (BMI, alcohol consumption, smoking and physical activity), loneliness, and mastery to regional differences in healthcare costs. Analyses are performed in a linked dataset (n = 334,721) from the Dutch Public Health Services, Statistics Netherlands, the National Institute for Public Health and the Environment (year 2016), and the healthcare claims database Vektis (year 2017) with Poisson and zero-inflated binomial regressions. Regional differences in general practitioner consult costs remain significant even after taking into account health, lifestyle, loneliness, and mastery. Regional differences in costs for mental, pharmaceutical, and specialized care are less pronounced and can be explained to a large extent. For total healthcare costs, regional differences are mostly explained through the factors included in this study. Hence, addressing lifestyle factors, loneliness and mastery can help policymakers in restraining healthcare costs. In this study, the region of Zuid-Limburg represents the reference region. Use compare regions for health and healthcare costs (Regiovergelijker gezondheid en zorgkosten) in order to select all other Dutch regions as reference region.SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12508-022-00369-4) contains supplementary material, which is available to authorized users.

Background The prevalence of inflicted femur fractures in young children varies (1.5–35.2%), but these data are based on small retrospective studies with high heterogeneity. Age and mobility of the child seem to be indicators of inflicted trauma. Objective This study describes other factors associated with inflicted and neglectful trauma that can be used to distinguish inflicted and neglectful from accidental femur fractures. Materials and methods This retrospective study included children (0–6 years) who presented with an isolated femur fracture at 1 of the 11 level I trauma centers in the Netherlands between January 2010 and January 2016. Outcomes were classified based on the conclusions of the Child Abuse and Neglect teams or the court. Cases in which conclusions were unavailable and there was no clear accidental cause were reviewed by an expert panel. Results The study included 328 children; 295 (89.9%) cases were classified as accidental trauma. Inflicted trauma was found in 14 (4.3%), while 19 (5.8%) were cases of neglect. Indicators of inflicted trauma were age 0–5 months (29%, positive likelihood ratio [LR +] 8.35), 6–12 months (18%, LR + 5.98) and 18–23 months (14%, LR + 3.74). Indicators of neglect were age 6–11 months (18%, LR + 4.41) and age 18–23 months (8%, LR + 1.65). There was no difference in fracture morphology among groups. Conclusion It is unlikely that an isolated femur fracture in ambulatory children age > 24 months is caused by inflicted trauma/neglect. Caution is advised in children younger than 24 months because that age is the main factor associated with inflicted trauma/neglect and inflicted femur fractures.

Buyer's clubs were first recognised during the HIV/AIDS pandemic in the 1980s and focussed on knowledge curation and distribution of treatments. In the past decade, there has been a resurgence of buyer's clubs, mostly focussed on hepatitis C treatment and PrEP. This paper aims to increase understanding of buyer's clubs and stimulate discussion on their role in achieving equitable access to medicines. Our proposed definition of a buyer's club is 'a community-led organisation or group which seeks to improve an individual's access to medication through knowledge sharing and/or distribution as its primary goal'. The logistical and relational infrastructures of buyer's clubs have been mapped out. Networks and communities are integral to buyer's clubs by facilitating practical aspects of buyer's clubs and creating a sense of community that serves as a foundation of trust. For a user to receive necessary medical support, doctors play a crucial role, yet, obtaining this support is difficult. Whilst buyer's clubs are estimated to have enabled thousands of people to access medicines, and they run the risk of perpetuating health inequities and injustices. They may have the potential to serve as a health activism tool to stimulate sustainable changes; however, this needs to be explored further.

BackgroundAnorectal infections with Chlamydia trachomatis (CT) are common in women visiting STI outpatient clinics. We here evaluated the risk posed by sexual exposure and by alternate anatomical site infection for incident anorectal and urogenital CT.MethodsProspective multicentre cohort study, FemCure. Participants were treated for CT, and after 4, 6, 8, 10 and 12 weeks, they self-collected anorectal and urogenital samples (swabs) for CT-DNA testing. We calculated the proportion with incident CT, that is, CT incidence (at weeks 6–12) by 2-week time-periods. Compared with no exposure (A), we estimated the risk of incident CT for (B) sexual exposure, (C) alternate site anatomic site infection and (D) both, adjusted for confounders and expressed as adjusted ORs with 95% CIs.ResultsWe analysed data of 385 participants contributing 1540 2-week periods. The anorectal CT incidence was 2.9% (39/1343) (95 CI 1.8 to 3.6); 1.3% (A), 1.3% (B), 27.8% (C) and 36.7% (D). The ORs were: 0.91 (95% CI 0.32 to 2.60) (B), 26.0 (95% CI 7.16 to 94.34) (C), 44.26 (95% CI 14.38 to 136.21) (D).The urogenital CT incidence was 3.3% (47/1428) (95% CI 2.4 to 4.4); 0.7% (A), 1.9% (B), 13.9% (C) and 25.4% (D). The ORs were: 2.73 (95% CI 0.87 to 8.61) (B), 21.77 (95% CI 6.70 to 70 71) (C) and 49.66 (95% CI 15.37 to 160.41) (D).ConclusionsAfter initial treatment, an alternate anatomical site CT infection increased the risk for an incident CT in women, especially when also sex was reported. This may suggest a key role for autoinoculation in the re-establishment or persistence of urogenital and anorectal chlamydia infections.

Background: The human parainfluenza virus 3 (HPIV-3) outbreak at the haemato-oncology ward of the Maastricht University Medical Centre in the summer of 2016. Aim: To describe an effective strategy to control the largest reported HPIV-3 outbreak at an adult haematology–oncology ward in the Netherlands by implementing infection control measures and molecular epidemiology investigation. Methods: Clinical, patient and diagnostic data were both pro- and retrospectively collected. HPIV-3 real-time polymerase chain reaction (HPIV-3 RT-PCR) was validated using oropharyngeal rinse samples. Screening of all new and admitted patients was implemented to identify asymptomatic infection or prolonged shedding of HPIV-3 allowing cohort isolation. Findings: The HPIV-3 outbreak occurred between 9 July and 28 September 2016 and affected 53 patients. HPIV-3 RT-PCR on oropharyngeal rinse samples demonstrated an up to 10-fold higher sensitivity compared with pharyngeal swabs. Monitoring showed that at first positive PCR, 20 patients (38%) were asymptomatic (of which 11 remained asymptomatic) and the average duration of shedding was 14 days (range 1–58). Asymptomatic patients had lower viral load, shorter period of viral shedding (≤14 days) and were mostly immune-competent oncology patients. The outbreak was under control five weeks after implementation of screening of asymptomatic patients. Conclusion: Implementation of a sensitive screening method identified both symptomatic and asymptomatic patients which had lower viral loads and allowed early cohort isolation. This is especially important in a ward that combines patients with varying immune status, because both immunocompromised and immune-competent patients are likely to spread the HPIV-3 virus, either through prolonged shedding or through asymptomatic course of disease.

The outbreak of the COVID-19 crisis severely afflicted the Dutch long-term care sector. To protect vulnerable residents of nursing homes the government took several measures, of which the complete nationwide visitors' ban was the most restrictive. These measures had not only a large impact on residents but they also greatly impacted nursing home personnel. Based on a descriptive review and a few interviews, this paper discusses the measures taken in the Dutch long-term care sector and the challenges healthcare personnel encountered in terms of workload and well-being. It further explores the strategies that were implemented to support personnel to cope with these challenges.

Early in the pandemic, many long-term care (LTC) homes struggled to manage resources and care for vulnerable residents. Using an appreciative inquiry approach, we analyzed exemplar homes in Ontario that remained free of COVID-19 in wave one and interviewed executive directors, directors of care and staff. Findings demonstrate the importance of leadership styles; clear, consistent communication; focusing on staff and resident safety; using a team-based approach; and adapting staff roles to meet care needs. The exemplar homes showed what works in practice. The decisions and approaches that they implemented could be used to develop standards to improve LTC and strengthen the sector.

Purpose To design a model based on the three pillars of new institutional theory (NIT), that facilitates cross-country comparison of labor participation (LP) of people with chronic diseases. This model should support getting a comprehensive overview of factors representing country differences, understanding these differences and should support estimating cross-country transferability of policies and interventions in the context of Work Disability Prevention. Methods Based on NIT, a draft model was designed by means of (1) a literature review of empirical studies; (2) theoretical books and articles; (3) a focus group with six expert researchers. This draft model was (4) adapted in the context of academic education. Literature was searched on Web of Science and EBSCO host. Feedback on (use of) the model was received from the focus group, four different academic courses at 28 occasions and two international conferences. Results The cross-country comparison model for labor participation (CCC model for LP) of persons with chronic diseases is proposed consisting of five factors: (1) Legislation; (2) Norms & values in practice; (3) Culture; (4) Organization of WDP in practice; (5) Labor market characteristics. Within these factors and based on (in)direct empirical evidence, subfactors are distinguished. The feedback received led to renaming (sub) factors, improved visual representation and a tool for estimating transferability. Conclusions The CCC model for LP of persons with chronic diseases allows for a comprehensive understanding of country differences and cross-country transferability of policies and interventions. The CCC model can be used for other populations when population-specific subfactors are included.

Antibiotic exposure disturbs the developing infant gut microbiota. The capacity of the gut microbiota to recover from this disturbance (resilience) depends on the type of antibiotic. In this study, infant gut microbiota was exposed to a combination of amoxicillin and clavulanate (amoxicillin/clavulanate) in an in vitro colon model (TIM-2) with fecal-derived microbiota from 1-month-old (1-M; a mixed-taxa community type) as well as 3-month-old (3-M; Bifidobacterium dominated community type) breastfed infants. We investigated the effect of two common infant prebiotics, 2′-fucosyllactose (2’-FL) or galacto-oligosaccharides (GOS), on the resilience of infant gut microbiota to amoxicillin/clavulanate-induced changes in microbiota composition and activity. Amoxicillin/clavulanate treatment decreased alpha diversity and induced a temporary shift of microbiota to a community dominated by enterobacteria. Moreover, antibiotic treatment increased succinate and lactate in both 1- and 3-M colon models, while decreasing the production of short-chain (SCFA) and branched-chain fatty acids (BFCA). The prebiotic effect on the microbiota recovery depended on the fermenting capacity of antibiotic-exposed microbiota. In the 1-M colon model, the supplementation of 2’-FL supported the recovery of microbiota and restored the production of propionate and butyrate. In the 3-M colon model, GOS supplementation supported the recovery of microbiota and increased the production of acetate and butyrate.

The rise of antibiotic resistance poses a global problem. To avoid this, alternative therapeutic options should be explored, e.g. lytic bacteriophage therapy. Well-designed and described research on effectivity of oral bacte-riophage therapy is lacking, therefore the aim of this study was to determine whether the in vitro model of the colon (TIM-2) could be used to investigate the survival and efficacy of therapeutic bacteriophages. For this, an antibiotic-resistant (CmR) E. coli DH5 alpha(pGK11) was used in combination with a corresponding bacteriophage. For the survival study, the TIM-2 model was inoculated with the microbiota of healthy individuals and a standard feeding (SIEM) was fed over the course of the 72 h experiment. To test the bacteriophage, different interventions were carried out. Survival of bacteriophages and bacteria was followed by plating of the lumen samples at different time points 0, 2, 4, 8, 24, 48, and 72 h. In addition, the stability of the bacterial community was determined with the use of 16S rRNA sequencing. Results showed that the phage titers could be decreased by activity from the commensal microbiota. Levels of the phage host (here E.coli) were decreased in the in-terventions with the phage shot. Multiple shots did not seem to be more effective than a single shot. At the same time, the bacterial community was not disturbed and remained stable throughout the experiment, which is in stark contrast to treatment with antibiotics. Mechanistic studies such as this one are required to optimize efficacy of phage therapy.

Storm surge disasters (SSD) have caused severe damage to China's coastal areas, and they have become an essential influencing factor for the social and economic development of China. This study uses an input-output model to assess the storm surge economic losses in 11 coastal regions of China for the period of 2007-2016, and also explores its influencing factors. The results show that: (1) From 2007 to 2016, the southeastern coastal areas were the most severely impacted by SSD, the Total Economic Losses (TEL) reached 742.8 billion CNY. Among them, Guangdong, Fujian and Zhejiang Provinces suffered the worst economic losses, with 81.3% contribution to TEL; (2) The Indirect Economic Losses (IEL) from SSD accounted for a total percentage of 74%-96%, and the TEL have not decreased over the years; (3) SSD have seriously impacted the Chinese manufacturing industry, accounting for an average of 50% of the TEL per year; (4) Different regions had different sectoral distributions of IEL, while the manufacturing and service industries were still the most affected sectors; (5) The more frequent the occurrence of SSD, the greater the losses caused by SSD, with no such correlation observed for the intensity of SSD; (6) The aggregation of marine industries and populations can significantly increase the damage from SSD, while the development of science and technology can reduce the damage from SSD. Overall, this study evaluates China's SSD economic losses on a long-term scale, which is of great significance for future disaster prevention and mitigation.

Complex phenomena such as antimicrobial resistance (AMR) are often explained in biomedical sciences by using analogies and metaphors. Metaphors play a crucial role in the knowledge production processes, as well as in ensuring the continuity of scientific models of thought. Novel conceptual metaphors, such as 'AMR is an apocalypse' or 'antibiotics are weapons' are usually immediately recognised as metaphors. Therefore, they have been scrutinised for their role in producing militaristic and even discriminatory discourses towards specific antibiotic use practices or populations, such as migrants or residents of low-income countries. At the same time, other terms have been presented as literal and descriptive, thus escaping critical analysis. Terms such as 'bacterial reservoirs' and 'bacterial colonies' have been conventionalised in biomedical sciences. However, the historical links between these terms and the sources of comparisons (reservoir - a source of something; and colony - a settlement in a foreign territory) are still present in biomedical discourses. As such, these terms stimulate a style of thinking about bacteria as foreign actors coming from foreign lands and bodies. Critical engagement with conventionalised metaphors helps to trace the continuity in scientific thought processes that links the historical context from where these metaphors are coming from to the present material practices and methods of science-making, including funding distribution.

The lack of accountability is considered to be a major cause of the crisis in health care in India. Physicians as key stakeholders in the health care delivery system have traditionally been accountable for health concerns at the doctor-patient interface. Following social and organizational dynamics, the interpretations of accountability have broadened and shifted in the recent literature, expanding accountability to the community, national and global levels and to social domains. The objective of this study is to provide a comprehensive framework of accountability in medical practice that can be used as a vehicle for further contextualized research and policy input. Through literature review, this paper is presented in two parts. First, a description of accountability of a physician inclusive of the social domains is extracted by posing three pertinent questions: who is accountable? accountability to whom? and accountability for what? which addresses the roles, relationships with other stakeholders and domains of accountability. Second, a framework of accountability of a physician is designed and presented to illustrate the professional and social domains. This study revealed a shift from individual physician's accountability to collective accountability involving multiple stakeholders through complex recip-rocal and multi-layered mechanisms inclusive of the social dimensions. We propose a comprehensive framework of accountability of the physician to include the social domains that its multidimensional and integrative of all stakeholders. Furthermore, we discuss the utility of the framework in the Indian health care system and how this can facilitate further research in understanding the social dimensions of all stakeholders.

Background This study aims to assess the uptake of maternal pertussis and COVID-19 vaccination and the intention towards accepting the maternal influenza vaccination. Insights into different socio-demographic factors related to maternal vaccination coverage might help to address vaccine acceptance and improve maternal vaccine uptake in the future. Methods We conducted a cross-sectional survey among pregnant women and recent mothers, up to 6 months post-partum. The primary outcome measures of this study were behaviour for maternal pertussis and COVID-19 vaccination, and maternal influenza vaccination intention. Associations between socio-demographic factors and maternal pertussis vaccination and maternal COVID-19 vaccination behaviour; and socio-demographic factors and maternal influenza vaccination intention were assessed using binary logistic regression analyses. Results In total 1361 respondents filled out the questionnaire. Almost all women (95%) were vaccinated against pertussis during pregnancy, while almost two-third were vaccinated against COVID-19 during pregnancy (58%) and almost one-third (28%) had a positive intention towards receiving the maternal influenza vaccination. Results show that young maternal age and low education level were associated with lower maternal vaccination acceptance. Conclusion Vaccination campaigns focusing on the severity of diseases that are prevented, are needed to increase maternal vaccine acceptance in younger and low-educated pregnant women. We expect that differences in vaccination coverage between the three maternal vaccinations might partly be explained by existing recommendations, campaigns and whether the vaccination is part of the national immunisation program.

Background Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD. Objective Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex. Design We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status. Results The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01]). The shape of the curve differed with sex (Pinteraction = 0.03), history of cardiovascular disease (Pinteraction interaction = 0.02). Conclusions The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions.

BACKGROUND:Dutch legislation encourages active participation of employees in their return-to-work (RTW) process. Empowering leadership may support employees’ self-direction in this process (i.e. by allowing and enabling their involvement in decision-making).OBJECTIVE:Building upon a previous study, we aimed to study (1) how representatives of a university, i.e. an employer for employees with high levels of education (EH), manage RTW, (2) the similarities and differences between the RTW management of employers (or representatives thereof) of employees with low (EL) and high levels of education, and (3) the degree to which the employers’ roles resemble empowering leadership.METHODS:Qualitative methodology was applied. A thematic analysis of interview transcripts (rq1) was followed by a comparison of themes (rq2) and pattern matching (rq3).RESULTS:(1) EH tend to engage in dialogue and accommodate their employees as much as possible. (2) EL and EH showed several similarities, such as aiming to meet legal requirements on RTW management. Compared to EL, EH tend to focus more on facilitating employees. (3) Empowering leadership seems to be more common among EH.CONCLUSIONS:Compared to employees with low levels of education, those with high levels of education may be granted more opportunity to self-direct their RTW. The study results provide starting points for employers for employees with both low and high levels of education who aim to enable employees’ self-direction in RTW, and help them to develop empowering leadership styles.

Background Ensuring patient rights is an extension of applying human rights principles to health care. A critical examination of how the notion of patient rights is perceived and enacted by various actors through critical discourse analysis (CDA) can help understand the impediments to its realization in practice. Methods We studied the discourses and discursive practices on patient rights in subnational policies and in ten health facilities in southern Karnataka, India. We conducted interviews (78), focus group discussions (3) with care-seeking individuals, care-providers, health care administrators and public health officials. We also conducted participant observation in selected health facilities and examined subnational policy documents of Karnataka pertaining to patient rights. We analyzed the qualitative data for major and minor themes. Results Patient rights discourses were not based upon human rights notions. In the context of neoliberalism, they were predominantly embedded within the logic of quality of care, economic, and consumerist perspectives. Relatively powerful actors such as care-providers and health facility administrators used a panoply of discursive strategies such as emphasizing alternate discourses and controlling discursive resources to suppress the promotion of patient rights among care-seeking individuals in health facilities. As a result, the capacity of care-seeking individuals to know and claim patient rights was restricted. With neoliberal health policies promoting austerity measures on public health care system and weak implementation of health care regulations, patient rights discourses remained subdued in health facilities in Karnataka, India. Conclusions The empirical findings on the local expression of patient rights in the discourses allowed for theoretical insights on the translation of conceptual understandings of patient rights to practice in the everyday lives of health system actors and care-seeking individuals. The CDA approach was helpful to identify the problematic aspects of discourses and discursive practices on patient rights where health facility administrators and care-providers wielded power to oppress care-seeking individuals. From the practical point of view, the study demonstrated the limitations of care-seeking individuals in the discursive realms to assert their agency as practitioners of (patient) rights in health facilities.

The human gut microbiome is an important reservoir of antimicrobial resistance genes (ARGs), collec-tively termed the 'resistome'. To date, few studies have examined the dynamics of the human gut resis-tome in healthy individuals. Previously, the authors observed high rates of ARG acquisition and significant abundance shifts during international travel. In order to provide insight into commonly occurring dynam-ics, this study investigated longitudinal fluctuations in prevalent ARGs (cfxA, tetM and ermB) in the resis-tomes of non-travelling healthy volunteers. In addition, this study assessed the prevalence of acquirable ARGs (blaCTX-M, qnrB, qnrS, vanA and vanB) over time. Faecal samples from 23 participants were collected at baseline and after 2 and 4 weeks. DNA was isolated, and ARG quantification was performed by quan-titative polymerase chain reaction adjusting for the total amount of bacterial 16S rDNA. vanA and qnrS were not detected in any of the samples, while the prevalence rates of vanB of non-enterococcal origin and qnrB were 73.9% and 5.7%, respectively. The ss-lactamase encoding blaCTX-M was detected in 17.4% of healthy participants. The results were compared with previous data from 122 travellers. ARG acquisitions observed in travellers were rare in non-travelling individuals during 4 weeks of follow-up, supporting the hypothesis of ARG acquisition during international travel. However, median -1.04-to 1.04-fold abun-dance changes were observed for 100% of cfxA, tetM and ermB, which did not differ from those found in travellers. Thus, common abundance shifts in prevalent ARGs of the gut resistome were found to occur independent of travel behaviour.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

This paper focuses on the recent interest in patient engagement (PE) in drug development, expressed in the growing number of calls for engagement, novel organizations dedicated to changing the culture of drug development, and guidelines for directing and evaluating PE. By reviewing materials produced by actors in the field and analyzing publications reporting on PE initiatives, I map sites of action where PE is being conceived and practiced, delineate how PE is being shaped, and analyze relationships emerging within and around the collectives involved. Pharmaceutical industry players actively mold the landscape of PE in drug development through creating tools and frameworks for PE. These instruments for guiding the implementation of PE are disseminated via training and dedicated events, concurrently disseminating a particular configuration of PE. PE emerges as an attempt to open new avenues for increasing productivity amidst concerns about the future of drug innovation, while PE practices fit smoothly into the arrangements for producing and distributing pharmaceutical knowledge largely shaped by the industry. The ongoing participatory turn in drug development is taking place without shifting the established concentration of epistemic power among commercial entities.

Context The timing of sleep, physical activity, and dietary intake show variation over the week, with different timings in the weekend compared to the weekdays, which may potentially lead to impaired glucose and lipid regulation on Mondays compared to other weekdays. Objective The aim of the study was to investigate differences in glucose metabolism and fasting triglyceride concentrations on Mondays compared to the rest of the week. Design, setting and participants This cross-sectional study is based on data from the Maastricht Study, including 6067 participants without known diabetes and 1568 previously diagnosed with type 2 diabetes. Main outcome measures Confounder-adjusted linear regression analysis was applied to study the associations of day of the week of examination with glucose and insulin responses to an oral glucose tolerance test and fasting triglyceride concentrations. Results In fully confounder-adjusted models, mean (95% CI) concentrations of fasting glucose, insulin, and triglycerides were slightly higher on Mondays compared with the other weekdays [glucose: 1% (0-2); insulin: 9% (1-18); triglycerides: 5% (2-8)]. Interaction analyses revealed that the association of weekday with insulin was only pronounced in men [18% (3-35)], but not in women [1% (−8-10)], whereas the associations with glucose and triglycerides were only apparent for individuals with known type 2 diabetes [glucose: 4% (0-7); triglycerides: 14% (6-23)] compared to the background population [glucose: 0% (0-1); triglycerides: 3% (0-6)]. Discussion Being examined on a Monday was associated with higher fasting insulin concentrations among men but not women.

Objectives: The detection of low levels of antibodies against HBsAg (anti-HBs) below 10 IU/L in non-responders after a primary hepatitis B vaccination, is associated with seroconversion after revaccination. We compared the diagnostic performance of four anti-HBs assays in non-responders in their ability to differentiate between absence or presence of low levels of anti-HBs and propose a revaccination strategy guided by anti-HBs titres. Methods: Non-responders were revaccinated with Fendrix 20 lg at 0, 1 and 2 months. Anti-HBs titres were determined by Abbott Architect, Diasorin Liaison, Roche Cobas and Siemens ADVIA Centaur. Inter-assay agreement was evaluated with Cohen's Kappa (k) in baseline samples between zero-responders without detectable antibodies and poor-responders with detectable antibodies < 10 IU/L. Seroconversion rates and geometric mean titres were analysed at 0, 1 and 3 months. A titre-based strategy (one revaccination dose and anti-HBs measurement followed by two more revaccination doses if required) was compared with the standard revaccination series of 3 doses. Results: 57 participants were included in the analysis. k was > 0.65 for all assays except ADVIA (k < 0.41). After one revaccination dose all assays detected a mean seroconversion rate in zero-responders of 42.9%, compared to 85.1% in poor-responders. The difference between zero-and poor-responders in seroconversion rate per assay was significant (p < 0.05). After three revaccination doses the mean seroconversion rate was 88.2% in zero-responders and 98.5% in poor-responders (p > 0.286 per assay). A titre-based strategy reduced the amount of revaccinations by 17% compared with the standard. Conclusions: All assays demonstrated a comparable difference in seroconversion rate between zero-and poor-responders after one revaccination dose. The revaccination strategy could be optimised by differentiation between zero-and poor-responders followed by a titre-guided schedule. (C) 2022 The Authors. Published by Elsevier Ltd.

BACKGROUND: Pharyngeal Chlamydia trachomatis in women might contribute to autoinoculation and transmission to sexual partners. Data for effectiveness of different testing practices for pharyngeal C trachomatis are scarce. We therefore aimed to assess the prevalence of pharyngeal C trachomatis, determinants, and effectiveness of different testing practices in women.METHODS: We did a retrospective cohort study, in which surveillance data for all women visiting sexually transmitted infection clinics in all regions in the Netherlands between Jan 1, 2008, and Dec 31, 2017, were used. We collected consultation-level data and individual-level data from 2016 onwards for sociodemographic characteristics, sexual behaviour in the past 6 months, self-reported symptoms, and STI diagnoses. The primary outcome was the positivity rate of pharyngeal C trachomatis infection compared between routine universal testing (>85% tested pharyngeally per clinic year), selective testing (5-85% tested pharyngeally per clinic year), and incidental testing (FINDINGS: Between Jan 1, 2008, and Dec 31, 2017, a total of 550 615 consultations with at least one C trachomatis test was recorded, of which 541 945 (98·4%) consultations (including repeat visits) were included in this analysis. Pharyngeal C trachomatis positivity was lower in the routine universal testing group than in the selective testing group (1081 [2·4%; 95% CI 2·2-2·5] of 45 774 vs 3473 [2·9%; 2·8-3·0] of 121 262; pINTERPRETATION: No optimal testing scenario was available for pharyngeal C trachomatis, in which only a selection of high-risk women needs to be tested to find most pharyngeal C trachomatis infections. The relative low prevalence of pharyngeal-only C trachomatis (0·5%) and probably limited clinical and public health effect do not provide support for routine universal testing.FUNDING: Public Health Service South Limburg.

Introduction: The presence of neuroglial tissue is considered a hallmark in limited dorsal myeloschisis (LDM). However, several reports have indicated that the presence of neuroglial tissue in LDM cannot always be demonstrated. Here, we present such a case of LDM and provide an alternative hypothesis for lacking the neuronal component. Case Description: An antenatal LDM suspected neonate was born with a cystic skin lesion and membranous sac typical for membranous LDM. Three days postpartum the otherwise healthy infant underwent surgery, during which the stalk was resected and the spinal cord was untethered. Histopathologically, no neuroglial tissue could be determined. Noteworthy, S-100 staining revealed numerous peripheral nerves. Discussion: The current paradigm explains the absence of neuroglial tissue in resected stalks of LDM by indicating that it should be present in the unresected part, more proximal to the dorsal spinal cord. We hypothesize a different mechanism in which following reopening of the neural tube, mesodermal invasion causes a tight and persistent strand between the cutaneous- and neuroectoderm. Elongation of this mesodermal strand during embryological development allows for the formation of a mesenchymal stalk without the presence of neuroglial tissue. Hydrodynamic forces can cause fistulation of the poorly differentiated mesodermal tissue and subsequently lead to a saccular defect.

AIMS: Heart failure (HF) represents a clinical syndrome resulting from different aetiologies and degrees of heart diseases. Among these, a key role is played by primary heart muscle disease (cardiomyopathies), which are the combination of multifactorial environmental insults in the presence or absence of a known genetic predisposition. The aim of the Maastricht Cardiomyopathy registry (mCMP-registry; NCT04976348) is to improve (early) diagnosis, risk stratification, and management of cardiomyopathy phenotypes beyond the limits of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: The mCMP-registry is an investigator-initiated prospective registry including patient characteristics, diagnostic measurements performed as part of routine clinical care, treatment information, sequential biobanking, quality of life and economic impact assessment, and regular follow-up. All subjects aged ≥16 years referred to the cardiology department of the Maastricht University Medical Center (MUMC+) for HF-like symptoms or cardiac screening for cardiomyopathies are eligible for inclusion, irrespective of phenotype or underlying causes. Informed consented subjects will be followed up for 15 years. Two central approaches will be used to answer the research questions related to the aims of this registry: (i) a data-driven approach to predict clinical outcome and response to therapy and to identify clusters of patients who share underlying pathophysiological processes; and (ii) a hypothesis-driven approach in which clinical parameters are tested for their (incremental) diagnostic, prognostic, or therapeutic value. The study allows other centres to easily join this initiative, which will further boost research within this field. CONCLUSIONS: The broad inclusion criteria, systematic routine clinical care data-collection, extensive study-related data-collection, sequential biobanking, and multi-disciplinary approach gives the mCMP-registry a unique opportunity to improve diagnosis, risk stratification, and management of HF and (early) cardiomyopathy phenotypes beyond the LVEF limits. ispartof: ESC HEART FAILURE vol:9 issue:2 pages:1463-1470 ispartof: location:England status: published

OBJECTIVES: Magnetic resonance imaging (MRI) is increasingly used in postmortem fetal imaging. Several factors influence the quality of MRI in this setting, such as small size, autolytic and maceration changes, and temperature. Knowing the fetal temperature at the time of scanning can improve the MRI interpretation. Temperature can be calculated using diffusion-weighted imaging with measurements of the apparent diffusion coefficient (ADC) in the cerebrospinal fluid (CSF). However, this is complicated by small ventricle size and hemorrhage and, therefore, may be unreliable in postmortem imaging. The current study evaluated the feasibility and reliability of using the ADC for temperature measurements of the vitreous body compared to that of CSF.MATERIALS AND METHODS: Two lambs were scanned postmortem at five different time points over 28 hours. Furthermore, 10 stillborn fetuses were scanned once, at 4 to 62 hours after birth. The temperature was measured with a digital thermometer and calculated using the ADCs of the vitreous body (lambs and fetuses) and CSF (fetuses).RESULTS: There was an excellent correlation between measured and calculated temperatures in vitreous bodies of lambs (r = 0.997, P CONCLUSION: The calculation of the temperature based on the ADC of the vitreous body is feasible and reliable for postmortem fetal imaging.

Ureaplasma species (spp.) are considered commensals of the adult genitourinary tract, but have been associated with chorioamnionitis, preterm birth, and invasive infections in neonates, including meningitis. Data on mechanisms involved in Ureaplasma-driven neuroinflammation are scarce. The present study addressed brain inflammatory responses in preterm lambs exposed to Ureaplasma parvum (UP) in utero. 7 days after intra-amniotic injection of UP (n = 10) or saline (n = 11), lambs were surgically delivered at gestational day 128–129. Expression of inflammatory markers was assessed in different brain regions using qRT-PCR and in cerebrospinal fluid (CSF) by multiplex immunoassay. CSF was analyzed for UP presence using ureB-based real-time PCR, and MRI scans documented cerebral white matter area and cortical folding. Cerebral tissue levels of atypical chemokine receptor (ACKR) 3, caspases 1-like, 2, 7, and C–X–C chemokine receptor (CXCR) 4 mRNA, as well as CSF interleukin-8 protein concentrations were significantly increased in UP-exposed lambs. UP presence in CSF was confirmed in one animal. Cortical folding and white matter area did not differ among groups. The present study confirms a role of caspases and the transmembrane receptors ACKR3 and CXCR4 in Ureaplasma-driven neuroinflammation. Enhanced caspase 1-like, 2, and 7 expression may reflect cell death. Increased ACKR3 and CXCR4 expression has been associated with inflammatory central nervous system (CNS) diseases and impaired blood–brain barrier function. According to these data and previous in vitro findings from our group, we speculate that Ureaplasma-induced caspase and receptor responses affect CNS barrier properties and thus facilitate neuroinflammation.

Copy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+ channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.

Background Individuals with intellectual and developmental disabilities (IDD) living in congregated settings have increased risk of COVID-19 infection and mortality. Little is known about variant B.1.1.519 with spike mutation T478K, dominant in Mexico. We describe a linked SARS-CoV-2 B.1.1.519 outbreak in three IDD facilities in the Netherlands. Methods Following notification of the index, subsequent cases were identified through serial PCR group testing. Positive specimens were submitted for whole-genome-sequencing. Clinical information was gathered through interviews with staff members of the three facilities. Results Attack rate (AR) in clients of the index facility was 92% (23/25), total AR in clients 45% (33/73) and in staff members 24% (8/34). 55% (18/33) of client cases were asymptomatic, versus 25% (2/8) of staff members. Five client cases (15%) were hospitalized, two died (6%). Sequencing yielded the same specific B.1.1.519 genotype in all three facilities. No significant difference in median viral load was established comparing the B.1.1.519 variant with other circulating variants. The index of the linked outbreak reported no travel history or link to suspected or confirmed cases suggesting regional surveillance. Observed peak regional prevalence of B.1.1.519 during the outbreak supports this. Conclusion AR, morbidity and mortality prior to control measures taking effect were high, probably related to the specific characteristics of the IDD setting and its clients. We assessed no evidence for intrinsic contributing properties of variant B.1.1.519. Our study argues for enhanced infection prevention protocols in the IDD setting, and prioritization of this group for vaccination against COVID-19.

SamenvattingNederland kent gezondheidsverschillen tussen regio’s. Het verklaren van deze verschillen kan beleidsmakers helpen om gericht te interveniëren en deze verschillen te verkleinen. Bij het verklaren van deze regionale gezondheidsverschillen wordt veelal gekeken naar de bijdrage van verschillen in demografische opbouw en sociaaleconomische status (SES). Tegelijkertijd worden leefstijl en psychosociale factoren ook in verband gebracht met de gezondheid van het individu. Daarom analyseert dit onderzoek, naast demografie en SES, de bijdrage van leefstijl, eenzaamheid en zelfregie aan de verklaring van regionale verschillen in zelfervaren gezondheid, aanwezigheid van chronische ziekten en het risico op het ontwikkelen van een angststoornis of depressie. We gebruiken daarvoor een gekoppelde dataset van de GGD, het CBS en het RIVM voor het jaar 2016 (n = 334.721). Uit de resultaten blijkt dat leefstijl, eenzaamheid en zelfregie ook bijdragen aan het verklaren van regionale verschillen in zelfervaren gezondheid (prevalentieratio’s (PR) variërend van 0,72–0,93 tot 0,83–0,95) en chronische ziekten (PR’s van 0,81–0,95 tot 0,85–0,96). Voor het risico op een angststoornis of depressie blijken vooral eenzaamheid en zelfregie bij te dragen aan de verklaring van regionale gezondheidsverschillen (oddsratio’s van 0,65–1,27 tot 0,76–1,22). Leefstijl- en psychosociale factoren kunnen dan ook beleidsmatige aanknopingspunten bieden voor de aanpak van regionale gezondheidsverschillen. In dit artikel is de regio Zuid-Limburg de referentieregio. Met de Regiovergelijker gezondheid en zorgkosten kunnen alle regio’s als referentieregio worden gekozen.

Background Within preventive Child Health Care (CHC), the 360°CHILD-profile has been developed. This digital tool visualises and theoretically orders holistic health data in line with the International Classification of Functioning, Disability and Health. It is anticipated that evaluating the effectiveness of the multifunctional 360°CHILD-profile within the preventive CHC-context is complex. Therefore, this study aimed at investigating the feasibility of RCT procedures and the applicability of potential outcome measures for assessing the accessibility and transfer of health information. Methods During the first introduction of the 360°CHILD-profile in CHC practice, a feasibility RCT with an explanatory-sequential mixed methods design was executed. CHC professionals (n=38) recruited parents (n=30) who visited the CHC for their child (age 0–16). Parents were randomised to “care as usual” (n=15) or “care as usual with, in addition, the availability of a personalised 360°CHILD-profile during 6 months” (n=15). Quantitative data on RCT feasibility were collected on recruitment, retention, response, compliance rates and outcome data on accessibility and transfer of health information (n=26). Subsequently, thirteen semi-structured interviews (5 parents, 8 CHC professionals) and a member check focus group (6 CHC professionals) were performed to further explore and gain a deeper understanding of quantitative findings. Results Integration of qualitative and quantitative data revealed that the recruitment of parents by CHC professionals was problematic and influenced by organisational factors. The used randomisation strategy, interventions and measurements were executable within the setting of this specific study. The outcome measures showed skewed outcome data in both groups and a low applicability to measure accessibility and transfer of health information. The study revealed points to reconsider regarding the randomisation and recruitment strategy and measures in the next steps. Conclusions This mixed methods feasibility study enabled us to gain a broad insight into the feasibility of executing an RCT within the CHC context. Trained research staff should recruit parents instead of CHC professionals. Measures, potentially for evaluating 360°CHILD-profile’s effectiveness, need further exploration and thorough piloting before proceeding with the evaluation process. Overall findings revealed that executing an RCT within the context of evaluating 360°CHILD-profile’s effectiveness in the CHC setting will be much more complex, time-consuming and costly than expected. Thereby, the CHC context requires a more complex randomisation strategy than executed during this feasibility study. Alternative designs including mixed methods research must be considered for the next phases of the downstream validation process. Trial registration NTR6909; https://trialsearch.who.int/.

The essay describes the adoption of an active ageing policy framework in Russia. Based on semi-structured interviews with elderly Russians, the essay provides evidence of confusion and uncertainty on how to perceive one's own ageing. Research participants understood that the 'paternalistic' view of old age as a time of troubles was now largely viewed as obsolete, yet the new 'optimistic' view of old age as a time of freedom and opportunities often did not reflect their experiences. This mismatch in discourses and practices reflects how participatory empowerment rhetoric, which promotes active ageing, is becoming a justification for more modest state social service provision.

Most studies of the microbiota in the human gut focus on the bacterial part, but increasing information shows that intestinal fungi are also important for maintaining health. This can be either by directly influencing the host or by indirectly influencing the gut bacteria that link to host health. Studies of fungal communities in large cohorts are scarce; therefore, this study aims at obtaining more insight into the mycobiome of healthy individuals and how this mycobiome interacts with the bacterial component of the microbiome. For this purpose, ITS2 and 16S rRNA gene amplicon sequencing was performed on fecal samples from 163 individuals which were available from two separate studies to analyze the fungal and bacterial microbiome, respectively, as well as the cross-kingdom interactions. The results showed a much lower fungal, as compared to bacterial, diversity. Ascomycota and Basidiomycota were the dominant fungal phyla across all the samples, but levels varied enormously between individuals. The ten most abundant fungal genera were Saccharomyces, Candida, Dipodascus, Aureobasidium, Penicillium, Hanseniaspora, Agaricus, Debaryomyces, Aspergillus, and Pichia, and here also extensive inter-individual variation was observed. Correlations were made between bacteria and fungi, and only positive correlations were observed. One of the correlations was between Malassezia restricta and the genus Bacteroides, which have both been previously described as alleviated in IBD. Most of the other correlations found were with fungi that are not known as gut colonizers but originate from food and the environment. To further investigate the importance of the observed correlations found, more research is needed to discriminate between gut colonizers and transient species.

Background Type 2 diabetes is associated with an increased risk of depression, but the extent to which risk factor modification can mitigate this risk is unclear. We aimed to examine the association between the incidence of major depression and clinically relevant depressive symptoms among individuals with type 2 diabetes, according to the number of risk factors within the recommended target range, compared with individuals without diabetes.Methods We did a prospective analysis of population-based data from the UK Biobank and the Maastricht Study. Individuals with type 2 diabetes were categorised according to the number of risk factors within the recommended target range (non-smoking, guideline-recommended levels of glycated haemoglobin (HbA1c), blood pressure, BMI, albuminuria, physical activity, and diet). The primary outcome, based on data from the UK Biobank, was the incidence of major depression ascertained from hospital records; the secondary outcome, based on data from the UK Biobank and the Maastricht Study, was clinically relevant depressive symptoms based on a score of 10 or higher on the Patient Health Questionnaire (PHQ-9).Findings The study population of the UK Biobank comprised 77 786 individuals (9047 with type 2 diabetes and 68 739 without diabetes; median age 59 years [IQR 51-64]; 34 136 [43middot9%] women and 43 650 [56middot1%] men). A median of 12middot7 years (IQR 11middot8-13middot4) after recruitment (between March 13, 2006, and Oct 1, 2010), 493 (5middot5%) of 9047 individuals with type 2 diabetes and 2574 (3middot7%) of 68 739 individuals without diabetes developed major depression. Compared with individuals without diabetes, those with type 2 diabetes had a higher risk of major depression (hazard ratio [HR] 1middot61 [95% CI 1middot49-1middot77]). Among individuals with type 2 diabetes, the excess risk of depression decreased stepwise with an increasing number of risk factors within the recommended target range (HR 2middot04 [95% CI 1middot65-2middot52] for up to two risk factors within the recommended target range; 1middot95 [1middot65-2middot30] for three risk factors within the recommended target range; 1middot38 [1middot16-1middot65] for four risk factors within the recommended target range; and 1middot34 [1middot12-1middot62] for five to seven risk factors within the recommended target range). In the UK Biobank dataset, a median of 7middot5 years (IQR 6middot8-8middot2) after the baseline examination, 147 (7middot5%) of 1953 individuals with type 2 diabetes and 954 (4middot5%) of 21 413 individuals without diabetes had developed clinically relevant depressive symptoms. The study population of the Maastricht Study comprised 4530 individuals (1158 with type 2 diabetes and 3372 without diabetes; median age 60 years [IQR 53-66]; 2244 [49middot5%] women and 2286 [50middot1%] men). A median of 5middot1 years (IQR 4middot1-6middot1) after recruitment (between Sept 1, 2010, and Dec 7, 2017), 170 (14middot7%) of 1158 individuals with type 2 diabetes and 227 (6middot7%) of 3372 individuals without diabetes developed clinically relevant depressive symptoms. Similarly, in both the UK Biobank dataset and the Maastricht Study cohort, among individuals with type 2 diabetes, the excess risk of clinically relevant depressive symptoms decreased stepwise with an increasing number of risk factors within the recommended target range.Interpretation Among individuals with type 2 diabetes, the excess risk of major depression and clinically relevant depressive symptoms decreased stepwise with an increasing number of risk factors within the recommended target range. This study provides further evidence to promote risk factor modification strategies in individuals with type 2 diabetes and to encourage the adoption of a healthy lifestyle.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

The tradition of intergenerational care and support exchanges in Indian families is assumed to be disturbed because of changes in family structure brought on by modern life, which is mainly based on studies investigating experiences of older adults regarding the impact of socio-economic change on their care arrangement. However, there is a large gap in understanding the experiences of adult children from a larger relational perspective, more than just care provision to their older relatives. Drawing on 26 in-depth interviews with adult children living in modern and traditional living arrangements from South India, the study explores their experiences with their parents with regard to reciprocity of care and support, the challenges they experience and strategies they adopt to overcome those challenges. The analysis shows adult children perceive the increased demands of modern work life and their older kin's preferences to be heard, lack of flexibility and related extra domestic work and costs, do cause a bigger burden for them in both living arrangements. However, adult children strive to uphold the traditional values of caring for their older kin and sharing emotional bonding with them. This inspiration helps them to employ strategies to accept their older relatives as they are, focus their attention on the benefits they receive from them and distribute care tasks with other relatives to overcome the challenges.

This thesis describes the results of the longitudinal Mixed Methods research project with the aim to develop and evaluate a new tool for visualizing and theoretically ordering personalized health information of a child’s health situation: the 360°CHILD-profile. Promising results were found on validity, reliability and usability of the 360°CHILD-profile for relevant stakeholders (parents, youth, professionals and policy-makers). On the other hand, the project revealed substantial (mostly organizational) barriers within the preventive Child Health Care with regard to the implementation and evaluation process. Findings provided insight in how to get ready for implementation and how to evaluate performance of the promising 360°CHILD-profile. The quick overview on holistic health data, this tool provides, is likely to be time saving and enables a comprehensible transfer of health information to parents and youth. Most importantly, the 360°CHILD-profile specifically is designed to intuitively guide thought processes in line with a more personalized and participative child health care.