Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic ...pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers. In human cohorts, NMDAR IgG and markers of barrier permeability were significantly associated with T. gondii exposure in schizophrenia compared with controls and independently of antipsychotic medication. Combined T. gondii and NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of cognitive impairment as measured by tests of delayed memory. These data underscore the necessity of disentangling the heterogeneous pathophysiology of schizophrenia so that relevant subsets eligible for NMDAR-related treatment can be identified. Our data aid to reconcile conflicting reports regarding a role of pathological NMDAR autoantibodies in this disorder.
Highlights • In schizophrenia, elevated Candida yeast antibody levels were lowered by probiotics. • Probiotics compared to placebo also relieved yeast-related bowel discomfort over time. • Candida ...albicans seropositivity was associated with worse psychiatric symptoms.
. Mouse mammary epithelial cell cultures previously described bring about extensive proliferation and a cell population with the appropriate markers for luminal ductal epithelial cells, and also the ...ability to form normal tissue after implantation into mice. This success may result from a culture environment that resembles certain aspects of the environment in the mammary gland. Mouse mammary epithelial cells, whose proliferation is limited when plated alone, can be stimulated to multiply by contact with lethally irradiated cells of the LA7 rat mammary tumour line. Most of the proliferative stimulus is imparted by direct cell contact between LA7 and mouse mammary cells. Junctions, including adherens junctions, form among all cells in the culture, much as junctions form in the mammary gland. LA7 cells secrete TGFα and bFGF, factors found in the mammary gland, and factors to which mouse mammary cells respond in culture. Mouse mammary cells express keratins 8 and 18, markers for luminal cells of the mammary duct. LA7 cells express keratin 14 and vimentin, markers for myoepithelial cells. These facts, taken together, fit a model of cell replacement in an epithelial tissue and also imitate the relationship between luminal ductal cells and myoepithelial cells in the mammary gland. This method of culturing cells is useful, not only for in vitro–in vivo carcinogenesis studies, but also for the study of mechanisms by which growth signals are imparted from one cell to another.
Objective
To identify the determinants of natural cause mortality in a cohort of individuals with serious mental illness assessed prospectively.
Method
Persons with schizophrenia (n = 789) and ...bipolar disorder (n = 498), mean age of 38 (s.d. 12.6) years, underwent an in‐person clinical assessment. They also had a blood sample drawn from which infectious disease markers were measured. Mortality was subsequently determined utilizing data from the National Death Index following a period of up to 16.9 years.
Results
A total of 6.8% (87 of 1287) of persons died of natural causes. Mortality was predicted in a multivariate model by baseline cigarette smoking (RR = 6.29, 95% CI 1.41, 3.72, P = 0.00076); divorced or widowed status (RR = 1.90, CI 1.21, 2.99); reduced cognitive score (RR = 0.73, CI 0.61, 0.87); receipt of antidepressant medication (RR = 1.74, CI 1.12, 2.71); elevated levels of antibodies to Epstein–Barr virus (EBV) (RR = 1.29, CI 1.01, 1.66); and a genitourinary (RR = 1.82, CI 1.16, 2.86), respiratory (RR = 1.82, CI 1.16, 2.86), or cardiac (RR = 2.09, CI 1.33, 3.29) condition. There was an additive effect of smoking and both a cardiac and a respiratory condition but not elevated EBV antibody levels.
Conclusion
Smoking is a modifiable behaviour which is associated with mortality in this population.
Recently adopted regulatory standards on infant and follow-on formula for the European Union stipulate that from February 2020 onwards, all such products marketed in the European Union must contain ...20–50 mg omega-3 DHA (22:6n–3) per 100 kcal, which is equivalent to about 0.5–1% of fatty acids (FAs) and thus higher than typically found in human milk and current infant formula products, without the need to also include ω-6 arachidonic acid (AA; 20:4n–6). This novel concept of infant formula composition has given rise to concern and controversy because there is no accountable evidence on its suitability and safety in healthy infants. Therefore, international experts in the field of infant nutrition were invited to review the state of scientific research on DHA and AA, and to discuss the questions arising from the new European regulatory standards. Based on the available information, we recommend that infant and follow-on formula should provide both DHA and AA. The DHA should equal at least the mean content in human milk globally (0.3% of FAs) but preferably reach 0.5% of FAs. Although optimal AA intake amounts remain to be defined, we strongly recommend that AA should be provided along with DHA. At amounts of DHA in infant formula up to ∼0.64%, AA contents should at least equal the DHA contents. Further well-designed clinical studies should evaluate the optimal intakes of DHA and AA in infants at different ages based on relevant outcomes.
Background: Health risks associated with the high consumption of sugar-sweetened beverages (SSBs) include overweight or obesity and their complications such as diabetes, as well as oral and dental ...decay, among others. Aim: The aim of the present statement is to inform health care professionals, parents, care-givers, teachers and school head teachers, stakeholders and governing bodies about the risks associated with drinking SSBs in infants, children and adolescents. Methods: We searched PubMed and the Cochrane databases for English language studies published from 2010 through October 1, 2018, for randomized clinical trials, meta-analyses, systematic reviews and observational studies (search terms are reported in eAppendix in the Supplement). We also manually searched the references of selected articles, reviews, meta-analyses and practice guidelines. Recommendations: Consumption of SSB by children and adolescents should be limited, and the consumption of water and other non-sweetened beverages should be promoted. Educational institutions such as nurseries, pre-schools and schools should offer unlimited access to drinking water, whereas the sale of SSBs should be banned.
This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was ...developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks’ gestation) and continue until approximately 37 weeks’ gestation or until childbirth if before 37 weeks’ gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners.
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Although it is known that differences in paediatric primary care (PPC) are found throughout Europe, little information exists as to where, how and who delivers this care. The aim of this study was to ...collect information on the current existing situation of PPC in Europe.
A survey, in the form of a questionnaire, was distributed to the primary or secondary care delegates of 31 European countries asking for information concerning their primary paediatric care system, demographic data, professionals involved in primary care and details of their training. All of them were active paediatricians with a broad knowledge on how PPC is organised in their countries.
Responses were received from 29 countries. Twelve countries (41%) have a family doctor/general practitioner (GP/FD) system, seven (24%) a paediatrician-based system and 10 (35%) a combined system. The total number of paediatricians in the 29 countries is 82 078 with 33 195 (40.4%) working in primary care. In only 15 countries (51.7%), paediatric age at the primary care level is defined as 0-18 years. Training in paediatrics is 5 years or more in 20 of the 29 countries. In nine countries, training is less than 5 years. The median training time of GPs/FDs in paediatrics is 4 months (IQR 3-6), with some countries having no formal paediatric training at all. The care of adolescents and involvement in school health programmes is undertaken by different health professionals (school doctors, GPs/FDs, nurses and paediatricians) depending on the country.
Systems and organisations of PPC in Europe are heterogeneous. The same is true for paediatric training, school healthcare involvement and adolescent care. More research is needed to study specific healthcare indicators in order to evaluate the efficacy of different systems of PPC.
A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the ...collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities. Therefore, communication documents should be seen as templates with essential information clearly indicated and the option for each country to tailor the material to reflect these differences. Future studies should consider setting up multidisciplinary networks of medical professionals and communication experts, and holding training workshops to discuss the interpretation of results and risk communication. Publicity and wide dissemination of the results helped to raise awareness of human biomonitoring to the general public, policy makers and other key stakeholders. Effective and timely communication, at all stages of a study, is essential if the potential of human biomonitoring research to improve public health is to be realised.
•A communication strategy was tested in a European human biomonitoring pilot study.•Public insight research can help develop effective communication materials.•Training workshops and professional networks help deliver develop a successful communication strategy.•Policymaker and stakeholder involvement is essential for translation into policy.
Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We ...investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut-brain mechanisms.
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