Highlights ► The VDR was present in dopamine neurons in adult human and rat substantia nigra. ► The VDR was restricted to the nuclear compartments. ► The rat VDR was expressed between E12 and E15 and ...its abundance increased till P21.
There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk ...factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l
. Compared with the 25OHD sufficient group (25OHD>50 nmol l
), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, β=0.06, P<0.001; cord blood n=1712, β=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny.
Summary
Background
Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma.
Objective
We examined whether 25‐hydroxyvitamin D levels in mid‐gestation and at ...birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school‐age children.
Methods
We performed a population‐based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid‐gestation and umbilical cord blood samples at birth were used to determine 25‐hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6.
Results
Maternal levels of 25‐hydroxyvitamin D in mid‐gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25‐hydroxyvitamin D levels at birth had a higher Rint (Z‐score (95% confidence interval 95% CI): −0.42 (−0.84, −0.01), P‐value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25‐hydroxyvitamin D level was taken into account Z‐score (95% CI): −0.55 (−1.08, 0.01).
Conclusion and Clinical Relevance
Low levels of 25‐hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25‐hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long‐term consequences.
Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells ...that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21
B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21
and CD21
B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction.
Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry.
Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21
B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21
CD27
subsets and CD21
CD27
IgD
subset. The only B cell subset found to associate with clinical factors was the CD21
double-negative (DN, CD27
IgD
) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21
DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL).
Cartilage destruction in eRA patients was associated with an expanded proportion of CD21
DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21
DN in RA pathogenesis.
Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 ...participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a "multidimensional entity" characterized by four "domains" that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are
) histological evidence of tissue injury,
) alteration of the alveolar-capillary barrier,
) presence of an inflammatory response, and
) physiologic dysfunction. For each domain, we present "relevant measurements," defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as "experimental ALI." Finally, we propose that a time criterion defining "acute" in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.
Summary There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to ...neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the “ Biological Plausibility ” of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that vitamin D acts as a neurosteroid with direct effects on brain development.
Maternal vitamin D deficiency during pregnancy may influence offspring kidney health. We aimed to examine the associations of 25-hydroxyvitamin D (25(OH)D) blood levels during fetal life with kidney ...outcomes at school age.
This study was embedded in a population-based prospective cohort study among 4212 mother-child pairs. We measured maternal second trimester (18-25 weeks) and fetal cord blood (at birth) 25(OH)D levels. At a median age of 6.0 years, we measured children's combined kidney volume, glomerular filtration rate (eGFR) from creatinine and cystatin C serum levels, and microalbuminuria from albumin and creatinine urine levels.
Of all mothers, 21.9% had severely deficient levels (25(OH)D <25.0 nmol/l), 25.7% had deficient levels (25.0-49.9 nmol/l), 25% had sufficient levels (50.0-74.9 nmol/l) and 27.4% had optimal levels (⩾75.0 nmol/l). Maternal 25(OH)D levels were not consistently associated with childhood combined kidney volume. Higher maternal 25(OH)D levels were associated with lower childhood eGFR (difference -0.94 ml/min per 1.73 m(2) (95% confidence interval, -1.73; -0.15) per 1 standard deviation (s.d.) increase in 25(OH)D). Maternal 25(OH)D levels were not associated with microalbuminuria. Cord blood 25(OH)D levels were not associated with childhood kidney outcomes. The associations of maternal 25(OH)D levels with childhood eGFR were partly explained by childhood vitamin D status.
Our findings suggest that maternal 25(OH)D levels during pregnancy may influence childhood kidney outcomes. These results should be considered hypothesis generating. Further studies are needed to replicate the observations, to examine the underlying mechanisms and to identify the long-term clinical consequences.
There is an urgent need to generate and test candidate risk factors that may explain gradients in the incidence of schizophrenia. Based on clues from epidemiology, we proposed that developmental ...vitamin D deficiency may contribute to the risk of developing schizophrenia. This hypothesis may explain diverse epidemiological findings including season of birth, the latitude gradients in incidence and prevalence, the increased risk in dark-skinned migrants to certain countries, and the urban-rural gradient. Animal experiments demonstrate that transient prenatal hypovitaminosis D is associated with persisting changes in brain structure and function, including convergent evidence of altered dopaminergic function. A recent case-control study based on neonatal blood samples identified a significant association between neonatal vitamin D status and risk of schizophrenia. This article provides a concise summary of the epidemiological and animal experimental research that has explored this hypothesis.
Background
The longitudinal associations between oral health (OH) and physical and mental health-related quality of life (HRQoL) are unclear.
Purpose
This study examined the relationship of ...self-reported OH with the trajectories of physical and mental HRQoL in Hong Kong at 3, 9, and 15 months after the measurement period using a latent growth curve model.
Methods
This study included 5,710 participants recruited in the FAMILY project cohort study during March–October 2009. Self-report OH was measured using a five-point single-item scale, and HRQoL was measured using the physical component scale (PCS) and mental component scale (MCS) of Short Form 12. Latent growth curve model was used to compute the relationship of self-reported OH with the trajectories on HRQoL over time, adjusted for age and sex.
Results
The latent growth curve model gave good fit to both the PCS (normed fit index (NFI) = 0.98, comparative fit index (CFI) = 0.99, and standardized root mean square residual (SRMR) = 0.03) and MCS (NFI = 0.97, CFI = 0.98, and SRMR = 0.03). Better self-reported OH was associated with higher PCS and MCS at the baseline. The longitudinal association with PCS remained constant over time (coefficient = −0.02,
p
= 0.07) but that with MCS diminished over time with baseline oral health status (coefficient = −0.04,
p
= 0.002).
Conclusion
Better self-reported OH status was associated with higher level of physical and mental HRQoL, and with negative change in mental HRQoL.
In cannibalistic species, small individuals often shift habitats to minimize risk of predation by larger conspecifics. The availability of diverse size-structured habitats may mediate the incidence ...of cannibalism by larger individuals on smaller individuals and increase fitness of smaller individuals. We tested these hypotheses in a series of laboratory studies with Gammarus pulex, a freshwater amphipod inhabiting substrates with varying interstitial pore space sizes. In the absence of larger, potentially cannibalistic individuals, small Gammarus actively used all pore space sizes offered. They used only substrates containing food and preferred food items that provided cover to food items that did not. In the presence of larger G. pulex, small individuals almost exclusively used smaller pore spaces from which larger individuals were excluded. Small individual survival was significantly lower in the presence of larger Gammarus than in controls without larger individuals regardless of substrate size, but availability of mixed pore sizes significantly increased survival. Food consumption and growth per individual were not affected by the presence of larger individuals or substrate composition. Our results suggest that the distribution and availability of complex and high-quality habitats may affect the occurrence and significance of cannibalism in size-structured populations.
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