Evaluation of the routine use of E-cadherin immunohistochemistry in the typing of breast carcinomas: results of a randomized diagnostic study.

AIMS: Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E-cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E-cadherin immunohistochemistry (IHC) in recognizing ILC. METHODS AND RESULTS: Five pathologists with experience in breast pathology from four Hungarian institutions histotyped 1001 breast cancers from diagnostic core biopsies or excision specimens randomly assigned to haematoxylin and eosin (HE) diagnosis first, followed by E-cadherin IHC; or to immediate HE and E-cadherin-based diagnosis. Of 524 cases with HE diagnosis, 73(14%) were deemed uncertain. E-cadherin made the initial histological type change in 14/524 cases (2.7%), including three with confident HE-based type allocation. Use of E-cadherin immunostaining was considered useful in 88/477 cases (18%) with immediate dual assessment, and typing uncertainty went down to 5% (25/477 cases), but was not zero. Collective assessment of 171 uncertain, difficult, nonclassical cases resulted in consensus diagnosis in most cases, but 15 cases were still doubtful as concerns their proper histological type. CDH1 gene sequencing was attempted and successful in 13; pathogenic genetic alterations were identified in seven cases. CONCLUSIONS: The routine use of E-cadherin IHC decreases the uncertainty in typing and improves the typing accuracy at the cost of potentially redundant additional immunostains. Furthermore, this procedure does not exclude uncertainty due to E-cadherin-positive ILCs, which are occasionally difficult to confidently label as ILC, especially when the growth pattern is not classic.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Recognizing Early Regulation Disorders in Pediatric Care: The For Healthy Offspring Project.

BACKGROUND Regulation disorders are already apparent in infancy. The For Healthy Offspring Project was the first Hungarian study aimed at building an effective model for screening and examining the prevalence and complex (medical and psychosocial) background of classic behavior regulation disorders (excessive crying, feeding, and sleep problems) in infancy. MATERIAL AND METHODS Data were collected from families of 0- to 3-year-old children in a pediatric hospital and its neighboring areas through questionnaires, medical examinations, and individual and small-group consultations. RESULTS In the questionnaire study about their children's behavior (n=1133), 15% of mothers reported excessive crying, 16% reported feeding problems, and 10% reported sleep problems. In a subsample (n=619) in which medical examinations were also conducted, the prevalence of medical diagnoses was 15.0% for excessive crying, 15.2% for sleep disorders, 10.3% for breastfeeding difficulties, and 14.8% for feeding disorders. Children who were referred to the screening program (n=183) had significantly more behavior regulation disorders than the other children in our study. Regulation disorders were found to be comorbid with other health conditions in some cases. CONCLUSIONS We developed a complex model to screen for regulatory problems in early childhood. This study adds more information about the relationship between regulation problems and other health conditions. The general incidence (5-15%) of early childhood regulation disorders in other countries is likely similar to that found in Hungary. In order to effectively recognize early regulation disorders, diagnostic instruments widely used in the international field should be adapted in general Hungarian pediatric care.

Waxholm Space atlas of the rat brain auditory system: Three-dimensional delineations based on structural and diffusion tensor magnetic resonance imaging.

The mammalian auditory system comprises a complex network of brain regions. Interpretations and comparisons of experimental results from this system depend on appropriate anatomical identification of auditory structures. The Waxholm Space (WHS) atlas of the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-86, 2014) is an open access, three-dimensional reference atlas defined in an ex-vivo magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volume. Version 2.0 of the atlas (Kjonigsen et al., Neuroimage 108:441-9, 2015) includes detailed delineations of the hippocampus and several major subcortical regions, but only few auditory structures. To amend this, we have delineated the complete ascending auditory system from the cochlea to the cerebral cortex. 40 new brain structure delineations have been added, and the delineations of 10 regions have been revised based on the interpretation of image features in the WHS rat brain MRI/DTI volumes. We here describe and validate the new delineations in relation to corresponding cell- and myelin-stained histological sections and previous literature. We found it possible to delineate all main regions and the majority of subregions and fibre tracts of the ascending auditory pathway, apart from the auditory cortex, for which delineations were extrapolated from a conventional two-dimensional atlas. By contrast, only parts of the descending pathways were discernible in the template. Version 3.0 of the atlas, with altogether 118 anatomical delineations, is shared via the NeuroImaging Tools and Resources Collaboratory (www.nitrc.org).

Elevated Levels of Estradiol in Human Immunodeficiency Virus-Infected Pregnant Women on Protease Inhibitor-Based Regimens.

Background: Human immunodeficiency virus (HIV)-infected pregnant women on protease inhibitor (PI)-based combination antiretroviral therapy (cART) have a greater risk for adverse birth outcomes, and an association with steroid hormone levels has been implicated. The objective of this study was to investigate the association between PI-cART and estradiol levels in pregnancy. Methods: Fifty-five HIV-infected and 49 HIV-uninfected Canadian pregnant women were followed prospectively throughout gestation. All HIV-infected women were on a PI-based cART regimen. Maternal plasma samples were collected at 12-18 weeks, 24-28 weeks, 34-38 weeks, at delivery, and from the cord. Birth outcomes were recorded. Levels of estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), cortisol, and adrenocorticotropic hormone (ACTH) were quantified by enzyme-linked immunosorbent assay. Results: (median [interquartile range] for cord estradiol: 23.9 ng/mL [16.4-36.4] for HIV-infected exposed to PI-cART and 15.7 ng/mL [12.2-21.2] for HIV-negative; P = .0025). HIV-infected women had higher DHEAS levels in cord plasma that correlated with cord and maternal delivery estradiol levels. Cortisol and ACTH levels did not differ between groups. In the HIV-infected women, cord estradiol levels correlated negatively with birth weight centile (r = -0.47, P = .0016). Conclusions: Our data suggest that PI-cART exposure in pregnancy is associated with elevated levels of estradiol, likely driven by higher fetal DHEAS production. Cord estradiol levels were inversely correlated with birth weight centile in infants born to PI-cART-exposed women, suggesting that fetal exposure to high estradiol levels may be contributing to cART-associated fetal growth restriction.

Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy.

Background: Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)-infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)-based or efavirenz (EFV)-based cART. Methods: Three hundred twenty-six women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy were included. Enrollment samples collected prior to cART initiation were used as a cART-naive comparator group. Hormone levels were quantified by enzyme-linked immunosorbent assay. Results: Estradiol levels were differentially affected by the 2 cART regimens. Exposure to LPV/r was associated with an increase in estradiol (P < .0001), whereas exposure to EFV was associated with a decrease in estradiol (P < .0001), relative to the cART-naive gestationally matched comparator group. Lower estradiol levels correlated with small for gestational age (SGA) (P = .0019) and low birth weight (P = .019) in the EFV arm, while higher estradiol levels correlated with SGA in the LPV/r arm (P = .027). Although progesterone levels were similar between treatment arms, we observed an association between SGA and lower progesterone in the LPV/r arm (P = .04). No association was observed between hormone levels and preterm birth in either arm. Levels of progesterone and estradiol were lower in cases of stillbirth, and levels of both hormones declined immediately prior to stillbirth in 5 of 8 cases. Conclusions: Combination ART regimens differentially affect estradiol levels in pregnancy, a hormone critical to the maintenance of a healthy pregnancy. Identifying cART regimens that minimize perinatal HIV transmission without contributing to hormonal dysregulation represents an urgent public health priority. Clinical Trials Registration: NCT00993031.

Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy.

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3+ cells and CD8+ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16+ and CD68+ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.

BACKGROUND: It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level. METHODS: We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism. RESULTS: HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels. CONCLUSIONS: Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.

Cost-effectiveness of a risk-based secondary screening programme of type 2 diabetes.

OBJECTIVE: The objective of this study was to develop a long-term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk-based screening programme in a country specific setting. METHODS: The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units. RESULTS: The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three-yearly screening gained 0.0229 quality adjusted life years for an additional €83 per person compared with no screening and resulted an incremental cost-effectiveness ratio of €3630/quality adjusted life years. CONCLUSION: From the economic perspective introduction of the 3-yearly screening programme is justifiable and it provides a good value for money. Copyright © 2016 John Wiley & Sons, Ltd.

Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial.

BACKGROUND: Early infancy is a high-risk period for severe acute respiratory infection (ARI), particularly in low-income countries with resource-limited health systems. Lower respiratory tract infection (LRTI) is commonly preceded by upper respiratory infection (URTI), and often caused by respiratory syncytial virus (RSV), influenza and other common community-acquired viral pathogens. Vitamin D status is a candidate modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk populations. METHODS/DESIGN: In the Maternal Vitamin D for Infant Growth (MDIG) study in Dhaka, Bangladesh (NCT01924013), 1300 pregnant women are randomized to one of five groups: placebo, 4200 IU/week, 16,800 IU/week, or 28,000 IU/week from 2nd trimester to delivery plus placebo from 0-6 months postpartum; or, 28,000 IU/week prenatal and until 6-months postpartum. In the Maternal Vitamin D for ARI in Infancy (MDARI) sub-study nested within the MDIG trial, trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a standardized clinical assessment. Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms. Mid-turbinate nasal swab samples are obtained from infants who meet standardized clinical ARI criteria. Specimens are tested by polymerase chain reaction (PCR) for 8 viruses (influenza A/B, parainfluenza 1/2/3, RSV, adenovirus, and human metapneumovirus), and nasal carriage density of Streptococcus pneumoniae. The primary outcome is the incidence rate of microbiologically-positive viral ARI, using incidence rate ratios to estimate between-group differences. We hypothesize that among infants 0-6 months of age, the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo. Secondary outcomes include incidence of ARI associated with specific pathogens (influenza A or B, RSV), clinical ARI, and density of pneumococcal carriage. DISCUSSION: If shown to reduce the risk of viral ARI in infancy, integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants. TRIAL REGISTRATION: NCT02388516 , registered March 9, 2015.

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

BACKGROUND: Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. METHODS: PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. RESULTS: PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. CONCLUSIONS: Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.

Addendum to "Waxholm Space atlas of the Sprague Dawley rat brain" [NeuroImage 97 (2014) 374-386].

The main focus of our original article was to describe the anatomical delineations constituting the first version of the WHS Sprague Dawley atlas, apply the Waxholm Space coordinate system, and publish the associated MRI/DTI template and segmentation volume in their original format. To increase usability of the dataset, we have recently shared an updated version of the volumetric image material (v1.01). The aims of this addendum are to inform about the improvements in the updated dataset, in particular related to navigation in the WHS coordinate system, and provide guidance for transforming coordinates acquired in the first version of the atlas.

The effect of kisspeptin on the regulation of vascular tone.

Kisspeptin has been implicated in cardiovascular control. Eicosanoids play a crucial role in the activation of platelets and the regulation of vascular tone. In the present study, we investigated the effect of kisspeptins on eicosanoid synthesis in platelets and aorta in vitro. Platelets and aorta were isolated from Wistar-Kyoto rats. After preincubation with different doses of kisspeptin, samples were incubated with [1-(14)C]arachidonic acid (0.172 pmol/mL) in tissue culture Medium 199. The amount of labeled eicosanoids was measured with liquid scintillation, after separation with overpressure thin-layer chromatography. Kisspeptin-13 stimulated the thromboxane synthesis. The dose-response curve was bell-shaped and the most effective concentration was 2.5 × 10(-8) mol/L, inducing a 27% increase. Lipoxygenase products of platelets displayed a dose-dependent elevation up to the dose of 5 × 10(-8) mol/L. In the aorta, kisspeptin-13 induced a marked elevation in the production of 6-keto-prostaglandin F1α, the stable metabolite of prostacyclin, and lipoxygenase products. Different effects of kisspeptin on cyclooxygenase and lipoxygenase products indicate that beyond intracellular Ca(2+) mobilization, other signaling pathways might also contribute to its actions. Our data suggest that kisspeptin, through the alteration of eicosanoid synthesis in platelets and aorta, may play a physiologic and (or) pathologic role in the regulation of vascular tone.

Waxholm Space atlas of the Sprague Dawley rat brain.

Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multi-level data integration and analysis across reference spaces.

TRPS1 expression in breast angiosarcoma.

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling.

Experimental Data Confirm Carrier-Cascade Model for Solid-State Conductance across Proteins.

The finding that electronic conductance across ultrathin protein films between metallic electrodes remains nearly constant from room temperature to just a few degrees Kelvin has posed a challenge. We show that a model based on a generalized Landauer formula explains the nearly constant conductance and predicts an Arrhenius-like dependence for low temperatures. A critical aspect of the model is that the relevant activation energy for conductance is either the difference between the HOMO and HOMO-1 or the LUMO+1 and LUMO energies instead of the HOMO-LUMO gap of the proteins. Analysis of experimental data confirms the Arrhenius-like law and allows us to extract the activation energies. We then calculate the energy differences with advanced DFT methods for proteins used in the experiments. Our main result is that the experimental and theoretical activation energies for these three different proteins and three differently prepared solid-state junctions match nearly perfectly, implying the mechanism's validity.

A neuroscientist's guide to using murine brain atlases for efficient analysis and transparent reporting.

Brain atlases are widely used in neuroscience as resources for conducting experimental studies, and for integrating, analyzing, and reporting data from animal models. A variety of atlases are available, and it may be challenging to find the optimal atlas for a given purpose and to perform efficient atlas-based data analyses. Comparing findings reported using different atlases is also not trivial, and represents a barrier to reproducible science. With this perspective article, we provide a guide to how mouse and rat brain atlases can be used for analyzing and reporting data in accordance with the FAIR principles that advocate for data to be findable, accessible, interoperable, and re-usable. We first introduce how atlases can be interpreted and used for navigating to brain locations, before discussing how they can be used for different analytic purposes, including spatial registration and data visualization. We provide guidance on how neuroscientists can compare data mapped to different atlases and ensure transparent reporting of findings. Finally, we summarize key considerations when choosing an atlas and give an outlook on the relevance of increased uptake of atlas-based tools and workflows for FAIR data sharing.

[Additional psychometric data for the DS1K mood questionnaire. Experience from a large sample study involving parents of young children]. / Kiegészítö pszichometriai adatok a DS1K hangulati kérdöívhez. Egy kisgyermekes szülöket bevonó nagymintás kutatás tapasztalatai.

AIMS: A new instrument for assessing depressive mood, the first version of Depression Scale Questionnaire (DS1K) was published in 2008 by Halmai et al. This scale was used in our large sample study, in the framework of the For Healthy Offspring project, involving parents of young children. The original questionnaire was developed in small samples, so our aim was to assist further development of the instrument by the psychometric analysis of the data in our large sample (n=1164). METHOD: The DS1K scale was chosen to measure the parents' mood and mental state in the For Healthy Offspring project. The questionnaire was completed by 1063 mothers and 328 fathers, yielding a heterogenous sample with respect to age and socio-demographic status. Analyses included main descriptive statistics, establishing the scales' inner consistency and some comparisons. Results were checked in our original and multiple imputed datasets as well. RESULTS: According to our results the reliability of our scale was much worse than in the original study (Cronbach alpha: 0.61 versus 0.88). During the detailed item-analysis it became clear that two items contributed to the observed decreased coherence. We assumed a problem related to misreading in case of one of these items. This assumption was checked by cross-analysis by the assumed reading level. According to our results the reliability of the scale was increased in both the lower and higher education level groups if we did not include one or both of these problematic items. However, as the number of items decreased, the relative sensitivity of the scale was also reduced, with fewer persons categorized in the risk group compared to the original scale. CONCLUSION: We suggest for the authors as an alternative solution to redefine the problematic items and retest the reliability of the measurement in a sample with diverse socio-demographic characteristics.

Cellular Immunity Is Critical for Assessing COVID-19 Vaccine Effectiveness in Immunocompromised Individuals.

COVID-19 vaccine clinical development was conducted with unprecedented speed. Immunity measurements were concentrated on the antibody response which left significant gaps in our understanding how robust and long-lasting immune protection develops. Better understanding the cellular immune response will fill those gaps, especially in the elderly and immunocompromised populations which not only have the highest risk for severe infection, but also frequently have inadequate antibody responses. Although cellular immunity measurements are more logistically complex to conduct for clinical trials compared to antibody measurements, the feasibility and benefit of doing them in clinical trials has been demonstrated and so should be more widely adopted. Adding significant cellular response metrics will provide a deeper understanding of the overall immune response to COVID-19 vaccination, which will significantly inform vaccination strategies for the most vulnerable populations. Better monitoring of overall immunity will also substantially benefit other vaccine development efforts, and indeed any therapies that involve the immune system as part of the therapeutic strategy.

Higher maternal parathyroid hormone concentration at delivery is not associated with smaller newborn size.

Intrauterine growth restriction (IUGR) reflects inadequate growth in-utero and is prevalent in low resource settings. This study aimed to assess the association of maternal delivery parathyroid hormone (PTH) - a regulator of bone turnover and calcium homeostasis - with newborn anthropometry, to identify regulators of PTH, and to delineate pathways by which maternal PTH regulates birth size using path analysis. This was a cross-sectional analysis of data from participants (n = 537) enrolled in the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh. Primary exposures were maternal delivery intact PTH (iPTH) or whole PTH (wPTH) and outcomes were gestational age- and sex-standardized z-scores for birth length (LAZ), weight (WAZ), and head circumference (HCAZ). Hypothesized regulators of PTH included calcium and protein intake, vitamin D, magnesium, fibroblast-like growth factor-23 (FGF23), and C-reactive protein. Maternal iPTH was not associated with birth size in linear regression analyses; however, in path analysis models, every SD increase in log(iPTH) was associated with 0.08SD (95% CI: 0.002, 0.162) higher LAZ. In linear regression and path analysis models, wPTH was positively associated with WAZ. Vitamin D suppressed PTH, while FGF23 was positively associated with PTH. In path analysis models, higher magnesium was negatively associated with LAZ; FGF23 was positively associated and protein intake was negatively associated with LAZ, WAZ, and HCAZ. Higher maternal PTH in late pregnancy is unlikely to contribute to IUGR. Future studies should investigate maternal FGF23, magnesium and protein intake as regulators of fetal growth, particularly in settings where food insecurity and IUGR are public health problems.