KRT5 in-frame deletion in a family of German Shepherd dogs with split paw pad disease resembling localized epidermolysis bullosa simplex in human patients.

Split paw pad disease is a scarcely defined phenotype characterized by skin lesions on the paw pads of dogs. We studied a family of German Shepherd dogs, in which four dogs developed intermittent paw pad lesions and lameness. The paw pads of two of the affected dogs were biopsied and demonstrated cleft formation in the stratum spinosum and stratum corneum, the outermost layers of the epidermis. Whole genome sequencing data from an affected dog revealed a private heterozygous 18 bp in frame deletion in the KRT5 gene. The deletion NM_001346035.1:c.988_1005del or NP_001332964.1:p.(Asn330_Asp335del) is predicted to lead to a loss of six amino acids in the L12 linker domain of the encoded keratin 5. KRT5 variants in human patients lead to various subtypes of epidermolysis bullosa simplex (EBS). Localized EBS is the mildest of the KRT5-related human diseases and may be caused by variants affecting the L12 linker domain of keratin 5. We therefore think that the detected KRT5 deletion in dogs represents a candidate causal variant for the observed skin lesions in dogs. However, while the clinical phenotype of KRT5-mutant dogs of this study closely resembles human patients with localized EBS, there are differences in the histopathology. EBS is defined by cleft formation within the basal layer of the epidermis while the cleft formation in the dogs described herein occurred in the outermost layers, a hallmark of split paw pad disease. Our study provides a basis for further studies into the exact relation of split paw pad disease and EBS.

Association between maternal pre-pregnancy body mass index and offspring's outcomes at 9 to 15 years of age.

OBJECTIVE: Maternal pre-pregnancy underweight, overweight and obesity might increase the risk for worse short- and long-term outcome in the offspring. There is a need for further study into the relationship between maternal pre-pregnancy body mass index (BMI) and the combined outcome of physical development, state of health and social behavior in children. QUESTION: Is maternal pre-pregnancy BMI associated with the child outcome in terms of physical development, state of health and social behavior (school and leisure time behavior) at the age of 9 to 15 years? METHODS: In the population-based birth cohort study Survey of Neonates in Pomerania (SNIP) children at the age 9-15 years and their families were re-examined by questionnaire-based follow-up. 5725 mother-child pairs were invited to SNiP-follow-up. This analysis is based on the recall fraction of 24.1% (n = 1379). Based on the maternal pre-pregnancy BMI (ppBMI), 4 groups were formed: underweight (ppBMI < 19 kg/m2, n = 117), normal weight (ppBMI 19-24.99 kg/m2, n = 913, reference), overweight (ppBMI 25-30 kg). /m2, n = 237) and obesity (ppBMI > 30 kg/m2, n = 109). RESULTS: In the multiple regression model, the BMI-z-score for children of mothers in the underweight group was -0.50 lower, and 0.50/1.07 higher in the overweight/obese group (p < 0.001) compared to reference at median age of 12 years. No differences were found in children of underweight mothers with regard to social behavior (interaction with friends and family), school and sports performance (coded from "very good" to "poor"), other leisure activities (watching television, using mobile phones, gaming), and health (occurrence of illnesses) compared to children of normal weight mothers. In contrast, maternal pre-pregnancy overweight and obesity were associated with lower school and sports performance, and higher screen time (smart phone, gaming, television) compared to children of normal weight mothers. CONCLUSION: Maternal pre-pregnancy overweight and obesity but not underweight was negatively associated with school performance and leisure time behavior in the offspring at 9-15 years of age.

Maternal socioeconomic and lifestyle factors and life dissatisfaction associated with a small for gestational age infant. The Survey of Neonates in Pomerania (SNiP).

PURPOSE: The aim is to investigate the associations of the mother's socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant. METHODS: Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models. RESULTS: After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06-3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01). CONCLUSIONS: Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates.

[Operating models and organizational structures: opportunities and challenges for human milk banking in Germany]. / Versorgungsstrukturen und Betreibermodelle: Chancen und Herausforderungen des Frauenmilchbankwesens in Deutschland.

BACKGROUND: Donor human milk is the recommended alternative for feeding preterm infants if mother's own milk is unavailable. Human milk banks collect, screen, store and distribute donated human milk according to pre-specified standard operating procedures to premature infants without mothers own milk. AIM: Herein we characterize current operating models and the structural organisation of German milk bank institutions. The analysis of current and future opportunities and challenges may support the development of a comprehensive donor milk service within Germany. MATERIAL AND METHODS: Summary of the panel discussion entitled "Operating models and organizational structures: opportunities and risks for donor human milk bank in Germany" during the 3rd Scientific Symposium of the German Human Milk Bank Initiative (FMBI), November 25th to 26th 2022, in Nuremberg, Germany. RESULTS AND DISCUSSION: Differing operator models may facilitate the use of donor human milk by incorporating unique site-specific factors, pre-existing infrastructure, and individual needs. In addition to the establishment of milk banks serving single neonatal units, high-capacity milk banks should be enabled to provide donor human milk using several hub-and-spoke systems. This may create a nationwide network for a sustainable human milk supply for preterm infants that is based on qualified breastfeeding and lactation support.

Maternal pre-pregnancy underweight as a risk factor for the offspring: Survey of Neonates in Pomerania.

AIM: The aim was to investigate socio-economic risk factors for maternal underweight before pregnancy and then associations of underweight with neonatal outcomes. METHODS: Data of 3401 mother-child dyads from the population-based birth cohort Survey of Neonates in Pomerania (SNiP) were analysed. RESULTS: Bivariate analysis showed that underweighted mothers were younger, smoked more often, had a lower equivalent income and lower socio-economic status (employment status and/or educational level) compared to women with normal weight. The final prediction model revealed that only younger maternal age (OR = 0.93; 95%-CI = 0.90-0.97) and maternal smoking during pregnancy (OR = 2.52; 95%-CI = 1.74-3.66) were associated with underweight. Compared to women with normal pre-pregnancy BMI, underweight women had an increased chance of premature labour (OR = 1.73; 95% CI: 1.29-2.31) and a reduced placental weight. The offspring of underweight women had an increased risk of late preterm birth (OR = 1.82; 95% CI: 1.21-2.74) and birthweight < 2500 g (OR = 1.91; 95% CI: 1.23-2.95). CONCLUSION: Smoking during pregnancy and a younger age were identified as risk factors for maternal pre-pregnancy underweight which then was associated with late preterm birth and low birthweight.

Natrix: a Snakemake-based workflow for processing, clustering, and taxonomically assigning amplicon sequencing reads.

BACKGROUND: Sequencing of marker genes amplified from environmental samples, known as amplicon sequencing, allows us to resolve some of the hidden diversity and elucidate evolutionary relationships and ecological processes among complex microbial communities. The analysis of large numbers of samples at high sequencing depths generated by high throughput sequencing technologies requires efficient, flexible, and reproducible bioinformatics pipelines. Only a few existing workflows can be run in a user-friendly, scalable, and reproducible manner on different computing devices using an efficient workflow management system. RESULTS: We present Natrix, an open-source bioinformatics workflow for preprocessing raw amplicon sequencing data. The workflow contains all analysis steps from quality assessment, read assembly, dereplication, chimera detection, split-sample merging, sequence representative assignment (OTUs or ASVs) to the taxonomic assignment of sequence representatives. The workflow is written using Snakemake, a workflow management engine for developing data analysis workflows. In addition, Conda is used for version control. Thus, Snakemake ensures reproducibility and Conda offers version control of the utilized programs. The encapsulation of rules and their dependencies support hassle-free sharing of rules between workflows and easy adaptation and extension of existing workflows. Natrix is freely available on GitHub ( https://github.com/MW55/Natrix ) or as a Docker container on DockerHub ( https://hub.docker.com/r/mw55/natrix ). CONCLUSION: Natrix is a user-friendly and highly extensible workflow for processing Illumina amplicon data.

Survey of Neonates in Pomerania (SNiP): Study design and cohort update.

BACKGROUND: The health status of newborns is a major concern for parents and medical personnel. Recent studies have provided increasing evidence that factors from the foetal and perinatal periods of life influence health later in life. The "Follow-up of the Survey of Neonates in Pomerania" (SNiP-I-Follow-up) is the first follow-up of the population-based birth cohort study, SNiP-I, established in north-east Germany. OBJECTIVES: The primary aim of SNiP-I-Follow-up study was the collection of longitudinal data on children and adolescents. The associations will be analysed between risk factors in pregnancy and the perinatal period and health status in infancy and later childhood. POPULATION: The population-based cohort study SNiP-I was conducted in Pomerania in north-east Germany between February 2002 and November 2008. All mothers from the SNiP-I birth cohort were recontacted when their children were from 9 to 15 years of age. DESIGN: The SNiP-I-Follow-up study was carried out between December 2016 and August 2017 and is a questionnaire-based survey. METHODS: Physical development, health status, and social behaviour (school and leisure behaviour) of children were analysed using a questionnaire comprising medical, epidemiological, and socio-economic data, associated health care risk factors, and life circumstances of newborns, children, and their parents. PRELIMINARY RESULTS: Out of 5725 children invited to participate in the SNiP-I-Follow-up study between December 2016 and August 2017, 29% (n = 1665) children participated in the SNiP-I-Follow-up study, providing data on 1665 mothers-child dyads. Responders had higher socio-economic status, especially in relation to maternal education status. CONCLUSION: As a longitudinal birth cohort from rural Germany, the SNiP cohort will be a resource to address urgent research needs and contribute to overall population health.

Cost analysis showed that feeding preterm infants with donor human milk was significantly more expensive than mother's milk or formula.

AIM: This study analysed the comparative cost of feeding donor human milk to preterm infants compared to mother's own milk and formula. METHODS: A document and process analysis and a time measurement study were carried out at the milk bank of the Level 1 Perinatal Center of the University Hospital of Greifswald, Germany, from April to June 2017. The cost analysis data were provided by the University's financial department. RESULTS: The total cost per year was €92 085.02 for 300 litres of donor human milk: 27% of this was material costs, 51% was personnel costs, and 22% was other overheads. The average cost per litre was €306.95, and staff time was 492 minutes per litre. The total marginal cost for each additional litre of donor human milk, formula or unpasteurised mother´s milk was €82.88, €10.28 and €38.42, respectively. Pasteurising a litre of donor milk cost €3.51. CONCLUSION: Providing preterm infants with donor milk was much more expensive than using formula or mother's own milk, but the cost of pasteurisation was minimal.

Median urinary iodine concentration reflected sufficient iodine supply in neonates from Northeast Germany in 2005-2006.

PURPOSE: Data from recent adult studies suggest a decline of median urinary iodine concentrations (UIC) in Germany, but since 1996 no German study investigated UIC in neonates. The aim of our study was to investigate UIC and serum thyroid-stimulating hormone (TSH) levels in neonates from Germany. METHODS: We used data from 399 neonates, which were born between April 2005 and November 2006 in the Northeast of Germany. UIC were evaluated by a photometric procedure with Sandell and Kolthoff reaction and afterwards corrected to be comparable with an ICP-MS method. TSH was determined from capillary blood, which was taken within 5 days after birth, by DELFIA. RESULTS: Median UIC were 150 µg/L (25th percentile: 104 µg/L; 75th percentile: 196 µg/L) and differed between boys (153.3 µg/L) and girls (131.5 µg/L; p = 0.012). The prevalence of serum TSH levels > 5 mIU/L was 14%. Neonates from mothers with intake of iodine supplementation (150 µg/L) had significantly higher median UIC than neonates from mothers without iodine supplementation (132 µg/L; p = 0.011). Multivariable linear regression adjusted for sex and iodine supplementation of the mother revealed a significant association between UIC and log-transformed serum TSH levels (ß = 0.003: 95% confidence interval (CI) = 0.0001-0.005; p = 0.028). CONCLUSIONS: Neonates in Northeast Germany did show a sufficient supply of iodine. This points towards the possibility of a sufficient iodine supply of neonates also in other regions of Germany, even though recent studies in adults may indicate mild iodine deficiency.

Model systems for investigating disease processes in neurocysticercosis.

Neurocysticercosis (NCC) occurs following brain infection by larvae of the cestode Taenia solium. It is the leading cause of preventable epilepsy worldwide and therefore constitutes a critical health challenge with significant global relevance. Despite this, much is still unknown about many key pathogenic aspects of the disease, including how cerebral infection with T. solium results in the development of seizures. Over the past century, valuable mechanistic insights have been generated using both clinical studies and animal models. In this review, we critically assess model systems for investigating disease processes in NCC. We explore the respective strengths and weaknesses of each model and summarize how they have contributed to current knowledge of the disease. We call for the continued development of animal models of NCC, with a focus on novel strategies for understanding this debilitating but often neglected disorder.

Analyses of pathological cranial ultrasound findings in neonates that fall outside recent indication guidelines: results of a population-based birth cohort: survey of neonates in Pommerania (SNiP-study).

BACKGROUND: Recent guidelines recommend a cranial ultrasound (CU) in neonates born at < 30 weeks gestation, admitted to the neonatal intensive care unit (NICU), or with a CU indication. Here, we addressed the need to extend these recommendations. METHODS: We retrospectively reviewed 5107 CUs acquired in the population-based Survey of Neonates in Pomerania, conducted in 2002 to 2008. Neonates with conspicuous CUs that were ≥ 30 weeks gestation without recent indications for CU were identified and assigned to the following groups: with (I) or without (II) admission to neonatal care. We designated CU conspicuities as mild (MC) or significant (SC), and we investigated related neurodevelopment during follow-up. RESULTS: Of 5107 neonates, 5064 were born at ≥30 weeks gestation and of those, 4306 received CUs without any indication for this examination. We found conspicuities in 7.7% (n = 47/610) of group I (n = 30 MC, n = 17 SC), and 3.2% (n = 117/3696) of group II (n = 100 MC, n = 17 SC). In group II, SC comprised, e.g., bilateral cysts, partial agenesis of the corpus callosum, and periventricular leukomalacia. Follow-up was available in 75% of infants in group II with MCs and SCs; of these, 12.8% had an abnormal neurological follow-up. CONCLUSIONS: We detected a high number of conspicuities in neonates without a CU indication. However, we could not demonstrate that ultrasound findings were associated with the neurological follow-up or any advantage to an earlier diagnosis. Our data did not support extending current guidelines or a general CU screening policy for all neonates.

Quantitative Comparison of Abundance Structures of Generalized Communities: From B-Cell Receptor Repertoires to Microbiomes.

The community, the assemblage of organisms co-existing in a given space and time, has the potential to become one of the unifying concepts of biology, especially with the advent of high-throughput sequencing experiments that reveal genetic diversity exhaustively. In this spirit we show that a tool from community ecology, the Rank Abundance Distribution (RAD), can be turned by the new MaxRank normalization method into a generic, expressive descriptor for quantitative comparison of communities in many areas of biology. To illustrate the versatility of the method, we analyze RADs from various generalized communities, i.e. assemblages of genetically diverse cells or organisms, including human B cells, gut microbiomes under antibiotic treatment and of different ages and countries of origin, and other human and environmental microbial communities. We show that normalized RADs enable novel quantitative approaches that help to understand structures and dynamics of complex generalized communities.

Contamination of dried blood spots - an underestimated risk in newborn screening.

BACKGROUND: Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. METHODS: Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. RESULTS: Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. CONCLUSIONS: A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

Evaluation of neonatal and maternal morbidity in mothers with gestational diabetes: a population-based study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. Untreated GDM is a severe threat to maternal and neonatal health. Based on recent evidence, up to 15% of all pregnancies may be affected by GDM. We hypothesized that in a rural birth cohort, higher maternal BMI and adverse socioeconomic conditions would promote GDM, which in turn would lead to adverse effects on pregnancy outcomes. METHODS: The current study is a part of a population-based cohort study examining the health and socioeconomic information from 5801 mothers and their children. The study, titled the Survey of Neonates in Pomerania (SNiP), was based in northeastern Pomerania, Germany (2002-2008). RESULTS: The cumulative incidence of GDM was 5.1%. Multiple logistic regression revealed prepregnancy overweight (OR 1.84 (95% CI 1.27-2.68)), prepregnancy obesity (OR 3.67 (2.48-5.44)) and maternal age (OR 1.06 (1.03-1.08)) as risk factors for GDM (p = 0.001). Alcohol use during pregnancy (OR 0.61 (0.41-0.90), a higher monthly income (OR 0.62 (0.46-0.83)), and the highest level of education (OR 0.44 (0.46-0.83)) decreased the risk of GDM. Newborns of GDM mothers had an increased risk of hypoglycaemia (OR 11.71 (7.49-18.30)) or macrosomia (OR 2.43 (1.41-4.18)) and were more often delivered by primary (OR 1.76 (1.21-2.60)) or secondary C-section (OR 2.00 (1.35-2.97)). Moreover, they were born 0.78 weeks (95% CI -1.09 - -0.48 weeks) earlier than infants of mothers without diabetes, resulting in higher percentage of late preterm infants with a gestational age of 32-36 weeks (11.1% vs. 6.96%). CONCLUSIONS: Age and BMI before pregnancy were the predominant mediators of the increased risk of GDM, whereas a higher income and educational level were protective. GDM affected relevant perinatal and neonatal outcomes based on its association with an increased risk of delivery by C-section, preterm birth, macrosomia at birth and neonatal hypoglycaemia.

Chronic diseases in pregnant women: prevalence and birth outcomes based on the SNiP-study.

BACKGROUND: The subject of "pregnancy and disease" is of particular importance for maternal well-being and neonatal outcomes. The international literature has focused on acute diseases during pregnancy; however, there are only a few studies investigating chronic diseases in pregnant women. The focus of this study is on diseases of women in childbearing age that are not related to the pregnancy. The objective of the paper is to deliver population based prevalences of chronic dieases in childbearing women and compare the two groups of chronically ill women and healthy women in detail regarding sociodemography, peri- and prenatal parameters and birth outcomes. METHODS: Data of n = 5320 childbearing women were evaluated in the context of the population-based Survey of Neonates in Pomerania (SNiP). Data were obtained via face-to-face interviews, self-applied questionnaires, and abstraction from medical records at the time of giving birth. Sociodemographic and health status data were assessed, including chronic diseases that were taken out of medical records. A comprehensive set of pre- and perinatal varaiables were assessed. RESULTS: In the SNiP, every fifth pregnant woman suffers from at least one chronic disease, and higher prevalence rates have been reported in the literature. There was a significant difference between chronically ill women and healthy women in age, education and income. Prenatal complications were more frequent in the healthy group than in the chronic disease group. Women with chronic diseases delivered by Cesarean section more frequently than women in the healthy group. Every tenth woman with at least one chronic disease gave birth to a premature infant, while only one in every 13 woman in the healthy control group gave birth to a premature infant. CONCLUSIONS: This analysis is the first population-based study in which all chronic diseases could be taken into consideration. The population-based prevalences rates in the SNiP data are consistently lower than those found in the literature. There are differences between chronically ill women and healthy women in peri- and prenatal variables as well as birth outcome on the population level. However, they are less frequent than expected and further analyses are need focusing on specific diseases.

Evidence for cooperative and domain-specific binding of the signal transducing adaptor molecule 2 (STAM2) to Lys63-linked diubiquitin.

As the upstream component of the ESCRT (endosomal sorting complexes required for transport) machinery, the ESCRT-0 complex is responsible for directing ubiquitinated membrane proteins to the multivesicular body pathway. ESCRT-0 is formed by two subunits known as Hrs (hepatocyte growth factor-regulated substrate) and STAM (signal transducing adaptor molecule), both of which harbor multiple ubiquitin-binding domains (UBDs). In particular, STAM2 possesses two UBDs, the VHS (Vps27/Hrs/Stam) and UIM (ubiquitin interacting motif) domains, connected by a 20-amino acid flexible linker. In the present study, we report the interactions of the UIM domain and VHS-UIM construct of STAM2 with monoubiquitin (Ub), Lys(48)- and Lys(63)-linked diubiquitins. Our results demonstrate that the UIM domain alone binds monoubiquitin, Lys(48)- and Lys(63)-linked diubiquitins with the same affinity and in the same binding mode. Interestingly, binding of VHS-UIM to Lys(63)-linked diubiquitin is not only avid, but also cooperative. We also show that the distal domain of Lys(63)-linked diubiquitin stabilizes the helical structure of the UIM domain and that the corresponding complex adopts a specific structural organization responsible for its greater affinity. In contrast, binding of VHS-UIM to Lys(48)-linked diubiquitin and monoubiquitin is not cooperative and does not show any avidity. These results may explain the better sorting efficiency of some cargoes polyubiquitinated with Lys(63)-linked chains over monoubiquitinated cargoes or those tagged with Lys(48)-linked chains.

What Causes Seizures in Neurocysticercosis?

Neurocysticercosis (NCC) is the most prevalent parasitic infection of the central nervous system. It is caused by the presence of larvae of the cestode Taenia solium in the brain. The most common symptom of NCC is seizures, and it is widely considered the world's leading cause of preventable epilepsy. Despite the prevalence and impact of NCC, a thorough, mechanistic understanding of seizure generation is still lacking. In this review, we address the question "What causes seizures in NCC?" by summarizing and discussing the major theories that seek to explain the seizurogenic and epileptogenic processes in this disorder. In addition, we highlight the potential for recent advances in disease modeling to help accelerate progress in this area.

Antenatal Care and Health Behavior of Pregnant Women-An Evaluation of the Survey of Neonates in Pomerania.

BACKGROUND: The German maternity guidelines require regular medical checkup (MC) during pregnancy as a measure of prevention. Socioeconomic factors such as education, profession, income and origin, but also age and parity may influence the preventive and health behavior of pregnant women. The aim was to investigate the influence of these factors on the participation rate in MC of pregnant women. METHOD: The current analysis is based on the prospective population-based birth cohort study Survey of Neonates in Pomerania, which was conducted in Western Pomerania, Germany. The data of 4092 pregnant women from 2004 to 2008 were analyzed regarding the antenatal care and health behavior. Up to 12 MC were regularly offered; participation in 10 MC is defined as standard screening according to maternity guidelines. RESULTS: Women participated in the first preventive MC on average in the 10th (±3.8 SD) week of pregnancy. 1343 (34.2%) women participated in standard screening and 2039 (51.9%) took a screening above standard. 547 (13.92%) women participated in less than the 10 standard MCs. In addition, about one-third of the pregnancies investigated in this study were unplanned. Bivariate analyses showed an association between better antenatal care behavior and higher maternal age, stabile partnerships and mother born in Germany, p < 0.05. On the contrary antenatal care below standard were more often found by women with unplanned pregnancies, less educational women and women with lower equivalent income, p < 0.001. Health behaviors also influenced antenatal care. Whereas the risk of antenatal care below standard increased by smoking during pregnancy (RRR 1.64; 95% CI 1.25, 2.14) and alcohol consumption (RRR 1.31; 95% CI 1.01, 1.69), supplementation intake was associated with decreased risk (iodine-RRR 0.66; 95% CI 0.53, 0.81; folic acid-RRR 0.56; 95% CI 0.44, 0.72). The health behavior of pregnant women also differs according to their social status. Higher maternal income was negatively correlated with smoking during pregnancy (OR 0.2; 95% CI 0.15, 0.24), but positively associated with alcohol consumption during pregnancy (OR 1.3; 95% CI 1.15, 1.48) and lower pre-pregnancy BMI (Coef. = 0.083, p < 0.001). Lower maternal education was positively correlated with smoking during pregnancy (OR 59.0; 95% CI 28.68, 121.23). CONCLUSIONS: Prenatal care according to maternity guidelines is well established with a high participation rate in MC during pregnancy of more than 85%. However, targeted preventive measures may address younger age, socioeconomic status and health-damaging behaviors (smoking, drinking) of the pregnant women because these factors were associated with antenatal care below standard.

Mouse Organotypic Brain Slice Cultures: A Novel Model for Studying Neuroimmune Responses to Cryptococcal Brain Infections.

Cryptococcal meningitis affects millions of people worldwide and is especially prevalent in regions with a high burden of HIV/AIDS. The study of the pathophysiology of this often fatal disease has been significantly hindered by the lack of reliable experimental models, especially at the level of the brain, which is the main organ of injury. Here we outline our novel protocol for the use of hippocampal organotypic brain slice cultures (HOCs) to study the host-fungal interactions during cryptococcal infections of the brain. HOCs are a powerful platform for investigating neuroimmune interactions as they allow for the preservation of all innate neuroglial cells including microglia, astrocytes, and neurons, all of which maintain their three-dimensional architecture and functional connectivity. We made HOCs from neonatal mice and infected these with a fluorescent strain of Cryptococcus neoformans for 24 h. Using immunofluorescent staining, we confirmed the presence and morphology of microglia, astrocytes, and neurons in HOCs prior to infection. Using fluorescent and light microscopy, we also confirmed that Cryptococcus neoformans encapsulates and buds in vitro, as it would in a host. Finally, we demonstrate that infection of HOCs with Cryptococcus neoformans results in close association of the fungal cells with host microglial cells. Our results demonstrate the utility of HOCs as a model to study the pathophysiology and host neuroimmune responses in neurocryptococcosis, which may assist in improving our collective understanding of the pathogenesis of this disease.

A Water-Free Omega-3 Fatty Acid Eye Drop Formulation for the Treatment of Evaporative Dry Eye Disease: A Prospective, Multicenter Noninterventional Study.

Purpose: NovaTears®+Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI©) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials.gov (NCT04521465).