Intrathecal IgM synthesis as a diagnostic marker in patients with suspected CNS lymphoma.

For CNS lymphomas (CNSL), there is a high need for minimally invasive and easily obtainable diagnostic markers. Intrathecal IgM synthesis can easily be determined in routine CSF diagnostics. The aim of this study was to systematically investigate the diagnostic potential of intrathecal IgM synthesis in primary and secondary CNSL (PCNSL and SCNSL). In this retrospective study, patients with a biopsy-proven diagnosis of PCNSL or SCNSL were compared with patients with other neurological diseases in whom CNSL was initially the primary radiological differential diagnosis based on MRI. Sensitivity and specificity of intrathecal IgM synthesis were calculated using receiver operating characteristic curves. Seventy patients with CNSL were included (49 PCNSL and 21 SCNSL) and compared to 70 control patients. The sensitivity and specificity for the diagnosis of CNSL were 49% and 87%, respectively, for the entire patient population and 66% and 91% after selection for cases with tumor access to the CSF system and isolated intrathecal IgM synthesis. In cases with MRI-based radiological suspicion of CNSL, intrathecal IgM synthesis has good specificity but limited sensitivity. Because of its low-threshold availability, analysis of intrathecal IgM synthesis has the potential to lead to higher diagnostic accuracy, especially in resource-limited settings, and deserves further study.

2D 1H sLASER Long-TE and 3D 31P Chemical Shift Imaging at 3 T for Monitoring Fasting-Induced Changes in Brain Tumor Tissue.

BACKGROUND: Emerging evidence suggests that fasting could play a key role in cancer treatment. Its metabolic effects on gliomas require further investigation. PURPOSE: To design a multi-voxel 1H/31P MR-spectroscopic imaging (MRSI) protocol for noninvasive metabolic monitoring of cerebral, fasting-induced changes on an individual patient/tumor level, and to assess its technical reliability/reproducibility. STUDY TYPE: Prospective. POPULATION: MRS phantom. Twenty-two patients (mean age = 61, 6 female) with suspected WHO grade II-IV glioma examined before and after 72-hour-fasting prior to biopsy/resection. FIELD STRENGTH/SEQUENCE: 3-T, 1H decoupled 3D 31P MRSI, 2D 1H sLASER MRSI at an echo time of 144 msec, 2D 1H MRSI (as water reference), T1-weighted, T1-weighted contrast-enhanced, T2-weighted, and FLAIR. sLASER and PRESS sequences were used for phantom measurements. ASSESSMENT: Phantom measurements and spectral simulations were performed with various echo-times for protocol optimization. In vivo spectral analyses were conducted using LCModel and AMARES, obtaining quality/fitting parameters (linewidth, signal-to-noise-ratio, and uncertainty measures of fitting) and metabolite intensities. The volume of glioma sub-regions was calculated and correlated with MRS findings. Ex-vivo spectra of necrotic tumor tissues were obtained using high-resolution magic-angle spinning (HR-MAS) technique. STATISTICAL TESTS: Wilcoxon signed-rank test, Bland-Altman plots, and coefficient of variation were used for repeatability analysis of quality/fitting parameters and metabolite concentrations. Spearman ρ correlation for the concentration of ketone bodies with volumes of glioma sub-regions was determined. A P-value <0.05 was considered statistically significant. RESULTS: 1H and 31P repeatability measures were highly consistent between the two sessions. ß-hydroxybutyrate and acetoacetate were detectable (fitting-uncertainty <50%) in glioma sub-regions of all patients who completed the 72-hour-fasting cycle. ß-hydroxybutyrate accumulation was significantly correlated with the necrotic/non-enhancing tumor core volume (ρ = 0.81) and validated using ex-vivo 1H HR-MAS. DATA CONCLUSION: We propose a comprehensive MRS protocol that may be used for monitoring cerebral, fasting-induced changes in patients with glioma. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Plasma boron concentrations and risk of all-cause mortality in the general population.

PURPOSE: Higher dietary intake or higher circulating levels of the trace element boron have been associated with beneficial effects on human health. However, the relationship between plasma boron levels and survival in the general population is not known. Therefore, we aimed to assess the association between plasma boron concentrations and all-cause mortality in a population-based cohort from northern Germany (n = 863 individuals; median age 62.3 years, 42.8% women). METHODS: Plasma boron concentrations (median 31.9 µg/L [22.9; 43.5]) were measured by inductively coupled plasma-mass spectrometry. Cox proportional hazards regression models adjusted for relevant confounders were used to associate plasma boron concentrations with all-cause mortality. RESULTS: After a median follow-up time of 11 years, n = 99 individuals had died. In the overall sample, plasma boron concentrations were associated with all-cause mortality in the crude model (HR: 1.07 [95% CI 1.03-1.11] per 5-unit-increment). However, multivariable adjustment rendered the association non-significant (HR: 1.03 [95% CI 0.99-1.07]). Sex-stratified analyses revealed slightly higher mortality hazards with increasing plasma boron concentrations in women (HR: 1.11 [95% CI 1.03-1.18], pInteraction = 0.034), but not in men (HR: 1.00 [95% CI 0.95-1.06]). CONCLUSION: We conclude that in a moderate-sized sample from the general population, higher plasma boron concentrations were associated with a higher risk of all-cause mortality in women, but not in men. Due to the low number of events in the female subsample (n = 27), this observation has to be interpreted with caution.

Greater adherence to the Healthy Nordic Food Index is associated with lower all-cause mortality in a population-based sample from northern Germany.

PURPOSE: Dietary pattern scores reflecting a high intake of beneficial food groups were associated with reduced mortality risk. Data on associations of such dietary pattern scores in population-based samples from northern Germany are lacking. Therefore, we examined the association of three dietary pattern scores with all-cause mortality in a moderate-sized prospective sample from northern Germany. METHODS: The study sample comprised 836 participants (43.8% females, median age 62.4 years). Based on a validated, self-administered Food Frequency Questionnaire, the dietary scores Dietary Approaches to Stop Hypertension (DASH), Modified Mediterranean Diet Score (MMDS), and Healthy Nordic Food Index (HNFI) were calculated. Cox proportional hazard regression models, adjusted for age, sex, body mass index, waist to hip ratio, education, smoking status, total energy intake, and physical activity, were used to separately relate DASH, MMDS, and HNFI to all-cause mortality. RESULTS: During a median follow-up period of 11 years, 93 individuals died. While DASH and MMDS scores were not associated with all-cause mortality, greater adherence to HNFI was associated with lower mortality hazards (HR: 0.47 [95% CI 0.25-0.89] when comparing the highest score quartile to the lowest; HR: 0.79 [95% CI 0.64-0.98] for HNFI modeled as a 1-Standard Deviation increment). Among different HNFI components, higher intake of oats and cereals displayed the most conclusive association with all-cause mortality (HR: 0.59 [95% CI 0.38-0.91] when comparing high and low intake). CONCLUSION: In an elderly general population sample from northern Germany, we observed greater adherence to HNFI to be associated with lower all-cause mortality.

Association of dietary patterns with diabetes-related comorbidities varies among diabetes endotypes.

BACKGROUND AND AIMS: Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes. METHODS AND RESULTS: The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %). Adherence to a Mediterranean diet score (MDS), Dietary Approaches to Stop Hypertension (DASH) score, overall plant-based diet (PDI), healthful (hPDI) and unhealthful plant-based diet index (uPDI) was derived from a food frequency questionnaire and associated with cardiovascular risk factors, kidney function, and neuropathy using multivariable linear regression analysis. Differences in dietary pattern adherence between endotypes were assessed using generalized mixed models. People with MARD showed the highest, those with SIDD and MOD the lowest adherence to the hPDI. Adherence to the MDS, DASH, overall PDI, and hPDI was inversely associated with high-sensitivity C-reactive protein (hsCRP) among people with MARD (ß (95%CI): -9.18 % (-15.61; -2.26); -13.61 % (-24.17; -1.58); -19.15 % (-34.28; -0.53); -16.10 % (-28.81; -1.12), respectively). Adherence to the PDIs was associated with LDL cholesterol among people with SAID, SIRD, and MOD. CONCLUSIONS: Minor differences in dietary pattern adherence (in particular for hPDI) and associations with markers of diabetes-related complications (e.g. hsCRP) were observed between endotypes. So far, evidence is insufficient to derive endotype-specific dietary recommendations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01055093.

[(Auto)immunity in focal epilepsy: mechanisms of (auto­)immune-inflammatory epileptogenic neurodegeneration]. / (Auto­)Immunität bei fokaler Epilepsie: Mechanismen (auto­)immun-inflammatorischer epileptogener Neurodegeneration.

OBJECTIVE: While the neuronal mechanisms of epileptic hyperexcitability (HE) have been studied in detail, recent findings suggest that extraneuronal, mainly immune-mediated inflammatory and vascular mechanisms play an important role in the development and progression of HE in epilepsy and the cognitive and behavioral comorbidities. MATERIAL AND METHODS: Narrative review. RESULTS: As in autoimmune (limbic) encephalitis (ALE/AIE) or Rasmussen's encephalitis (RE), the primary adaptive and innate immune responses and associated changes in the blood-brain barrier (BBB) and neurovascular unit (NVU) can cause acute cortical hyperexcitability (HE) and the development of hippocampal sclerosis (HS) and other structural cortical lesions with chronic HE. Cortical HE, which is associated with malformation of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT), for example, can be accompanied by secondary adaptive and innate immune responses and alterations in the BBB and NVU, potentially modulating the ictogenicity and epileptogenicity. These associations illustrate the influence of adaptive and innate immune mechanisms and associated changes in the BBB and NVU on cortical excitability and vice versa, suggesting a dynamic and complex interplay of these factors in the development and progression of epilepsy in general. DISCUSSION: The described concept of a neuro-immune-vascular interaction in focal epilepsy opens up new possibilities for the pathogenetic understanding and thus also for the selective therapeutic intervention.

COVID-19, Pregnancy, and Diabetes Mellitus.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.

The iron chelator and OXPHOS inhibitor VLX600 induces mitophagy and an autophagy-dependent type of cell death in glioblastoma cells.

Induction of alternative, non-apoptotic cell death programs such as cell-lethal autophagy and mitophagy represent possible strategies to combat glioblastoma (GBM). Here we report that VLX600, a novel iron chelator and oxidative phosphorylation (OXPHOS) inhibitor, induces a caspase-independent type of cell death that is partially rescued in adherent U251 ATG5/7 (autophagy related 5/7) knockout (KO) GBM cells and NCH644 ATG5/7 knockdown (KD) glioma stem-like cells (GSCs), suggesting that VLX600 induces an autophagy-dependent cell death (ADCD) in GBM. This ADCD is accompanied by decreased oxygen consumption, increased expression/mitochondrial localization of BNIP3 (BCL2 interacting protein 3) and BNIP3L (BCL2 interacting protein 3 like), the induction of mitophagy as demonstrated by diminished levels of mitochondrial marker proteins [e.g., COX4I1 (cytochrome c oxidase subunit 4I1)] and the mitoKeima assay as well as increased histone H3 and H4 lysine tri-methylation. Furthermore, the extracellular addition of iron is able to significantly rescue VLX600-induced cell death and mitophagy, pointing out an important role of iron metabolism for GBM cell homeostasis. Interestingly, VLX600 is also able to completely eliminate NCH644 GSC tumors in an organotypic brain slice transplantation model. Our data support the therapeutic concept of ADCD induction in GBM and suggest that VLX600 may be an interesting novel drug candidate for the treatment of this tumor.NEW & NOTEWORTHY Induction of cell-lethal autophagy represents a possible strategy to combat glioblastoma (GBM). Here, we demonstrate that the novel iron chelator and OXPHOS inhibitor VLX600 exerts pronounced tumor cell-killing effects in adherently cultured GBM cells and glioblastoma stem-like cell (GSC) spheroid cultures that depend on the iron-chelating function of VLX600 and on autophagy activation, underscoring the context-dependent role of autophagy in therapy responses. VLX600 represents an interesting novel drug candidate for the treatment of this tumor.

Plasma Ferritin Concentrations in the General Population: A Cross-Sectional Analysis of Anthropometric, Metabolic, and Dietary Correlates.

BACKGROUND: Elevated concentrations of ferritin seem to be detrimental to human health while being quite common in the elderly. Data on dietary, anthropometric, and metabolic correlates of circulating ferritin levels in the elderly are scant. OBJECTIVES: We aimed to identify a dietary pattern, anthropometric, and metabolic traits associated with plasma ferritin status in an elderly cohort (n = 460, 57% male, age: 66 ± 12 y) from Northern Germany. METHODS: Plasma ferritin levels were measured by immunoturbidimetry. Reduced rank regression (RRR) yielded a dietary pattern explaining 13% of the variation in circulating ferritin concentrations. Cross-sectional associations of anthropometric and metabolic traits with plasma ferritin concentrations were assessed using multivariable-adjusted linear regression analysis. Restricted cubic spline regression was used to identify nonlinear associations. RESULTS: The RRR pattern was characterized by a high intake of potatoes, certain vegetables, beef, pork, processed meat, fats (frying and animal fat), and beer and a low intake of snacks, representing elements of the traditional German diet. BMI, waist circumference, and CRP were directly, HDL cholesterol inversely, and age nonlinearly associated with plasma ferritin concentrations (all P < 0.05). After additional adjustment for CRP, only the association of ferritin with age remained statistically significant. CONCLUSION: Higher plasma ferritin concentrations were associated with a traditional German dietary pattern. The associations of ferritin with unfavorable anthropometric traits and low HDL cholesterol were rendered statistically nonsignificant upon additional adjustment for chronic systemic inflammation (measured as elevated biomarker of the measurement of inflammation (CRP)), suggesting that these associations were largely driven by the proinflammatory role of ferritin (an acute-phase reactant).

Creating Hydrophobic Foils From Biopolymer Blends Using Mechanical Microimprinting.

The surface topography of biodegradable polymer foils is modified by mechanical imprinting on a submillimeter length scale. The created patterns strongly influence the wetting behavior and allow the preparation of hydrophobic surfaces with controlled solid-liquid interaction. A detailed analysis of anisotropic surface patterns reveals that the observed effect arises from a combination of topographical and compositional changes that are introduced to the surface. As a main result it is found that an individual combination of material and structure is required for the production of water-repellent biopolymer foils that are highly attractive for packaging applications.

Creating Hydrophobic Foils From Biopolymer Blends Using Mechanical Microimprinting.

The front cover artwork is provided by Hang Liu from Prof. Dr. Joachim Albrecht's and Prof. Dr. Katharina Weber's group at Aalen University. The image depicts the wetting properties of a biopolymer foil. Surface microstructuring allows the tailoring of physical chemical properties that can lead to biodegradable packaging foils. Read the full text of the Research Article at 10.1002/cphc.202300301.

3D-Printed Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-Cellulose-Based Scaffolds for Biomedical Applications.

While biomaterials have become indispensable for a wide range of tissue repair strategies, second removal procedures oftentimes needed in the case of non-bio-based and non-bioresorbable scaffolds are associated with significant drawbacks not only for the patient, including the risk of infection, impaired healing, or tissue damage, but also for the healthcare system in terms of cost and resources. New biopolymers are increasingly being investigated in the field of tissue regeneration, but their widespread use is still hampered by limitations regarding mechanical, biological, and functional performance when compared to traditional materials. Therefore, a common strategy to tune and broaden the final properties of biopolymers is through the effect of different reinforcing agents. This research work focused on the fabrication and characterization of a bio-based and bioresorbable composite material obtained by compounding a poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) matrix with acetylated cellulose nanocrystals (CNCs). The developed biocomposite was further processed to obtain three-dimensional scaffolds by additive manufacturing (AM). The 3D printability of the PHBH-CNC biocomposites was demonstrated by realizing different scaffold geometries, and the results of in vitro cell viability studies provided a clear indication of the cytocompatibility of the biocomposites. Moreover, the CNC content proved to be an important parameter in tuning the different functional properties of the scaffolds. It was demonstrated that the water affinity, surface roughness, and in vitro degradability rate of biocomposites increase with increasing CNC content. Therefore, this tailoring effect of CNC can expand the potential field of use of the PHBH biopolymer, making it an attractive candidate for a variety of tissue engineering applications.

Treatment of very elderly glioblastoma patients ≥ 75 years of age: whom to treat.

PURPOSE: The prognosis of patients ≥ 75 years suffering from glioblastoma is poor. Novel therapies are usually reserved for patients ≤ 70 years. In an aging population, treatment of very elderly patients remains a challenge. METHODS: Between 2010 and 2018, a total of 977 glioblastoma patients were treated at our institution. Of these, 143 patients were ≥ 75 years at diagnosis. Primary procedure was surgical resection or biopsy followed by adjuvant treatment, whenever possible. We retrospectively investigated overall survival (OS) and potential prognostic factors influencing survival, including Karnofsky Performance Status (KPS), surgical therapy, adjuvant therapy as well as MGMT promotor status. RESULTS: In very elderly patients, median age was 79 years (range: 75-110). Biopsy only was performed in 104 patients; resection was performed in 39 patients. Median OS for the entire cohort was 5.9 months. Univariate analysis showed that KPS at presentation (≥ 70 vs. ≤60), surgery vs. biopsy, adjuvant chemotherapy and adjuvant radiotherapy were significantly associated with OS (6 vs. 3, p < 0.0111; 12 vs. 4, p = 0.0011; 11 vs. 4, p = 0.0003 and 10 vs. 1.5 months, p < 0.0001, respectively). Multivariate analysis confirmed adjuvant radiotherapy (p < 0.0001) and chemotherapy (p = 0.0002) as independent factors influencing OS. CONCLUSION: For very elderly patients, the natural course of disease without treatment is devastating. These patients benefit from multimodal treatment including adjuvant radiotherapy and chemotherapy. A beneficial effect of resection has not been demonstrated. Treatment options and outcomes should be thoughtfully discussed before treatment decisions are made.

Tissue Shrinkage of Resected Specimens in Hirschsprung's Disease: Why Pediatric Surgeons Think the Bowel Specimen was Longer Than Indicated in the Pathology Report.

BACKGROUND: Hirschsprung disease (HD) is an aganglionosis of variable length starting at the rectosigmoid colon with surgery as sole therapeutic option. The length of the resected bowel segment is a crucial information for the treating surgeons and influences the prognosis of the patient. It is often artificially altered due to post operative tissue shrinkage. The objective of this study is to quantify the extent tissue shrinkage of HD specimens. MATERIAL AND METHODS: Colorectal HD specimens were measured at the time of surgery and at the time of cut-up, either fresh or after formalin fixation and statistically analyzed. RESULTS: Sixteen colorectal specimens were included. Following formalin fixation the specimen length decreased by 22.7% (P < .001). Without formalin fixation the specimens shrank by an average of 24.9% (P = .05). There was no significant difference in the extent of tissue shrinkage with or without formalin fixation (P = .76). CONCLUSION: This study showed that there is significant tissue shrinkage in HD specimens. The 2 different cohorts revealed that tissue shrinkage is mostly caused by tissue retraction/alteration after organ removal but also to a lesser extent by fixation with formalin. Surgeons and (neuro-)pathologists should be aware of the sizeable shrinking artifact to avoid unnecessary confusion.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Plasma boron concentrations in the general population: a cross-sectional analysis of cardio-metabolic and dietary correlates.

PURPOSE: Experimental evidence suggests positive effects of boron on health and metabolism, but human data are still scarce. We aimed to identify dietary and cardio-metabolic correlates of plasma boron concentrations in the general population. METHODS: In a community-based sample (n = 899, 57% men, mean age 61 years), plasma boron (median [IQR]: 33.80 µg/L [25.61; 44.65]) concentrations were measured by inductively coupled plasma-mass spectrometry. Overall (PDI), healthy (hPDI), and unhealthy (uPDI) plant-based diet indices were derived from a validated food frequency questionnaire. Reduced rank regression (RRR) yielded a dietary pattern explaining 30% of the variation of circulating boron. Cross-sectional associations of dietary indices and cardio-metabolic traits with plasma boron concentrations were assessed using multivariable-adjusted linear regression analysis. RESULTS: The RRR pattern was characterized by high intake of fruits, nuts/seeds, tea, wine and low intake of e.g. bread, poultry, processed meat, chocolate/sweets, and soft drinks. 10-point increments in PDI, hPDI, and uPDI were associated with 8.7% (95% CI: 4.2; 13.4), 10.4% (95% CI: 6.6; 14.3), and -8.8% (95% CI: -12.1; -5.4) change in plasma boron concentrations, respectively. Age and phosphate were directly, while BMI, plasma lipid concentrations, and CRP were inversely associated with circulating boron. Plasma boron concentrations were higher in summer vs. winter, in individuals taking vs. not taking antihypertensive medication, and in individuals with high or medium vs. low education level. CONCLUSION: Higher plasma boron concentrations appeared to associate with a healthier diet, were related to lower BMI and a more favorable cardio-metabolic risk profile, and showed seasonal variations.

Maternal pregnancy weight or gestational weight gain and offspring's blood pressure: A systematic review.

AIMS: An increasing number of studies suggest that maternal weight parameters in pregnancy are associated with offspring's blood pressure (BP). The aim of this systematic review - following the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement - was to assess and judge the evidence for an association between maternal pregnancy weight/body mass index (BMI) or gestational weight gain (GWG) with offspring's BP in later life. DATA SYNTHESIS: MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science were searched without limits. Risk of bias was assessed using the "US National Heart, Lung and Blood Institute"-tool, and an evidence grade was allocated following the "World Cancer Research Fund" criteria. Of 7,124 publications retrieved, 16 studies (all cohort studies) were included in the systematic review. Overall data from 52,606 participants (0 years [newborns] to 32 years) were enclosed. Association between maternal pregnancy BMI and offspring's BP were analyzed in 2 (both "good-quality" rated) studies, without consistent results. GWG and offspring's BP was analyzed in 14 studies (2 "good-quality", 9 "fair-quality", 3 "poor-quality" rated). Of these, 3 "fair-quality" studies described significant positive results for systolic BP and significant results, but partly with varying directions of effect estimates for diastolic BP. Mean arterial pressure (MAP) was analyzed in 1 "poor-quality" congress paper. Overall, based on the small number of "good-quality"-rated studies and the inconsistency of effect direction, no firm conclusion can be drawn. CONCLUSION: Evidence for an association of maternal pregnancy weight determinants with offspring's BP was overall graded as "limited - no conclusion".

Relative validity of a glycemic index extended food-frequency questionnaire.

BACKGROUND AND AIMS: The dietary glycemic index (GI) and glycemic load (GL) are increasingly recognized as important for the prevention and management of diabetes mellitus. To extend the portfolio of assessment methods for large-scale epidemiological studies, we propose a GI-specific addition to an already established FFQ. METHODS AND RESULTS: The German version of the EPIC-FFQ was extended by GI-specific questions for major carbohydrate sources varying notably in GI (breakfast cereals, bread, pasta, rice, potato etc.). We performed relative validation analyses comparing the GI-extended FFQ to three to four 3-day weighted dietary records (3-d WDR) in 100 middle-aged individuals with diabetes mellitus participating in the German Diabetes Study (GDS). Level of agreement between the two methods was assessed by correlation and cross-classification analyses as well as Bland-Altman-Plots, conducted separately for women and men. Spearman correlation analysis for female participants suggested good agreement between the GI-extended FFQ and 3-d WDRs for energy adjusted dietary GL (r = 0.52, p = 0.0004). For both women and men, agreement with the estimations of dietary GI, GL (for men) and carbohydrates from low and higher-GI food sources from the GI-extended FFQ was acceptable (r: 0.28-0.45). Classification of the dietary GI and GL in the opposite quartile was <10% comparing the GI-extended FFQ and 3-d WDR. Bland-Altman plots suggested a tendency for an overestimation of the dietary GI from the GI-extended FFQ in the lower GI-ranges, particularly for men. CONCLUSION: Compared to the 3-d WDR, the GI-extended FFQ showed a moderate to good relative validity for parameters of carbohydrate quality.

A comparative analysis of the intrauterine transcriptome in fertile and subfertile mares using cytobrush sampling.

BACKGROUND: Subfertility is a major problem in modern horse breeding. Especially, mares without clinical signs of reproductive diseases, without known uterine pathogens and no evidence of inflammation but not becoming pregnant after several breeding attempts are challenging for veterinarians. To obtain new insights into the cause of these fertility problems and aiming at improving diagnosis of subfertile mares, a comparative analysis of the intrauterine transcriptome in subfertile and fertile mares was performed. Uterine cytobrush samples were collected during estrus from 57 mares without clinical signs of uterine diseases. RNA was extracted from the cytobrush samples and samples from 11 selected subfertile and 11 fertile mares were used for Illumina RNA-sequencing. RESULTS: The cytobrush sampling was a suitable technique to isolate enough RNA of high quality for transcriptome analysis. Comparing subfertile and fertile mares, 114 differentially expressed genes (FDR = 10%) were identified. Metascape enrichment analysis revealed that genes with lower mRNA levels in subfertile mares were related to 'extracellular matrix (ECM)', 'ECM-receptor interaction', 'focal adhesion', 'immune response' and 'cytosolic calcium ion concentration', while DEGs with higher levels in subfertile mares were enriched for 'monocarboxyl acid transmembrane transport activity' and 'protein targeting'. CONCLUSION: Our study revealed significant differences in the uterine transcriptome between fertile and subfertile mares and provides leads for potential uterine molecular biomarkers of subfertility in the mare.

Virus pH-Dependent Interactions with Cationically Modified Cellulose and Their Application in Water Filtration.

Norovirus and Rotavirus are among the pathogens causing a large number of disease outbreaks due to contaminated water. These viruses are nanoscale particles that are difficult to remove by common filtration approaches which are based on physical size exclusion, and require adsorption-based filtration methods. This study reports the pH-responsive interactions of viruses with cationic-modified nanocellulose and demonstrates a filter material that adsorbs nanoscale viruses and can be regenerated by changing the solution's pH. The bacteria viruses Qbeta and MS2, with diameters below 30 nm but different surface properties, are used to evaluate the pH-dependency of the interactions and the filtration process. Small angle X-ray scattering, cryogenic transmission electron microscopy, and ζ-potential measurements are used to study the interactions and analyze changes in their nanostructure and surface properties of the virus upon adsorption. The virus removal capacity of the cationic cellulose-based aerogel filter is 99.9% for MS2 and 93.6% for Qbeta, at pH = 7.0; and desorption of mostly intact viruses occurs at pH = 3.0. The results contribute to the fundamental understanding of pH-triggered virus-nanocellulose self-assembly and can guide the design of sustainable and environmentally friendly adsorption-based virus filter materials as well as phage and virus-based materials.