Comparison of aggregated exposure to perfluorooctanoic acid (PFOA) from diet and personal care products with concentrations in blood using a PBPK model - Results from the Norwegian biomonitoring study in EuroMix.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) constitute a large group of compounds that are water, stain, and oil repellent. Numerous sources contribute to the blood levels of PFAS in the European population. The main contributor for perfluorooctanoic acid (PFOA) is food, house dust, consumer products and personal care products (PCPs). OBJECTIVES: The purpose of the present work is to calculate the dietary and dermal external exposure to PFOA, estimate the aggregated internal exposure from diet and PCPs using a PBPK model, and compare estimates with measured concentrations. METHODS: Detailed information on diet and PCP use from the EuroMix study is combined with concentration data of PFOA in food and PCPs in a probabilistic exposure assessment. A physiologically based pharmacokinetic model (PBPK) was further refined by incorporating a dermal exposure pathway, and changes in the kidney and faecal excretion. RESULTS: The aggregated internal exposure using the PBPK model shows that the major contributor to the internal exposure is diet for both males and females. The estimated internal exposure of PFOA for the EuroMix population was in the same range but lower than the measured blood concentrations using the lower bound (LB) external exposure estimates, showing that the LB estimates are underestimations. For seven females the internal exposure of PFOA were higher from PCPs than from diet. CONCLUSION: PCPs and diet contributed in the same range to the internal PFOA exposure for several women participating in EuroMix. This calls for additional studies on exposure to PFOA and possibly other PFAS from PCPs, especially for women. Overall, PBPK modelling was shown as valuable tool in understanding the sources of PFOA exposure and in guiding risk assessments and regulatory decisions.

Suicide-Specific Training Experiences and Needs Among Military Mental Health Providers.

BACKGROUND: Military suicide rates have risen over the past two decades, with a notable spike in recent years. To address this issue, military mental health providers must be equipped with the skills required to provide timely and effective care; yet little is known about the suicide-specific training experiences or needs of these professionals. METHODS: Thirty-five mental health care providers who treat active duty personnel at military treatment facilities participated in this mixed-methods study. All participants completed a survey assessing training and clinical experiences, comfort and proficiency in working with patients at risk for suicide, and perceived barriers to obtaining suicide-specific training. A sub-set of participants (n = 8) completed a telephone interview to further describe previous experiences and perceived challenges to obtaining training. RESULTS: The majority of participants (79.4%) had 6+ years of clinical experience, had a patient who had attempted suicide (85.3%), and completed at least one suicide-related training since finishing their education (82.4%). Survey results showed the leading barrier to enrolling in suicide-specific trainings was perceived lack of training opportunities (40.7% reported it was a barrier "quite often" or more), followed by lack of time (25%). Interview results revealed lack of time, location and logistical issues, and low perceived need for additional training among providers could impede enrollment. CONCLUSIONS: Study results identified several modifiable barriers to receiving suicide-specific continuing education among military mental health providers. Future efforts should develop accessible training programs that can be easily integrated into routine clinical operations to mount the best defense against suicide. HIGHLIGHTSMilitary mental health providers report significant experience and relatively high degrees of comfort and proficiency working with patients at high risk for suicide.Most providers reported receiving training in suicide assessment and screening; few reported prior training in management of suicidality.Study results identified several modifiable barriers to receiving suicide-prevention continuing education among military mental health care providers; future efforts should seek to develop accessible training programs that can be easily integrated into routine clinical operations to mount the best defense against suicide.

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data.

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021).

BACKGROUND: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. METHODS: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. RESULTS: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 µg/L (1.63-2.78)], PFOA ([0.97 µg/L (0.75-1.26)]), PFNA [0.30 µg/L (0.19-0.45)] and PFHxS [0.41 µg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. CONCLUSION: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.

Oestrus status does not alter breeding suitability assessments regarding medial patellar luxation in female small breed dogs: A blinded multi-observer study.

Study aims were to evaluate if medial patellar luxation clinical grades changed with oestrus status, and to determine interobserver agreement for different classification methods for grading patellar luxation. Intact female dogs were recruited for grading by 3 independent observers on 2 occasions (pro-oestrus/oestrus and dioestrus/anoestrus) using a published grading system. Observers were blinded to oestrus status. Oestrus status was confirmed by vaginal cytology. Observer agreement was determined using Fleiss' multirater kappa on the original grading scores, simplification to the Norwegian Kennel Club system, and further simplification to a binary suitable/not-suitable for breeding system. The exact McNemar's test was used to assess the effect of oestrus on classification. Of 70 dogs recruited, 53 underwent paired observations. Interobserver agreement was considered moderate to very good for the study sub-groups, with overall kappa values of 0.68 (95% CI 0.63-0.72), 0.79 (0.73-0.84) and 0.92 (0.85-0.99), and percentage agreements of 65%, 81% and 94%, for the original, simplified and binary classifications. Oestrus status did not have a significant effect on classification of breeding suitability. Clinicians and owners should not be concerned about the timing of patellar luxation grading in relation to oestrus. Experienced observers show good or very good agreement using the Norwegian Kennel Club and binary categorisations.

HLA-DRB1 polymorphism in recurrent pregnancy loss: New evidence for an association to HLA-DRB1*07.

Many cases of recurrent pregnancy loss (RPL) defined as ≥3 consecutive pregnancy losses are suggested to be caused by an aberrant maternal immune response against the fetus or trophoblast. Human leukocyte antigen (HLA)-DRB1 and -DQB1 polymorphisms are associated with most autoimmune disorders and studies of HLA-DBB1 polymorphism in RPL patients are thus relevant. In previous studies, the HLA-DRB1*03 allele was found with increased prevalence in RPL patients. We wanted to clarify whether HLA-DRB1 alleles indeed were associated with RPL among women of Caucasian descent. A total of 1078 women with unexplained RPL and 2066 bone marrow donors were HLA-DRB1-typed and subsets were also HLA-DQB1 typed. All patients were initially HLA-DRB1-typed by DNA-based low-resolution techniques and subsets of patients and all controls were typed by high-resolution techniques. Among patients, the HLA-DRB1*07 allele frequency was significantly increased compared with controls; OR 1.29 (95 % CI 1.09-1.52), p < 0.0025; after correction for multiple comparisons pc = 0.031. The HLA-DRB1*07/*07 genotype was highly increased in patients with RPL compared with controls: OR 2.27 (1.31-3.93), p = 0.0027. The frequency of the HLA-DRB1*07 phenotype in RPL patients had increased significantly (p = 0.002) in three studies from our group published 1994-2021. The allele frequency of HLA-DRB1*03 was not increased in RPL patients compared with controls; OR 0.96 (0.83-1.12). In conclusion, the previous association between HLA-DRB1*03 and RPL could not be confirmed in our study whereas an association to HLA-DRB1*07 was detected for the first time. Since the latter association is a new finding, it should be confirmed in future studies.

Comparison of aggregated exposure to di(2-ethylhexyl) phthalate from diet and personal care products with urinary concentrations of metabolites using a PBPK model - Results from the Norwegian biomonitoring study in EuroMix.

Phthalates are widely used as plasticisers in flexible plastics and containers for food and personal care products (PCPs) and contaminates foods and PCPs. A human biomonitoring (BM) study was performed to study exposure of chemicals from foods and PCPs. For two 24-h periods, adult volunteers (n = 144) in Norway kept diaries on food eaten and usage of PCPs, and collected 24-h urine. Aggregated exposure to di(2-ethylhexyl) phthalate (DEHP) from dietary and PCPs was estimated by Monte-Carlo simulation using Oracle Crystal Ball©. Simulated urinary concentrations using physiologically based pharmacokinetic (PBPK) models were compared with measured urinary metabolites of DEHP, mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl 5-carboxypentyl phthalate (MECCP). DEHP exposure from food are approximately 10 times higher than exposure than from PCPs. The main contributors to dietary exposure are dairy, grain, fruits and vegetables, meat and fish. Body lotion contribute most to the exposure of DEHP from PCPs. Forward-dosimetry gives good convergence with 24-h urinary concentrations of simulated and measured BM data. The measured concentration of the MECCP metabolite correlated well with simulated high exposure, while the measured concentrations of MEHP, MEHHP and MEOHP partly overlapped with both simulated low, medium and high metabolite exposure.

Structural brain maturation differs between preterm and term piglets, whereas brain activity does not.

AIM: The aim of the study was to investigate whether amplitude-integrated electroencephalography (aEEG) and cerebral magnetic resonance imaging (MRI) in preterm piglets would provide measures of cerebral functional, microstructural and anatomical maturation, which might reflect the signs of functional brain immaturity, documented in preterm piglets. METHODS: During July-October 2013 at the NEOMUNE Centre, Copenhagen University, Denmark, 31 preterm (90% gestation) and 10 term piglets underwent aEEG on days 1, 2, 4 and 11, and MRI on day 25. Physical activity levels were recorded. RESULTS: Preterm showed delayed neonatal arousal and physical activity, relative to term piglets. Preterm piglets had lower growth rates and brain volume than term piglets, but aEEG patterns were similar. MRI mean diffusivity was also similar, but fractional anisotropy (FA) was lower in preterm piglets (p < 0.001). CONCLUSION: Functional brain maturation, as assessed by aEEG, was relatively advanced in preterm piglets. Conversely, the low FA in the preterm piglets suggests that the white matter microstructure remains less mature in preterm compared to term piglets at postnatal day 25. The results might be utilised to define whether and how preterm piglets may contribute to preclinical models for brain development in preterm infants.

Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.

BACKGROUND: Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). METHODS: The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease. RESULTS: RAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. CONCLUSIONS: The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time.

Patient-controlled hospital admission for patients with severe mental disorders: a nationwide prospective multicentre study.

OBJECTIVE: To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients. METHODS: During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before. RESULTS: No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003). CONCLUSION: Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

MALT1 is an intrinsic regulator of regulatory T cells.

Regulatory T cells (Tregs) are crucial for the maintenance of immunological self-tolerance and their absence or dysfunction can lead to autoimmunity. However, the molecular pathways that govern Treg biology remain obscure. In this study, we show that the nuclear factor-κB signalling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus ('natural' or nTregs) and Tregs induced to differentiate from naive thymocyte helper (Th) cells in the periphery ('induced' or iTregs). Our examination of mice deficient for MALT1 revealed that these mutants have a reduced number of total Tregs. In young Malt1-/- mice, nTregs are totally absent and iTreg are diminished in the periphery. Interestingly, total Treg numbers increase in older Malt1-/- mice as well as in Malt1-/- mice subjected to experimentally induced inflammation. iTregs isolated from WT and Malt1-/- mice were indistinguishable with respect to their ability to suppress the activities of effector T cells, but Malt1-/- iTregs expressed higher levels of Toll-like receptor (TLR) 2. Treatment of WT and Malt1-/- Th cells in vitro with the TLR2 ligand Pam3Cys strongly enhanced the induction and proliferation of Malt1-/- iTregs. Our data suggest that MALT1 supports nTreg development in the thymus but suppresses iTreg induction in the periphery during inflammation. Our data position MALT1 as a key molecule that contributes to immune tolerance at steady-state while facilitating immune reactivity under stress conditions.

Relationships between estimated flame retardant emissions and levels in indoor air and house dust.

A significant number of consumer goods and building materials can act as emission sources of flame retardants (FRs) in the indoor environment. We investigate the relationship between the emission source strength and the levels of 19 brominated flame retardants (BFRs) and seven organophosphate flame retardants (OPFRs) in air and dust collected in 38 indoor microenvironments in Norway. We use modeling methods to back-calculate emission rates from indoor air and dust measurements and identify possible indications of an emission-to-dust pathway. Experimentally based emission estimates provide a satisfactory indication of the relative emission strength of indoor sources. Modeling results indicate an up to two orders of magnitude enhanced emission strength for OPFRs (median emission rates of 0.083 and 0.41 µg h-1 for air-based and dust-based estimates) compared to BFRs (0.52 and 0.37 ng h-1 median emission rates). A consistent emission-to-dust signal, defined as higher dust-based than air-based emission estimates, was identified for four of the seven OPFRs, but only for one of the 19 BFRs. It is concluded, however, that uncertainty in model input parameters could potentially lead to the false identification of an emission-to-dust signal.

Muscle involvement in limb-girdle muscular dystrophy with GMPPB deficiency (LGMD2T).

OBJECTIVE: In this study, muscle involvement assessed by MRI and levels of GMPPB and glycosylation of α-dystroglycan expression in muscle were examined in patients with limb-girdle muscular dystrophy (LGMD) type 2T. METHODS: Six new patients with genetically verified mutations in GMPPB were studied. T1-weighted magnetic resonance images were obtained in 4 participants. Muscle strength and potential involvement of extramuscular organs were examined. Glycosylation of α-dystroglycan in muscle was studied, and GMPPB and α-dystroglycan expression was analyzed by Western blotting. Prevalence of LGMD2T was calculated from the total LGMD population in Denmark. GMPPB was sequenced in all unclassified cases. RESULTS: Two patients carried 3 new mutations in GMPPB. The other 4 patients carried previously described pathogenic mutations in GMPPB. MRI showed that the paraspinal muscles were the most affected, followed by involvement of hamstrings. Our results showed a loss of glycosylation of α-dystroglycan as well as secondary loss of merosin expression on Western blotting. The prevalence of LGMD2T in the Danish cohort of patients with LGMD is 1.5%. CONCLUSIONS: The new findings of this study are (1) the consistent finding of a preferential affection of paraspinal and hamstring muscles in LGMD2T, (2) 3 new mutations in GMPPB, (3) variable loss of glycosylation tested with IIH6 and VIA4 antibodies, and (4) a prevalence of LGMD2T of 1.5% in a well-characterized Danish LGMD cohort.

Chronophin is a glial tumor modifier involved in the regulation of glioblastoma growth and invasiveness.

Glioblastoma is the most aggressive primary brain tumor in adults. Although the rapid recurrence of glioblastomas after treatment is a major clinical challenge, the relationships between tumor growth and intracerebral spread remain poorly understood. We have identified the cofilin phosphatase chronophin (gene name: pyridoxal phosphatase, PDXP) as a glial tumor modifier. Monoallelic PDXP loss was frequent in four independent human astrocytic tumor cohorts and increased with tumor grade. We found that aberrant PDXP promoter methylation can be a mechanism leading to further chronophin downregulation in glioblastomas, which correlated with shorter glioblastoma patient survival. Moreover, we observed an inverse association between chronophin protein expression and cofilin phosphorylation levels in glioma tissue samples. Chronophin-deficient glioblastoma cells showed elevated cofilin phosphorylation, an increase in polymerized actin, a higher directionality of cell migration, and elevated in vitro invasiveness. Tumor growth of chronophin-depleted glioblastoma cells xenografted into the immunodeficient mouse brain was strongly impaired. Our study suggests a mechanism whereby the genetic and epigenetic alterations of PDXP resulting in altered chronophin expression may regulate the interplay between glioma cell proliferation and invasion.

Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function.

Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty-four patients, aged 6-35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF-oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age-inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.

Quality of Life after Ventral Hernia Repair with Endoscopic Component Separation Technique.

BACKGROUND AND AIMS: Large ventral hernias are often associated with physical, social, and health problems for the patient, and surgical repair remains a challenge. Open components separation has widely been applied to obtain closure of the midline and recently a minimally invasive technique has been introduced (endoscopic components separation). The effectiveness and safety of endoscopic components separation have been demonstrated in previous reports, whereas little is known about quality of life in these patients. With a focus on quality of life, we present the first patients from our center operated on with endoscopic components separation. MATERIAL AND METHODS: A total of 19 consecutive patients scheduled for open hernia repair with endoscopic components separation from October 2010 to June 2012 were included. All procedures included endoscopic components separation because of the hernia size. Demographic data, operative information, and postoperative complications were recorded. All patients completed two similar questionnaires regarding their function level, cosmetic satisfaction, analgesic medication, alcohol consumption, and self-estimated physical and mental health before and after the hernia repair. Patients were assessed as outpatient median 2 months and 16 months after operation for exclusion of hernia recurrence and completion of the postoperative questionnaire. RESULTS AND CONCLUSIONS: Operating room time was median 204 min and correlated significantly with the hernia size. A total of 21 postoperative complications occurred in 14 patients. The length of stay was median 6 days and correlated significantly with duration of the operation. Of these, 15 patients participated in late follow-up visit. Two patients experienced recurrent hernias. Postoperative function level, cosmetic satisfaction, and self-estimated physical and mental health improved significantly. Alcohol consumption was significantly reduced. Endoscopic components separation is a reliable method to repair large ventral hernias, although further studies are required to determine the exact benefits for endoscopic components separation hernia repair versus conventional hernia repair.

Effects of magnetic field gradients on the aggregation dynamics of colloidal magnetic nanoparticles.

We have used low-field (1)H nuclear-magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) to investigate the aggregation dynamics of magnetic particles in ionic ferrofluids (IFFs) in the presence of magnetic field gradients. At the beginning of the experiments, the measured NMR spectra were broad and asymmetric, exhibiting two features attributed to different dynamical environments of water protons, depending on the local strength of the field gradients. Hence, the spatial redistribution of the magnetic particles in the ferrofluid caused by the presence of an external magnetic field in a time scale of minutes can be monitored in real time, following the changes in the features of the NMR spectra during a period of about an hour. As previously reported [Heinrich et al., Phys. Rev. Lett., 2011, 106, 208301], in the homogeneous magnetic field of a NMR spectrometer, the aggregation of the particles of the IFF proceeds in two stages. The first stage corresponds to the gradual aggregation of monomers prior to and during the formation of chain-like structures. The second stage proceeds after the chains have reached a critical average length, favoring lateral association of the strings into hexagonal zipped-chain superstructures or bundles. In this work, we focus on the influence of a strongly inhomogeneous magnetic field on the aforementioned aggregation dynamics. The main observation is that, as the sample is immersed in a certain magnetic field gradient and kept there for a time τinh, magnetophoresis rapidly converts the ferrofluid into an aggregation state which finds its correspondence to a state on the evolution curve of the pristine sample in a homogeneous field. From the degree of aggregation reached at the time τinh, the IFF sample just evolves thereafter in the homogeneous field of the NMR spectrometer in exactly the same way as the pristine sample. The final equilibrium state always consists of a colloidal suspension of zipped-chain bundles with the chain axes aligned along the magnetic field direction.

Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study.

Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant-toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children.

Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated. METHODS AND RESULTS: A cross-sectional descriptive study examining 98 stable adult patients with CCHD with a medical questionnaire, blood samples, MRI of the cerebrum (n=72), multidetector CT imaging (MDCT) of the thorax (n=76) and pulmonary scintigraphy (ventilation/perfusion/single-photon emission computerised tomography/CT) (n=66). The prevalence of cerebral infarction and pulmonary thrombosis according to imaging were 47% and 31%, respectively. Comparing the findings with previous medical history revealed a large under-reporting of thrombosis with only 22% of the patients having a clinical history of stroke and 25% of pulmonary thrombosis. There was no association between the degree of erythrocytosis or haemostatic abnormalities and the prevalence of thrombosis. CONCLUSIONS: Patients with CCHD have a prevalence of both cerebral and pulmonary thrombosis of around 30%-40%, which is much higher than that reported previously. Furthermore, there is a large discrepancy between clinical history and imaging findings, suggesting a high prevalence of silent thrombotic events. Neither erythrocytosis nor haemostatic abnormalities were associated with the prevalence of thrombosis in patients with CCHD. TRIAL REGISTRATION NUMBER: http://www.cvk.sum.dk/CVK/Home/English.aspx (H-KF-2006-4068).