Impact of parenthood on eating pathology in young adults.

OBJECTIVE: Few studies investigated parenthood as a predictor of eating pathology in young adulthood. We studied the association between parenthood, in the first year after becoming a parent and beyond, and eating pathology. Furthermore, we examined whether moving in together with a partner affected this association. METHOD: This study used data of four measurement waves from TRAILS (Tracking Adolescents' Individual Lives Survey), a Dutch community cohort study (N = 2229) from preadolescence into young adulthood. The Eating Disorder Diagnostic Scale (EDDS), a measure to assess eating pathology, was assessed at ages 22, 26, and 29. Risk for eating disorder was assessed at age 19. Pregnant participants were excluded. RESULTS: Parenthood was not associated with an increase of eating pathology in the first year after becoming a parent and beyond. Instead, parents were more likely to report being free from eating pathology symptoms compared to childless individuals (OR 2.07, 95% CI: 1.11-3.84). Among those who reported experiencing at least one eating problem, parenthood was not associated with the number of eating problems. Moving in together with a partner did not alter the association between parenthood and eating problems and neither did this association differ between males and females. DISCUSSION: Parenthood in young adulthood was associated with a decreased risk of having eating pathology. PUBLIC SIGNIFICANCE STATEMENT: In this longitudinal study among young adults, parenthood was not associated with the development of eating pathology.

Effect of Saccharomyces cerevisiae fermentation product on oxidative status, inflammation, and immune response in transition dairy cattle.

Dairy cattle are subjected to oxidative stress, inflammation, and altered immune function during the transition to lactation. The objective of this study was to evaluate the effects of a dietary Saccharomyces cerevisiae fermentation product (SCFP; NutriTek, Diamond V) on oxidative status, inflammation, and innate and adaptive immune responses during the transition period. Holstein cows were blocked by parity, expected calving date, and previous milk yield and then randomly assigned to treatment within block. Treatment was a control total mixed ration (n = 30) or SCFP total mixed ration (n = 34) fed from -29 ± 5 to 42 d relative to calving (RTC). Blood was sampled during wk -4, -2, 1, 2, and 5 and liver tissue at wk -3 and 2 RTC. Oxidative status was evaluated in plasma by retinol, α-tocopherol, and malondialdehyde concentrations, glutathione peroxidase activity, and Trolox equivalent antioxidant capacity, and in liver by mRNA abundance of nuclear factor E2-related factor 2 (NFE2L2), metallothionein 1E (MT1E), and glutathione peroxidase 3 (GPX3). Inflammation was evaluated in plasma by haptoglobin (HP) and serum amyloid A (SAA) concentrations and in liver by mRNA abundance of HP, serum amyloid A3 (SAA3), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB1). Innate immune response was measured by stimulated oxidative burst of polymorphonuclear cells (neutrophils) isolated from blood. Ovalbumin (OVA) was administered with adjuvant on d 7 and 21 RTC, and adaptive immune response was evaluated by serum anti-OVA IgG content on d 28 and 35. Mixed models were used to assess effects of treatment, time, parity, and all interactions. We previously reported that SCFP had limited effects on productivity in this cohort, although milk fat yield was transiently increased and subclinical ketosis incidence was increased. Supplementation with SCFP did not affect overall oxidative, inflammatory, or immune parameters. The only treatment × week interaction detected was for plasma α-tocopherol concentration, which tended to be greater in control cows during wk 2 RTC. A tendency for a treatment × parity interaction was detected for serum anti-OVA IgG titer, which tended to be greater for SCFP than for controls among primiparous cows. Plasma inflammatory biomarkers were not affected by SCFP but, unexpectedly, plasma HP was elevated at both prepartum time points and plasma SAA was elevated during wk -2 RTC compared with the expected increases in both biomarkers postpartum. In this cohort of transition cows with low disease incidence, SCFP generally did not affect oxidative, inflammatory, or immune parameters.

Aligning tumor mutational burden (TMB) quantification across diagnostic platforms: phase II of the Friends of Cancer Research TMB Harmonization Project.

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.

Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose.

PURPOSE: Dose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions. MATERIALS AND METHODS: This was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3â€¯× 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided. RESULTS: In all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found. CONCLUSIONS: This planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Cryoneurolysis' outcome on pain experience (COPE) in patients with low-back pain: study protocol for a single-blinded randomized controlled trial.

BACKGROUND: Low-back pain, including facet joint pain, accounts for up to 20 % of all sick leaves in DenmarkA proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome. METHODS: A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity ≥ 50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is the patients' impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are a reduction in low-back pain intensity (numeric rating scale) and quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory). Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months (T6). DISCUSSION: This study will provide information on the effectiveness of cryoneurolysis vs. the effectiveness of radiofrequency ablation or placebo for patients with facet joint pain, and help to establish whether cryoneurolysis should be implemented in clinical practice for this patient population. TRIAL REGISTRATION: The trial is approved by the ethical committee of Central Jutland Denmark with registration number 1-10-72-27-19 and the Danish Data Protection Agency with registration number 666,852. The study is registered at Clinicaltrial.gov with the ID number NCT04786145 .

Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016.

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri-operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre-operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri-operative myocardial infarction, stroke and all-cause mortality at 30 days. Peri-operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86-0.90) in 2012 to 0.51 (0.50-0.51) in 2016 (p < 0.001). Pre-operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90-1.02) and 1.05 (0.99-1.11) for myocardial infarction, 0.91 (0.83-0.99) and 0.99 (0.92-1.07) for stroke and 0.98 (0.94-1.02) and 0.99 (0.96-1.03) for all-cause mortality. Use of peri-operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.

COMPARISON BETWEEN PADC AND FNTD NEUTRON DETECTOR SYSTEMS IN BLIND TESTS.

The objective of this study was to compare a neutron dosimetry system based on polyallyl diglycol carbonate (PADC) detectors with a new system based on Al2O3:C,Mg fluorescence nuclear track detectors (FNTD). The irradiations, performed as part of an intercomparison organized by the Physikalisch-Technische Bundesanstalt (PTB), Germany, were on a PMMA phantom with 252Cf or 241Am-Be source, usually with the phantom surface perpendicular to the radiation beam (0° angle), and with Hp(10) values between 0.3 and 7 mSv. One 252Cf irradiation was performed at 30° angle, and one with an additional 1 mSv gamma irradiation. The results showed an agreement between the two techniques with an average and maximum difference between PADCs and FNTDs of 1.5 and 22%, respectively, if one compares only cases of doses >1 mSv. For one of the irradiation conditions with dose of 0.9 mSv, use of the incorrect calibration factor for the FNTD (252Cf instead of 241Am-Be) led to reported values ~×2 larger than the given doses, due to low statistics in the determination of the ratio between 6Li-doped glass and polyethylene neutron converters. Although the FNTD track analysis algorithm may need further development, the results presented here demonstrate the feasibility of the FNTD technology and indicate areas requiring improvements.

HIGH DOSE FAST NEUTRON DOSIMETRY USING PADC PLASTIC NUCLEAR TRACK DETECTORS AND GREY LEVEL ANALYSIS.

The objective of this work is to demonstrate the possibility of performing fast neutron dosimetry up to 5 Sv using optical absorbance of polyallyl diglycol carbonate (PADC) detectors, obtained through grey level analysis of PADC images acquired with a commercial track-counting dosimetry system, and estimate the uncertainties involved. PADCs were irradiated with doses from 100 mSv to 5 Sv (252Cf source) and etched. PADC images were acquired using the TASLIMAGE™ Neutron Dosimetry System (Track Analysis Systems Ltd.) and analysed to obtain the grey levels and the optical absorbance. The absorbance from different detectors and batches was analysed to determine the uncertainties involved, from which the final uncertainty in the method, ~30% and dominated by the uncertainty in the calibration curve, was estimated. A dose estimation <2 Sv can also be performed using a 'universal curve' by normalising the absorbance to that of a detector irradiated with 1 Sv. The data presented here allows the extension of the dose range of track counting systems using no additional equipment, only the images already acquired by the systems.

The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

Systematic evaluation of characteristics of the membrane-based fed-batch shake flask.

BACKGROUND: The initial part of process development involves extensive screening programs to identify optimal biological systems and cultivation conditions. For a successful scale-up, the operation mode on screening and production scale must be as close as possible. To enable screening under fed-batch conditions, the membrane-based fed-batch shake flask was developed. It is a shake flask mounted with a central feed reservoir with an integrated rotating membrane tip for a controlled substrate release. Building on the previously provided proof of principle for this tool, this work extends its application by constructive modifications and improved methodology to ensure reproducible performance. RESULTS: The previously limited operation window was expanded by a systematic analysis of reservoir set-up variations for cultivations with the fast-growing organism Escherichia coli. Modifying the initial glucose concentration in the reservoir as well as interchanging the built-in membrane, resulted in glucose release rates and oxygen transfer rate levels during the fed-batch phase varying up to a factor of five. The range of utilizable membranes was extended from dialysis membranes to porous microfiltration membranes with the design of an appropriate membrane tip. The alteration of the membrane area, molecular weight cut-off and liquid volume in the reservoir offered additional parameters to fine-tune the duration of the initial batch phase, the oxygen transfer rate level of the fed-batch phase and the duration of feeding. It was shown that a homogeneous composition of the reservoir without a concentration gradient is ensured up to an initial glucose concentration of 750 g/L. Finally, the experimental validity of fed-batch shake flask cultivations was verified with comparable results obtained in a parallel fed-batch cultivation in a laboratory-scale stirred tank reactor. CONCLUSIONS: The membrane-based fed-batch shake flask is a reliable tool for small-scale screening under fed-batch conditions filling the gap between microtiter plates and scaled-down stirred tank reactors. The implemented reservoir system offers various set-up possibilities, which provide a wide range of process settings for diverse biological systems. As a screening tool, it accurately reflects the cultivation conditions in a fed-batch stirred tank reactor and enables a more efficient bioprocess development.

Tumescent local anaesthesia for early dermatosurgery in infants.

BACKGROUND: Early paediatric dermatosurgery reveals excellent cosmetic results due to high skin elasticity and pronounced capacity to recover from trauma. Furthermore, the size of skin lesions increases during life proportionally to skin growth and therefore early removal is of major importance. Selected local anaesthetics like prilocaine can cause methaemoglobinemia. However, in contrast to general anaesthesia, many other local anaesthetics do not bare any major risks for infants. OBJECTIVE: In this retrospective study, we analysed infants aged less than 7 months receiving tumescent local anaesthesia (TLA) followed by dermatosurgery at our department between 2005 and 2015. The analysis is mainly based on our records. Additional information for a subset of patients was gained by a postoperative survey. METHODS: Ninety-two infants (39 male, 53 female) with a median age of 4.2 months (range: 1.5 months; 6.7 months) were included in this study. Additional postoperative information was available for 33 of the 92 studied patients (35%). RESULTS: Infants were mainly operated for removal of a melanocytic naevus (n = 54), followed by haemangioma (n = 23), naevus sebaceous (n = 6) and other lesions (n = 9). The lesions were located on the scalp or neck (n = 31), on the extremities (n = 31), on the trunk (n = 21), in the face (n = 6) or on the buttocks (n = 3). The median size of excision was 509 mm2 (range: 16 mm2 ; 3600 mm2 ). Primary defect closure was performed by intracutaneous (n = 68) or extracutaneous (n = 24) suture techniques. No side-effects of local anaesthesia were observed in any patient. Postoperative complications include pain (1/33; 3%), wound-healing disorder (1/33; 3%) and visible severe scarring (2/33; 6%). CONCLUSIONS: The combination of TLA and dermatosurgery in infants is a suitable outpatient treatment option for small lesions without any major risks or side-effects and the benefit of prolonged postoperative analgesia.

Waking the dead: morphological and molecular characterization of extant †Posoniella tricarinelloides (Thoracosphaeraceae, Dinophyceae).

The Thoracosphaeraceae are dinophytes that produce calcareous shells during their life history, whose optical crystallography has been the basis for the division into subfamilies. To evaluate the validity of the classification (mainly applied by palaeontologists), living material of phylogenetic key species is necessary albeit frequently difficult to access for contemporary morphological and molecular analyses. We isolated and established five living strains of the rare fossil-taxon †Posoniella tricarinelloides from different sediment samples collected in the South China Sea, Yellow Sea and in the Mediterranean Sea (west coast off Italy). Here, we provide detailed descriptions of its morphology and conducted phylogenetic analyses based on hundreds of accessions and thousands of informative sites on concatenated rRNA datasets. Within the monophyletic Peridiniales, †P. tricarinelloides was reliably nested in the Thoracosphaeraceae and exhibited two distinct morphological types of coccoid cells. The two morphologies of coccoid cells would have been assigned to different taxa at the subfamily level if found separately in fossil samples. Our results thus challenge previous classification concepts within the dinophytes and underline the importance of comparative morphological and molecular studies to better understand the complex biology of unicellular organisms such as †P. tricarinelloides.

Visibility conditions and diel period affect small-scale spatio-temporal behaviour of pike Esox lucius in the absence of prey and conspecifics.

Pike Esox lucius in the absence of prey and conspecifics were shown to have the highest habitat-change activity during dusk and to decrease preference for complex habitats in turbid water. As the behaviours indicate routine responses in the absence of behavioural interactions, E. lucius spatio-temporal distributions should be directly affected and thereby more easily assessed and avoided by prey, with potential consequences for encounter rates.