The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: a statement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

A significant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.7-1%) of the development of second primary cancers compared to patients treated with surgery up to 25 years after treatment. However, current evidence suggests that the implementation of intensity modulated radiation therapy is not increasing the risk of second primary cancers compared to conformal 3D-planned radiotherapy. Furthermore, increasing evidence indicates that highly conformal radiotherapy techniques may not increase the probability of second primary cancers compared to radical prostatectomy. Consequently, future studies should consider the radiotherapy technique and other confounding factors to provide a more accurate estimation of the occurrence of second primary cancers.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Consistency of convolutional neural networks in dermoscopic melanoma recognition: A prospective real-world study about the pitfalls of augmented intelligence.

BACKGROUND: Deep-learning convolutional neural networks (CNNs) have outperformed even experienced dermatologists in dermoscopic melanoma detection under controlled conditions. It remains unexplored how real-world dermoscopic image transformations affect CNN robustness. OBJECTIVES: To investigate the consistency of melanoma risk assessment by two commercially available CNNs to help formulate recommendations for current clinical use. METHODS: A comparative cohort study was conducted from January to July 2022 at the Department of Dermatology, University Hospital Basel. Five dermoscopic images of 116 different lesions on the torso of 66 patients were captured consecutively by the same operator without deliberate rotation. Classification was performed by two CNNs (CNN-1/CNN-2). Lesions were divided into four subgroups based on their initial risk scoring and clinical dignity assessment. Reliability was assessed by variation and intraclass correlation coefficients. Excisions were performed for melanoma suspicion or two consecutively elevated CNN risk scores, and benign lesions were confirmed by expert consensus (n = 3). RESULTS: 117 repeated image series of 116 melanocytic lesions (2 melanomas, 16 dysplastic naevi, 29 naevi, 1 solar lentigo, 1 suspicious and 67 benign) were classified. CNN-1 demonstrated superior measurement repeatability for clinically benign lesions with an initial malignant risk score (mean variation coefficient (mvc): CNN-1: 49.5(±34.3)%; CNN-2: 71.4(±22.5)%; p = 0.03), while CNN-2 outperformed for clinically benign lesions with benign scoring (mvc: CNN-1: 49.7(±22.7)%; CNN-2: 23.8(±29.3)%; p = 0.002). Both systems exhibited lowest score consistency for lesions with an initial malignant risk score and benign assessment. In this context, averaging three initial risk scores achieved highest sensitivity of dignity assessment (CNN-1: 94%; CNN-2: 89%). Intraclass correlation coefficients indicated 'moderate'-to-'good' reliability for both systems (CNN-1: 0.80, 95% CI:0.71-0.87, p < 0.001; CNN-2: 0.67, 95% CI:0.55-0.77, p < 0.001). CONCLUSIONS: Potential user-induced image changes can significantly influence CNN classification. For clinical application, we recommend using the average of three initial risk scores. Furthermore, we advocate for CNN robustness optimization by cross-validation with repeated image sets. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04605822).

Accuracy of ultrasound signs on two-dimensional transvaginal ultrasound in prediction of adenomyosis: prospective multicenter study.

OBJECTIVE: Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis. METHODS: This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed. RESULTS: A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs. CONCLUSIONS: Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Probing Parton Saturation and the Gluon Dipole via Diffractive Jet Production at the Electron-Ion Collider.

We demonstrate that hard dijet production via coherent inelastic diffraction is a promising channel for probing gluon saturation at the Electron-Ion Collider. By inelastic diffraction, we mean a process in which the two hard jets-a quark-antiquark pair generated by the decay of the virtual photon-are accompanied by a softer gluon jet, emitted by the quark or the antiquark. This process can be described as the elastic scattering of an effective gluon-gluon dipole. The cross section takes a factorized form, between a hard factor and a unintegrated ("Pomeron") gluon distribution describing the transverse momentum imbalance between the hard dijets. The dominant contribution comes from the black disk limit and leads to a dijet imbalance of the order of the target saturation momentum Q_{s} evaluated at the rapidity gap. Integrating out the dijet imbalance, we obtain a collinear factorization where the initial condition for the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution is set by gluon saturation.

The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: a randomised, double-blind placebo-controlled trial.

Delirium occurs commonly following major non-cardiac and cardiac surgery and is associated with: postoperative mortality; postoperative neurocognitive dysfunction; increased length of hospital stay; and major postoperative complications and morbidity. The aim of this study was to investigate the effect of peri-operative administration of dexmedetomidine on the incidence of postoperative delirium in non-cardiac and cardiac surgical patients. In this randomised, double-blind placebo-controlled trial we included 63 patients aged ≥ 60 years undergoing major open abdominal surgery or coronary artery bypass graft surgery with cardiopulmonary bypass. The primary outcome was the incidence of postoperative delirium, as screened for with the Confusion Assessment Method. Delirium assessment was performed twice daily until postoperative day 5, at the time of discharge from hospital or until postoperative day 14. We found that dexmedetomidine was associated with a reduced incidence of postoperative delirium within the first 5 postoperative days, 43.8% vs. 17.9%, p = 0.038. Severity of delirium, screened with the Intensive Care Delirium Screening Checklist, was comparable in both groups, with a mean maximum score of 1.54 vs. 1.68, p = 0.767. No patients in the dexmedetomidine group died while five (15.6%) patients in the placebo group died, p = 0.029. For patients aged ≥ 60 years undergoing major cardiac or non-cardiac surgery, we conclude that the peri-operative administration of dexmedetomidine is associated with a lower incidence of postoperative delirium.

People with type 1 diabetes and impaired awareness of hypoglycaemia have a delayed reaction to performing a glucose scan during hypoglycaemia: a prospective observational study.

AIMS: Considering that people with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) have a delayed perception of hypoglycaemia, the question arises whether they perform scans later in case of hypoglycaemia than people without IAH. We assessed whether time to performing a scan after reaching hypoglycaemia while using a flash glucose monitoring (flash GM) system is different in people with IAH compared with people without IAH. METHODS: Ninety-two people with type 1 diabetes [mean (± sd) age 42 ± 14 years, HbA1c 57 ± 9 mmol/mol] using a flash GM system for 3 months were included. Flash GM data were assessed for time until scan after reaching hypoglycaemia level 1 (< 3.9 mmol/l) and level 2 (< 3.0 mmol/l) and compared for type 1 diabetes with vs. without IAH via unpaired t-test/Mann-Whitney U test (P < 0.05). RESULTS: Significant differences were found only for the delay between reaching hypoglycaemia and scan between people with and without IAH for Gold score [hypoglycaemia level 1: IAH 78 (51-105) min vs. without IAH 63 (42-89) min, P = 0.03; night-time hypoglycaemia level 2: IAH 140 (107-227) min vs. without IAH 96 (41-155) min, P = 0.004] and Pedersen-Bjergaard score [hypoglycaemia level 1: IAH 76 (52-97) min vs. without IAH 54 (38-71) min, P = 0.011; night-time hypoglycaemia level 1: IAH 132 (79-209) min vs. without IAH 89 (59-143) min, P = 0.011; night-time hypoglycaemia level 2: IAH 134 (66-212) min vs. without IAH 80 (37-131) min, P = 0.002). Data are shown as median (i.q.r.). CONCLUSIONS: Time until scan after reaching hypoglycaemia might be an objective assessment tool for IAH, but needs to be investigated comprehensively in future studies.

Citrin deficiency mimicking mitochondrial depletion syndrome.

BACKGROUND: Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. CASE PRESENTATION: We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70-1)_(212 + 1_231-1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. CONCLUSIONS: As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome.

Ubiquitylome profiling of Parkin-null brain reveals dysregulation of calcium homeostasis factors ATP1A2, Hippocalcin and GNA11, reflected by altered firing of noradrenergic neurons.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder in the old population. Among its monogenic variants, a frequent cause is a mutation in the Parkin gene (Prkn). Deficient function of Parkin triggers ubiquitous mitochondrial dysfunction and inflammation in the brain, but it remains unclear how selective neural circuits become vulnerable and finally undergo atrophy. We attempted to go beyond previous work, mostly done in peripheral tumor cells, which identified protein targets of Parkin activity, an ubiquitin E3 ligase. Thus, we now used aged Parkin-knockout (KO) mouse brain for a global quantification of ubiquitylated peptides by mass spectrometry (MS). This approach confirmed the most abundant substrate to be VDAC3, a mitochondrial outer membrane porin that modulates calcium flux, while uncovering also >3-fold dysregulations for neuron-specific factors. Ubiquitylation decreases were prominent for Hippocalcin (HPCA), Calmodulin (CALM1/CALML3), Pyruvate Kinase (PKM2), sodium/potassium-transporting ATPases (ATP1A1/2/3/4), the Rab27A-GTPase activating protein alpha (TBC1D10A) and an ubiquitin ligase adapter (DDB1), while strong increases occurred for calcium transporter ATP2C1 and G-protein subunits G(i)/G(o)/G(Tr). Quantitative immunoblots validated elevated abundance for the electrogenic pump ATP1A2, for HPCA as neuron-specific calcium sensor, which stimulates guanylate cyclases and modifies axonal slow afterhyperpolarization (sAHP), and for the calcium-sensing G-protein GNA11. We assessed if compensatory molecular regulations become insufficient over time, leading to functional deficits. Patch clamp experiments in acute Parkin-KO brain slices indeed revealed alterations of the electrophysiological properties in aged noradrenergic locus coeruleus (LC) neurons. LC neurons of aged Parkin-KO brain showed an acceleration of the spontaneous pacemaker frequency, a reduction in sAHP and shortening of action potential duration, without modulation of KCNQ potassium currents. These findings indicate altered calcium-dependent excitability in a PARK2 model of PD, mediated by diminished turnover of potential Parkin targets such as ATP1A2 and HPCA. The data also identified further novel Parkin substrate candidates like SIRT2, OTUD7B and CUL5. Our elucidation of neuron-specific mechanisms of PD pathogenesis helps to explain the known exceptional susceptibility of noradrenergic and dopaminergic projections to alterations of calcium homeostasis and its mitochondrial buffering.

The role of PKC and PKD in CXCL12 directed prostate cancer migration.

Cancer metastasis is the cause of most cancer related deaths and many cancers are becoming resistant to current therapies. An alternative approach is to investigating signalling pathways that cause cancer cell migration such as chemokine signalling pathways. Such downstream signalling proteins are PKC and PKD. Therefore, we investigated the role of these two proteins in CXCL12 mediated PC3 prostate cancer migration. Whereas PKC and PKD inhibitors do not affect the release of calcium in PC3 prostate cancer cells, both are involved in migration, particularly inhibition of the atypical PKC isoform PKCζ causes the greatest reduction in PC3 cell migration. Classical and/or Novel PKC isoform inhibition changes the shape of the PC3 cells, they show a more rounded morphology, whereas PKD inhibition causes prostate cancer cell to elongate. PKCζ inhibition causes the enlargement of PC3 area possibly due to dysregulated actin cytoskeletal control. These results highlight the importance of verifying which signalling proteins, in which cell and in which chemokine signalling cascade enable cancer cellular migration.

Acoplanarity of a Lepton Pair to Probe the Electromagnetic Property of Quark Matter.

We investigate the P_{T}-broadening effects in dilepton production through photon-photon scattering in heavy ion collisions. The QED multiple interaction effect with the medium is found to be consistent with the recent observation of a low transverse momentum lepton pair from the ATLAS Collaboration at the LHC. We further comment on the magnetic broadening effect and point out a number of ways to disentangle these two mechanisms. In particular, the rapidity dependence of the P_{T}-broadening effect provides a unique probe to the magnetic effect.

Impact of physical exercise on sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system in people with Type 1 diabetes: a randomized crossover trial.

AIMS: To evaluate the sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system using reference blood glucose levels during moderate-intensity exercise while on either full or reduced basal insulin dose in people with Type 1 diabetes. METHODS: Ten participants with Type 1 diabetes [four women, mean ± sd age 31.4 ± 9.0 years, BMI 25.5±3.8 kg/m2 , HbA1c 55±7 mmol/mol (7.2±0.6%)] exercised on a cycle ergometer for 55 min at a moderate intensity for 5 consecutive days at the clinical research facility, while receiving either their usual or a 75% basal insulin dose. After a 4-week washout period, participants performed the second exercise period having switched to the alternative basal insulin dose. During exercise, reference capillary blood glucose values were analysed using the fully enzymatic-amperometric method and compared with the interstitial glucose values obtained. Intermittently viewed continuous glucose monitoring accuracy was analysed according to median (interquartile range) absolute relative difference, and Clarke error grid and Bland-Altman analysis for overall glucose levels during exercise, stratified by glycaemic range and basal insulin dosing scheme (P<0.05). RESULTS: A total of 845 glucose values were available during exercise to evaluate intermittently viewed continuous glucose monitoring sensor performance. The median (interquartile range) absolute relative difference between the reference values and those obtained by the sensor across the glycaemic range overall was 22 (13.9-29.7)%, and was 36.3 (24.2-45.2)% during hypoglycaemia, 22.8 (14.6-30.6)% during euglycaemia and 15.4 (9-21)% during hyperglycaemia. Usual basal insulin dose was associated with a worse sensor performance during exercise compared with the reduced (75%) basal insulin dose [median (interquartile range) absolute relative difference: 23.7 (17.2-30.7)% vs 20.5 (12-28.1)%; P<0.001). CONCLUSIONS: The intermittently viewed continuous glucose monitoring sensor showed diminished accuracy during exercise. Absolute glucose readings derived from the sensor should be used cautiously and need confirmation by additional finger-prick blood glucose measurements.

Diffractive Electron-Nucleus Scattering and Ancestry in Branching Random Walks.

We point out an analogy between diffractive electron-nucleus scattering events and realizations of one-dimensional branching random walks selected according to the height of the genealogical tree of the particles near their boundaries. This correspondence is made transparent in an event-by-event picture of diffraction, emphasizing the statistical properties of gluon evolution, from which new quantitative predictions straightforwardly follow: we are able to determine the distribution of the total invariant mass produced diffractively, which is an interesting observable that can potentially be measured at a future electron-ion collider.

Vacuumlike Jet Fragmentation in a Dense QCD Medium.

We study the fragmentation of a jet propagating in a dense quark-gluon plasma. Using a leading, double-logarithmic approximation in perturbative QCD, we compute for the first time the effects of the medium on multiple vacuumlike emissions. We show that, due to the scatterings off the plasma, the in-medium parton showers differ from the vacuum ones in two crucial aspects: their phase-space is reduced and the first emission outside the medium can violate angular ordering. We compute the jet fragmentation function and find results in qualitative agreement with LHC measurements.

Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.

Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs.

Feeding reduced-fat dried distillers grains with solubles to lactating Holstein dairy cows does not alter milk composition or cause late blowing in cheese.

Feeding dried distillers grains with solubles (DDGS) to lactating dairy cows has been implicated as a cause of late blowing defects in the production of Swiss-style cheeses. Our objectives were (1) to test the effect of feeding reduced-fat DDGS (RF-DDGS; ∼6% fat) to lactating dairy cows on the composition of milk and on the suitability of the milk for production of baby Swiss cheese and (2) to evaluate the effect of diet on cow lactation performance. Lactating Holstein dairy cows were fed both dietary treatments in a 2 × 2 crossover design. Cows were housed in a 48-cow freestall pen equipped with individual feeding gates to record feed intake. The control diet was a corn, corn silage, and alfalfa hay diet supplemented with mechanically expelled soybean meal. The experimental diet was the same base ration, but 20% (dry matter basis) RF-DDGS were included in place of the expelled soybean meal. The RF-DDGS diet was additionally supplemented with rumen-protected lysine; diets were formulated to be isoenergetic and isonitrogenous. Cows were allowed ad libitum access to feed and water, fed twice daily, and milked 3 times daily. For cheese production, milk was collected and pooled 6 times for each dietary treatment. There was no treatment effect on milk yield (35.66 and 35.39 kg/d), milk fat production (1.27 and 1.25 kg/d), milk fat percentage (3.65 and 3.61%), milk protein production (1.05 and 1.08 kg/d), lactose percentage (4.62 and 4.64%), milk total solids (12.19 and 12.28%), and somatic cell count (232.57 and 287.22 × 103 cells/mL) for control and RF-DDGS, respectively. However, dry matter intake was increased by treatment, which implied a reduction in feed efficiency. Milk protein percentage also increased (3.01 and 3.11%), whereas milk urea nitrogen decreased (14.18 and 12.99 mg/dL), indicating that protein utilization may be more efficient when cows are fed RF-DDGS. No differences in cheese were observed by a trained panel except cheese appearance; control cheese eyes were significantly, but not practically, larger than the RF-DDGS cheese. These results indicate that RF-DDGS can be effectively used in the rations of lactating Holstein cows with no deleterious effects on milk production and composition and metrics of the physiology of the cow (i.e., blood glucose and nonesterified fatty acids); however, feeding RF-DDGS increased dry matter intake, which decreased feed efficiency. Finally, feeding RF-DDGS did not negatively influence quality and suitability of milk for production of baby Swiss cheese.

Gender-specific impairment of in vitro sinoatrial node chronotropic responses and of myocardial ischemia tolerance in rats exposed prenatally to betamethasone.

Excessive fetal glucocorticoid exposure has been linked to increased susceptibility to hypertension and cardiac diseases in the adult life, a process called fetal programming. The cardiac contribution to the hypertensive phenotype of glucocorticoid-programmed progeny is less known, therefore, we investigated in vitro cardiac functional parameters from rats exposed in utero to betamethasone. Pregnant Wistar rats received vehicle (VEH) or betamethasone (BET, 0.1mg/kg, i.m.) at gestational days 12, 13, 18 and 19. Male and female offspring were killed at post-natal day 30 and the right atrium (RA) was isolated to in vitro evaluation of drug-induced chronotropic responses. Additionally, whole hearts were retrograde-perfused in a Langendorff apparatus and infarct size in response to in vitro ischemia/reperfusion (I/R) protocol was evaluated. Male and female progeny from BET-exposed pregnant rats had reduced birth weight, a hallmark of fetal programming. Male BET-progeny had increased basal RA rate, impaired chronotropic responses to noradrenaline and adenosine, and increased myocardial damage to I/R. Though a 12-fold reduction in the negative chronotropic responses to adenosine, the effects of non-metabolisable adenosine receptor agonists 5'-(N-ethylcarboxamido)adenosine or 2-Chloro-adenosine were not different between VEH- and BET-exposed male rats. BET-exposed female offspring presented no cardiac dysfunction. Prenatal BET exposure engenders male-specific impairment of sinoatrial node function and on myocardial ischemia tolerance resulting, at least in part, from an increased adenosine metabolism in the heart. In light of the importance of adenosine in the cardiac physiology our results suggest a link between reduced adenosinergic signaling and the cardiac dysfunctions observed in glucocorticoid-induced fetal programming.

Inpatient treatment of patients with acute idiopathic peripheral facial palsy: A population-based healthcare research study.

OBJECTIVES: To determine the inpatient management for patients with acute idiopathic facial palsy (IFP) in Thuringia, Germany. DESIGN: Population-based study. SETTING: All inpatients with IFP in all hospitals with departments of otolaryngology and neurology in 2012, in the German federal state, Thuringia. MAIN OUTCOME MEASURES: Patients' characteristics and treatment were compared between departments, and the probability of recovery was tested. RESULTS: A total of 291 patients were mainly treated in departments of otolaryngology (55%) and neurology (36%). Corticosteroid treatment was the predominant therapy (84.5%). The probability to receive a facial nerve grading (odds ratio [OR=12.939; 95% confidence interval [CI]=3.599 to 46.516), gustatory testing (OR=6.878; CI=1.064 to 44.474) and audiometry (OR=32.505; CI=1.485 to 711.257) was significantly higher in otolaryngology departments, but lower for cranial CT (OR=0.192; CI=0.061 to 0.602), cerebrospinal fluid examination (OR=0.024; CI=0.006 to 0.102). A total of 131 patients (45%) showed a recovery to House-Brackmann grade≤II. A pathological stapedial reflex test (Hazard ratio [HR]=0.416; CI=0.180 to 0.959) was the only independent diagnostic predictor of worse outcome. Prednisolone dose >500 mg (HR=0.579; CI 0.400 to 0.838) and no adjuvant physiotherapy (HR=0.568; CI=0.407 to 0.794) were treatment-related predictors of worse outcome. CONCLUSIONS: Inpatient treatment of IFP seems to be highly variable in daily practice, partly depending on the treating discipline and despite the availability of evidence-based guidelines. The population-based recovery rate was worse than reported in clinical trials.

Biomonitoring of prenatal analgesic intake and correlation with infantile anti-aeroallergens IgE.

An association between prenatal acetaminophen or ibuprofen intake and an increased risk of asthma and increased IgE level in children is discussed in various epidemiological studies. Although the molecular mechanistic link is still unknown, the question whether or not acetaminophen and/or ibuprofen are safe pain medications during pregnancy arose. In this study, we associate maternal acetaminophen and ibuprofen intake during pregnancy and breastfeeding to infantile asthma phenotypes and elevated IgE level. Therefore, we analysed questionnaires from a local mother-child cohort and monitored drug intake by LC-MS biomonitoring in urine. No association was found between drug intake and any analysed health outcome using questionnaire data. For the information obtained from biomonitoring, no association was found for ibuprofen and acetaminophen intakes during breastfeeding. However, an association between prenatal acetaminophen intake and increased infantile IgEs related to aeroallergens was statistically detected, but not for asthma phenotypes.

Long-term effective population size dynamics of an intensively monitored vertebrate population.

Long-term genetic data from intensively monitored natural populations are important for understanding how effective population sizes (Ne) can vary over time. We therefore genotyped 1622 common buzzard (Buteo buteo) chicks sampled over 12 consecutive years (2002-2013 inclusive) at 15 microsatellite loci. This data set allowed us to both compare single-sample with temporal approaches and explore temporal patterns in the effective number of parents that produced each cohort in relation to the observed population dynamics. We found reasonable consistency between linkage disequilibrium-based single-sample and temporal estimators, particularly during the latter half of the study, but no clear relationship between annual Ne estimates () and census sizes. We also documented a 14-fold increase in between 2008 and 2011, a period during which the census size doubled, probably reflecting a combination of higher adult survival and immigration from further afield. Our study thus reveals appreciable temporal heterogeneity in the effective population size of a natural vertebrate population, confirms the need for long-term studies and cautions against drawing conclusions from a single sample.