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Both the transfrontal and the suboccipital-transcerebellar approach are frequently used trajectories for frame-based stereotactic biopsies of brainstem lesions. Nevertheless, it remains unclear which approach is more favorable in terms of complications, diagnostic success and outcome, especially considering the location of the lesion within the brainstem. This study compared the safety and diagnostic yield of these two approaches. Furthermore, a brainstem zone model was created to answer the question, whether there is a favorable approach depending on the location of the lesion in the brainstem. A retrospective analysis of 84 consecutive cases of frame-based stereotactic biopsies for brainstem lesions via either transfrontal or suboccipital-transcerebellar approaches over a 16-year period was performed. Clinical and surgical data regarding trajectories, histopathology, complications and outcome was collected. The brainstem was divided in anatomical zones to compare the use of the two approaches depending on the location of the lesions. A total of n = 84 cases of stereotactic biopsies for brainstem lesions were performed. In 36 cases the suboccipital-transcerebellar approach was used, while in 48 cases surgery was performed via the transfrontal approach. The patient's demographic data were comparable between the two approaches. Overall diagnostic yield was 90.5% (93.8% transfrontal vs. 86.1% suboccipital, p = 0.21, Risk Difference (RD) 0.077, CI [-0.0550, 0.2090]). Complications occurred in 11 cases (total complication rate: 13.1%; 12.5% transfrontal vs. 13.9% suboccipital, p = 0.55, RD 0.014, CI [-0.1607, 0.1327]). The brainstem model showed a more frequent use of the suboccipital approach in lesions of the dorsal pons. The transfrontal approach was used more frequently in mesencephalic targets. No significant differences in terms of complications and diagnostic yield were observed, even though complications in medullary lesions appeared higher using the transfrontal approach. This study showed, that if the approaches are used for their intended target locations there are no significant differences between the transfrontal and the suboccipital-transcerebellar approach for frame-based stereotactic biopsies of brainstem lesions in terms of diagnostic yield and safety. Therefore, our data suggests that both approaches should be considered for stereotactic biopsy of brainstem lesions. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative pupillometry (QP) has been increasingly applied in neurocritical care as an easy-to-use and reliable technique for evaluating the pupillary light reflex (PLR). Here, we report our preliminary findings on using QP for clinical brain death (BD) determination. Materials: This retrospective study included 17 patients ≥ 18 years (mean age, 57.3 years; standard deviation, 15.8 years) with confirmed BD, as defined by German Guidelines for the determination of BD. The PLR was tested using the NPi®-200 Pupillometer (Neuroptics, Laguna Hill, USA), a handheld infrared device automatically tracking and analyzing pupil dynamics over 3 s. In addition, pupil diameter and neurological pupil index (NPi) were also evaluated. Results: Intracerebral bleeding, subarachnoid hemorrhage, and hypoxic encephalopathy were the most prevalent causes of BD. In all patients, the NPi was 0 for both eyes, indicating the cessation of mid-brain function. The mean diameter was 4.9 mm (± 1.3) for the right pupil and 5.2 mm (±1.2) for the left pupil. Conclusions: QP is a valuable tool for the BD certification process to assess the loss of PLR due to the cessation of brain stem function. Furthermore, implementing QP before the withdrawal of life-sustaining therapy in brain-injured patients may reduce the rate of missed organ donation opportunities. Further studies are warranted to substantiate the feasibility and potential of this technique in treating patients and identify suitable candidates for this technique during the BD certification process. [ABSTRACT FROM AUTHOR]

Objective: Lesions of the posterior fossa (brainstem and cerebellum) are challenging in diagnosis and treatment due to the fact that they are often located eloquently and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital-transcerebellar approach. Methods: We performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007. The aim was to identify all surgical cases for infratentorial lesion biopsies via the suboccipital-transcerebellar approach. We collected clinical data regarding outcomes, complications, diagnostic success, radiological appearances, and stereotactic trajectories. Results: A total of n = 79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital-transcerebellar approach (41 female and 38 male) utilizing the Zamorano-Duchovny stereotactic system were identified. The mean age at the time of surgery was 42.5 years (± 23.3; range, 1–87 years). All patients were operated with intraoperative stereotactic imaging (n = 62 MRI, n = 17 CT). The absolute diagnostic success rate was 87.3%. The most common diagnoses were glioma, lymphoma, and inflammatory disease. The overall complication rate was 8.7% (seven cases). All patients with complications showed new neurological deficits; of those, three were permanent. Hemorrhage was detected in five of the cases having complications. The 30-day mortality rate was 7.6%, and 1-year survival rate was 70%. Conclusions: Our data suggests that frame-based stereotactic biopsies with the Zamorano-Duchovny stereotactic system via the suboccipital-transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal of minimizing complications and maximizing diagnostic success. [ABSTRACT FROM AUTHOR]

Chemical signals are frequently utilised by male mammals for intersexual communication and females are often attracted to male scent. However, the mechanism underlying female attraction has only been identified in a small number of mammalian species. Mammalian scents contain airborne volatiles, that are detected by receivers at a distance from the scent source, as well as non-volatile molecules, such as proteins, that require physical contact for detection. Lipocalin proteins, produced within the scent secretions of many terrestrial mammals, are thought to be particularly important in chemical signalling. Here, we explore if the male-specific protein, glareosin, expressed by adult male bank voles, Myodes glareolus, stimulates female attraction to male scent. We show that female bank voles are more attracted to male compared to female scent, supporting the results of previous studies. Increased investigation and attraction to male scent occurred to both airborne volatiles and non-volatile proteins when they were presented separately. However, we found no evidence that attraction to male scent was driven by glareosin. Our results differ from those previously described in house mice, where a single protein induces female attraction to male scent, suggesting the mechanism underlying female attraction to male scent differs between species. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory and infectious diseases of the pituitary gland (IIPD) are rare lesions often misdiagnosed preoperatively. Immediate surgery is indicated especially in cases of neurological impairment. However, (chronic) inflammatory processes can mimic other pituitary tumors, such as adenomas, and data on the preoperative diagnostic criteria for IIPD are sparse. Methods: We retrospectively reviewed medical records of 1317 patients who underwent transsphenoidal surgery at our institution between March 2003 and January 2023. A total of 26 cases of histologically confirmed IIPD were identified. Patient records, laboratory parameters, and postoperative course were analyzed and compared with an age, sex, and tumor volume-matched control group of nonfunctioning pituitary adenomas. Results: Pathology confirmed septic infection in ten cases, most commonly caused by bacteria (3/10) and fungi (2/10). In the aseptic group, lymphocytic hypophysitis (8/26) and granulomatous inflammation (3/26) were most frequently observed. Patients with IIPD commonly presented with endocrine and/or neurological dysfunction. No surgical mortality occurred. Preoperative radiographic findings (cystic/solid tumor mass, contrast enhancement) did not significantly differ between IIPD and adenomas. At follow-up, 13 patients required permanent hormone substitution. Conclusion: In conclusion, correct preoperative diagnosis of IIPD remains challenging, as neither radiographic findings nor preoperative laboratory workup unequivocally identify these lesions. Surgical treatment facilitates decompression of supra- and parasellar structures. Furthermore, this low-morbidity procedure enables the identification of pathogens or inflammatory diseases requiring targeted medical treatment, which is crucial for these patients. Establishing a correct diagnosis through surgery and histopathological confirmation thus remains of utmost importance. [ABSTRACT FROM AUTHOR]

Breeding females can cooperate by rearing their offspring communally, sharing synergistic benefits of offspring care but risking exploitation by partners. In lactating mammals, communal rearing occurs mostly among close relatives. Inclusive fitness theory predicts enhanced cooperation between related partners and greater willingness to compensate for any partner under-investment, while females are less likely to bias investment towards own offspring. We use a dual isotopic tracer approach to track individual milk allocation when familiar pairs of sisters or unrelated house mice reared offspring communally. Closely related pairs show lower energy demand and pups experience better access to non-maternal milk. Lactational investment is more skewed between sister partners but females pay greater energetic costs per own offspring reared with an unrelated partner. The choice of close kin as cooperative partners is strongly favoured by these direct as well as indirect benefits, providing a driver to maintain female kin groups for communal breeding. A dual isotope tracer approach assessed milk allocation when pairs of sisters or unrelated female house mice reared offspring communally, revealing that females pay greater energetic costs when rearing offspring with an unrelated partner. [ABSTRACT FROM AUTHOR]

The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson's disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. Whilst acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD. [ABSTRACT FROM AUTHOR]

Background: Epigenomic dysregulation has been linked to solid tumour malignancies, including ovarian cancers. Profiling of re-programmed enhancer locations associated with disease has the potential to improve stratification and thus therapeutic choices. Ovarian cancers are subdivided into histological subtypes that have significant molecular and clinical differences, with high-grade serous carcinoma representing the most common and aggressive subtype. Methods: We interrogated the enhancer landscape(s) of normal ovary and subtype-specific ovarian cancer states using publicly available data. With an initial focus on H3K27ac histone mark, we developed a computational pipeline to predict drug compound activity based on epigenomic stratification. Lastly, we substantiated our predictions in vitro using patient-derived clinical samples and cell lines. Results: Using our in silico approach, we highlighted recurrent and privative enhancer landscapes and identified the differential enrichment of a total of 164 transcription factors involved in 201 protein complexes across the subtypes. We pinpointed SNS-032 and EHMT2 inhibitors BIX-01294 and UNC0646 as therapeutic candidates in high-grade serous carcinoma, as well as probed the efficacy of specific inhibitors in vitro. Conclusion: Here, we report the first attempt to exploit ovarian cancer epigenomic landscapes for drug discovery. This computational pipeline holds enormous potential for translating epigenomic profiling into therapeutic leads. [ABSTRACT FROM AUTHOR]

Machine learning (ML) models have long overlooked innateness: how strong pressures for survival lead to the encoding of complex behaviors in the nascent wiring of a brain. Here, we derive a neurodevelopmental encoding of artificial neural networks that considers the weight matrix of a neural network to be emergent from well-studied rules of neuronal compatibility. Rather than updating the network's weights directly, we improve task fitness by updating the neurons' wiring rules, thereby mirroring evolutionary selection on brain development. We find that our model (1) provides sufficient representational power for high accuracy on ML benchmarks while also compressing parameter count, and (2) can act as a regularizer, selecting simple circuits that provide stable and adaptive performance on metalearning tasks. In summary, by introducing neurodevelopmental considerations into ML frameworks, we not only model the emergence of innate behaviors, but also define a discovery process for structures that promote complex computations. Neuroscience has long inspired AI, however the neuroevolutionary search that produces sophisticated behaviors has not been systematized. This paper defines neurodevelopmental ML as a discovery process for structures that promote complex computations. [ABSTRACT FROM AUTHOR]

Preliminary evidence points to a link between C-reactive protein (CRP) and spinal pain in adults. However, there is a paucity of research in younger populations. Therefore, we aimed to determine associations between CRP and spinal pain in childhood and adolescence. We identified trajectories of spinal pain from childhood to adolescence and investigated the associations between CRP and trajectory subgroups. Six- to 11-year-old children from 13 primary schools, were followed from October 2008 and until 2014. High-sensitivity CRP collected at baseline (2008) was measured using serum samples. The outcome was the number of weeks with non-traumatic spinal pain between November 2008 and June 2014. We constructed a trajectory model to identify different spinal pain trajectory subgroups. The associations between CRP and spinal pain trajectory subgroups were modelled using mixed-effects multinominal logistic regression. Data from 1556 participants (52% female), with a mean age of 8.4 years at baseline, identified five spinal pain trajectory subgroups: "no pain" (55.3%), "rare" (23.7%), "rare, increasing" (13.6%), "moderate, increasing" (6.1%), and "early onset, decreasing" (1.3%). There were no differences in baseline high-sensitivity CRP levels between spinal pain trajectory subgroups. Thus, the heterogeneous courses of spinal pain experienced were not defined by differences in CRP at baseline. [ABSTRACT FROM AUTHOR]

There is a significant association between obesity and nocturia, which can cause a significant negative impact on quality of life. This meta-analysis aims to determine the effects of bariatric surgery on nocturia in both men and women. Studies searched via MEDLINE and Embase databases. The primary outcome was difference in nocturia scores before and after bariatric surgery. A total of 522 patients were included in the analysis of this paper. Statistically significant decreases in nocturia scores were observed post-bariatric surgery. Bariatric surgery also resulted in statistically significant reduction of BMI. Bariatric surgery can have significant improvements on nocturia symptoms in men and women with obesity. This would thereby reduce morbidity and improve quality of life following bariatric surgery. [ABSTRACT FROM AUTHOR]

Purpose: Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality. Methods: We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews. In stage one, both text mining of published literature and expert opinion identified testosterone as a plausible biological mechanism. In stage two, we performed a systematic review and meta-analysis to assess the evidence from both human and animal studies examining the effect of vitamin D on testosterone, and testosterone on advanced prostate cancer (diagnostic Gleason score of ≥ 8, development of metastasis) or prostate cancer-specific mortality. Results: A meta-analysis of ten human RCTs showed evidence of an effect of vitamin D on total testosterone (standardised mean difference (SMD) = 0.133, 95% CI = − 0.003–0.269, I2 = 0.0%, p = 0.056). Five human RCTs showed evidence of an effect of vitamin D on free testosterone (SMD = 0.173, 95% CI = − 0.104–0.450, I2 = 52.4%, p = 0.220). Three human cohort studies of testosterone on advanced prostate cancer or prostate cancer-specific mortality provided inconsistent results. In one study, higher levels of calculated free testosterone were positively associated with advanced prostate cancer or prostate cancer-specific mortality. In contrast, higher levels of dihydrotestosterone were associated with lowering prostate cancer-specific mortality in another study. No animal studies met the study eligibility criteria. Conclusion: There is some evidence that vitamin D increases levels of total and free testosterone, although the effect of testosterone levels within the normal range on prostate cancer progression is unclear. The role of testosterone as a mechanism between vitamin D and prostate cancer progression remains inconclusive. [ABSTRACT FROM AUTHOR]

This series sought to evaluate the role of intraoperative MRI (iMRI) for resection of functional pituitary adenomas (FPAs). We retrospectively reviewed clinical data of 114 consecutive FPAs with excessive hormone secretion treated with transsphenoidal surgery and iMRI during 01/2010–12/2017. We focused on iMRI findings, extend of resection and postoperative hormonal remission. Variables of incomplete resections and persistent hormone excess were evaluated by binary regression. Patients with FPAs presented with hypercortisolism (n = 23, 20%), acromegaly (n = 56, 49%), and as prolactinomas (n = 35, 31%) resistant to medical treatment. Preoperative MRI showed 81 macroadenomas (71%) and optic system involvement in 41 cases (36%). IMRI was suggestive for residual tumor in 51 cases (45%). Re-inspection of the cavity cleared equivocal findings in 16 cases (14%). Additional tumor was removed in 22 cases (19%). Complete resection was achieved in 95 cases (83%). Postoperative morbidity was low (1.7% revision surgeries, 0.8% permanent diabetes insipidus). Overall hormonal remission-rate was 59% (hypercortisolism 78%, acromegaly 52%, prolactinoma 57%). Supra- and parasellar invasion and preoperative visual impairment were significant predictors for incomplete resections despite use of iMRI. Risk for persistent hormone excess was increased sevenfold after incomplete resections. IMRI enabled reliable identification of tumor remnants during surgery and triggered further resection in a considerable proportion of cases. Nevertheless, tumor size and invasiveness set persistent boundaries to the completeness of resections. The low rate of surgical complications could point at a less invasive iMRI-guided surgical approach while achieving a complete tumor resection was a crucial determinant for hormonal outcome. [ABSTRACT FROM AUTHOR]

Background: Pituitary tumors may cause compression of the optic chiasm, resulting in decreased visual acuity. Therefore, decompression of the optic chiasm is a major goal of surgical treatment in such patients. Quantitative pupillometry has been used in various clinical settings for assessing the optic system but has not been applied in patients with pituitary tumors. This study aimed to evaluate the potential of this technique to improve treatment modalities in patients undergoing surgical resection of pituitary tumors. Method: Pupillometry using the automated NPi 200® Pupillometer was performed in seven patients who underwent surgical resection of large pituitary tumors at the University of Heidelberg in 2018. The neurological pupil index (NPi) was assessed preoperatively and postoperatively, and correlations with visual acuity and magnetic resonance imaging (MRI) findings regarding optic chiasm compression were determined. Results: All patients experienced visual disturbance due to a large pituitary tumor. The NPi was < 4.0 in all patients in at least one pupil. Intraoperative MRI demonstrated successful decompression of the optic chiasm in all cases. Postoperatively, the NPi values increased, and this increase was correlated with improved visual acuity. Conclusions: We found that quantitative pupillometry can detect optic chiasm compression in patients with pituitary tumors. Furthermore, postoperative improvement of NPi values may indicate sufficient decompression of the optic chiasm. Further studies are warranted to substantiate the granularity of this technique to gain valuable information for patients with pituitary tumors who are indicated for surgery. [ABSTRACT FROM AUTHOR]

We investigated the longitudinal associations between physical activity (PA), lumbar multifidus morphology, and impactful low back pain (LBP) in young people. Nine-year-old children were recruited from 25 primary schools and followed up at age 13, 16, and 21 years. We measured PA with accelerometers at age 9, 13, and 16; quantified patterns of lumbar multifidus intramuscular adipose tissue (IMAT) change from 13 to 16 years using magnetic resonance imaging; and recorded LBP and its impact with standardised questionnaires and interviews. Associations were examined with crude and adjusted logistic or multinomial models and reported with odds ratios (OR) or relative risk ratios (RRR). We included data from 364 children (mean[SD] age = 9.7[.4] years). PA behaviour was not associated with LBP. Having persistently high IMAT levels at age 13 and 16 was associated with greater odds of LBP (OR[95% CI] = 2.98[1.17 to 7.58]). Increased time in moderate and vigorous intensity PA was associated with a lower risk of higher IMAT patterns (RRR[95% CI] =.67[.46 to.96] to.74[.55 to 1.00]). All associations became non-significant after adjusting for sex and body mass index (BMI). Future studies investigating the relationships between PA behaviour, lumbar multifidus IMAT, and impactful LBP should account for potential confounding by sex and BMI. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the trajectories of spinal pain frequency from 6 to 17 years of age and describe the prevalence and frequency of spinal pain and related diagnoses in children following different pain trajectories. First through fifth-grade students from 13 primary schools were followed for 5.5 years. Occurrences of spinal pain were reported weekly via text messages. Children reporting spinal pain were physically evaluated and classified using International Classification of Disease criteria. Trajectories of spinal pain frequency were modeled from age 6 to 17 years with latent class growth analysis. We included data from 1556 children (52.4% female, mean (SD) baseline age = 9.1 (1.9) years) and identified 10,554 weeks of spinal pain in 329,756 weeks of observation. Sixty-three percent of children reported one or more occurrences of spinal pain. We identified five trajectories of spinal pain frequency. Half the children (49.8%) were classified as members of a "no pain" trajectory. The remaining children followed "rare" (27.9%), "rare, increasing" (14.5%), "moderate, increasing" (6.5%), or "early-onset, decreasing" (1.3%) spinal pain trajectories. The most common diagnoses in all trajectory groups were non-specific (e.g., "back pain"). Tissue-specific diagnoses (e.g., muscle strain) were less common and pathologies (e.g., fracture) were rare.  Conclusion: From childhood through adolescence, spinal pain was common and followed heterogeneous courses comprising stable, increasing, and early-onset trajectories. These findings accord with recommendations from adult back pain guidelines that most children with spinal pain can be reassured that they do not have a serious disease and encouraged to stay active. What is Known: • Spinal pain imposes a large burden on individuals and society. • Although many people first experience the condition in childhood, little is known about the developmental trajectories of spinal pain from childhood to adolescence. What is New: • Data from 1556 children and 329,756 participant weeks showed five unique spinal pain trajectories from 6 to 17 years: most children rarely reported spinal pain, while one in five followed increasing or early-onset trajectories. • Most pain occurrences were non-specific; pathological diagnoses were rare. [ABSTRACT FROM AUTHOR]

When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation—known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells. Metabolically active organelles compete for cytosolic space and resources during metabolism rewiring. Here, the authors develop a computational model of yeast metabolism and resource allocation to predict condition- and compartment-specific proteome constraints that govern metabolic strategies. [ABSTRACT FROM AUTHOR]

Purpose: Before being marketed, hernia mesh must undergo in vivo testing, which often includes biomechanical and histological assessment. Currently, there are no universal standards for this testing and methods vary greatly within the literature. A scoping review of relevant studies was undertaken to analyse the methodologies used for in vivo mesh testing. Methods: Medline and Embase databases were searched for relevant studies. 513 articles were identified and 231 duplicates excluded. 126 papers were included after abstract and full text review. The data extraction was undertaken using standardised forms. Results: Mesh is most commonly tested in rats (53%). 78% of studies involve the formation of a defect; in 52% of which the fascia is not opposed. The most common hernia models use mesh to bridge an acute defect (50%). Tensile strength testing is the commonest form of mechanical testing (63%). Testing strip widths and test speeds vary greatly (4–30 mm and 1.625–240 mm/min, respectively). There is little consensus on which units to use for tensile strength testing. Collagen is assessed for its abundance (54 studies) more than its alignment (18 studies). Alignment is not measured quantitatively. At least 21 histological scoring systems are used for in vivo mesh testing. Conclusions: The current practice of in vivo mesh testing lacks standardisation. There is significant inconsistency in every category of testing, both in methodology and comparators. We would call upon hernia organisations and materials testing institutions to discuss the need for a standardised approach to this field. [ABSTRACT FROM AUTHOR]

In an aging Western society, the incidence of chronic subdural hematomas (cSDH) is continuously increasing. In this study, we reviewed our clinical management of cSDH patients and identified predictive factors for the need of reoperation due to residual or recurrent hematomas with a focus on the use of antithrombotic drugs. In total, 623 patients who were treated for cSDH with surgical evacuation between 2006 and 2016 at our department were retrospectively analyzed. Clinical and radiological characteristics and laboratory parameters were investigated as possible predictors of reoperation with univariate and multivariate analyses. Additionally, clinical outcome measures were compared between patients on anticoagulants, on antiplatelets, and without antithrombotic medication. In univariate analyses, patients on anticoagulants and antiplatelets presented significantly more often with comorbidities, were significantly older, and their risk for perioperative complications was significantly increased. Nevertheless, their clinical outcome was comparable to that of patients without antithrombotics. In multivariate analysis, only the presence of comorbidities, but not antithrombotics, was an independent predictor for the need for reoperations. Patients on antithrombotics do not seem to necessarily have a significantly increased risk for residual hematomas or rebleeding requiring reoperation after cSDH evacuation. More precisely, the presence of predisposing comorbidities might be a key independent risk factor for reoperation. Importantly, the clinical outcomes after surgical evacuation of cSDH are comparable between patients on anticoagulants, antiplatelets, and without antithrombotics. [ABSTRACT FROM AUTHOR]

Cattle vary in their susceptibility to infection and immunopathology, but our ability to measure and longitudinally profile immune response variation is limited by the lack of standardized immune phenotyping assays for high-throughput analysis. Here we report longitudinal innate immune response profiles in cattle using a low-blood volume, whole blood stimulation system—the ImmunoChek (IChek) assay. By minimizing cell manipulation, our standardized system minimizes the potential for artefactual results and enables repeatable temporal comparative analysis in cattle. IChek successfully captured biological variation in innate cytokine (IL-1β and IL-6) and chemokine (IL-8) responses to 24-hr stimulation with either Gram-negative (LPS), Gram-positive (PamCSK4) bacterial or viral (R848) pathogen-associated molecular patterns (PAMPs) across a 4-month time window. Significant and repeatable patterns of inter-individual variation in cytokine and chemokine responses, as well as consistent high innate immune responder individuals were identified at both baseline and induced levels. Correlation coefficients between immune response read-outs (IL-1β, IL-6 and IL-8) varied according to PAMP. Strong significant positive correlations were observed between circulating monocytes and IL-6 levels for null and induced responses (0.49–0.61) and between neutrophils and cytokine responses to R848 (0.38–0.47). The standardized assay facilitates high-throughput bovine innate immune response profiling to identify phenotypes associated with disease susceptibility and responses to vaccination. [ABSTRACT FROM AUTHOR]

Objectives and design: This study aimed to understand the longitudinal relationship between C-reactive protein (CRP) and body mass index (BMI) from adolescence to early adulthood. Methods: CRP and BMI were collected from participants of the Raine Study Gen2 at 14-, 17-, 20- and 22-year follow-ups (n = 1312). A dual trajectory analysis was conducted to assess the association between CRP and BMI trajectories, providing conditional probabilities of membership of CRP trajectory membership given BMI trajectory membership. Best model fit was assessed by systematically fitting two to eight trajectory groups with linear and quadratic terms and comparing models according to the Bayesian Information Criterion statistic. Results: The three CRP trajectories were; "stable-low" (71.0%), "low-to-high" (13.8%) and "stable-high" (15.2%). Participants in a "high-increasing" BMI trajectory had a higher probability of being in the "stable-high" CRP trajectory (60.4% of participants). In contrast, individuals in the "medium-increasing" BMI trajectory did not have a significantly increased probability of being in the "stable-high" CRP trajectory. Conclusions: These findings support that chronic sub-clinical inflammation is present through adolescence into early adulthood in some individuals. Targeting chronic sub-clinical inflammation though obesity prevention strategies may be important for improving future health outcomes. [ABSTRACT FROM AUTHOR]

How thylakoid membranes are generated to form a metabolically active membrane network and how thylakoid membranes orchestrate the insertion and localization of protein complexes for efficient electron flux remain elusive. Here, we develop a method to modulate thylakoid biogenesis in the rod-shaped cyanobacterium Synechococcus elongatus PCC 7942 by modulating light intensity during cell growth, and probe the spatial-temporal stepwise biogenesis process of thylakoid membranes in cells. Our results reveal that the plasma membrane and regularly arranged concentric thylakoid layers have no physical connections. The newly synthesized thylakoid membrane fragments emerge between the plasma membrane and pre-existing thylakoids. Photosystem I monomers appear in the thylakoid membranes earlier than other mature photosystem assemblies, followed by generation of Photosystem I trimers and Photosystem II complexes. Redistribution of photosynthetic complexes during thylakoid biogenesis ensures establishment of the spatial organization of the functional thylakoid network. This study provides insights into the dynamic biogenesis process and maturation of the functional photosynthetic machinery. Cyanobacterial thylakoid membranes host the molecular machinery for the light-dependent reactions of photosynthesis and respiratory electron flow. Here, the authors show that newly synthesized thylakoids emerge between the plasma membrane and pre-existing thylakoids and describe the time-dependent assembly process of photosynthetic complexes. [ABSTRACT FROM AUTHOR]

Cranioplasty (CP) is a standard procedure in neurosurgical practice for patients after (decompressive) craniectomy. However, CP surgery is not standardized, is carried out in different ways, and is associated with considerable complication rates. Here, we report our experiences with the use of different CP materials and analyze long-term complications and implant survival rates. We retrospectively studied patients who underwent CP surgery at our institution between 2004 and 2014. Binary logistic regression analysis was performed in order to identify risk factors for the development of complications. Kaplan-Meier analysis was used to estimate implant survival rates. A total of 392 patients (182 females, 210 males) with a mean age of 48 years were included. These patients underwent a total of 508 CP surgeries. The overall complication rate of primary CP was 33.2%, due to bone resorption/loosening (14.6%) and graft infection (7.9%) with a mean implant survival of 120 ± 5 months. Binary logistic regression analysis showed that young age (< 30 years) (p = 0.026, OR 3.150), the presence of multidrug-resistant bacteria (p = 0.045, OR 2.273), and cerebrospinal fluid (CSF) shunt (p = 0.001, OR 3.137) were risk factors for postoperative complications. The use of titanium miniplates for CP fixation was associated with reduced complication rates and bone flap osteolysis as well as longer implant survival rates. The present study highlights the risk profile of CP surgery. Young age (< 30 years) and shunt-dependent hydrocephalus are associated with postoperative complications especially due to bone flap autolysis. Furthermore, a rigid CP fixation seems to play a crucial role in reducing complication rates. [ABSTRACT FROM AUTHOR]

Purpose: To identify low back pain (LBP) trajectories from early adolescence through to early adulthood and to investigate whether sustained levels of elevated subclinical C-reactive protein (CRP) are linked with these LBP trajectories. Methods: We analysed longitudinal data from 1513 participants who were enrolled in the Raine Study cohort. Data on LBP with impact on daily living and CRP were collected at the ages of 14, 17, 20, and 22. We constructed group-based trajectory models to identify discrete trajectories of LBP with impact. We then evaluated how the CRP trajectories and the LBP with impact trajectories evolved jointly over time using a multi-trajectory analysis. Results: The model identified three LBP trajectories. One subgroup included almost half the participants (46.1%) who had a consistently low probability of LBP. Another subgroup comprising 43.5% of participants had an increasing probability of LBP, while one in ten participants (10.4%) had a decreasing probability of LBP. There were no associations between elevated CRP and LBP trajectory subgroup membership. Conclusion: Although young people follow distinct trajectories of LBP, CRP trajectories do not appear to be a distinguishing factor of the LBP trajectories. Previously reported associations between CRP and LBP may be explained by comorbidity or other factors. Future studies undertaking trajectory analysis should consider comorbidity clusters. Level of Evidence I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding [ABSTRACT FROM AUTHOR]

Background: Family planning is an important consideration for women with multiple sclerosis (MS), who are often diagnosed during their reproductive years. Currently, limited data are available on pregnancy outcomes in patients exposed to interferon-beta (IFN-beta) before or during pregnancy. Here, we present the cumulative pregnancy exposure data and prevalence of pregnancy and infant outcomes in IFN-beta-exposed pregnant women with MS from the European IFN-beta Pregnancy Registry. Methods: Using spontaneous and solicited reports, the registry collected data from 26 countries of the European Economic Area, consisting of information on women with MS identifying themselves to one of the Marketing Authorisation Holders (Bayer, Biogen, Merck KGaA, and Novartis) or healthcare professionals as pregnant and exposed to IFN-beta during pregnancy or within 1 month before conception. The outcomes collected by the registry included ectopic pregnancies, spontaneous abortions, elective terminations, live, and stillbirths with or without congenital anomalies. The prevalence of pregnancy outcomes was put in context with those reported in the general population. Results: Between 2009 and 2017, the registry collected 948 pregnancy reports with a known pregnancy outcome. Overall, 82.0% (777/948) of pregnancies resulted in live birth without congenital anomaly. When comparing IFN-beta-exposed pregnancies with the general population, the prevalence of spontaneous abortions (10.7% vs. 10–21%) and congenital anomalies in live births (2.1% vs. 2.1–4.1%) were found to be within reported ranges. Conclusions: The data gathered from these pregnancy cases suggest no evidence that IFN-beta exposure before conception and/or during pregnancy adversely increases the rate of congenital anomalies or spontaneous abortions. [ABSTRACT FROM AUTHOR]

Objectives: The faecal-oral route is a predominant mode of infectious disease transmission and yet the immunology of the bovine oral cavity is poorly understood. The objectives of this study were to develop an in vitro cell model of bovine salivary gland cells and to characterize the role of vitamin D on the expression of innate immune genes induced by stimulation with bacterial and viral pathogen-associated molecular patterns (PAMPs). Methods: Submandibular glandular tissue was excised post-mortem, processed, cells isolated and cultured until confluency after which cells were incubated with the active form of vitamin D (1,25(OH)D) for 18 h before stimulation with lipopolysaccharide (LPS μg/ml), lipoteichoic acid (LTA μg/ml) or polyinosinic:polycytidylic acid (poly I:C-20 μg/ml) PAMPs for 6 h and immune gene expression was assessed by Quantitative Real-Time PCR (RT-qPCR). Results: RT-qPCR analysis of vimentin expression in cells derived from the bovine submandibular gland shows that cultured cells were fibroblast in origin. These cells significantly induce the pro-inflammatory cytokine IL1B, β-defensin and cathelicidin genes but these were not significantly altered in response to 1,25(OH)D. In contrast, 1,25(OH)D significantly up-regulates the expression of the NOS2 gene encoding iNOS in bovine submandibular stromal cells compared to EtOH (vehicle) control and this is a maintained response to all three bacterial and viral ligands. We have developed a new in vitro model to allow detailed investigations of mechanisms to enhance oral immunity in cattle. We show that these cells are fibroblast in nature, immunologically competent and vitamin D responsive. Their vitamin D-mediated enhancement of NOS2 expression warrants further investigation in saliva as a potential mechanism to boost oral immunity against infectious agents. [ABSTRACT FROM AUTHOR]

Some enteric bacteria including Salmonella have evolved the propanediol-utilising microcompartment (Pdu MCP), a specialised proteinaceous organelle that is essential for 1,2-propanediol degradation and enteric pathogenesis. Pdu MCPs are a family of bacterial microcompartments that are self-assembled from hundreds of proteins within the bacterial cytosol. Here, we seek a comprehensive understanding of the stoichiometric composition and organisation of Pdu MCPs. We obtain accurate stoichiometry of shell proteins and internal enzymes of the natural Pdu MCP by QconCAT-driven quantitative mass spectrometry. Genetic deletion of the major shell protein and absolute quantification reveal the stoichiometric and structural remodelling of metabolically functional Pdu MCPs. Decoding the precise protein stoichiometry allows us to develop an organisational model of the Pdu metabolosome. The structural insights into the Pdu MCP are critical for both delineating the general principles underlying bacterial organelle formation, structural robustness and function, and repurposing natural microcompartments using synthetic biology for biotechnological applications. Enteric pathogens such as Salmonella depend on propanediol-utilising microcompartments (Pdu MCP), which self-assemble from cytosolic proteins. Using mass spectrometry-based absolute quantification, the authors here define the protein stoichiometry and propose an organizational model of a Salmonella Pdu MCP. [ABSTRACT FROM AUTHOR]

Purpose: To report evidence of chronic physical illnesses, mental health disorders, and psychological features as potential risk factors for back pain in children, adolescents, and young adults.Methods: This systematic review and meta-analysis included cohort and inception cohort studies that investigated potential risk factors for back pain in young people. Potential risk factors of interest were chronic physical illnesses, mental health disorders (e.g. depression, anxiety), and other psychological features (e.g. coping, resistance). Searches were conducted in MEDLINE, Embase, CINAHL, and Scopus from inception to July 2019.Results: Nineteen of 2167 screened articles were included in the qualitative synthesis, and data from 12 articles were included in the meta-analysis. Evidence from inception cohort studies demonstrated psychological distress, emotional coping problems, and somatosensory amplification to be likely risk factors for back pain. Evidence from non-inception cohort studies cannot distinguish between risk factors or back pain triggers. However, we identified several additional factors that were associated with back pain. Specifically, asthma, headaches, abdominal pain, depression, anxiety, conduct problems, somatization, and 'feeling tense' are potential risk factors or triggers for back pain. Results from the meta-analyses demonstrated the most likely risk factors for back pain in young people are psychological distress and emotional coping problems.Conclusion: Psychological features are the most likely risk factors for back pain in young people. Several other factors were associated with back pain, but their potential as risk factors was unclear due to risk of bias. Additional high-quality research is needed to better elucidate these relationships. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]