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The goal of this study was to evaluate the diagnostic accuracy of perfusion computed tomography (CT) parameters obtained by different mathematical-kinetic methods for distinguishing pancreatic adenocarcinoma from normal tissue. To determine cut-off values and to assess the interchangeability of cut-off values, which were determined by different methods. Perfusion CT imaging of the pancreas was prospectively performed in 23 patients. 19 patients with histopathologically confirmed pancreatic adenocarcinoma were included in the study. Blood flow (BF), blood volume (BV) and permeability-surface area product (PS) were measured in pancreatic adenocarcinoma and normal tissue with the deconvolution (BF, BV, PS), maximum slope (BF), and Patlak methods (BV, PS). The interchangeability of cut-off values was examined by assessing agreement between BF, BV, and PS measured with different mathematical-kinetic methods. Bland-Altman analysis demonstrated poor agreement between perfusion parameters, measured with different mathematical-kinetic methods. According to receiver operating characteristic (ROC) analysis, PS measured with the Patlak method had the significantly lowest diagnostic accuracy (area under ROC curve = 0.748). All other parameters were of high diagnostic accuracy (area under ROC curve = 0.940-0.997), although differences in diagnostic accuracy were not statistically different. Cut-off values for BF of ≤ 91.83 ml/100 ml/min and for BV of ≤ 5.36 ml/100 ml, both measured with the deconvolution method, appear to be the most appropriate cut-off values to distinguish pancreatic adenocarcinoma from normal tissue. Perfusion parameters obtained by different methods are not interchangeable. Therefore, cut-off values, which were determined using different methods, are not interchangeable either. Perfusion parameters can help to distinguish pancreatic adenocarcinoma from normal tissue with high diagnostic accuracy, except for PS measured with the Patlak method. · Perfusion CT parameters showed high diagnostic accuracy in differentiating between pancreatic adenocarcinoma and normal tissue.. · Only PS measured with the Patlak method showed a significantly lower diagnostic accuracy.. · Perfusion parameters measured with different mathematical-kinetic methods are not interchangeable.. · A specific cut-off value must be determined for each method and each perfusion parameter..· Koell M, Klauss M, Skornitzke S et al. Computed Tomography Perfusion Analysis of Pancreatic Adenocarcinoma with the Deconvolution, Maximum Slope, and Patlak Methods - Evaluation of Diagnostic Accuracy and Interchangeability of Cut-Off Values. Fortschr Röntgenstr 2021; 193: 1062 - 1073.ZIEL: Ziel dieser Studie war es, die diagnostische Güte von Perfusions-Computertomografie (CT) -Parametern zu evaluieren, die mit verschiedenen mathematisch-kinetischen Methoden gemessen wurden, für die Differenzierung zwischen Pankreaskarzinom und Normalgewebe. Es sollten zudem Cut-off-Werte bestimmt und die Austauschbarkeit von Cut-off-Werten, die mit verschiedenen Methoden ermittelt wurden, evaluiert werden. Bei 23 Patienten wurde prospektiv eine Perfusions-CT-Bildgebung des Pankreas durchgeführt. 19 Patienten mit histopathologisch bestätigtem Pankreaskarzinom wurden in die Studie eingeschlossen. Der Blutfluss (BF), das Blutvolumen (BV) und das Permeabilitätsoberflächenprodukt (PS) wurden im Pankreaskarzinom und Normalgewebe mit der Deconvolution- (BF, BV, PS), Maximum-Slope- (BF) und Patlak-Methode (BV, PS) gemessen. Die Austauschbarkeit der Cut-off-Werte wurde evaluiert, indem die Übereinstimmung zwischen BF, BV und PS untersucht wurde, die mit verschiedenen mathematisch-kinetischen Methoden gemessen wurden. Die Bland-Altman-Analyse zeigte eine schlechte Übereinstimmung zwischen den Perfusionsparametern, die mit verschiedenen mathematisch-kinetischen Methoden gemessen wurden. Gemäß ROC-Analyse (Receiver Operating Characteristic) hatte das mit der Patlak-Methode gemessene PS die signifikant niedrigste diagnostische Güte (Fläche unter der ROC-Kurve = 0,748). Alle anderen Parameter hatten eine hohe diagnostische Güte (Fläche unter der ROC-Kurve = 0,940–0,997); deren diagnostische Güte unterschied sich jedoch nicht statistisch signifikant. Cut-off-Werte für BF von ≤ 91,83 ml/100 ml/min und für BV von ≤ 5,36 ml/100 ml, beide mit der Deconvolution-Methode gemessen, scheinen die geeignetsten Cut-off-Werte zu sein, mit denen das Pankreaskarzinom von Normalgewebe abgegrenzt werden kann. Perfusionsparameter, die mit verschiedenen Methoden gemessen wurden, sind nicht austauschbar. Daraus folgt, dass Cut-off-Werte, die mit unterschiedlichen Methoden ermittelt wurden, ebenfalls nicht austauschbar sind. Perfusionsparameter können dazu beitragen, das Pankreaskarzinom mit hoher diagnostischer Güte vom Normalgewebe abzugrenzen, mit Ausnahme von PS, das mit der Patlak-Methode gemessen wurde. · Perfusions-CT-Parameter zeigten eine hohe diagnostische Güte bei der Differenzierung zwischen Pankreaskarzinom und Normalgewebe.. · Nur PS, gemessen mit der Patlak-Methode, zeigte eine signifikant niedrigere diagnostische Güte.. · Perfusionsparameter, die mit unterschiedlichen mathematisch-kinetischen Methoden gemessen wurden, sind nicht austauschbar.. · Für jede Methode und jeden Perfusionsparameter muss ein spezifischer Cut-off-Wert bestimmt werden..

X-ray computed tomography (CT) is a cardinal tool in clinical practice. It provides cross-sectional images within seconds. The recent introduction of clinical photon-counting CT allowed for an increase in spatial resolution by more than a factor of two resulting in a pixel size in the center of rotation of about 150 µm. This level of spatial resolution is in the order of dedicated preclinical micro-CT systems. However so far, the need for different dedicated clinical and preclinical systems often hinders the rapid translation of early research results to applications in men. This drawback might be overcome by ultra-high resolution (UHR) clinical photon-counting CT unifying preclinical and clinical research capabilities in a single machine. Herein, the prototype of a clinical UHR PCD CT (SOMATOM CounT, Siemens Healthineers, Forchheim, Germany) was used. The system comprises a conventional energy-integrating detector (EID) and a novel photon-counting detector (PCD). While the EID provides a pixel size of 0.6 mm in the centre of rotation, the PCD provides a pixel size of 0.25 mm. Additionally, it provides a quantification of photon energies by sorting them into up to four distinct energy bins. This acquisition of multi-energy data allows for a multitude of applications, e.g. pseudo-monochromatic imaging. In particular, we examine the relation between spatial resolution, image noise and administered radiation dose for a multitude of use-cases. These cases include ultra-high resolution and multi-energy acquisitions of mice administered with a prototype bismuth-based contrast agent (nanoPET Pharma, Berlin, Germany) as well as larger animals and actual patients. The clinical EID provides a spatial resolution of about 9 lp/cm (modulation transfer function at 10%, MTF

Introduction: Previous research has suggested that the Amish may experience a relatively high prevalence of Parkinson’s disease (PD) and/or parkinsonian motor signs. Methods: In a large sample from the Amish community in Lancaster County, Pennsylvania, age ≥18 years, we assessed the prevalence of self-reported PD diagnosis. For those without self-reported PD diagnosis, we assessed the frequency of PD-related motor symptoms using a 9-item questionnaire that was designed by the PD Epidemiology Research Group. Lastly, we queried study participants for the presence of 2 nonmotor symptoms that have been commonly linked to PD: bowel movement frequency and daytime sleepiness. Results: Among 2,025 subjects who answered the PD questionnaire, 430 were older than 60 years. Of 430 participants ≥60 years, 5 (1.2%) reported a PD diagnosis. Of those without a PD diagnosis, 10.5% reported ≥1 and 1.2% ≥ 4 motor symptoms for the 9-item PD screening questionnaire. Of the 3,789 subjects who answered the question about bowel movement frequency, 0.7% reported ≤3 bowel movements per week. Among 1,710 subjects who answered the question about daytime sleepiness, 8.1% of the participants reported “always” sleepy during the day. Discussion: These data neither support a markedly higher PD prevalence in the older Lancaster Amish nor do they show dramatically higher motor and/or selected nonmotor symptoms than the general population. Future studies that employ more rigorous procedures for case identification and PD-specific preclinical symptoms/tests are needed to determine the potential differences and similarities among different Amish populations and between Amish and non-Amish populations.

Purpose of Review We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. Recent Findings Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. “Long-COVID” non-syndromal presentations include “brain-fogginess,” autonomic instability, fatigue, and insomnia. Summary SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.

Given the increasing rate of death by suicide in the United States, it is imperative to examine specific risk factors and to identify possible etiologies of suicidal behavior in at-risk clinical subpopulations. There is accumulating evidence to support an elevated risk of death by suicide in individuals with a history of traumatic brain injury (TBI). In this review article, after defining terms used in suicidology, we discuss the associations of TBI with death by suicide, suicide attempt, and suicidal ideation. A model for repetitive TBIs, leading to chronic traumatic encephalopathy, is also discussed as a neuroinflammatory process, with discussion about its possible link with suicide. The review concludes with an overview of interventions to prevent suicidal behavior.

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. Results: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p < 0.005) and earlier mid-sleep time (p < 0.05). Conclusions: It seems unlikely that sleep mediates the previously reported associations between T. gondii and mental illness. Future longitudinal studies with objective measures are necessary to replicate our findings.

Objectives Virtual non-calcium (VNCa) images could improve assessment of plasma cell dyscrasias by enhancing visibility of bone marrow. Thus, VNCa images from dual-layer spectral CT (DLCT) were evaluated at different calcium suppression (CaSupp) indices, correlating results with apparent diffusion coefficient (ADC) values from MRI. Methods Thirty-two patients with initial clinical diagnosis of a plasma cell dyscrasia before any chemotherapeutic treatment, who had undergone whole-body low-dose DLCT and MRI within 2 months, were retrospectively enrolled. VNCa images with CaSupp indices ranging from 25 to 95 in steps of 10, conventional CT images, and ADC maps were quantitatively analyzed using region-of-interests in the vertebral bodies C7, T12, L1-L5, and the iliac bone. Independent two-sample t-test, Wilcoxon-signed-rank test, Pearson’s correlation, and ROC analysis were performed. Results Eighteen patients had a non-diffuse, 14 a diffuse infiltration in conventional MRI. A significant difference between diffuse and non-diffuse infiltration was shown for VNCa-CT with CaSupp indices from 55 to 95, for conventional CT, and for ADC (each p < 0.0001). Significant quantitative correlation between VNCa-CT and MRI could be found with strongest correlation at CaSupp index 65 for L3 (r = 0.68, p < 0.0001) and averaged L1-L5 (r = 0.66, p < 0.0001). The optimum CT number cut-off point for differentiation between diffuse and non-diffuse infiltration at CaSupp index 65 for averaged L1-L5 was −1.6 HU (sensitivity 78.6%, specificity 75.0%). Conclusion Measurements in VNCa-CT showed the highest correlation with ADC at CaSupp index 65. VNCa technique may prove useful for evaluation of bone marrow infiltration if MRI is not feasible. Key Points • VNCa-CT images can support the evaluation of bone marrow infiltration in plasma cell dyscrasias. • VNCa measurements of vertebral bodies show significant correlation with ADC in MRI. • Averaging L1-L5 at CaSupp index 65 allowed quantitative detection of infiltration comparable to MRI ADC.

An evaluation of energy thresholding and acquisition mode for metal artifact reduction in Photon-counting detector CT (PCD-CT) compared to conventional energy-integrating detector CT (EID-CT) was performed. Images of a hip prosthesis phantom placed in a water bath were acquired on a scanner with PCD-CT and EID-CT (tube potentials: 100, 120 and 140 kVp) and energy thresholds (above 55–75 keV) in Macro and Chess mode. Only high-energy threshold images (HTI) were used. Metal artifacts were quantified by a semi-automated segmentation algorithm, calculating artifact volumes, means and standard deviations of CT numbers. Images of a human cadaver with hip prosthesis were acquired on the PCD-CT in Macro mode as proof-of-concept. Images at 140 kVp showed less metal artifacts than 120 kVp or 100 kVp. HTI (70, 75 keV) had fewer artifacts than low energy thresholds (55, 60, 65 keV). Fewer artifacts were observed in the Macro-HTI (8.9–13.3%) for cortical bone compared to Chess-HTI (9.4–19.1%) and EID-CT (10.7–19.0%) whereas in bone marrow Chess-HTI (19.9–45.1%) showed less artifacts compared to Macro-HTI (21.9–38.3%) and EID-CT (36.4–54.9%). Noise for PCD-CT (56–81 HU) was higher than EID-CT (33–36 HU) irrespective of tube potential. High-energy thresholding could be used for metal artifact reduction in PCD-CT, but further investigation of acquisition modes depending on target structure is required.

Objectives To investigate the value of spectral-detector computed tomography (SDCT) parameters for the quantitative differentiation between atelectasis and pneumonia on contrast-enhanced chest CT. Material and methods Sixty-three patients, 22 clinically diagnosed with pneumonia and 41 with atelectasis, underwent contrast-enhanced SDCT scans during the venous phase. CT numbers (Hounsfield Units [HU]) were measured on conventional reconstructions (CON120kVp) and the iodine concentration (Ciodine, [mg/ml]), and effective atomic number (Zeff) on spectral reconstructions, using region-of-interest (ROI) analysis. Receiver operating characteristics (ROC) and contrast-to-noise ratios (CNRs) were calculated to assess each reconstruction's potential to differentiate between atelectasis and pneumonia. Results On contrast-enhanced SDCT, the difference between atelectasis and pneumonia was significant on CON120kVp, Ciodine, and Zeff images (p < 0.001). On CON120kVp images, a threshold of 81 HU achieved a sensitivity of 93 % and a specificity of 95 % for identifying pneumonia, while Ciodine and Zeff images reached the same sensitivity but lower specificities of 85 % and 83 %. CON120kVp images showed significantly higher CNRs between normal lung and atelectasis or pneumonia with 30.63 and 27.69 compared to Ciodine images with 3.54 and 1.27 and Zeff images with 4.22 and 7.63 (p < 0.001). None of the parameters could differentiate atelectasis and pneumonia without contrast media. Conclusions Contrast-enhanced SDCT can differentiate atelectasis and pneumonia based on the spectral parameters Ciodine, and Zeff. However, they had no added value compared to CT number measurement on CON120kVp images. Furthermore, contrast media is still needed for a differentiation based on quantitative SDCT parameters., Highlights • Spectral CT parameters Ciodine and Zeff can differentiate atelectasis from pneumonia on contrast-enhanced images. • Spectral CT parameters Ciodine and Zeff have no added value compared to CT number measurement on CON120kVp images. • CNRs between normal and consolidated lung were higher on conventional on spectral images., Pneumonia, Atelectasis, Diagnosis, SDCT

IntroductionPrevious studies have suggested that the Amish may experience a relatively high prevalence of Parkinson’s disease (PD) and/or parkinsonian-motor signs.MethodsWe assessed the frequency of PD-related motor and no-motor symptoms in a large sample from the Amish Community in Lancaster County, Pennsylvania age ≥ 18 y.ResultsOf 430 participants ≥ 60 years, five (1.2%) reported a PD diagnosis, a prevalence similar to estimates in the general older adult populations. Of those without a PD diagnosis, 10.5% reported ≥ 1 and 1.2% ≥ 4 motor symptoms for the nine-item PD screening questionnaire. We also used questionnaires to assess non-motor symptoms. Constipation was reported in 0.7%, and daytime sleepiness in 8.1% of the participants. These frequencies are similar to, or lower than, corresponding frequencies reported in the US National Health and Nutrition Examination Surveys.DiscussionThese data neither support a markedly higher PD prevalence in the Lancaster Amish, nor do they show that non-motor symptoms occur with prevalence different that the general US population. It is possible that the Lancaster Amish differ from other US Amish populations in genetics or environmental exposures, or that there were methodological differences between this study and prior ones.

Overlapping pathways between mood and metabolic regulation have increasingly been reported. Although impaired regulation of adiponectin, a major metabolism-regulating hormone, has been implicated in major depressive disorder, its role in seasonal changes in mood and seasonal affective disorder-winter type (SAD), a disorder characterized by onset of mood impairment and metabolic dysregulation (e.g., carbohydrate craving and weight gain) in fall/winter and spontaneous alleviation in spring/summer, has not been previously studied. We studied a convenience sample of 636 Old Order Amish (mean (± SD), 53.6 (±14.8) years; 50.1% males), a population with self-imposed restriction on network electric light at home, and low prevalence of total SAD (t-SAD = syndromal + subsyndromal). We calculated the global seasonality score (GSS), estimated SAD and subsyndromal-SAD after obtaining Seasonal Pattern Assessment Questionnaires (SPAQs), and measured overnight fasting plasma adiponectin levels. We then tested associations between plasma adiponectin levels and GSS, t-SAD, winter-summer difference in self-reported sleep duration, and self-reported seasonal weight change, by using analysis of co-variance (ANCOVA) and linear regression analysis after adjusting for age, gender, and BMI. Participants with t-SAD (N = 14; 2.2%) had significantly lower plasma adiponectin levels (mean ± SEM, 8.76 ± 1.56 μg/mL) than those without t-SAD (mean ± SEM, 11.93 ± 0.22 μg/mL) (p = 0.035). In addition, there was significant negative association between adiponectin levels and winter-summer difference in self-reported sleep duration (p = 0.025) and between adiponectin levels and self-reported seasonal change in weight (p = 0.006). There was no significant association between GSS and adiponectin levels (p = 0.88). To our knowledge, this is the first study testing the association of SAD with adiponectin levels. Replication and extension of our findings longitudinally and, then, interventionally, may implicate low adiponectin as a novel target for therapeutic intervention in SAD.

There is an increasing evidence that inflammation contributes to clinical and functional outcomes in traumatic brain injury (TBI). Many successful target-engaging, lesion-reducing, symptom-alleviating, and function-improving interventions in animal models of TBI have failed to show efficacy in clinical trials. Timing and immunological context are paramount for the direction, quality, and intensity of immune responses to TBI and the resulting neuroanatomical, clinical, and functional course. We present components of the immune system implicated in TBI, potential immune targets, and target-engaging interventions. The main objective of our article is to point toward modifiable molecular and cellular mechanisms that may modify the outcomes in TBI, and contribute to increasing the translational value of interventions that have been identified in animal models of TBI.

Red algae are the oldest identifiable multicellular eukaryotes, with a fossil record dating back more than a billion years. During that time two major rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels of morphological complexity. These two groups are distinguished, in part, by different patterns of multicellular development, with florideophytes exhibiting a far greater diversity of morphologies. Interestingly, during their long evolutionary history, there is no record of a rhodophyte achieving the kinds of cellular and tissue-specific differentiation present in other multicellular algal lineages. To date, the genetic underpinnings of unique aspects of red algal development are largely unexplored; however, they must reflect the complements and patterns of expression of key regulatory genes. Here we report comparative evolutionary and gene expression analyses of core subunits of the SWI/SNF chromatin-remodeling complex, which is implicated in cell differentiation and developmental regulation in more well studied multicellular groups. Our results suggest that a single, canonical SWI/SNF complex was present in the rhodophyte ancestor, with gene duplications and evolutionary diversification of SWI/SNF subunits accompanying the evolution of multicellularity in the common ancestor of bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling evolved subsequently, in particular gene losses and more rapid divergence of SWI3 and SNF5 in bangiophytes, could help to explain why they exhibit a more limited range of morphological complexity than their florideophyte cousins.

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1–7To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.

Purpose Due to the difficult differentiation from non-specific postoperative soft tissue formation (PSF), early diagnosis of pancreatic carcinoma recurrence remains challenging. Thus, we investigated the diagnostic potential of dual-energy (DE) contrast-enhanced CT. Method After potentially curative pancreatic carcinoma resection, 31 consecutive patients with PSF were examined via DE perfusion CT, acquiring 34 images (80 kVp/140 kVp) every 1.5 s, as the initial purpose of this study was evaluating CT-Perfusion. Corresponding time points of arterial, pancreatic, and early venous phase were calculated from bolus trigger times in prior conventional CT. Iodine and 120 kVp-equivalent images were calculated. Regions of interest were placed in each soft tissue formation. Diagnosis of local recurrence was confirmed by regular follow-up or histopathology. Results Final diagnosis was local recurrence in 17 patients and non-specific PSF in 14 patients. Iodine concentrations in early venous phase were significantly higher in recurrent carcinoma than in non-specific PSF (1.47 mg/ml vs. 0.96 mg/ml, p = 0.007). In earlier contrast phases iodine concentrations tended to be higher, but not significantly. CT numbers in recurrent carcinoma in 120 kVp-equivalent images in venous phase were significantly higher, too (74HU vs 47HU, p = 0.002). ROC-curve analysis for iodine concentrations in early venous phase suggests a cut-off value of ≥ 1.55 mg/ml for local recurrence (AUC = 0.78, specificity = 1.0, sensitivity = 0.53) and for CT numbers in 120kVp-equivalent images a cut-off value of ≥ 57HU (AUC = 0.82, specificity = 0.82, sensitivity = 0.71). Conclusion In difficult cases, measuring iodine concentrations or CT numbers in PSF in (early) venous phase DECT could be a valuable additional parameter for differentiating local recurrence from non-specific PSF.

Toxoplasma gondii(T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked toT. gondii as well.We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link betweenT. gondiiinfection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption andT. gondii. The mechanisms for such an association may involve dopamine (DA) production byT. gondii, or collateral effects of immune activation necessary to keepT. gondiiin check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship toT. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA).Toxoplasma gondiiseropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p=0.07). In conclusion, it is unlikely that sleep disruption mediates links betweenT. gondiiand mental illness or behavioral dysregulation. Trending gender differences in associations betweenT. gondiiand shorter sleep need further investigation.

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1±16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n=280] and PHQ-2 [n=26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p=0.045) and current combined anhedonia and dysphoria/hopelessness (p=0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.

Background We tested the hypothesis that the early improvement in mood after the first hour of bright light treatment compared to control dim-red light would predict the outcome at six weeks of bright light treatment for depressed mood in patients with Seasonal Affective Disorder (SAD). We also analyzed the value of Body Mass Index (BMI) and atypical symptoms of depression at baseline in predicting treatment outcome. Methods Seventy-eight adult participants were enrolled. The first treatment was controlled crossover, with randomized order, and included one hour of active bright light treatment and one hour of control dim-red light, with one-hour washout. Depression was measured on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). The predictive association of depression scores changes after the first session. BMI and atypical score balance with treatment outcomes at endpoint were assessed using multivariable linear and logistic regressions. Results No significant prediction by changes in depression scores after the first session was found. However, higher atypical balance scores and BMI positively predicted treatment outcome. Limitations Absence of a control intervention for the six-weeks of treatment (only the first session in the laboratory was controlled). Exclusion of patients with comorbid substance abuse, suicidality and bipolar I disorder, and patients on antidepressant medications, reducing the generalizability of the study. Conclusion Prediction of outcome by early response to light treatment was not replicated, and the previously reported prediction of baseline atypical balance was confirmed. BMI, a parameter routinely calculated in primary care, was identified as a novel predictor, and calls for replication and then exploration of possible mediating mechanisms.

Background The aim of this study was to assess the potential for radiation dose reduction using knowledge-based iterative model reconstruction (K-IMR) algorithms in combination with ultra-low dose body mass index (BMI)-adapted protocols in coronary CT angiography (coronary CTA). Methods Forty patients undergoing clinically indicated coronary CTA were randomly assigned to two groups with BMI-adapted (I: 2 , II: 2 , III: 2 , IV: ≥30.0 kg/m 2 ) low dose (LD, I: 100kV p /75 mAs, II: 100kV p /100 mAs, III: 100kV p /150 mAs, IV: 120kV p /150 mAs, n = 20) or ultra-low dose (ULD, I: 100kV p /50 mAs, II: 100kV p /75 mAs, III: 100kV p /100 mAs, IV: 120kV p /100 mAs, n = 20) protocols. Prospectively-triggered coronary CTA was performed using a 256-MDCT with the lowest reasonable scan length. Images were generated with filtered back projection (FBP), a noise-reducing hybrid iterative algorithm (iD, levels 2/5) and K-IMR using cardiac routine (CR) and cardiac sharp settings, levels 1–3. Results Groups were comparable regarding anthropometric parameters, heart rate, and scan length. The use of ULD protocols resulted in a significant reduction of radiation exposure (0.7 (0.6–0.9) mSv vs. 1.1 (0.9–1.7) mSv; p Conclusions The combination of K-IMR with BMI-adapted ULD protocols results in significant radiation dose savings while simultaneously improving image quality compared to LD protocols with FBP or hybrid iterative algorithms. Therefore, K-IMR allows for coronary CTA examinations with high diagnostic value and very low radiation exposure in clinical routine.

Vitamin D deficiency is associated with immune dysregulation, increased vulnerability to infections, depression, and suicidal behavior. One mediator of vitamin D-dependent immune regulation and antimicrobial defense is the cathelicidin antimicrobial peptide (LL-37), encoded by the cathelicidin-related antimicrobial peptide (CRAMP) gene. We compared the mRNA expression of the CRAMP gene, the vitamin D receptor (VDR) gene, as well as the CYP27B1 and CYP24A1 genes (involved in vitamin D metabolism) in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) between depressed individuals who died by suicide (n = 15) and matched (age, gender, and post-mortem interval) non-psychiatric controls (n = 15). Gene expression was measured through qRT-PCR with TaqMan® primers and probes, with GAPDH and β-actin genes as endogenous controls. Statistical analyses included t-tests and Pearson correlations. CRAMP mRNA expression was downregulated and VDR mRNA expression was upregulated in both dlPFC and ACC in suicides relative to controls, with no significant differences in expression of CYP24A1 and CYP27B1. To our knowledge, this is the first study on brain cathelicidin expression in the human brain in relationship to suicide. Increased VDR and decreased CRAMP expression are consistent with previously reported associations between vitamin D deficiency, immune dysregulation, and suicidal behavior, and should lead to future studies uncovering novel interactive targets for suicide prevention.

Objectives To systematically evaluate the influence of acquisition settings in conjunction with raw-data based iterative image reconstruction (IR) on lung densitometry based on multi-row detector computed tomography (CT) in an anthropomorphic chest phantom. Materials and methods Ten porcine heart-lung explants were mounted in an ex vivo chest phantom shell, six with highly and four with low attenuating chest wall. CT (Somatom Definition Flash, Siemens Healthineers) was performed at 120kVp and 80kVp, each combined with current-time products of 120, 60, 30, and 12mAs, and was reconstructed with filtered back projection (FBP) and IR (Safire, Siemens Healthineers). Mean lung density (LD), air density (AD) and noise were measured by semi-automated region-of interest (ROI) analysis, with 120kVp/120 mAs serving as the standard of reference. Results Using IR, noise in lung parenchyma was reduced by ~ 31% at high attenuating chest wall and by ~ 22% at low attenuating chest wall compared to FBP, respectively (p

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression analysis using Nanostring as well as immunohistochemistry to assess remodelling-associated angiogenesis.Morphometrical assessment of vessel diameters and intervascular distances showed significant differences in neoangiogenesis in characteristically remodelled areas of UIP, NSIP and AFE lungs. Likewise, gene expression analysis revealed distinct and specific angiogenic profiles in UIP, NSIP and AFE lungs.Whereas UIP lungs showed a higher density of upstream vascularity and lower density in perifocal blood vessels, NSIP and AFE lungs revealed densely packed alveolar septal blood vessels. Vascular remodelling in NSIP and AFE is characterised by a prominent intussusceptive neoangiogenesis, in contrast to UIP, in which sprouting of new vessels into the fibrotic areas is characteristic. The molecular analyses of the gene expression provide a foundation for understanding these fundamental differences between AFE and UIP and give insight into the cellular functions involved.

To investigate the association of vertebral CT attenuation between virtual non-contrast (VNC) and true non-contrast (TNC) images and to evaluate if VNC vertebral CT attenuation could be used for phantom-less osteoporosis detection in dual-layer spectral-detector CT (SDCT).200 patients with non-contrast and portal-venous phase SDCT were retrospectively assigned to a test and a validation group of 100 patients each. CT attenuation of L1 vertebrae were measured on VNC and TNC. The test group was used to determine the difference between VNC and TNC CT attenuation and to calculate a statistical model for TNC CT attenuation prediction. The validation group was used to assess the capability of the model to predict TNC from VNC CT attenuation and its accuracy to identify osteoporosis. Osteoporosis was defined as a TNC CT attenuation of ≤110HU.In both groups, CT attenuation was lower in VNC than in TNC (P 0.001). VNC and TNC CT attenuation was correlated strongly (r = 0.958). Using the regression equation established in the test group (TNC = 23.677 + 1.540 × VNC), the predicted TNC CT attenuation did not differ from the real TNC CT attenuation in the validation group (P = 0.359). A VNC CT attenuation cut-off of 52HU yielded an AUC of 0.978 for osteoporosis detection.L1 CT attenuation is systematically underestimated in VNC compared with TNC images. However, TNC L1 CT attenuation can be predicted reliably from VNC. VNC may perform well in phantom-less osteoporosis detection.

Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked to T. gondii as well. We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link between T. gondii infection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption and T. gondii. The mechanisms for such an association may involve dopamine (DA) production by T. gondii, or collateral effects of immune activation necessary to keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p = 0.07). In conclusion, it is unlikely that sleep disruption mediates links between T. gondii and mental illness or behavioral dysregulation. Trending gender differences in associations between T. gondii and shorter sleep need further investigation.

Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1 ± 16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n = 280] and PHQ-2 [n = 26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p = 0.045) and current combined anhedonia and dysphoria/hopelessness (p = 0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.