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Inflammatory and immunological processes interfering with brain development are discussed as one cause of schizophrenia. Various signs of overactivation of the immune system were often found in this disease. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, PolyI:C incubation of pregnant dams was used as animal model of schizophrenia, and the number and shape of microglia were assessed in the offspring in the early phase of this disease, using fluorescence immunostaining (Iba1). Descendants of mice exposed to PolyI:C at embryonic day 9 showed higher number of microglial cells in the hippocampus and striatum, but not in the frontal cortex at postnatal day 30, which is similarly to adolescence in man, as compared to those exposed to saline. Furthermore, offspring microglia from PolyI:C treated mothers were morphologically characterized by a reduced arborization indicative for a status of higher activation compared to the offspring microglia from vehicle treated mice. This study supports the hypothesis that maternal infection during embryogenesis contributes to microglial activation in the offspring, which may therefore represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options in this regard. [ABSTRACT FROM AUTHOR]

Background: Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy., Materials and Methods: 57 patients (age, 11.8-81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7-82.5) in 22-36 fractions., Results: LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5-24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC., Conclusion: Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

Purpose: The success of bariatric surgery varies largely, which may relate to variance in adopting a physically active lifestyle. This study aimed to determine whether two-year changes in physical activity (PA) were associated with weight loss, fat-free mass, cardiorespiratory fitness and quality of life up to two years after bariatric surgery., Materials and Methods: In this retrospective study, 3879 post-bariatric patients were divided into three groups: 1) decreased PA (n = 388), 2) maintained PA (n = 2002) or 3) increased PA (n = 1498). Measurements regarding PA (Baecke questionnaire), body composition (bioelectrical impedance analysis), estimated cardiorespiratory fitness (Åstrand test) and health-related quality of life (RAND-36) were performed preoperatively and two years post-surgery., Results: Bariatric patients with increased PA had greater excess weight loss (76.3% vs. 73.2% vs. 72.9%, P < 0.001), greater increases in %fat-free mass (Δ14.0% vs. 13.0% vs. 12.8%; P < 0.001), larger improvements in VO 2 max (Δ11.8 vs. 10.2 vs. 8.0 ml/kg/min, P < 0.001), and larger increases in health related quality of life subscale scores (P < 0.05) compared to patients with maintained- and decreased PA., Conclusions: Bariatric patients who managed to induce improvements in habitual physical activity had better body composition, fitness and quality of life at 2 years post-surgery, compared to patients who maintained or even reduced their PA levels. These findings underscore the importance of perioperative-bariatric care programs to change lifestyle and achieve sustainable improvements in PA levels.

Background: Low cardiorespiratory fitness is strongly associated with cardiovascular diseases and mortality. Although increased physical activity can improve cardiorespiratory fitness, this relationship has not been examined in a large bariatric population undergoing perioperative care focusing on long-term lifestyle change., Objectives: To evaluate changes in physical activity, weight loss, and cardiorespiratory fitness up to 24 months after bariatric surgery, and to evaluate the relationships of change in physical activity with weight loss and change in cardiorespiratory fitness., Materials and Methods: Four thousand seven hundred eighty-five patients who underwent primary Roux-en-Y gastric bypass or sleeve gastrectomy between January 2012 and December 2014 were included. Physical activity was assessed by the Baecke questionnaire (work, leisure, and sport activity) and cardiorespiratory fitness, defined as VO 2 max relative to fat-free mass (VO 2 max/FFM), was assessed by the Åstrand test., Results: Twenty-four months postoperative, significant improvements were seen in sport and leisure activity assessments (n = 3548, P < 0.001), weight loss (n = 3695, P < 0.001), and VO 2 max/FFM (n = 1852, P < 0.001). Furthermore, regression analysis showed that change in leisure activity was positively associated with weight loss (n = 3535, ß = 1.352, P < 0.001) and change in sport activity was positively associated with change in VO 2 max/FFM (n = 1743, ß = 1.730, P < 0.001)., Conclusion: Bariatric surgery complemented by a comprehensive bariatric care program can lead to improvement in physical activity, as well as weight loss and improvement in cardiorespiratory fitness. The positive associations of change in leisure activity with weight loss and change in sport activity with cardiorespiratory fitness suggest that bariatric care programs can enhance postoperative outcomes by improving the patient's physical activity.

Background: Adequate prediction of survival plays an important role in treatment decisions for patients with spinal bone metastases (SBM). Several prognostic factors are already used in daily clinical practice, but factors related to stability of SBM are still unknown. Therefore, we designed this study to identify these prognostic factors., Methods: We retrospectively assessed 915 patients from solid tumors with commonly metastased into the bone treated at our department between January 2000 and January 2012. Lung cancer (NSCLC), breast and renal cancer listed in Table 1 are the most common solid tumors with bone metastasis in this study. Prostate carcinoma was excluded due to osteoblastic SBM with no influence for stability. We calculated overall survival (OS) and bone survival (BS; time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with the log-rank test and a Cox regression model separately for patients with stable and unstable SBM., Results: Median follow-up was 9.3 months. OS after 6 months, 1, 2, and 5 years was 81, 62, 42, and 25 % in patients with stable SBM and 78, 57, 38, and 22 % in patients with unstable SBM (p = 0.851). BS was 57, 38, 22, and 5 % in the group of stable SBM after 6 months, 1, 2, and 5 years. For patients with unstable SBM BS after 6 months, 1, 2, and 5 years was 59, 39, 19, and 8 % (p = 0.755). In multivariate analysis we found male gender (HR = 1.27 [95 % CI 1.01-1.60], p = 0.04), Karnofsky performance status (KPS) <80 % (HR = 1.27 [95%CI 1.04-1.55], p = 0.02) and non-small cell lung cancer (NSCLC; HR = 2.77 [95%CI 1.99-3.86], p < 0.0001) to be independent prognostic factors for shortened survival in patients with stable SBM. Independent prognostic factors for unstable SBM were age per year (HR = 1.01 [95 % CI 1.0-1.02], p = 0.025), multiple SBM (HR = 1.35 [95 % CI 1.1-1.65], p = 0.003), and NSCLC (HR = 2.0 [95 % CI 1.43-2.80], p < 0.0001). Additionally, not wearing an orthopedic corset (HR = 0.77 [95 % CI 0.62-0.96], p = 0.02) was associated with prolonged BS in patients with unstable SBM and in both groups BS was significantly longer in patients without liver metastases (stable SBM: HR = 0.72 [95 % CI 0.56-0.92], p = 0.008; unstable SBM: HR = 0.71 [95 % CI 0.54-0.92], p = 0.01)., Conclusions: Survival was equal for patients with stable and unstable SBM. However, prognostic factors differed in both groups and stability should therefore be considered in treatment decision-making.

Pancreatic cancer is one of the leading cancer-related causes of death in the western world with an urgent need for new treatment strategies. Recently, hyperforin and nemorosone have been described as promising anti-cancer lead compounds. While hyperforin has been thoroughly investigated in vitro and in vivo, in vivo data for nemorosone are still missing. Thus, we investigated the growth-inhibitory potential of nemorosone on pancreatic cancer xenografts in NMRI nu/nu mice and determined basic pharmacokinetic parameters. Xenograft tumors were treated with nemorosone and gemcitabine, the current standard of care. Tumor sections were subjected to H&E as well as caspase 3 and Ki-67 staining. Nemorosone plasma kinetics were determined by HPLC and mass spectrometry. Induction of CYP3A4 and other metabolizing enzymes by nemorosone and hyperforin was tested on primary hepatocytes using qRT-PCR. At a dose of 50 mg/kg nemorosone per day, a significant growth-inhibitory effect was observed in pancreatic cancer xenografts. The compound was well tolerated and rapidly absorbed into the bloodstream with a half-life of approximately 30 min. Different metabolites were detected, possibly resembling CYP3A4-independent oxidation products. It is concluded that nemorosone is a potential anti-cancer lead compound with good bioavailability, little side-effects and promising growth-inhibitory effects, thus representing a valuable compound for a combination therapy approach.

Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r=-0.86, p=0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.

Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.

Purpose: Although studies obtained with triple-dose contrast administration can show more brain metastases than those obtained with single-dose contrast material in patients with multiple metastases, such studies are costly and of limited clinical benefit. Since most patients who undergo screening have negative findings or a single metastasis, this study was performed to compare the clinical utility of single-dose versus triple-dose contrast administration in this large group of patients who could benefit from the possible increased sensitivity in lesion detection., Methods: Ninety-two consecutive patients with negative or equivocal findings or a solitary metastasis on single-dose contrast-enhanced MR images underwent triple-dose studies. Findings were compared with a standard of reference composed of panel review and long-term follow-up. Further analysis was performed by comparing results with those obtained by two blinded readers., Results: In all 70 negative single-dose studies, the triple-dose studies depicted no additional metastases in terms of the standard of reference. No statistically significant difference was seen between the results of the single- and triple-dose studies. For 10 equivocal single-dose studies, the triple-dose study helped clarify the presence or absence of metastases in 50% of the cases. In 12 patients with a solitary metastasis seen on the single-dose study, the triple-dose study depicted additional metastases in 25% of the cases. In the results of one of the two blinded readers, use of triple-dose contrast led to a statistical difference by decreasing the number of equivocal readings but at the expense of increasing the number of false-positive readings., Conclusion: Routine triple-dose contrast administration in all cases of suspected brain metastasis is not helpful. On the basis of our investigation, we conclude that the use of triple-dose contrast material is beneficial in selected cases with equivocal findings or solitary metastasis, although with the disadvantage of increasing the number of false-positive results.

We report a neonate in whom clinical and radiologic studies revealed features of both neurocutaneous melanosis and a Dandy-Walker malformation. We suggest that the association of these two conditions is perhaps not chance.

In evaluating primary parathyroid adenomas with high-resolution color Doppler sonography, initial detection relied on the observation of a hypoechoic soft tissue mass adjacent to the thyroid gland. Using color Doppler sonography, many adenomas had a demonstrable blood supply from the inferior thyroidal artery branches, identified as a vascular arc surrounding the gland from 90 to 270 degrees. The vascular arc assists the interpreter with establishing the nature of the mass, differentiating it from masses such as regional lymph nodes, which demonstrate hilar flow. Sixty-three percent (20 of 32) of parathyroid adenomas had a color arc. The identification of a vascular arc is a useful adjunctive finding, improving diagnostic specificity and quickly confirming the diagnosis of parathyroid adenoma.

The content analysis of five-minute speech samples obtained from detoxified chronic alcoholic patients is a valid test for measuring cognitive impairment during the course of treatment. Such cognitive impairment scores six months after hospital discharge can be predicted using the variables of age, educational level, certain drinking patterns and cognitive impairment scores at the time of hospital admission. Patients who abstain for six months following hospital discharge have less cognitive impairment than those patients who resume drinking.

Sober chronic alcoholic males, sober nonalcoholic males, and intoxicated nonalcoholic males were assessed along several psychological dimensions by means of the content analysis of speech. Average cognitive impairment scores were significantly greater among intoxicated nonalcoholics than sober chronic alcoholics and significantly greater in sober chronic alcoholics than in sober nonalcoholics. Sober chronic alcoholics, also, had a significantly higher score than sober nonalcoholics on depression, social alienation-personal disorganization (schizoid traits), separation, guilt, and diffuse anxiety, and hostility inward. The general mental health, including cognitive function, of sober chronic alcoholics is clearly impaired when compared to sober nonalcoholic individuals.