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

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

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

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

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

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

Deactivation of cardiovascular implantable electronic devices in patients nearing end of life : Reality or only recommendation?

BACKGROUND: Current guidelines recommend considering deactivation of cardiac implantable electronic devices (CIEDs) in patients nearing death. We evaluated the implementation of this recommendation in unselected deceased individuals with CIEDs. METHODS: Over a 7-month period in 2016, all deceased persons taken to the Rostock crematorium were prospectively screened for CIEDs and these were interrogated in situ. Pacing rate, pacing mode, and lead output were documented as well as patient data including location and time of death. In implantable cardioverter-defibrillators (ICDs), tachycardia therapy adjustment and occurrence of shocks 24 h prior to death were also recorded. RESULTS: We examined 2297 subjects, of whom 154 (6.7%) had CIEDs. Of these subjects, 125 (100%) pacemakers (PMs) and 27 (96.4%) ICDs were eligible for analysis. Death in persons with ICDs occurred most frequently in hospital (55.6%), while this was less frequently the case for individuals with PMs (43.2%). Furthermore, 33.3% of subjects with ICDs and 18.5% with PMs died in palliative care units (PCU). Shock therapies were switched off in three (60%) individuals with ICDs who died in the PCU, whereas antibradycardia therapy was not withdrawn in any PM patient in the PCU. Therapy withdrawal occurred in two patients with PMs (1.3%) who died in hospital. Patients with PMs had high ventricular pacing rates at the last interrogation (69 ± 36.0%) and often suffered atrioventricular block (39.2%). Six (25%) of the 24 active ICDs presented shocks near the time of death. CONCLUSION: Many CIED patients died in hospital; nonetheless, in practice, CIED deactivation near death is rarely performed and might be less feasible in subjects with PMs. However, there is still a need to consider deactivation, especially in individuals with ICDs, as one fourth of them received at least one shock within 24 h prior to death.

Individual programming of current multiprogrammable pacemakers : Still unsatisfactory?

BACKGROUND: Pacemaker (PM) technology has developed tremendously in recent decades. We evaluated the extent of individual programming in current PMs. METHODS: Over a 7-month period in 2016, all deceased persons taken to the Rostock crematorium were prospectively screened for cardiac implantable electronic devices (CIEDs) and these were interrogated in situ. Programming of patient data, leads, and study parameters including mode, lower rate, upper tracking or sensor rate (UTSR), ventricular refractory time, sleeping function, hysteresis, and PM-mediated tachycardia intervention were analyzed and compared with delivery settings. Alterations in atrial/ventricular capture management and atrial/ventricular sensing assurance as well as changes in sensitivity and lead output were evaluated. RESULTS: We examined 2297 subjects, of whom 154 (6.7%) had CIEDs, with 125 (81.2%) being PMs. Finally, 72 (57.6%) PMs were eligible for analysis with an operation time of 31.0 ± 27.0 months. We excluded 28 (18.2%) implantable cardioverter defibrillators (ICDs), 51 (41%) PMs presenting elective replacement indicator (ERI), two (1.6%) PMs with programming to insufficient function prior to death, and the left ventricle parameter of one (1.4%) cardiac resynchronization therapy pacemaker (CRT-P); further one CIED (0.6%) was not contactable. PMs offered in mean 75.2% of study parameters thereof 88.0% were to adjust manually, whereof 49.3% stayed unchanged to delivery mode. Lead output, UTSR, lower rate, and mode were the most frequently changed parameters (>85.7%, 65.3%, 54.2%, and 52.8%, respectively) compared with unmodified ventricular refractory time and hysteresis (91.7% and. 85.4%, respectively); 2.8% of PMs had out-of-the-box settings. The most frequent personalized data were last (88.9%) and first name (73.6%), while atrial and ventricular serial lead numbers were rarely entered (18.2% and 23.4%, respectively). CONCLUSION: The programming possibilities of PMs have advanced greatly. Nonetheless, improvements in individual PM programming are still needed as demonstrated by the findings in this study, e.g., PMs with manufacturer settings and lack of individual data.

Evolutionary bottlenecks in brackish water habitats drive the colonization of fresh water by stingrays.

Species richness in freshwater bony fishes depends on two main processes: the transition into and the diversification within freshwater habitats. In contrast to bony fishes, only few cartilaginous fishes, mostly stingrays (Myliobatoidei), were able to colonize fresh water. Respective transition processes have been mainly assessed from a physiological and morphological perspective, indicating that the freshwater lifestyle is strongly limited by the ability to perform osmoregulatory adaptations. However, the transition history and the effect of physiological constraints on the diversification in stingrays remain poorly understood. Herein, we estimated the geographic pathways of freshwater colonization and inferred the mode of habitat transitions. Further, we assessed habitat-related speciation rates in a time-calibrated phylogenetic framework to understand factors driving the transition of stingrays into and the diversification within fresh water. Using South American and Southeast Asian freshwater taxa as model organisms, we found one independent freshwater colonization event by stingrays in South America and at least three in Southeast Asia. We revealed that vicariant processes most likely caused freshwater transition during the time of major marine incursions. The habitat transition rates indicate that brackish water species switch preferably back into marine than forth into freshwater habitats. Moreover, our results showed significantly lower diversification rates in brackish water lineages, whereas freshwater and marine lineages exhibit similar rates. Thus, brackish water habitats may have functioned as evolutionary bottlenecks for the colonization of fresh water by stingrays, probably because of the higher variability of environmental conditions in brackish water.

Psychometric properties of the German version of the Diabetes Eating Problem Survey-Revised: additional benefit of disease-specific screening in adolescents with Type 1 diabetes.

AIM: To examine the psychometric properties of the German version of the abbreviated 16-item Diabetes Eating Problem Survey-Revised in a sample of young people with Type 1 diabetes. METHODS: A total of 246 young people, aged 11-19 years, with Type 1 diabetes from six pediatric diabetes centres in Germany were assessed using the Diabetes Eating Problem Survey-Revised. In addition, they underwent screening with two generic tools as well as the WHO five-question well-being index. A clinician's report was also obtained. RESULTS: The Diabetes Eating Problem Survey-Revised was found to have good internal consistency (Cronbach's α = 0.84). The Diabetes Eating Problem Survey-Revised scores significantly correlated with those provided by the non-specific screening tools (r = 0.37, P ≤ 0.000 and r = 0.50, P ≤ 0.000 for boys and r = 0.62, P ≤ 0.000 and r = 0.79, P ≤ 0.000 for girls), indicating convergent validity. The mean (sd) total of the scores was 12.0 (9.6). Criterion validity was confirmed against HbA1c value, BMI standard deviation score and expert (clinician) report. Of the boys included in the study, 11 scored higher than the threshold score on the Diabetes Eating Problem Survey-Revised, of whom only three (27%) were classified as 'suspected to have a disordered eating behaviour' by their clinicians. CONCLUSIONS: The Diabetes Eating Problem Survey-Revised delivered more specific information than generic screening instruments and identified more young people with eating disorders than did clinician report, especially regarding the detection of boys at risk. The results of this study support the utility of the German version of the Diabetes Eating Problem Survey-Revised to identify eating disorders in young people with Type 1 diabetes at an early stage. (German Clinical Trials Registry no.: DRKS00004699).

Effects of oral phytoextract intake on phenolic concentration and redox homeostasis in murine encephalic regions.

Vegetable infusions (VI) are one of the main phenolic sources for humans. They may act as antioxidants in the central nervous system, but data about their effect are insufficient. The main objective of the study was to determinate the effects of oral VI of Argentinean plants on phenolic concentration and redox homeostasis in different murine encephalic regions. Redox changes (peroxides -HP-, anion superoxide -SO- and γ-glutamyltranspeptidase activity) and tissue phenolics were assessed in Balb/c mice of both sexes treated with the following VI extracts: Lantana grisebachii Seckt. var. grisebachii (Verbenaceae) (LG), Aspidosperma quebracho-blanco Schltdl. (Apocynaceae) (AQB), and Ilex paraguariensis A. St.-Hil. (Aquifoliaceae) (IP). Brain (telencephalon and diencephalon), midbrain, brainstem, and cerebellum were studied (analysis of variance, P < 0.05). A redox homeostasis depending on an appropriate phenolic balance was detected after marker analysis. Under situations without exogenous challenges, the excessive or deficient levels were deleterious on each region. This finding was confirmed independently of the utilized phytoextracts. LG and AQB caused such phenolic imbalance and triggered oxidative stress. IP group showed region-specific differential redox effects. Overall, the last extract exhibited the best redox profile when the complete encephalon was analyzed. Since this plant has sanitary impact due to its high human intake, new studies about it are warranted.

Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung.

There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.

Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation.

The transition from the nonlactating to the lactating state represents a critical period for dairy cow lipid metabolism because body reserves have to be mobilized to meet the increasing energy requirements for the initiation of milk production. The purpose of this study was to provide a comprehensive overview on cholesterol homeostasis in transition dairy cows by assessing in parallel plasma, milk, and hepatic tissue for key factors of cholesterol metabolism, transport, and regulation. Blood samples and liver biopsies were taken from 50 multiparous Holstein dairy cows in wk 3 antepartum (a.p.), wk 1 postpartum (p.p.), wk 4 p.p., and wk 14 p.p. Milk sampling was performed in wk 1, 4, and 14 p.p. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, and lipoproteins], enzyme activities (phospholipid transfer protein and lecithin:cholesterol acyltransferase) were analyzed using enzymatic assays. Hepatic gene expression patterns of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF)-1 and -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1, liver X receptor (LXR) α and peroxisome proliferator activated receptor (PPAR) α and γ were measured using quantitative RT-PCR. Plasma TG, cholesterol, and lipoprotein concentrations decreased from wk 3 a.p. to a minimum in wk 1 p.p., and then gradually increased until wk 14 p.p. Compared with wk 4 p.p., phospholipid transfer protein activity was increased in wk 1 p.p., whereas lecithin:cholesterol acyltransferase activity was lowest at this period. Total cholesterol concentration and mass, and cholesterol concentration in the milk fat fraction decreased from wk 1 p.p. to wk 4 p.p. Both total and milk fat cholesterol concentration were decreased in wk 4 p.p. compared with wk 1 and 14 p.p. The mRNA abundance of genes involved in cholesterol synthesis (SREBF-2, HMGCS1, and HMGCR) markedly increased from wk 3 a.p. to wk 1 p.p., whereas SREBF-1 was downregulated. The expression of ABCA1 increased from wk 3 a.p. to wk 1 p.p., whereas ABCG1 was increased in wk 14 p.p. compared with other time points. In conclusion, hepatic expression of genes involved in the biosynthesis of cholesterol as well as the ABCA1 transporter were upregulated at the onset of lactation, whereas plasma concentrations of total cholesterol, phospholipids, lipoprotein-cholesterol, and TG were at a minimum. Thus, at the gene expression level, the liver seems to react to the increased demand for cholesterol after parturition. Whether the low plasma cholesterol and TG levels are due to impaired hepatic export mechanisms or reflect an enhanced transfer of these compounds into the milk to provide essential nutrients for the newborn remains to be elucidated.

In vivo redox effects of Aspidosperma quebracho-blanco Schltdl., Lantana grisebachii Stuck and Ilex paraguariensis A. St.-Hil. on blood, thymus and spleen of mice.

Argentinian native plants Aspidosperma quebracho-blanco, Lantana grisebachii and Ilex paraguariensis are known to have antiinflammatory and antioxidant properties. We demonstrated it in vivo by the redox changes in murine hemolymphatic tissues after infusive extract intake of these plants as revealed in organic trophism, tissue phenolics, hydroperoxides, superoxide, nitrites and gamma-glutamyltranspeptidase in thymus, blood and spleen. A. quebracho-blanco reduced hydroperoxidation in blood and spleen of both sexes, with gamma-glutamyltranspeptidase negativization in lymphatic organs and thymic nitrosative up-regulation. Males have shown increased phenolic content in blood after treatment. L. grisebachii and I. paraguariensis treatment exhibited incomplete antioxidation and oxidative induction in the studied tissues. Different results according to sex were found in redox response to phenolics and their kinetics, with males showing antioxidant effects, whereas females showed oxidative susceptibility. A. quebracho-blanco exhibited protection of murine tissues against oxidation in both sexes and modulation of their trophism, supporting its therapeutic uses in inflammatory diseases. Also, gender had significant influence in phenolic biodistribution and redox response.

The two pathways to being an (un-)popular narcissist.

OBJECTIVE: Narcissism affects social relationships from the very first interactions. The overall positivity of social impressions narcissists evoke is, however, unclear-with previous research reporting positive, negative, or null effects on popularity at short-term acquaintance. Here we postulate a dual-pathway model, which explains the effects of narcissism on (un-)popularity as the result of two opposing behavioral pathways: assertiveness and aggressiveness. METHOD: In two studies, unacquainted German college students (N = 100; N = 68) met in groups of four to six persons and engaged in group discussions. Afterward, they provided ratings of each other's assertiveness, aggressiveness, and likeability. In Study 2, we additionally videotaped the sessions and assessed participants' actual behavior. RESULTS: Results of both studies confirm our dual-pathway hypothesis: There was a "positive" and a "negative" path from targets' narcissism to being liked or not-dependent upon being seen as assertive or aggressive. Behavioral observations showed that expressive and dominant behaviors mediated the positive path, whereas arrogant and combative behaviors mediated the negative path. CONCLUSIONS: Initial (un-)popularity of narcissists at early stages of interpersonal interactions depends on the behavioral pathway that is triggered in the given situational context.

MOON-test - determination of motor performance in the pediatric oncology.

BACKGROUND: Pediatric cancer patients suffer from various negative consequences due to the disease, the medical therapy and the inactivity during the intensive treatment. Only few studies have systematically identified the adverse effects of cancer on motor performance in childhood. METHODS: To determine the motor performance of pediatric cancer patients, a motor performance test was developed which is applicable for this specific patient group. Eight test items with reference values for healthy children were merged to the MOON-test (test for motor performance in the oncology). RESULTS: MOON was tested for feasibility and acceptance in 33 patients aged 4-18 years. Feasibility was confirmed for children with different types of cancer (hematological malignancies and solid tumors) and with amputation, endoprosthesis, during aplasia as well as reduced general condition. Furthermore the patients showed a broad acceptance. CONCLUSION: Based on the study findings, the use of MOON-test as a standardized motor performance diagnostic tool in clinical routine of oncological acute clinics as well as rehabilitation clinics can be recommended.·

Age and gender differences in narcissism: A comprehensive study across eight measures and over 250,000 participants.

Age and gender differences in narcissism have been studied often. However, considering the rich history of narcissism research accompanied by its diverging conceptualizations, little is known about age and gender differences across various narcissism measures. The present study investigated age and gender differences and their interactions across eight widely used narcissism instruments (i.e., Narcissistic Personality Inventory, Hypersensitive Narcissism Scale, Dirty Dozen, Psychological Entitlement Scale, Narcissistic Personality Disorder Symptoms from the Diagnostic and Statistical Manual of Mental Disorders, Version IV, Narcissistic Admiration and Rivalry Questionnaire-Short Form, Single-Item Narcissism Scale, and brief version of the Pathological Narcissism Inventory). The findings of Study 1 (N = 5,736) revealed heterogeneity in how strongly the measures are correlated. Some instruments loaded clearly on one of the three factors proposed by previous research (i.e., Neuroticism, Extraversion, Antagonism), while others cross-loaded across factors and in distinct ways. Cross-sectional analyses using each measure and meta-analytic results across all measures (Study 2) with a total sample of 270,029 participants suggest consistent linear age effects (random effects meta-analytic effect of r = -.104), with narcissism being highest in young adulthood. Consistent gender differences also emerged (random effects meta-analytic effect was -.079), such that men scored higher in narcissism than women. Quadratic age effects and Age × Gender effects were generally very small and inconsistent. We conclude that despite the various conceptualizations of narcissism, age and gender differences are generalizable across the eight measures used in the present study. However, their size varied based on the instrument used. We discuss the sources of this heterogeneity and the potential mechanisms for age and gender differences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Process × Domain Assessment of Narcissism: The Domain-Specific Narcissistic Admiration and Rivalry Questionnaire.

Research on grandiose narcissism distinguishes between self-promotional processes (i.e., narcissistic admiration) and other-derogative processes (i.e., narcissistic rivalry; Back et al., 2013). Moreover, research has begun to assess and investigate narcissistic manifestations in different domains (e.g., communal narcissism). To integrate these two lines of research, we developed the Domain-Specific Narcissistic Admiration and Rivalry Questionnaire (D-NARQ), a 72-item narcissism questionnaire that contains a self-promotional process scale (narcissistic admiration) and an other-derogatory process scale (narcissistic rivalry) for four domains: intellectual ability, social dominance, communal care, and physical attractiveness. We investigated the psychometric properties of the D-NARQ in a large online study (N = 1,635). Model fit statistics were largely in line with the theorized factor structure. The D-NARQ scales had good to very good measurement precision, and their correlations with established narcissism scales, the Big Five personality traits, and comparative self-evaluations largely supported their convergent and discriminant validity.

Gene expression and cell differentiation in matrix-associated chondrocyte transplantation grafts: a comparative study.

OBJECTIVE: Although scaffold composition and architecture are considered to be important parameters for tissue engineering, their influence on gene expression and cell differentiation is rarely investigated in scaffolds used for matrix-associated autologous chondrocyte transplantation (MACT). In this study we have therefore comparatively analyzed the gene expression of important chondrogenic markers in four clinical applied cell-graft systems with very different scaffold characteristics. METHODS: Residuals (n=165) of four different transplant types (MACI®, Hyalograft®C, CaReS® and Novocart®3D) were collected during surgery and analyzed for Col1, Col2, aggrecan, versican, melanoma inhibitory activity (MIA) and IL-1ß by real-time PCR. Scaffold and cell morphology were evaluated by histology and electron microscopy. RESULTS: Despite the cultivation on 3D scaffolds, the cell differentiation on all transplant types didn't reach the levels of native cartilage. Gene expression highly differed between the transplant types. The highest differentiation of cells (Col2/Col1 ratio) was found in CaReS®, followed by Novocart®3D, Hyalograft®C and MACI®. IL-1ß expression also exhibited high differences between the scaffolds showing low expression levels in Novocart®3D and CaReS® and higher expression levels in MACI® and Hyalograft®C. CONCLUSIONS: Our data indicate that scaffold characteristics as well as culture conditions highly influence gene expression in cartilage transplants and that these parameters may have profound impact on the tissue regeneration after MACT.

Identification of ABCA1 and ABCG1 in milk fat globules and mammary cells--implications for milk cholesterol secretion.

The ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 play an important role in cellular cholesterol homeostasis, but their function in mammary gland (MG) tissue remains elusive. A bovine MG model that allows repeated MG sampling in identical animals at different functional stages was used to test whether 1) ABCA1 and ABCG1 protein expression and subcellular localization in mammary epithelial cells (MEC) change during the pregnancy-lactation cycle, and 2) these 2 proteins were present in milk fat globules (MFG). Expression and localization in MEC were investigated in bovine MG tissues at the end of lactation, during the dry period (DP), and early lactation using immunohistochemical and immunofluorescence approaches. The presence of ABCA1 and ABCG1 in MFG isolated from fresh milk was determined by immunofluorescence. The ABCA1 protein expression in MEC, expressed as arbitrary units, was higher during the end of lactation (12.2±0.24) and the DP (12.5±0.22) as compared with during early lactation (10.2±0.65). In contrast, no significant change in ABCG1 expression existed between the stages. Throughout the cycle, ABCA1 and ABCG1 were detected in the apical (41.9±24.8 and 49.0±4.96% of cows, respectively), basal (56.2±28.1 and 54.6±7.78% of cows, respectively), or entire cytoplasm (56.8±13.4 and 61.6±14.4% of cows, respectively) of MEC, or showed combined localization. Unlike ABCG1, ABCA1 was absent at the apical aspect of MEC during early lactation. Immunolabeling experiments revealed the presence of ABCA1 and ABCG1 in MFG membranes. Findings suggest a differential, functional stage-dependent role of ABCA1 and ABCG1 in cholesterol homeostasis of the MG epithelium. The presence of ABCA1 and ABCG1 in MFG membranes suggests that these proteins are involved in cholesterol exchange between MEC and alveolar milk.

A multispectral-sensor-based colorimetric reader for biological assays.

Tests that depend on changes in color are commonly used in biosensing. Here, we report on a colorimetric reader for such applications. The device is simple to construct and operate, making it ideal for research laboratories with limited resources or skilled personnel. It consists of a commercial multispectral sensor interfaced with a Raspberry Pi and a touchscreen. Unlike camera-based readers, this instrument requires no calibration of wavelengths by the user or extensive image processing to obtain results. We demonstrate its potential for colorimetric biosensing by applying it to the birefringent enzyme-linked immunosorbent assay. It was able to prevent certain false positives that the assay is susceptible to and lowered its limit of detection for glucose by an order of magnitude.

Rosuvastatin reduces neointima formation in a rat model of balloon injury.

BACKGROUND: Processes of restenosis, following arterial injury, are complex involving different cell types producing various cytokines and enzymes. Among those enzymes, smooth muscle cell-derived matrix metalloproteinases (MMPs) are thought to take part in cell migration, degrading of extracellular matrix, and neointima formation. MMP-9, also known as gelatinase B, is expressed immediately after vascular injury and its expression and activity can be inhibited by statins. Using an established in vivo model of vascular injury, we investigated the effect of the HMG-CoA reductase inhibitor rosuvastatin on MMP-9 expression and neointima formation. MATERIALS AND METHODS: 14-week old male Sprague Dawley rats underwent balloon injury of the common carotid artery. Half of the animals received rosuvastatin (20 mg/kg body weight/day) via oral gavage, beginning 3 days prior to injury. Gelatinase activity and neointima formation were analyzed 3 days and 14 days after balloon injury, respectively. 14 days after vascular injury, proliferative activity was assessed by staining for Ki67. RESULTS: After 14 days, animals in the rosuvastatin group showed a decrease in total neointima formation (0.194±0.01 mm2 versus 0.124±0.02 mm2, p<0.05) as well as a reduced intima/media ratio (1.26±0.1 versus 0.75±0.09, p<0.05). Balloon injury resulted in increased activity of MMP-9 3 days after intervention for both rosuvastatin treated animals and controls with no significant difference observed between the groups. There was a trend towards a reduction in the number of Ki67-positive cells 14 days after injury. CONCLUSIONS: Rosuvastatin attenuates neointima formation without affecting early MMP-9 activity in a rat model of vascular injury.

Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows.

A long-term study over 25 months was conducted to evaluate the effects of genetically modified corn on performance of lactating dairy cows. Thirty-six dairy cows were assigned to two feeding groups and fed with diets based on whole-crop silage, kernels and whole-crop cobs from Bt-corn (Bt-MON810) or its isogenic not genetically modified counterpart (CON) as main components. The study included two consecutive lactations. There were no differences in the chemical composition and estimated net energy content of Bt-MON810 and CON corn components and diets. CON feed samples were negative for the presence of Cry1Ab protein, while in Bt-MON810 feed samples the Cry1Ab protein was detected. Cows fed Bt-MON810 corn had a daily Cry1Ab protein intake of 6.0 mg in the first lactation and 6.1 mg in the second lactation of the trial. Dry matter intake (DMI) was 18.8 and 20.7 kg/cow per day in the first and the second lactation of the trial, with no treatment differences. Similarly, milk yield (23.8 and 29.0 kg/cow per day in the first and the second lactation of the trial) was not affected by dietary treatment. There were no consistent effects of feeding MON810 or its isogenic CON on milk composition or body condition. Thus, the present long-term study demonstrated the compositional and nutritional equivalence of Bt-MON810 and its isogenic CON.