Comparative analysis of the use of natural and synthetic antioxidants in chicken meat: an update review.

The search for healthy foods has attracted the industry's attention to developing products that use natural ingredients, including natural antioxidants. Antioxidants act as free radicals or oxygen scavengers, inhibiting lipid oxidation and adversely affecting meat products' sensory and nutritional quality. Several synthetic antioxidants have been used in the meat industry; however, studies point to health risks related to their consumption. Such fact drives research into natural antioxidants extracted from grains, oilseeds, spices, fruits, and vegetables, which may have a health-promoting effect. This manuscript evaluates the effectiveness of several natural antioxidants in improving the quality and shelf life of chicken meat products during processing, storage, and distribution. The potential effects of natural antioxidants widely used in chicken products are also discussed. It can be concluded that these natural antioxidants are possible substitutes for synthetic ones. However, their use can affect the product's characteristics.

Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial.

BACKGROUND: Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested. OBJECTIVE: To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. METHODS: PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. RESULTS: The study is ongoing. Results will be published when the study is completed. CONCLUSION: PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. TRIAL REGISTRATION: The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588 ). Registered 30 November 2018.

Comprehensive flow cytometric reference intervals of leukocyte subsets from six study centers across Europe.

A group of European FOCIS Centers of Excellence adapted panels of the Human Immunophenotyping Consortium (HIPC) for whole blood analysis. Using four core panels [T/regulatory T cell/B/natural killer (T/Treg /B/NK) and myeloid cells] the main leukocyte populations were analyzed in a clinical-diagnostic setting in a harmonized manner across different platforms. As a first step, the consortium presents here the absolute and relative frequencies of the leukocyte subpopulations in the peripheral blood of more than 300 healthy volunteers across six different European centers.

Circulating ß cell-specific CD8+ T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes.

In type 1 diabetes (T1D), autoreactive cytotoxic CD8+ T cells are implicated in the destruction of insulin-producing ß cells. The HLA-B*3906 and HLA-A*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8+ T cells that recognize peptides presented by these class I molecules on pancreatic ß cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)-specific and insulin B (InsB)-specific CD8+ T cells in HLA-B*3906+ children newly diagnosed with T1D and in high-risk HLA-A*2402+ children before the appearance of disease-specific autoantibodies and before diagnosis of T1D. Antigen-specific CD8+ T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLA-B*3906+ children with T1D, we observed an increase in PPI5-12 -specific transitional memory CD8+ T cells compared to non-diabetic, age- and HLA-matched subjects. Furthermore, PPI5-12 -specific CD8+ T cells in HLA-B*3906+ children with T1D showed a significantly more antigen-experienced phenotype compared to polyclonal CD8+ T cells. In longitudinal samples from high-risk HLA-A*2402+ children, the percentage of terminal effector cells within the InsB15-24 -specific CD8+ T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLA-B*3906-restricted autoreactive CD8+ T cells in T1D. Collectively, our results provide evidence that ß cell-reactive CD8+ T cells restricted by disease-associated HLA class I molecules display an antigen-experienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.

Resonance signatures in the body-frame valence photoionization of CF4.

We present a combined experimental and theoretical investigation of the electron dynamics and body-frame angular dependence of valence photo-single ionization of CF4 and subsequent dissociation into CF3+ and F. Ionization from a valence t2 orbital shows overlapping shape resonances close to threshold that couple to the same total symmetry, leading to striking changes in the photoelectron angular distributions when viewed in the body-frame.

High probability of comorbidities in bronchial asthma in Germany.

Clinical experience has shown that allergic and non-allergic respiratory, metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial asthma. However, no study has been carried out that calculates the chance of manifestation of these disorders with bronchial asthma in Saarland and Rhineland-Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the present study systematically analyzed the co-prevalence and odds ratios of comorbidities in the asthma population in Germany. The odds ratios were adjusted for age and sex for all comorbidities for patients with asthma vs. without asthma. Bronchial asthma was strongly associated with allergic and with a lesser extent to non-allergic comorbidities: OR 7.02 (95%CI:6.83-7.22) for allergic rhinitis; OR 4.98 (95%CI:4.67-5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33-2.52) atopic dermatitis; OR 2.47 (95%CI:2.16-2.82) food allergy, and OR 1.69 (95%CI:1.61-1.78) drug allergy. Interestingly, increased ORs were found for respiratory diseases: 2.06 (95%CI:1.64-2.58) vocal dysfunction; 1.83 (95%CI:1.74-1.92) pneumonia; 1.78 (95%CI:1.73-1.84) sinusitis; 1.71 (95%CI:1.65-1.78) rhinopharyngitis; 2.55 (95%CI:2.03-3.19) obstructive sleep apnea; 1.42 (95%CI:1.25-1.61) pulmonary embolism, and 3.75 (95%CI:1.64-8.53) bronchopulmonary aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79-0.94) did not coexist with asthma. Based on the calculated chances of manifestation for these comorbidities, especially allergic and respiratory, to a lesser extent also metabolic, cardiovascular, and mental disorders should be taken into consideration in the diagnostic and treatment strategy of bronchial asthma. BRONCHIAL ASTHMA: PREVALENCE OF CO-EXISTING DISEASES IN GERMANY: Patients in Germany with bronchial asthma are highly likely to suffer from co-existing diseases and their treatments should reflect this. Quoc Thai Dinh at Saarland University Hospital in Homburg, Germany, and co-workers conducted a large-scale study of patients presenting with bronchial asthma in the Saarland region between 2009 and 2012. Patients with asthma made up 5.4% of the region's total population, with a higher prevalence occurring in females. They found that bronchial asthma was strongly associated with allergic comorbidities such as rhinitis. Indeed, asthmatic patients had a seven times higher chance to suffer from allergic rhinitis than the rest of the population, and were at higher risk of respiratory diseases like pneumonia and obstructive sleep apnea syndrome. Further associations included cardiovascular, metabolic and mental disorders. Dinh's team call for asthma treatments to take such comorbidities into account.

The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer.

Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells. Elevated BCAT1 expression was confirmed in relapsed tamoxifen-resistant breast tumor specimens. High intratumoral BCAT1 levels were associated with a reduced relapse-free survival in adjuvant tamoxifen-treated patients and overall survival in unselected patients. On a tissue microarray (n=1421), BCAT1 expression was detectable in 58% of unselected primary breast carcinomas and linked to a higher Ki-67 proliferation index, as well as histological grade. Interestingly, BCAT1 was predominantly expressed in estrogen receptor-α-negative/human epidermal growth factor receptor-2-positive (ERα-negative/HER-2-positive) and triple-negative breast cancers in independent patient cohorts. The inverse relationship between BCAT1 and ERα was corroborated in various breast cancer cell lines and pharmacological long-term depletion of ERα induced BCAT1 expression in vitro. Mechanistically, BCAT1 indirectly controlled expression of the cell cycle inhibitor p27Kip1 thereby affecting pRB. Correspondingly, phenotypic analyses using a lentiviral-mediated BCAT1 short hairpin RNA knockdown revealed that BCAT1 sustains proliferation in addition to migration and invasion and that its overexpression enhanced the capacity of antiestrogen-sensitive cells to grow in the presence of antiestrogens. Importantly, silencing of BCAT1 in an orthotopic triple-negative xenograft model resulted in a massive reduction of tumor volume in vivo, supporting our findings that BCAT1 is necessary for the growth of hormone-independent breast tumors.

[Pathophysiology, diagnostics and therapy of chronic cough: neuronal reflexes and antitussiva]. / Pathophysiologie, Diagnostik und Therapie von chronischem Husten: Neuronale Reflexe und Antitussiva.

Cough is the number one symptom for patients to visit a physician worldwide. It is an important neuronal reflex which serves to protect the airways from inhaled exogenous microorganisms, thermal and chemical irritants. Moreover, it prevents the airways from mucus retention.The cough reflex is initiated by activation of different cough receptors. These cough receptors can be divided into three groups according to their electrophysiological properties: into the two Aδ-fiber types "rapid-adapting mechanoreceptor" (RAR) and "slow-adapting mechanoreceptor" (SAR), and the C-fiber receptor.The stimulus is detected by cough receptors which conduct the signal to the cerebral cough centre via vagal-sensory neurons. The cough itself is mediated by efferent motoneurons. Hence the cough reflex consists of 5 functionally sequential parts 1: the cough receptors 2, the primary afferent fibres of the N. vagus 345, N. trigeminus and N. glossopharyngeus 1, the cough centre in the medulla oblongata (N. tractus solitarius) 678, the afferent fibres of the N. phrenicus, spinal nerve and N. laryngeus recurrens, as well as the diaphragm and the abdominal, intercostal and laryngeal muscles. The cough receptors are mainly located in the larynx, trachea and main bronchi 2.The event of coughing can be divided into four subsequent parts: After the first phase of fast inspiration with an opened glottis, there is compression with a closed glottis and increasing tracheal pressure, acceleration and ultimately maximum expiration with an opened glottis 9. According to its characteristics, cough can be split into two distinct types, "aspiration cough", which is loud and involuntary, and "urge-to-cough sensation", which describes an irritant, scratchy, and controlled cough of slowly increasing intensity 10.Acute cough mostly develops because of infection of the respiratory system 111213 and ends spontaneously after 4 weeks. In contrast to this, bacterial infection with pathogens like Adenovirus, Bordetella pertussis and Mycoplasms can last up to 8 weeks 121314. In additional to the division of cough according to its cause, it can also be differentiated according to its manner: dry and mucus-producing cough.With this review we want to give an overview of neuronal processes and mechanisms, as well as diagnostics of and therapy for chronic cough. Thereby the focus is also placed on the efficiency of already established and potential future antitussive agents.

[Treatment of proximal humerus fractures: relative position of different locking plates to the axillary nerve]. / Versorgung von Humeruskopffrakturen: Lagebeziehung proximaler Verriegelungsplatten zum N. axillaris.

OBJECTIVES: Placement of a proximal humerus locking plate through a percutaneous transdeltoid approach bears the advantages of a minimally invasive approach but may compromise the anterior branches of the axillary nerve. This anatomic study aimed to develop a risk profile for 6 types of modern proximal humerus locking plates as to their interference with the axillary nerve. MATERIALS AND METHODS: In this study six different implants (Arthrex®, DePuy®, Königsee®, Smith & Nephew®, Stryker® and Synthes®) were placed on the intact proximal humerus of 33 embalmed cadaveric upper extremities and the relative positioning between the axillary nerve and the screw holes was determined. RESULTS: All locking plates displayed an area of risk which concerned 3 out of 7 (Arthrex®), 4 out of 10 (DePuy®), 2 out of 9 (Königsee®), 3 out of 11 (Smith & Nephew®), 3 out of 11 (Stryker®) and 6 out of 12 (Synthes®) screw holes of the plate. CONCLUSIONS: Using the anterolateral percutaneous deltoid splitting approach the relative position of the axillary nerve to the holes of a specific implant is of relevance for avoidance of iatrogenic lesions to the nerve.

[Distraction arthroplasty for treatment of posttraumatic elbow stiffness]. / Distraktionsarthroplastik zur Behandlung der posttraumatischen Ellenbogensteife.

A stiff elbow is usually defined as having less than 30° in extension or less than 130° in flexion. Most activities of daily living are possible if the elbow has a range of motion of 100° (30-130° of flexion, Morrey's arc of motion). Loss of mobility of the elbow is not uncommon after trauma, burns or coma and severely impairs upper limb function. Loss of mobility may be difficult to avoid and is challenging to treat. Detailed analysis of the etiology and diagnostic evaluation is of utmost importance for planning any surgical intervention for elbow stiffness. Current operative techniques, such as closed distraction with external fixation (arthroplasty), are presented and evaluated. Elbow arthrolysis is a technically demanding procedure but if the indications and techniques are used correctly and the surgeon, physiotherapist and even the patient are familiar with the procedure, good long-term results may be achieved. Contraindications are poor compliance, poorly controlled diabetes mellitus, active hepatitis B and C infections, HIV infection and acute articular infections.

[Fixator with motion capacity and distraction arthrodiatasis in post-traumatic elbow stiffness]. / Bewegungsfixateur und Distraktionsarthroplastik zur Behandlung der posttraumatischen Ellenbogensteife.

Elbow stiffness may result from trauma, burns and head injuries. It is defined as a total range of motion of <100° with no relevant loss of forearm rotation. Of particular relevance is the flexion deficit. A detailed analysis regarding the development of the elbow stiffness is required together with an exact diagnosis in order to plan the surgical intervention. Closed distraction of the elbow joint as arthrodiatasis with an external fixator is described and evaluated. Adequate long-term results can be achieved with this technique, which reflects proper selection of patients as well as coordination between surgeon, aftercare and physiotherapist. Contraindications are poor compliance, poorly controlled diabetes mellitus, active hepatitis B and C infection, HIV infection and acute articular infection.

[External fixation with motion capacity in acute dislocations and fracture dislocations of the elbow. Fixation with motion capacity]. / Die Behandlung der akuten Luxation und Luxationsfraktur des Ellenbogens. Bewegungsfixateur.

Dislocations and fracture dislocations with their typical fracture patterns may substantially affect the complex anatomy and integrity of the elbow joint. The more components of the joint are injured, the more technically demanding is the therapy. Standardized diagnostic and therapeutic algorithms help to avoid misinterpretations regarding the severity of the injury and the subsequent complications. In elbow dislocations and fracture dislocations with persistent instability the hinged external fixator is an excellent device to improve joint stability and allows physiotherapeutic assistance at an early stage.

[External fixation with motion capacity and radius fractures. Methods and results]. / Bewegungsfixateur und distale Radiusfraktur. Methodik und Ergebnisse.

Both the radiocarpal and distal radioulnar joints are often affected in"distal radius fractures". The incidence of this injury increases markedly among women over the age of 40. Bearing in mind the wide variety of distal radius fractures, a fixation system should be used which permits trans- and extra-articular application and subsequent reduction by means of distraction, as well as wrist mobilization. It is important that both reduction and position of the carpal bones can be checked. The possibility of extra-articular (radioradial) fixation should always be considered. AO group A2 and A3 fractures with sufficiently large fragments are suitable for this procedure. In other cases, transarticular application is advised. Complementary measures are justified in the case where two or more cortices in AP and lateral X-rays are destroyed. Adequate implants are also used to stabilize the articular surface. Large bone defects should be filled with corticocancellous material.

In vivo differentiation and genomic evolution in adult male germ cell tumors.

Germ cell tumors (GCTs) are the most common solid malignancy in young adult men, but the genes and genomic regions involved in their etiology are not fully defined. We report here an investigation of DNA copy number changes in GCTs using 1 Mb BAC arrays. As expected, 12p gain was the defining genomic alteration, occurring in 72/74 GCTs. Parallel expression profiling of these tumors identified potential oncogenes from gained regions (LYN and RAB25) and potential tumor suppressor genes in regions of loss (SYNPO2, TTC12, IGSF4, and EPB41L3). Notably, we observed specific genomic alterations associated with histology, including gain of 17p11.2-q21.32 and loss of 2p25.3 in embryonal carcinoma, gain of 8p23.3-12 and loss of 5p15.33-35.3, 11q23.1-25, and 13q12.11-34 in seminoma, and gain of 1q31.3-42.3, 3p, 14q11.2-32.33, and 20q and loss of 8q11.1-23.1 in yolk sac tumors (YST). Many significant genes that mapped to these regions had previously been associated with specific histologies, such as EOMES (chr3) and BMP2 (chr20) in YST and SPRY2 (chr13) and SOX17 (chr8) in seminomas. Additionally, our results suggest a model in which histologic differentiation of GCTs may drive genomic evolution.

Phototrophic transformation of phenol to 4-hydroxyphenylacetate by Rhodopseudomonas palustris.

Newly isolated and culture collection strains of Rhodopseudomonas palustris were able to transform phenol to 4-hydroxyphenylacetate under phototrophic conditions in the presence of acetate, malate, benzoate, or cinnamate as growth substrates. The reaction was examined with uniformly (14)C-labelled phenol and the product was identified by HPLC retention time, UV-scans, and (1)H- and (13)C-NMR analysis. The transformation reaction was detectable in cell-free extracts in the presence of NAD(+) and acetyl-CoA. For further degradation of 4-hydroxyphenylacetate by R. palustris, low partial pressures of oxygen were essential, presumably for aerobic aromatic ring fission reactions by mono- and di-oxygenases.

Estrogen induces a rapid secretion of amyloid beta precursor protein via the mitogen-activated protein kinase pathway.

The female sex hormone estrogen (17beta-estradiol; E2) may function as a neurohormone and has multiple neuromodulatory functions in the brain. Its potent neuroprotective activities can be dependent and independent of estrogen receptors (ERs). In addition, E2 influences the processing of the amyloid beta precursor protein (APP), one central step in the pathogenesis of Alzheimer's disease. Here, we show: (a) that physiological concentrations of E2 very rapidly cause an increased release of secreted nonamyloidogenic APP (sAPPalpha) in mouse hippocampal HT22 and human neuroblastoma SK-N-MC cells; and (b) that this effect is mediated through E2 via the phosphorylation of extracellular-regulated kinase 1 and 2 (ERK1/2), prominent members of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, we show that the activation of MAPK-signaling pathway and the enhancement of the sAPP release is independent of ERs and could be induced by E2 to a similar extent in neuronal cells either lacking or overexpressing a functional ER.

The multicomponent reactions and their libraries for natural and preparative chemistry.

It was recently recognized that three different types of multi-component reactions (MCRs) exist. In preparative chemistry, the MCRs of type II form their products particularly efficiently. These reactions correspond to equilibria of educts and intermediate products, whose final products are formed practically irreversibly. In recent years, the four component reaction of the isocyanides (U-4CR) of type II and their unions with various reactions and MCRs have become an important industrial process for preparing products and their libraries. It has been demonstrated that all conceivable collections of U-4CR educts can be converted into the corresponding products. In the usual chemical reactions, only the substituents of the products can be varied, whereas the U-4CR and related reactions can also produce skeletally different types of products with diverse substituents. The preparative advantages of forming products by the one-pot MCRs and the great variety of the possible products are illustrated in this review.

Agency and communion in the structure of parental representations.

We administered the revised Assessment of Qualitative and Structural Dimensions of Object Representations (Blatt, Chevron, Quinlan, Schaffer, & Wein, 1992) to 279 male and female undergraduate students and carried out independent principal components analyses of maternal and paternal ratings. Three stable factors, Agency, Communion, and Structure, were found in both sets of ratings. This factor structure differed from that reported by Quinlan, Blatt, Chevron, and Wein (1992). Results found here are consistent with contemporary interpersonal personality theory.

A new screen for protein interactions reveals that the Saccharomyces cerevisiae high mobility group proteins Nhp6A/B are involved in the regulation of the GAL1 promoter.

The split-ubiquitin assay detects protein interactions in vivo. To identify proteins interacting with Gal4p and Tup1p, two transcriptional regulators, we converted the split-ubiquitin assay into a generally applicable screen for binding partners of specific proteins in vivo. A library of genomic Saccharomyces cerevisiae DNA fragments fused to the N-terminal half of ubiquitin was constructed and transformed into yeast strains carrying either Gal4p or Tup1p as a bait. Both proteins were C-terminally extended by the C-terminal half of ubiquitin followed by a modified Ura3p with an arginine in position 1, a destabilizing residue in the N-end rule pathway. The bait fusion protein alone is stable and enzymatically active. However, upon interaction with its prey, a native-like ubiquitin is reconstituted. RUra3p is then cleaved off by the ubiquitin-specific proteases and rapidly degraded by the N-end rule pathway. In both screens, Nhp6B was identified as a protein in close proximity to Gal4p as well as to Tup1p. Direct interaction between either protein and Nhp6B was confirmed by coprecipitation assays. Genetic analysis revealed that Nhp6B, a member of the HMG1 family of DNA-binding proteins, can influence transcriptional activation as well as repression at a specific locus in the chromosome of the yeast S. cerevisiae.