Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer.

The emergence of resistance to targeted therapies restrains their efficacy. The development of rationally guided drug combinations could overcome this currently insurmountable clinical challenge. However, our limited understanding of the trajectories that drive the outgrowth of resistant clones in cancer cell populations precludes design of drug combinations to forestall resistance. Here, we propose an iterative treatment strategy coupled with genomic profiling and genome-wide CRISPR activation screening to systematically extract and define preexisting resistant subpopulations in an EGFR-driven lung cancer cell line. Integrating these modalities identifies several resistance mechanisms, including activation of YAP/TAZ signaling by WWTR1 amplification, and estimates the associated cellular fitness for mathematical population modeling. These observations led to the development of a combination therapy that eradicated resistant clones in large cancer cell line populations by exhausting the spectrum of genomic resistance mechanisms. However, a small fraction of cancer cells was able to enter a reversible nonproliferative state of drug tolerance. This subpopulation exhibited mesenchymal properties, NRF2 target gene expression, and sensitivity to ferroptotic cell death. Exploiting this induced collateral sensitivity by GPX4 inhibition clears drug-tolerant populations and leads to tumor cell eradication. Overall, this experimental in vitro data and theoretical modeling demonstrate why targeted mono- and dual therapies will likely fail in sufficiently large cancer cell populations to limit long-term efficacy. Our approach is not tied to a particular driver mechanism and can be used to systematically assess and ideally exhaust the resistance landscape for different cancer types to rationally design combination therapies. SIGNIFICANCE: Unraveling the trajectories of preexisting resistant and drug-tolerant persister cells facilitates the rational design of multidrug combination or sequential therapies, presenting an approach to explore for treating EGFR-mutant lung cancer.

Lipocalin-2 Deficiency Diminishes Canonical NLRP3 Inflammasome Formation and IL-1ß Production in the Subacute Phase of Spinal Cord Injury.

Spinal cord injury (SCI) results in the production of proinflammatory cytokines due to inflammasome activation. Lipocalin 2 (LCN2) is a small secretory glycoprotein upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 secretion is induced by infection, injury, and metabolic disorders. In contrast, LCN2 has been implicated as an anti-inflammatory regulator. However, the role of LCN2 in inflammasome activation during SCI remains unknown. This study examined the role of Lcn2 deficiency in the NLRP3 inflammasome-dependent neuroinflammation in SCI. Lcn2-/- and wild-type (WT) mice were subjected to SCI, and locomotor function, formation of the inflammasome complex, and neuroinflammation were assessed. Our findings demonstrated that significant activation of the HMGB1/PYCARD/caspase-1 inflammatory axis was accompanied by the overexpression of LCN2 7 days after SCI in WT mice. This signal transduction results in the cleaving of the pyroptosis-inducing protein gasdermin D (GSDMD) and the maturation of the proinflammatory cytokine IL-1ß. Furthermore, Lcn2-/- mice showed considerable downregulation in the HMGB1/NLRP3/PYCARD/caspase-1 axis, IL-1ß production, pore formation, and improved locomotor function compared with WT. Our data suggest that LCN2 may play a role as a putative molecule for the induction of inflammasome-related neuroinflammation in SCI.

[Is oral care for dysphagic patients wasted time? A narrative review on the effects of oral care on pneumonia risk and guidelines for an effective and structured approach]. / Ist die therapeutische Mundpflege bei Dysphagiepatient*innen verschwendete Zeit? Ein narrativer Review zu Effekten der Mundpflege auf die Pneumoniehäufigkeit und Ableitung einer Handlungsempfehlung.

Aspiration pneumonia is a common cause of death in dysphagia patients. In this review, we investigate whether a structured oral care approach can help to reduce pneumonia risk in dysphagic patients. In addition, guidelines for the implementation of oral care on the basis of the analyzed studies are presented. Oral care has positive effects on the risk of pneumonia in dysphagia patients. Oral care should be based on the principles of simplicity, safety, efficiency and effectiveness, universality and economy and it should include all parts of the oral cavity. Effective oral care takes less than five minutes a day. The tactile stimulation prepares the patient for dysphagia therapy and can be considered wisely-invested time.

Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity.

BACKGROUND: Natural killer group 2D (NKG2D) is an activating receptor of natural killer (NK) cells and other lymphocytes that mediates lysis of malignant cells through recognition of stress-induced ligands such as MICA and MICB. Such ligands are broadly expressed by cancer cells of various origins and serve as targets for adoptive immunotherapy with effector cells endogenously expressing NKG2D or carrying an NKG2D-based chimeric antigen receptor (CAR). However, shedding or downregulation of NKG2D ligands (NKG2DL) can prevent NKG2D activation, resulting in escape of cancer cells from NKG2D-dependent immune surveillance. METHODS: To enable tumor-specific targeting of NKG2D-expressing effector cells independent of membrane-anchored NKG2DLs, we generated a homodimeric recombinant antibody which harbors an N-terminal single-chain fragment variable (scFv) antibody domain for binding to NKG2D, linked via a human IgG4 Fc region to a second C-terminal scFv antibody domain for recognition of the tumor-associated antigen ErbB2 (HER2). The ability of this molecule, termed NKAB-ErbB2, to redirect NKG2D-expressing effector cells to ErbB2-positive tumor cells of different origins was investigated using peripheral blood mononuclear cells, ex vivo expanded NK cells, and NK and T cells engineered with an NKG2D-based chimeric receptor. RESULTS: On its own, bispecific NKAB-ErbB2 increased lysis of ErbB2-positive breast carcinoma cells by peripheral blood-derived NK cells endogenously expressing NKG2D more effectively than an ErbB2-specific IgG1 mini-antibody able to induce antibody-dependent cell-mediated cytotoxicity via activation of CD16. Furthermore, NKAB-ErbB2 synergized with NK-92 cells or primary T cells engineered to express an NKG2D-CD3ζ chimeric antigen receptor (NKAR), leading to targeted cell killing and greatly enhanced antitumor activity, which remained unaffected by soluble MICA known as an inhibitor of NKG2D-mediated natural cytotoxicity. In an immunocompetent mouse glioblastoma model mimicking low or absent NKG2DL expression, the combination of NKAR-NK-92 cells and NKAB-ErbB2 effectively suppressed outgrowth of ErbB2-positive tumors, resulting in treatment-induced endogenous antitumor immunity and cures in the majority of animals. CONCLUSIONS: Our results demonstrate that combining an NKAB antibody with effector cells expressing an activating NKAR receptor represents a powerful and versatile approach to simultaneously enhance tumor antigen-specific as well as NKG2D-CAR and natural NKG2D-mediated cytotoxicity, which may be particularly useful to target tumors with heterogeneous target antigen expression.

Lipocalin 2 as a Putative Modulator of Local Inflammatory Processes in the Spinal Cord and Component of Organ Cross talk After Spinal Cord Injury.

Lipocalin 2 (LCN2), an immunomodulator, regulates various cellular processes such as iron transport and defense against bacterial infection. Under pathological conditions, LCN2 promotes neuroinflammation via the recruitment and activation of immune cells and glia, particularly microglia and astrocytes. Although it seems to have a negative influence on the functional outcome in spinal cord injury (SCI), the extent of its involvement in SCI and the underlying mechanisms are not yet fully known. In this study, using a SCI contusion mouse model, we first investigated the expression pattern of Lcn2 in different parts of the CNS (spinal cord and brain) and in the liver and its concentration in blood serum. Interestingly, we could note a significant increase in LCN2 throughout the whole spinal cord, in the brain, liver, and blood serum. This demonstrates the diversity of its possible sites of action in SCI. Furthermore, genetic deficiency of Lcn2 (Lcn2-/-) significantly reduced certain aspects of gliosis in the SCI-mice. Taken together, our studies provide first valuable hints, suggesting that LCN2 is involved in the local and systemic effects post SCI, and might modulate the impairment of different peripheral organs after injury.

Can Acute Cough Characteristics From Sound Recordings Differentiate Common Respiratory Illnesses in Children?: A Comparative Prospective Study.

BACKGROUND: Acute respiratory illnesses cause substantial morbidity worldwide. Cough is a common symptom in these childhood respiratory illnesses, but no large cohort data are available on whether various cough characteristics can differentiate between these etiologies. RESEARCH QUESTION: Can various clinically based cough characteristics (frequency [daytime/ nighttime], the sound itself, or type [wet/dry]) be used to differentiate common etiologies (asthma, bronchiolitis, pneumonia, other acute respiratory infections) of acute cough in children? STUDY DESIGN AND METHODS: Between 2017 and 2019, children aged 2 weeks to ≤16 years, hospitalized with asthma, bronchiolitis, pneumonia, other acute respiratory infections, or control subjects were enrolled. Spontaneous coughs were digitally recorded over 24 hours except for the control subjects, who provided three voluntary coughs. Coughs were extracted and frequency defined (coughs/hour). Cough sounds and type were assessed independently by two observers blinded to the clinical data. Cough scored by a respiratory specialist was compared with discharge diagnosis using agreement (Cohen's kappa coefficient [қ]), sensitivity, and specificity. Caregiver-reported cough scores were related with objective cough frequency using Spearman coefficient (rs). RESULTS: A cohort of 148 children (n = 118 with respiratory illnesses, n = 30 control subjects), median age = 2.0 years (interquartile range, 0.7-3.9), 58% males, and 50% First Nations children were enrolled. In those with respiratory illnesses, caregiver-reported cough scores and wet cough (range, 42%-63%) was similar. Overall agreement in diagnosis between the respiratory specialist and discharge diagnosis was slight (қ = 0.13; 95% CI, 0.03 to 0.22). Among diagnoses, specificity (8%-74%) and sensitivity (53%-100%) varied. Interrater agreement in cough type (wet/dry) between blinded observers was almost perfect (қ = 0.89; 95% CI, 0.81 to 0.97). Objective cough frequency was significantly correlated with reported cough scores using visual analog scale (rs = 0.43; bias-corrected 95% CI, 0.25 to 0.56) and verbal categorical description daytime score (rs = 0.39; bias-corrected 95% CI, 0.22 to 0.54). INTERPRETATION: Cough characteristics alone are not distinct enough to accurately differentiate between common acute respiratory illnesses in children.

Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the α4-Integrin Deficient NOD Mouse.

BACKGROUND: The spontaneously diabetic "non-obese diabetic" (NOD) mouse is a faithful model of human type-1 diabetes (T1D). METHODS: Given the pivotal role of α4 integrin (CD49d) in other autoimmune diseases, we generated NOD mice with α4-deficient hematopoiesis (NOD.α4-/-) to study the role of α4 integrin in T1D. RESULTS: NOD.α4-/- mice developed islet-specific T-cells and antibodies, albeit quantitatively less than α4+ counterparts. Nevertheless, NOD.α4-/- mice were completely and life-long protected from diabetes and insulitis. Moreover, transplantation with isogeneic α4-/- bone marrow prevented progression to T1D of pre-diabetic NOD.α4+ mice despite significant pre-existing islet cell injury. Transfer of α4+/CD3+, but not α4+/CD4+ splenocytes from diabetic to NOD.α4-/- mice induced diabetes with short latency. Despite an only modest contribution of adoptively transferred α4+/CD3+ cells to peripheral blood, pancreas-infiltrating T-cells were exclusively graft derived, i.e., α4+. Microbiota of diabetes-resistant NOD.α4-/- and pre-diabetic NOD.α4+ mice were identical. Co- housed diabetic NOD.α4+ mice showed the characteristic diabetic dysbiosis, implying causality of diabetes for dysbiosis. Incidentally, NOD.α4-/- mice were protected from autoimmune sialitis. CONCLUSION: α4 is a potential target for primary or secondary prevention of T1D.

"No Innovation Without Cooperation" - How Switzerland Innovation Promotes Cooperation Between Industry, Research and Startups.

Switzerland Innovation, the Swiss innovation park with its five branches, is facilitating collaborations for companies, startups, and universities to find solutions to some of the world's most pressing challenges in the fields of health and the life sciences, in particular in the areas of chemistry, biochemistry, biomedicine, biotech, medtech and digital health. Together with its numerous and diverse partners, Switzerland Innovation creates an ecosystem for universities and research-based companies, accelerating the transformation of research results into marketable products and services.

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis.

In colorectal cancer patients, a high density of cytotoxic CD8+ T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/ß-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8+ T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Subsequent release of proteases into the cytoplasm augments MHC class I presentation and activation of CD8+ T cells via cross-dressing of dendritic cells. Thus, our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer.

Generation of alloreactivity-reduced donor lymphocyte products retaining memory function by fully automatic depletion of CD45RA-positive cells.

BACKGROUND AIMS: For patients needing allogeneic stem cell transplantation but lacking a major histocompatibility complex (MHC)-matched donor, haplo-identical (family) donors may be an alternative. Stringent T-cell depletion required in these cases to avoid lethal graft-versus-host disease (GVHD) can delay immune reconstitution, thus impairing defense against virus reactivation and attenuating graft-versus-leukemia (GVL) activity. Several groups reported that GVHD is caused by cells residing within the naive (CD45RA+) T-cell compartment and proposed use of CD45RA-depleted donor lymphocyte infusion (DLI) to accelerate immune reconstitution. We developed and tested the performance of a CD45RA depletion module for the automatic cell-processing device CliniMACS Prodigy and investigated quality attributes of the generated products. METHODS: Unstimulated apheresis products from random volunteer donors were depleted of CD45RA+ cells on CliniMACS Prodigy, using Good Manufacturing Practice (GMP)-compliant reagents and methods throughout. Using phenotypic and functional in vitro assays, we assessed the cellular constitution of CD45RA-depleted products, including T-cell subset analyses, immunological memory function and allo-reactivity. RESULTS: Selections were technically uneventful and proceeded automatically with minimal hands-on time beyond tubing set installation. Products were near-qualitatively CD45RA+ depleted, that is, largely devoid of CD45RA+ T cells but also of almost all B and natural killer cells. Naive and effector as well as γ/δ T cells were greatly reduced. The CD4:CD8 ratio was fivefold increased. Mixed lymphocyte reaction assays of the product against third-party leukocytes revealed reduced allo-reactivity compared to starting material. Anti-pathogen responses were retained. DISCUSSION: The novel, closed, fully GMP-compatible process on Prodigy generates highly CD45RA-depleted cellular products predicted to be clinically meaningfully depleted of GvH reactivity.

Curative-intent radical en bloc resection using a minimum of a 3 cm margin in feline injection-site sarcomas: a retrospective analysis of 131 cases.

Objectives Owing to its highly infiltrative growth, feline injection-site sarcoma (FISS) carries a significant risk of local tumour recurrence. Parameters of possible prognostic significance (eg, tumour size and location, resection of de novo vs recurrent tumours, and achievement of tumour-free surgical margins) were examined with regard to their influence on recurrence rate (RR), disease-free interval (DFI) and survival time (ST). Methods This was a retrospective analysis of cats with FISSs located on the chest or abdominal wall or the interscapular region treated in a single institution using a standardised radical resection technique with 3 cm lateral margins and full-thickness body wall resection (tumours over chest/abdominal wall) or a minimum of two fascial planes (interscapular tumours). Results Median postoperative DFI and ST of 131 cats with FISSs was 21 and 24 months, respectively. Patients operated on for recurrent tumours were significantly more likely to die from tumour-related reasons compared with patients with de novo tumours ( P <0.001). RR and DFI in the different tumour locations were comparable ( P = 0.544 and P = 0.17, respectively). Local tumour recurrence occurred in 38.1% of the cats. Cats operated on for tumour recurrences had a significantly higher chance of another recurrence (RR 55.5% vs 33.3%; P = 0.005). Completeness of excision was determined by taking tumour bed biopsies. Tumour bed biopsies that did not contain tumour cells were associated with a significantly lower RR compared with those with tumour cells (30.5% vs 76.2%). Conclusions and relevance Depending on prognostic factors such as surgery for primary vs recurrent tumour, tumour-free resection margins and tumour location, the RR in FISS ranges from 33-55%, despite curative intent radical surgery. This study may help in identifying patients at risk for recurrence.

H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast.

A/B toxins such as cholera toxin, Pseudomonas exotoxin and killer toxin K28 contain a KDEL-like amino acid motif at one of their subunits which ensures retrograde toxin transport through the secretory pathway of a target cell. As key step in host cell invasion, each toxin binds to distinct plasma membrane receptors that are utilized for cell entry. Despite intensive efforts, some of these receptors are still unknown. Here we identify the yeast H/KDEL receptor Erd2p as membrane receptor of K28, a viral A/B toxin carrying an HDEL motif at its cell binding ß-subunit. While initial toxin binding to the yeast cell wall is unaffected in cells lacking Erd2p, binding to spheroplasts and in vivo toxicity strongly depend on the presence of Erd2p. Consistently, Erd2p is not restricted to membranes of the early secretory pathway but extends to the plasma membrane where it binds and internalizes HDEL-cargo such as K28 toxin, GFP(HDEL) and Kar2p. Since human KDEL receptors are fully functional in yeast and restore toxin sensitivity in the absence of endogenous Erd2p, toxin uptake by H/KDEL receptors at the cell surface might likewise contribute to the intoxication efficiency of A/B toxins carrying a KDEL-motif at their cytotoxic A-subunit(s).

Hyperspectral Imaging Using Flexible Endoscopy for Laryngeal Cancer Detection.

Hyperspectral imaging (HSI) is increasingly gaining acceptance in the medical field. Up until now, HSI has been used in conjunction with rigid endoscopy to detect cancer in vivo. The logical next step is to pair HSI with flexible endoscopy, since it improves access to hard-to-reach areas. While the flexible endoscope's fiber optic cables provide the advantage of flexibility, they also introduce an interfering honeycomb-like pattern onto images. Due to the substantial impact this pattern has on locating cancerous tissue, it must be removed before the HS data can be further processed. Thereby, the loss of information is to minimize avoiding the suppression of small-area variations of pixel values. We have developed a system that uses flexible endoscopy to record HS cubes of the larynx and designed a special filtering technique to remove the honeycomb-like pattern with minimal loss of information. We have confirmed its feasibility by comparing it to conventional filtering techniques using an objective metric and by applying unsupervised and supervised classifications to raw and pre-processed HS cubes. Compared to conventional techniques, our method successfully removes the honeycomb-like pattern and considerably improves classification performance, while preserving image details.

The influence of season on the sensory profile of Egyptian goose (Alopochen aegyptiacus) meat.

The feeding activities of Egyptian geese are becoming a problem for crop farmers in South Africa. Their grain-based diet during the harvesting season compared to the diet during the rest of the year may have an influence on the meat quality, especially the sensory profile. Descriptive sensory analysis, physical measurements, and the proximate composition were used to investigate these effects. Season was a major influential factor with the meat from summer associating with sweet-oily-duck and beef attributes in contrast to the strong association towards the game, metallic, and fish attributes of the winter meat. This is due to the difference in the main fatty acids; winter was higher (P ≤ 0.05) in polyunsaturated fatty acids ( PUFA: ) (C18:3 n-3) and summer higher (P ≤ 0.05) in monounsaturated fatty acid (C18:1 n-9). This study established that season has a significant effect on the sensory profile of Egyptian goose meat and should be considered regarding the utilization and consumption.

The influence of post-mortem conditioning on the tenderness of Egyptian goose (Alopochen aegyptiacus) breast meat (M. pectoralis major).

BACKGROUND: Egyptian goose breast meat has been found to be very tough compared to the meat of other well-known fowl species. In attempting to clarify the toughness of the meat, the physical and biochemical changes during post-mortem conditioning (14 days) was investigated. RESULTS: Although there was increased cathepsin (B, B & L and H) activity, together with a decrease (P ≤ 0.05) in myofibrillar fragmentation lengths (32-25 µm) with conditioning, no change (decline) in shear force values was observed. The higher (P ≤ 0.05) shear force of the male breast portions may be linked to the higher (P ≤ 0.05) concentrations of total and insoluble collagen. CONCLUSIONS: No significant change (decline) in shear force values was observed. Conditioning of Egyptian goose meat as a means of improving the overall toughness cannot therefore not be proposed. The higher shear force and lower sensory tenderness of the male breast portions, as previously observed, may be linked to higher concentrations of total and insoluble collagen.

Development of an image pre-processor for operational hyperspectral laryngeal cancer detection.

Hyperspectral imaging (HSI) is a technology with high potential in the field of non-invasive detection of cancer. However, in complex imaging situations like HSI of the larynx with a rigid endoscope, various image interferences can disable a proper classification of cancerous tissue. We identified three main problems: i) misregistration of single images in a HS cube due to patient heartbeat ii) image noise and iii) specular reflections (SR). Consequently, an image pre-processor is developed in the current paper to overcome these image interferences. It encompasses i) image registration ii) noise removal by minimum noise fraction (MNF) transformation and iii) a novel SR detection method. The results reveal that the pre-processor improves classification performance, while the newly developed SR detection method outperforms global thresholding technique hitherto used by 46%. The novel pre-processor will be used for future studies towards the development of an operational scheme for HS-based larynx cancer detection. RGB image of the larynx derived from the hyperspectral cube and corresponding specular reflections (a) manually segmented and (b) detected by a novel specular reflection detection method.

Post mortem rigor development in the Egyptian goose (Alopochen aegyptiacus) breast muscle (pectoralis): factors which may affect the tenderness.

BACKGROUND: Baseline research on the toughness of Egyptian goose meat is required. This study therefore investigates the post mortem pH and temperature decline (15 min-4 h 15 min post mortem) in the pectoralis muscle (breast portion) of this gamebird species. It also explores the enzyme activity of the Ca(2+)-dependent protease (calpain system) and the lysosomal cathepsins during the rigor mortis period. RESULTS: No differences were found for any of the variables between genders. The pH decline in the pectoralis muscle occurs quite rapidly (c = -0.806; ultimate pH ∼ 5.86) compared with other species and it is speculated that the high rigor temperature (>20 °C) may contribute to the increased toughness. No calpain I was found in Egyptian goose meat and the µ/m-calpain activity remained constant during the rigor period, while a decrease in calpastatin activity was observed. The cathepsin B, B & L and H activity increased over the rigor period. CONCLUSION: Further research into the connective tissue content and myofibrillar breakdown during aging is required in order to know if the proteolytic enzymes do in actual fact contribute to tenderisation.

Depressive Symptoms are the Main Predictor for Subjective Sleep Quality in Patients with Mild Cognitive Impairment--A Controlled Study.

OBJECTIVE: Controlled data on predictors of subjective sleep quality in patients with memory complaints are sparse. To improve the amount of comprehensive data on this topic, we assessed factors associated with subjective sleep quality in patients from our memory clinic and healthy individuals. METHODS: Between February 2012 and August 2014 patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) from our memory clinic and healthy controls were recruited. Apart from a detailed neuropsychological assessment, the subjective sleep quality, daytime sleepiness and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory (BDI-II). RESULTS: One hundred fifty eight consecutive patients (132 (84%) MCI patients and 26 (16%) SCD patients) and 75 healthy controls were included in the study. Pairwise comparison of PSQI scores showed that non-amnestic MCI (naMCI) patients (5.4 ± 3.5) had significantly higher PSQI scores than controls (4.3 ± 2.8, p = .003) Pairwise comparison of PSQI subscores showed that naMCI patients (1.1 ± 0.4) had significantly more "sleep disturbances" than controls (0.9 ± 0.5, p = .003). Amnestic MCI (aMCI) (0.8 ± 1.2, p = .006) and naMCI patients (0.7 ± 1.2, p = .002) used "sleep medication" significantly more often than controls (0.1 ± 0.6) Both, aMCI (11.5 ± 8.6, p < .001) and naMCI (11.5 ± 8.6, p < .001) patients showed significantly higher BDI-II scores than healthy controls (6.1 ± 5.3). Linear regression analysis showed that the subjective sleep quality was predicted by depressive symptoms in aMCI (p < .0001) and naMCI (p < .0001) patients as well as controls (p < .0001). This means, that more depressive symptoms worsened subjective sleep quality. In aMCI patients we also found a significant interaction between depressive symptoms and global cognitive function (p = .002). DISCUSSION: Depressive symptoms were the main predictor of subjective sleep quality in MCI patients and controls, but not in SCD patients. Better global cognitive function ameliorated the negative effect of depressive symptoms on the subjective sleep quality in aMCI patients.

The fatty acid, amino acid, and mineral composition of Egyptian goose meat as affected by season, gender, and portion.

With the current absence of scientific information on the nutritive aspects it is essential to investigate the fatty acid, mineral, and amino acid composition of Egyptian geese as well as the factors of influence. The forage vs. grain based diets of Egyptian geese during certain periods of the yr leads to variation in the content of the key fatty acids such as oleic acid, linoleic acid, and α-linolenic acid. The differences in these fatty acids results in variation between the n-6/n-3 ratios of the seasons; the portions from winter (July) are within the recommendations (ratio <5) and those from summer (November) not. This study indicates that Egyptian goose meat does not only vary in nutritional composition but season may also have a substantial effect on the flavor profile and ultimate uniformity of the meat. The season and portion effects were, however, interlinked but the general tendency shows that the portions, especially the breast and thigh do differ concerning the major fatty acids. No substantial differences were found in the mineral composition of the breast portion on account of season and gender; however there were some variation in certain amino acids such as lysine and arginine due to season/diet. This research provides essential information that should be considered not only regarding the everyday consumption of Egyptian goose meat but the potential utilization and ultimate consistency of this meat product.