The Effect of Dietary Supplementation with Probiotic and Postbiotic Yeast Products on Ewes Milk Performance and Immune Oxidative Status.

The administration of yeast products as feed additives has been proven to beneficially affect animal productivity through energy, oxidative, and immune status improvement. This study evaluated a combination of Saccharomyces cerevisiae live yeast (LY) with yeast postbiotics (rich in mannan-oligosaccharides (MOS) and beta-glucans) and selenium (Se)-enriched yeast on ewes' milk performance and milk quality, energy and oxidative status, and gene expression related to their immune system during the peripartum period. Ewes were fed a basal diet (BD; F:C = 58:42 prepartum and 41:59 postpartum) including inorganic Se (CON; n = 27), the BD supplemented with a LY product, and inorganic Se (AC; n = 29), as well as the combination of the LY, a product of yeast fraction rich in MOS and beta-glucans, and organic-Se-enriched yeast (ACMAN; n = 26) from 6 weeks prepartum to 6 weeks postpartum. The ß-hydroxybutyric acid concentration in the blood of AC and ACMAN ewes was lower (compared to the CON) in both pre- and postpartum periods (p < 0.010). Postpartum, milk yield was increased in the AC and ACMAN Lacaune ewes (p = 0.001). In addition, the activity of superoxide dismutase (p = 0.037) and total antioxidant capacity (p = 0.034) measured via the 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) method was increased in the blood plasma of the ACMAN postpartum. Higher ABTS values were also found (p = 0.021), while protein carbonyls were reduced (p = 0.023) in the milk of the treated groups. The relative transcript levels of CCL5 and IL6 were downregulated in the monocytes (p = 0.007 and p = 0.026 respectively), and those of NFKB were downregulated in the neutrophils of the ACMAN-fed ewes postpartum (p = 0.020). The dietary supplementation of ewes with yeast postbiotics rich in MOS and beta-glucans, and organic Se, improved energy status, milk yield and some milk constituents, and oxidative status, with simultaneous suppression of mRNA levels of proinflammatory genes during the peripartum period.

Cognizant Fiber-Reinforced Polymer Composites Incorporating Seamlessly Integrated Sensing and Computing Circuitry.

Structural fiber-reinforced polymer (FRP) composite materials consisting of a polymer matrix reinforced with layers of high-strength fibers are used in numerous applications, including but not limited to spacecraft, vehicles, buildings, and bridges. Researchers in the past few decades have suggested the necessary integration of sensors (e.g., fiber optic sensors) in polymer composites to enable health monitoring of composites' performance over their service lives. This work introduces an innovative cognizant composite that can self-sense, compute, and implement decisions based on sensed values. It is a critical step towards smart, resilient infrastructure. We describe a method to fabricate textile sensors with flexible circuitry and a microcontroller within the polymer composite, enabling computational operations to take place in the composite without impacting its integrity. A microstructural investigation of the sensors showed that the amount of oxidative agent and soaking time of the fabric play a major role in the adsorption of polypyrrole (PPy) on fiberglass (FG). XPS results showed that the 10 g ferric chloride solution with 6 h of soaking time had the highest degree of protonation (28%) and, therefore, higher adsorption of PPy on FG. A strain range of 30% was achieved by examining different circuitry and sensor designs for their resistance and strain resolution under mechanical loading. A microcontroller was added to the circuit and then embedded within a composite material. This composite system was tested under flexural loading to demonstrate its self-sensing, computing, and actuation capabilities. The resulting cognizant composite demonstrated the ability to read resistance values and measure strain using the embedded microcontroller and autonomously actuate an LED light when the strain exceeds a predefined limit of 2000 µÎµ. The application of the proposed FRP system would provide in situ monitoring of structural composite components with autonomous response capabilities, as well as reduce manufacturing, production, and maintenance costs.

Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.

BACKGROUND/AIM: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice. MATERIALS AND METHODS: A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA). RESULTS: Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants. CONCLUSION: In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.

Effect of Spirulina Dietary Supplementation in Modifying the Rumen Microbiota of Ewes.

Supplementing ruminant diets with microalgae, may prove an effective nutritional strategy to manipulate rumen microbiota. Forty-eight ewes were divided into four homogenous groups (n = 12) according to their fat-corrected milk yield (6%), body weight, age, and days in milk, and were fed individually with concentrate, alfalfa hay, and wheat straw. The concentrate of the control group (CON) had no Spirulina supplementation, while in the treated groups 5 (SP5), 10 (SP10), and 15 g (SP15) of Spirulina were supplemented as an additive in the concentrate. An initial screening using metagenomic next-generation sequencing technology was followed by RT-qPCR analysis for the targeting of specific microbes, which unveiled the main alterations of the rumen microbiota under the Spirulina supplementation levels. The relative abundance of Eubacterium ruminantium and Fibrobacter succinogenes in rumen fluid, as well as Ruminococcus albus in rumen solid fraction, were significantly increased in the SP15 group. Furthermore, the relative abundance of Prevotella brevis was significantly increased in the rumen fluid of the SP5 and SP10 groups. In contrast, the relative abundance of Ruminobacter amylophilus was significantly decreased in the rumen fluid of the SP10 compared to the CON group, while in the solid fraction it was significantly decreased in the SP groups. Moreover, the relative abundance of Selenomonas ruminantium was significantly decreased in the SP5 and SP15 groups, while the relative abundance of Streptococcus bovis was significantly decreased in the SP groups. Consequently, supplementing 15 g Spirulina/ewe/day increased the relative abundance of key cellulolytic species in the rumen, while amylolytic species were reduced only in the solid fraction.

Inclusion of Camelina sativa Seeds in Ewes' Diet Modifies Rumen Microbiota.

Supplementing ruminant diets with unconventional feedstuffs (Camelina sativa seeds; CS) rich in bioactive molecules such as polyunsaturated fatty acids, may prove a potential eco-efficient strategy to manipulate rumen microbiome towards efficiency. Forty-eight ewes were divided into four homogenous groups (n = 12) according to their fat-corrected milk yield (6%), body weight, and age, and were fed individually with concentrate, alfalfa hay, and wheat straw. The concentrate of the control group (CON) had no CS inclusion, whereas the treated groups were supplemented with CS at 60 (CS6), 110 (CS11), and 160 (CS16) g·kg-1 of concentrate, respectively. Rumen digesta was collected using an esophageal tube and then liquid and solid particles were separated using cheesecloth layers. An initial bacteriome screening using next-generation sequencing of 16S was followed by specific microbes targeting with a RT-qPCR platform, which unveiled the basic changes of the rumen microbiota under CS supplementation levels. The relative abundances of Archaea and methanogens were significantly reduced in the solid particles of CS11 and CS16. Furthermore, the relative abundance of Protozoa was significantly increased in both rumen fluid and solid particles of the CS6, whereas that of Fungi was significantly reduced in the rumen particle of the CS16. In rumen fluid, the relative abundance of Fibrobacter succinogens and Ruminobacter amylophilus were significantly increased in the CS6 and CS11, respectively. In the solid particles of the CS11, the relative abundance of Ruminococcus flavefaciens was significantly reduced, whereas those of Butyrivibrio proteoclasticus and Ruminobacter amylophilus were significantly increased. Additionally, the relative abundance of Selenomonas ruminantium was significantly increased in both CS11 and CS16. Consequently, the highest CS content in the concentrate reduced the relative abundance of methanogens without inducing radical changes in rumen microorganisms that could impair ruminal fermentation and ewes' performance.

Investigation of prognostic biomarkers in patients with urothelial carcinoma treated with platinum-based regimens.

BACKGROUND: Bladder cancer (BC) is a heterogeneous malignancy with dismal outcome. PATIENTS AND METHODS: Mutations in genes, altered or linked to platinum sensitivity in BC, were examined in 66 patients' tumors along with tumor infiltrating lymphocytes (TILs) density and MMR, PD-L1 and CD8 protein expression, as well as basal and luminal subtypes, defined by protein expression of markers, including CK5/6 and GATA3 or CK20, respectively. RESULTS: 41 tumors harbored mutations, mainly in TP53 (38%), ARID1A (17%) and the DNA damage response and repair (DDR) genes ERCC2 (17%) and BRCA2 (15%). Mutations in other DDR relevant genes were also present. Age showed unfavorable prognosis for overall survival (HR=1.07, P = 0.026); no benefit was seen for patients with TP53, ARID1A, ERCC2 or BRCA2 mutations or mutations in 1 or more DDR genes. PD-L1 status positively correlated with stromal (rho=0.46, P < 0.001) and intratumoral (rho=0.53, P < 0.001) CD8 expression or TILs (rho=0.29, P = 0.018); none associated with overall survival (OS). A statistically significant difference was observed between PD-L1 status and immunohistochemistry (IHC)­based subtypes, with tumors classified as luminal (GATA3+ and/or CK20+ and CK5/6-) showing lower PD-L1 expression relative to basal (CK5/6+ and GATA3- and/or CK20-) (median value 0 vs. 2.5, P = 0.029). Concerning OS, no statistically significant difference was seen among patients with basal or luminal tumors. CONCLUSION: No association was seen herein between DDR mutations, TILs, PD-L1, CD8 expression or IHC-based subtypes and patient survival; these observations warrant validation within a larger cohort.

Effectiveness of a hybrid arts-based Cognitive Behavioral Therapy intervention for patients with non-malignant chronic pain.

Chronic Pain (CP) is defined as pain that persists or recurs for more than 3 to 6 months and may be conceived as a health condition in its own right. CP is a frequent condition, affecting an estimated 20% of people worldwide and requires special treatment and care. CP can contribute to depression, anxiety, sleep disturbances, poor quality of life and increased health care costs. Psychosocial approaches based on a cognitive conceptualization of pain can provide a solid foundation for research and clinical work. The development of a 10 week-session group treatment was based on key principles from the literature on Cognitive Behavioral Therapy for Chronic Pain (CBT-CP) and Creative Arts Therapy, integrated with advances in research on CP management framework. The aim of this study is to evaluate a CBT-CP arts-based group intervention for patients with non-malignant CP addressing the biopsychosocial factors that influence pain perception. A total of 100 University Pain Management Unit outpatients participated, 50 in the intervention group and 50 in the control group (treatment as usual). In analyses of the pretest-posttest research design intervention including all participants, treatment gains were observed in almost all domains examined: severity of pain measured by the Brief Pain Inventory, conceptualization of mental pain measured by the Orbach and Mikulincer Mental Pain Scale, tolerance for psychological pain measured by the Tolerance for Mental Pain Scale, anxiety and depression levels measured by the Hospital Anxiety and Depression Scale, and quality of life measured by the WHO Quality of Life-BREF Questionnaire. The participants' mean age was 52.3 years and most were female (84%). Findings suggest that postprogram, there was significant reduction in pain intensity (p<0.001), depressive symptoms (p<0.001), confusion about pain (p=0.037), and improvement of emotional distress tolerance (p=0.012) and global health-related quality of life (p<0.001) in the intervention group. Beneficial effects can be expected from the implementation of an integrated CP intervention (including: creative and CBT techniques) reappraising some of the coping responses defined as adaptive within current psychosocial non-malignant CP regimens.

Effect of a Carotenoid Extract from Citrus reticulata By-Products on the Immune-Oxidative Status of Broilers.

Although carotenoids generally possess antimicrobial and antioxidant properties, the in vivo synergistic action of carotenoid blends derived from plant-based by-products has not been thoroughly studied. Therefore, the carotenoid characterization and antimicrobial potential of Citrus reticulata extract as well as the impact of this carotenoid-rich extract (CCE) dietary supplementation on the performance, meat quality, and immune-oxidative status of broiler chickens were determined. One hundred and twenty one-day-old hatched chicks (Ross 308) were allocated to two dietary groups, with four replicate pens of 15 birds each. Birds were fed either a basal diet (CON) or the basal diet supplemented with 0.1% CCE (25 mg carotenoid extract included in 1 g of soluble starch) for 42 d. ß-Cryptoxanthin, ß-Carotene, Zeaxanthin, and Lutein were the prevailing carotenoid compounds in the Citrus reticulata extract. The CCE feed additive exerted inhibitory properties against both Gram-positive (Staphylococcus aureus) and negative (Klebsiella oxytoca, Escherichia coli, and Salmonella typhimurium) bacteria. Both the broiler performance and meat quality did not substantially differ, while the breast muscle malondialdehyde (MDA) concentration tended to decrease (p = 0.070) in the CCE-fed broilers. The inclusion of CCE decreased the alanine aminotransferase and MDA concentration, and the activity of glutathione peroxidase, while the activity of superoxide dismutase was increased in the blood. Catalase and NADPH oxidase 2 relative transcript levels were significantly downregulated in the livers of the CCE-fed broilers. Additionally, Interleukin 1ß and tumor necrosis factor (TNF) relative transcript levels were downregulated in the livers of the CCE- fed broilers, while TNF and interferon γ (IFNG) tended to decrease in the spleens and bursa of Fabricius, respectively. The present study provided new insights regarding the beneficial properties of carotenoids contained in Citrus reticulata in broilers' immune-oxidative status. These promising outcomes could be the basis for further research under field conditions.

mRNA expression of specific HER ligands and their association with clinical outcome in patients with metastatic breast cancer treated with trastuzumab.

Prognostic and predictive biomarkers are being studied for the diagnosis and treatment of breast cancer. The present study retrospectively assessed the mRNA expression of HER family receptor ligands and of other potential prognostic biomarkers and their association with time to progression (TTP), survival and clinicopathological characteristics in patients with metastatic breast cancer (MBC) treated with trastuzumab. A total of 145 tumour tissue samples were analysed. mRNA expression analysis of the transcripts of interest was performed and the association of these markers with selected clinicopathological parameters was examined. HER2 status was centrally re-evaluated. Only 67.6% of patients were truly HER2-positive according to the central HER2 re-evaluation. Heparin binding epidermal growth factor (EGF)-like growth factor, transforming growth factor ß1 (TGFB1) and thyroid hormone receptor α (THRA) mRNA expression was higher in HER2-positive patients (P=0.026, P<0.001 and P<0.001). Insulin-like growth factor binding protein 4 was correlated with retinoic acid receptor α, TGFB1 and THRA (rho=0.45, rho=0.60 and rho=0.45). In HER2-positive patients, high neuregulin 1 and high betacellulin were unfavourable factors for TTP [hazard ratio (HR) = 1.78, P=0.040 and HR=2.00, P=0.043, respectively]. In patients with de novo MBC, high EGF expression was associated with a non-significant prolongation of TTP (HR=0.52, P=0.080) and significantly longer survival (HR=0.40, P=0.020). The present study examined clinical and biological implications of specific genes and it was concluded that their expression has an impact on the outcome of trastuzumab-treated patients with MBC.

Botulinum toxin type A treatment is associated with improved social and psychological behavior: A retrospective study.

BACKGROUND: The human face significantly affects the individuals' quality of life, attitude, and mental state. The study of anatomy would always be on the spotlight, as the beauty of the face is desired by humans worldwide. However, age, stress, and negative emotions could lead to stimulation of the corrugator supercilii and procerus muscles in the glabellar region and, subsequently, to alterations in face's characteristics, which could be associated with isolation and avoidance of engaging in social contacts. AIMS: Here, we aimed to examine the degree to which treatment with botulinum toxin type A (BoNT A) can affect patients' quality of life and mental state. PATIENTS/METHODS: The data collection was performed using 11 questionnaires, which were filled by 83 individuals who underwent BoNT A treatment (sex, 95% female and 5% male; mean age, 48 years). RESULTS: The results showed that the treatment with BoNT A improved the patients' social and psychological behavior, and their opinion regarding their appearance. This effect developed within 1 month following completion of the treatment. Moreover, the effect was higher in patients' social behavior and was better in patients aged 40-49 years compared to those aged <40 and ≥49 years. CONCLUSIONS: Thus, BoNT A treatment could be considered as an important way to improve the social behavior and socialization of individuals by raising their psychology and self-esteem.

Real-World Data on Treatment Management and Outcomes of Patients with Newly Diagnosed Advanced Epithelial Ovarian Cancer in Greece (The EpOCa Study).

New treatment modalities have been recently introduced in the management of ovarian cancer (OC). Herein, we sought to investigate their implementation in routine clinical practice and examine the real-world management of OC in Greece. EpOCa was a non-interventional, multicenter, retrospective study in patients with advanced epithelial OC. The primary outcome was to estimate the proportions of the different treatment regimens used per line of therapy, while progression-free survival (PFS) and overall survival (OS) were the key secondary endpoints. A total of 154 patients were enrolled in the study, among whom, 40% were tested for BRCA mutations and 30% were found to be positive. Nearly 90% of patients underwent debulking surgery at diagnosis, with few operations being also recorded upon relapse. Platinum-based chemotherapy (CT) was predominantly used in the first line with half of patients also receiving angiogenesis inhibitor (AI), while non-platinum-based CT was preferred in later lines. The median PFS was 18.2 and 8.8 months in the first- and second-line setting, respectively, whereas the median OS was approximately 50 months. Our study adds to the available, but limited, real world data on the management of ovarian cancer providing evidence regarding the applied treatment strategies and outcomes of patients in Greece.

Assessing the Optimum Level of Supplementation with Camelina Seeds in Ewes' Diets to Improve Milk Quality.

Camelina sativa seeds are rich in bioactive compounds such as polyunsaturated fatty acids (PUFA) and antioxidants, thus, their supplementation in ewes' diets, may be an effective way to develop high nutritional dairy products. Therefore, the present study investigates the effect of the dietary inclusion of Camelina sativa seeds in ewes' oxidative status and milk quality. Forty-eight dairy Chios ewes were divided into four homogenous groups and were fed individually. The concentrate of the control group (CON) had no inclusion of Camelina seeds, while the treatment groups (CSS6, CSS11, CSS16) were supplemented with 6%, 11%, and 16%, respectively. Including Camelina seeds in 6% and 11%, had no impact on milk performance, while in the CSS16, milk fat was significantly decreased compared to the CON. Supplementing Camelina seeds improved milk quality from a human health perspective by modifying the content of saturated fatty acid, the proportions of α-linolenic (C18:3 n-3), and C18:2 cis-9, trans-11 (CLA), and the ω6/ω3 ratio. Furthermore, the activity of catalase (CAT) was significantly increased in the CSS11 and CSS16, and superoxide dismutase (SOD) activity also significantly upsurged in the CSS16. Still, the levels of malondialdehyde (MDA) were significantly increased in the CSS11 compared to the CON and CSS6, and in the CSS16 compared to the CSS6. In CSS16, protein carbonyls were significantly increased. Finally, in the CSS-fed ewes, milk oxidative stability was fortified, as suggested by the modifications in the activities of SOD, CAT, and glutathione peroxidase (GSH-Px), in the antioxidant capacity, and the oxidative stress biomarkers. Consequently, the incorporation of 6% Camelina seeds in the concentrates of ewes improves milk's fatty acid profile and oxidative status. However, more research is required regarding the possible negative effects of the constant consumption of Camelina seeds by ewes.

Effects of Supplementing Rumen-Protected Methionine and Lysine on Milk Performance and Oxidative Status of Dairy Ewes.

There is limited information on the impact of dietary supplementation with separate rumen-protected (RP) amino acids (AA), or with their combination, on ewes' oxidative status. Sixty ewes were divided into five groups; C: basal diet (control); M: basal diet + 6 g/ewe RP methionine; L: basal diet + 5 g/ewe RP lysine; LML: basal diet + 6 g methionine and 5 g lysine/ewe; and HML: basal diet + 12 g methionine + 5 g lysine/ewe. Milk's fat content increased in RP-AA fed ewes, while that of protein in M and L only. In blood plasma, the malondialdehyde (MDA) content was reduced in the M, LML, and HML compared to C-fed ewes. An increase in glutathione transferase activity in the blood plasma of the M and LML compared to the C and HML-fed ewes were found. In milk, lower values of the ferric reducing ability of plasma (FRAP) in the LML and HML-fed ewes and of 2,2'-Azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) in LML only, were found. Lysine increased milk's FRAP values and MDA content. Both L and HML diets increased milk's protein carbonyls content. Methionine improves the organism's oxidative status, without adversely affecting milk's oxidative stability. Lysine dietary inclusion affects negatively the oxidative stability of milk.

Clinical Utility of Functional RNA Analysis for the Reclassification of Splicing Gene Variants in Hereditary Cancer.

BACKGROUND: Classification of splicing variants (SVs) in genes associated with hereditary cancer is often challenging. The aim of this study was to investigate the occurrence of SVs in hereditary cancer genes and the clinical utility of RNA analysis. MATERIAL AND METHODS: 1518 individuals were tested for cancer predisposition, using a Next Generation Sequencing (NGS) panel of 36 genes. Splicing variant analysis was performed using RT-PCR and Sanger Sequencing. RESULTS: In total, 34 different SVs were identified, 53% of which were classified as pathogenic or likely pathogenic. The remaining 16 variants were initially classified as Variant of Uncertain Significance (VUS). RNA analysis was performed for 3 novel variants. CONCLUSION: The RNA analysis assisted in the reclassification of 20% of splicing variants from VUS to pathogenic. RNA analysis is essential in the case of uncharacterized splicing variants, for proper classification and personalized management of these patients.

Evaluation of the Role of p95 HER2 Isoform in Trastuzumab Efficacy in Metastatic Breast Cancer.

BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. MATERIALS AND METHODS: A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other markers possibly affecting trastuzumab efficacy in regards to progression-free survival and overall survival. RESULTS: HER2 was centrally negative in 54 cases. P95 expression was significantly higher in HER2-positive tumors. High p95 was associated with gain of HER2 copy number variations (CNVs), high pHER2Tyr877, Ki67 and HER2 mRNA. P95 as a continuous variable was positively correlated with mRNA expression of HER2 and negatively correlated with HER4 and IGF1. HER2-negative p95-high patients had a marginally higher risk for death (HR=2.15, p=0.055). CONCLUSION: p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.

Androgen Receptor and PIM1 Expression in Tumor Tissue of Patients With Triple-negative Breast Cancer.

BACKGROUND/AIM: Effective targeted therapies for triple-negative breast cancer (TNBC) are limited. In a subset of TNBC, androgen receptor (AR) plays an important role, while the human proviral integration site for Moloney murine leukemia virus-1 (PIM1) overexpression is also implicated. PIM1 kinases phosphorylate AR, thus regulating its transcriptional activity, regardless of the presence or not of androgens. We evaluated the expression of AR and PIM1 and their prognostic significance in TNBC. MATERIALS AND METHODS: AR and PIM1 transcripts were quantified by quantitative reverse transcription polymerase chain reaction in formalin-fixed paraffin-embedded tumor from 141 patients with TNBC. RESULTS: AR was expressed in 38.3%, PIM1 in 10.6%, while co-expression of AR and PIM1 was detected in 7/141 cases (5.0%). No prognostic significance of AR or PIM1 was reached for overall or disease-free survival. CONCLUSION: Co-expression of AR and PIM1 exists in only in a small percentage of patients with TNBC. The implications of this finding in the therapeutic management of patients with TNBC should be investigated in larger patient cohorts.

Comparative Study of Quality of Life and Psychological Aspects in Patients with Psoriasis and Hidradenitis Suppurativa.

Psoriasis and hidradenitis suppurativa are two common dermatological diseases that affect physical, social, and psychological aspects of the patients' lives. The aim of this study was to compare quality of life, depression, anxiety, self-esteem, and loneliness in patients with psoriasis and hidradenitis suppurativa. One hundred and eight patients with psoriasis, 113 patients with hidradenitis suppurativa and 116 healthy controls were included in the study. The quality of life, depression, anxiety, and loneliness of the patients as well as their self-esteem were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), the UCLA loneliness Scale (UCLA-Version 3) and the Rosenberg's Self-esteem Scale (RSES), respectively. Patients with psoriasis (12.77±4.43) reported a higher mean impairment in DLQI than patients with hidradenitis suppurativa (11.10±6.53, P=0.028), in the univariate comparisons. Patients with psoriasis presented statistically significantly higher levels of anxiety and depression than both patients with hidradenitis suppurativa and healthy controls, while patients with hidradenitis suppurativa also had higher anxiety and depression compared with healthy controls. Patients with psoriasis (46.31±6.36) reported statistically significantly higher loneliness than both patients with hidradenitis suppurativa (43.18±7.40) and controls (40.42±4.41), while the patients with hidradenitis suppurativa also presented higher loneliness in comparison with controls. Lower levels of self-esteem were found in patients with psoriasis (15.08±3.11) compared with both patients with hidradenitis suppurativa (18.89±1.69) and controls (20.25±2.60), while patients with hidradenitis suppurativa also had lower self-esteem than controls. Significant levels of depression, anxiety, and impaired quality of life were strongly associated with disease severity. When patients with mild disease were compared, those with psoriasis presented with both higher levers of loneliness and lower scores for quality of life. Although both psoriasis and hidradenitis suppurativa are associated with impaired quality of life and psychological aspects, significantly worse scores were recorded in patients with psoriasis.

Dietary Supplementation of a Live Yeast Product on Dairy Sheep Milk Performance, Oxidative and Immune Status in Peripartum Period.

This study evaluated the dietary administration of Saccharomyces cerevisiae live yeast on milk performance and composition, oxidative status of both blood plasma and milk, and gene expression related to the immune system of lactating ewes during the peripartum period. Chios ewes were fed either a basal diet (BD) (Control, n = 51) or the BD supplemented with 2 g of a live yeast product/animal (ActiSaf, n = 53) from 6 weeks prepartum to 6 weeks postpartum. Fatty acid profile, oxidative, and immune status were assessed in eight ewes per treatment at 3 and 6 weeks postpartum. The ß-hydroxybutyric acid concentration in blood of ActiSaf fed ewes was significantly lower in both pre- and postpartum periods. A numerical increase was found for the milk yield, fat 6% corrected milk (Fat corrected milk (FCM6%)), and energy corrected milk yield (ECM) in ActiSaf fed ewes, while daily milk fat production tended to increase. The proportions of C15:0, C16:1, C18:2n6t, and C18:3n3 fatty acids were increased in milk of ActiSaf fed ewes, while C18:0 was decreased. Glutathione reductase in blood plasma was increased (p = 0.004) in ActiSaf fed ewes, while total antioxidant capacity measured by 2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) method was decreased (p < 0.001). Higher ABTS values were found in the milk of the treated group. The relative transcript levels of CCL5, CXCL16, and IL8 were suppressed, while that of IL1B tended to decrease (p = 0.087) in monocytes of ActiSaf fed ewes. In conclusion, the dietary supplementation of ewes with S. cerevisiae, improved the energy utilization and tended to enhance milk performance with simultaneous suppression on mRNA levels of pro-inflammatory genes during the peripartum period.

Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group. METHODS: We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated. RESULTS: The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman's rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (all p values < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively. CONCLUSIONS: Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports.

BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects.

Germline BRCA1 and BRCA2 loss-of-function variants have been linked to increased breast and ovarian cancer risk, with more than 5,000 distinct pathogenic variants being reported worldwide. Among individuals of Greek descent, the BRCA1/2 variant spectrum is heterogeneous, but characterized by strong founder effects. As patients from certain geographical regions of Greece (like Crete) were underrepresented in previous studies, we hypothesized that isolated Cretans, a southern Greece islanders' population with distinct demographic, cultural and genetic features, could harbor founder BRCA1/2 mutations. A total of 304 breast or/and ovarian cancer patients of Cretan descent, fulfilling NCCN criteria for genetic testing, were tested by NGS or Sanger sequencing, followed by MLPA. Haplotype analysis was subsequently performed to investigate potential founder effects of recurrent alleles. Overall, 16.5% (50/304) of the tested patients carried 22 different pathogenic variants; 48% in BRCA1, 52% in BRCA2. Three variants, namely two in BRCA2 (Δexons 12 and 13 and c.7806-2A>T) and one in BRCA1 (c.5492del), constituting approximately half (48%) of all detected pathogenic variants, were shown to have a founder effect, with all carriers sharing common haplotypes. Remarkably, these variants were confined to Cretans and have not been identified in other regions of Greece. The high prevalence of specific BRCA1/2 pathogenic variants among Cretans, provides the possibility of cost- and time-efficient screening of the Cretan population. Integrating this knowledge in local public health services may have a significant impact on cancer prevention, and may serve as a starting point for the implementation of testing on a population level.