Iron/Copper/Phosphate nanocomposite as antimicrobial, antisnail, and wheat growth-promoting agent.

BACKGROUND: One of the current challenges is to secure wheat crop production to meet the increasing global food demand and to face the increase in its purchasing power. Therefore, the current study aimed to exploit a new synthesized nanocomposite to enhance wheat growth under both normal and drought regime. The effectiveness of this nanocomposite in improving the microbiological quality of irrigation water and inhibiting the snail's growth was also assessed. RESULTS: Upon the employed one-step synthesis process, a spherical Fe/Cu/P nanocomposite was obtained with a mean particle size of 4.35 ± 1.524 nm. Cu2+, Fe2+, and P4+ were detected in the dried nanocomposite at 14.533 ± 0.176, 5.200 ± 0.208, and 34.167 ± 0.203 mg/ml concentration, respectively. This nanocomposite was found to exert antibacterial activity against Escherichia coli and Salmonella typhi. It caused good inhibition percent against Fusarium oxysporum (43.5 ± 1.47%) and reduced both its germination rate and germination efficiency. The lethal concentration 50 (LC50) of this nanocomposite against Lanistes carinatus snails was 76 ppm. The treated snails showed disturbance in their feeding habit and reached the prevention state. Significant histological changes were observed in snail digestive tract and male and female gonads. Drought stress on wheat's growth was mitigated in response to 100 and 300 ppm treatments. An increase in all assessed growth parameters was reported, mainly in the case of 100 ppm treatment under both standard and drought regimes. Compared to control plants, this stimulative effect was accompanied by a 2.12-fold rise in mitotic index and a 3.2-fold increase in total chromosomal abnormalities. CONCLUSION: The finding of the current study could be employed to mitigate the effect of drought stress on wheat growth and to enhance the microbiological quality of irrigation water. This is due to the increased efficacy of the newly synthesized Fe/Cu/P nanocomposite against bacteria, fungi, and snails. This methodology exhibits potential for promoting sustainable wheat growth and water resource conservation.

Effects of pharmacogenetics on pharmacokinetics and toxicity of doxorubicin in Egyptian breast cancer patients.

This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients with breast cancer.Patients administered DOX (60 mg/m2) for 4 cycles every 3 weeks. The peak DOX plasma concentration was measured using a validated chromatographic method. The genotyping for the selected SNPs, SLC22A16 T > C (rs714368), and CBR1 C > T (rs20572), was performed by RT-PCR. Patients were monitored for hematological and cardiac toxicities.The variant carriers of CBR1 C > T (rs20572) exhibited significantly higher DOX concentration, but no significant association to DOX-induced hematological toxicity. On the other hand, SLC22A16 T > C (rs714368) had no significant influence on DOX plasma concentration, but was significantly correlated with lower risk of neutropenia (OR 0.31, 95% CI 0.12-0.75, p = 0.01) and leukopoenia (OR 0.18, 95% CI 0.07-0.5, p = 0.001). DOX-related cardiotoxicity was correlated with the cumulative dose of DOX (R = 0.238, p = 0.017), but not with any of the two examined SNPs.Genetic polymorphisms in SLC22A16 and CBR1 may explain the inter-individual variations in DOX pharmacokinetics and toxicity. Using pharmacogenetic testing is important to customise drug therapy for cancer patients treated with anthracyclines.

Co-expression of candidate genes regulating growth performance and carcass traits of Barki lambs in Egypt.

Sheep are considered one of the main sources of animal protein in Egypt and the producers of sheep mutton eagers to find biological criteria for selecting fast-growing lambs that reach market weight early. Therefore, the present study aimed to find a link between the expression profile of selected candidate genes with growth performance and carcass traits of Barki lambs. Thirty-eight Barki lambs were kept and fed individually after weaning till 12 months of age and were divided into 3 groups according to growth performance (fast, intermediate, and slow-growing). Three samples were taken from different body tissues (eye muscle, liver, and fat tail) of each group, directly during slaughtering and stored at - 80 °C until RNA isolation. Real-time PCR was used to profile selected candidate genes (RPL7, CTP1, FABP4, ADIPOQ, and CAPN3) and GAPDH was used as a housekeeping gene. The results indicated that the final body weight was significantly (P ≤ 0.05) greater in the fast (49.9 kg) and intermediate (40.7 kg) compared to slow-growing animals (30.8 kg). The hot carcass weight was heavier (P ≤ 0.05) in the fast and intermediate-growing (24.57 and 19.07 kg) than slow-growing lambs (15.10 kg). The blood profiles of T3 and T4 hormones in addition to other parameters such as total protein, total lipids, and calcium level showed no clear variations among different experimental groups. At the molecular level, our data demonstrated upregulation of genes involved in protein biosynthesis (RPL7), fatty acid oxidation (CPT1), and lipolysis (FABP4) in the fast and intermediate-growing lambs in all studied tissues which facilitate protein accretion, energy expenditure, and fatty acid partitioning required for muscle building up. Moreover, the expression profile of the gene involved in muscle development (CAPN3) was increased in fast and intermediate-growing compared to slow-growing lambs in order to support muscle proper development. On the other hand, a candidate gene involved in lipogenesis (ADIPOQ) was expressed similarly in fat and liver tissues; however, its expression was increased in muscles of fast and intermediate-growing lambs compared to slow-growing animals. In conclusion, the current study indicated that the expression profile of genes involved in metabolic activities of liver, muscle, and adipose tissue is linked with the growth performance of lambs although no variations were detected in blood parameters. This provides an evidence for the importance of co-expression of these genes in body tissues to determine the final body weight and carcass characteristics of Barki sheep.

Moxifloxacin Hydrochloride Electrochemical Detection at Gold Nanoparticles Modified Screen-Printed Electrode.

It appeared that either the carbon paste or the screen-printed carbon electrodes that were modified with gold nanoparticles (AuNPs) gave rise to the largest current responses after a rapid screening of various nanomaterials as modifiers of carbon composite electrodes in view of designing an electrochemical sensor for Moxifloxacin Hydrochloride (Moxi). The screen-printed electrode (SPE) support was preferred over the carbon paste one for its ability to be used as disposable single-use sensor enabling the circumvention of the problems of surface fouling encountered in the determination of Moxi. The response of AuNPs modified SPE to Moxi was investigated by cyclic voltammetry (CV) (including the effect of the potential scan rate and the pH of the medium), chronoamperometry, and differential pulse voltammetry (DPV) after morphological and physico-chemical characterization. DPV was finally applied to Moxi detection in phosphate buffer at pH 7, giving rise to an accessible concentration window ranging between 8 µM and 0.48 mM, and the detection and quantification limits were established to be 11.6 µM and 38.6 µM, correspondingly. In order to estimate the applicability of Moxi identification scheme in actual trials, it was practiced in a human baby urine sample with excellent recoveries between 99.8 % and 101.6 % and RSDs of 1.1-3.4%, without noticeable interference.

Potential removal of organic loads from petroleum wastewater and its effect on the corrosion behavior of municipal networks.

A potential and cost-effective treatment method utilizing thermally activated bentonite was evaluated for the treatment of highly loaded real petroleum processing wastewater (COD = 4500 mg/L) in order to reduce its COD and improve the corrosion properties. A save discharging COD limit of the treated effluent (800 mg/L) is achieved by using 6 g/L of calcinated bentonite after reaching the steady state (1 h of shaking) at pH 5. The durability of bentonite is proved. The corrosion behavior of the treated wastewater was investigated for mild steel by using electrochemical and weight loss measurements. The results proved that the corrosion rate of the wastewater was slightly reduced after the treatment process. More improvement of the corrosion resistance was achieved by adding sodium hexa-meta-phosphate (SHMP) corrosion inhibitor to the treated water. Tri-methyl ammonium bromide (CTAB) biocide was also added before discharging into municipal networks.

DNA double-strand breaks caused by new and contemporary endodontic sealers.

AIM: To investigate the cytotoxicity and genotoxicity of a new silicate-based BioRoot RCS® sealer in comparison with contemporary sealers. METHODOLOGY: A periodontal ligament cell line using lentiviral gene transfer of human telomerase reverse transcriptase (hTERT) was used and exposed to subtoxic concentrations of 24-h eluates from two epoxy resin-based (AH Plus Jet® and Acroseal® ), four various methacrylate-based endodontic sealers (EndoREZ® , RealSeal® , RealSeal SE® and Hybrid Root SEAL® ) and three silicate-based sealers (BioRoot RCS® , iRootSP® and MTA Fillapex® ). The XTT-based cell viability assay was used for cytotoxicity screening of materials. The γ-H2AX assay was used for genotoxicity screening. In the γ-H2AX immunofluorescence assay, PDL-hTERT cells were exposed to eluates of the substances for 6 h and DNA double-strand breaks (DSB) were detected microscopically. Induced foci represented DSBs, which can induce ATM-dependent phosphorylation of the histone H2AX. The statistical significance of the differences between the experimental groups was compared using the Student's t-test (P < 0.05). RESULTS: The cytotoxicity of the 24-h eluates could be ranked in the following order: Hybrid Root SEAL® >RealSeal® >Acroseal® >RealSeal SE® ≥ AH Plus Jet® > EndoREZ® >MTA Fillapex® > iRoot SP® >BioRoot RCS® . In negative controls (cells which received medium only) 4.08 ± 0.53 DSB foci (mean ± SEM) whilst in positive controls 10.76 ± 4.05 DSB foci/cell were found. BioRoot RCS® and RealSeal SE® exhibited significant differences in foci formation at 1/3 EC50 compared with their 1/10 EC50 concentration (P < 0.05). Both concentrations (1/10 and 1/3 of EC50) of AH Plus Jet® , Acroseal® , RealSeal® and MTA Fillapex® sealers were not significantly different when compared with the medium control (P < 0.05). CONCLUSIONS: New BioRoot RCS® was not toxic whilst Hybrid Root SEAL® demonstrated more toxicity and DNA double-strand breaks when compared with other resin- and silicate-based root canal sealers.

Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.

We describe a novel spike pseudoparticle neutralisation assay (ppNT) for seroepidemiological studies on Middle East respiratory syndrome coronavirus (MERSCoV) and apply this assay together with conventional microneutralisation (MN) tests to investigate 1,343 human and 625 animal sera. The sera were collected in Egypt as a region adjacent to areas where MERS has been described, and in Hong Kong, China as a control region. Sera from dromedary camels had a high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and 10,240 and higher in ppNT assays. No other investigated species had any antibody reactivity to MERS-CoV. While seropositivity does not exclude the possibility of infection with a closely related virus, our data highlight the need to attempt detection of MERSCoV or related coronaviruses in dromedary camels. The data show excellent correlation between the conventional MN assay and the novel ppNT assay. The newly developed ppNT assay does not require Biosafety Level 3 containment and is thus a relatively high-throughput assay, well suited for large-scale seroepidemiology studies which are needed to better understand the ecology and epidemiology of MERS-CoV.

New Au/chitosan nanocomposite modified carbon paste sensor for voltammetric detection of nicotine.

A profoundly touchy voltammetric sensor for detection of nicotine (NIC) in urine and tobacco specimens has been developed in light of the boosted electrochemical response of NIC at gold and chitosan nanocomposite modified carbon paste electrode (ACMCPE). Material characterization techniques Scanning Electron Microscope and Energy Dispersive X-ray (SEM & EDX) were utilized to describe the ACMCPE surface material. The impedance spectroscopy technique (EIS), cyclic voltammetry (CV), chronoamperometry (CA), and differential pulse voltammetry (DPV) were employed to explore the electrochemical sensing of NIC at ACMCPE. The created sensor exhibits an exceptional electrochemical sensitivity to NIC in a universal Britton-Robinson (B-R) buffer solution with a pH range of 2.0 to 8.0. The sensor shows a linear response over NIC concentration ranges of 4.0-320.0 µM, with the detection limit (LOD) of 7.6 µM. The prepared sensor has been shown to be exceptionally viable in detecting NIC with amazing selectivity and reproducibility. We suggest it as a trustworthy and useful electrochemical sensor for NIC location.

Correction to: 'Current strategies with implementation of 3D cell culture: The challenge of quantification' (2022) by Temple et al.

[This corrects the article DOI: 10.1098/rsfs.2022.0019.][This corrects the article DOI: 10.1098/rsfs.2022.0019.].

Expression status of circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 in patients with colorectal cancer.

Colorectal cancer (CRC) poses a significant burden on both the healthcare systems as well as individuals. The high mortality rate of CRC may be attributed to its metastatic potential, heterogeneity, and delayed diagnosis. CircRNAs are an essential class of regulatory RNAs that play significant roles in cancers. This study aimed to detect the expression status of circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 in patients with CRC. This study included 50 CRC patients, 30 individuals with colorectal diseases (non-cancer), and 20 healthy volunteers. By using real-time PCR, the relative expression of circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 was determined in the collected blood samples. In addition, ECLIA was used to quantify carcinoembryonic antigen (CEA) level. All circRNAs expression and CEA levels were significantly up-regulated in cancer patients (CRC, colon, rectum) as compared to healthy controls, except circ-SMARCA5. Moreover, there was a significant up-regulation of circRNAs in most non-cancer patients (UC, polyp, piles). Insignificant upregulation was observed in circRNAs and CEA when comparing cancer with non-cancer patients. No correlations were found between the studied parameters and most clinicopathological characteristics of cancer and non-cancer patients. Circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 were differentially expressed in patients with CRC as well as in non-cancer patients. Circ-SMARCA5 and circ-NOL10 may act as tumor suppressors, while circ-LDLRAD3 and circ-RHOT1 may be oncogenes. Circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 could be promising markers for the early detection of CRC.

Pediatric liver transplantation using reduced and hyper-reduced left lateral segment grafts: a 10-year single-center experience.

Few studies have examined the long-term outcomes and prognostic factors associated with pediatric living living-donor liver transplantation (LDLT) using reduced and hyper-reduced left lateral segment grafts. We conducted a retrospective, single-center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft-to-recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

Induction of DNA double-strand breaks by monochlorophenol isomers and ChKM in human gingival fibroblasts.

Phenol has been traditionally used in dental treatment as a sedative for the pulp or as disinfectant for carious cavity and root canal. However, phenol is regarded as a mutagenic and carcinogenic agent and its use in dental practice is now therefore restricted. Monochlorophenols are derivatives of phenol, which are still used clinically as root canal disinfectants, they are even more active antiseptics/disinfectants than phenol, and the so-called Walkhoff (ChKM) solution makes use of monochlorophenol for root canal disinfection. Ingredients in the ChKM solution are the monochlorophenol compound 4-chlorophenol (4-CP), camphor, and menthol. In literature, the use of the ChKM solution is controversial because of a possible DNA toxicity of the ingredient 4-CP. However, it is unknown whether ChKM can really induce DNA damage in human oral cells. In this study, the induction of DNA double-strand breaks (DSBs) by ChKM and monochlorophenol compounds (2-chlorophenol, 2-CP; 3-chlorophenol, 3-CP; and 4-chlorophenol, 4-CP) was tested in human gingival fibroblasts (HGFs). DNA DSBs (foci) induced in HGFs unexposed and exposed to monochlorophenols or ChKM solution were investigated using the γ-H2AX DNA focus assay, which is a direct marker for DSBs. DSBs result in the ATM-dependent phosphorylation of the histone H2AX. When cells were exposed to medium or medium + DMSO (1 %) (negative controls), an average of 3 foci per cell were found. In positive control cells (H2O2 + medium, or H2O2 + medium + DMSO (1 %), an average of 35 foci each were found. About 20 DSB foci per cell were found, when HGFs were exposed to 2-CP (4 mM), 3-CP (2.3 mM), 4-CP (2.1 mM), or ChKM (corresponding to 1.5 mM 4-CP). Our results show increasing DNA toxicities in the order of 2-CP < 3-CP < 4-CP < ChKM solution. An additive DNA toxicity was found for 4-CP in combination with camphor in the ChKM solution, compared to the 4-CP alone. No significant differences regarding multi-foci cells (cells that contain more than 40 foci) were found when HGFs were exposed to the EC50 concentrations (given in parenthesis) of ChKM (1.5 mM), 4-CP (2.1 mM), or 2-CP (4 mM). Significantly fewer multi-foci cells were found when HGFs were exposed to the EC50 concentration (given in parenthesis) of 3-CP (2.3 mM), compared to the EC50 concentrations of ChKM, 4-CP, or 2-CP. Monochlorophenol compounds and/or ChKM solution can induce DSBs in primary human oral (cavity) cells, which underscores their genotoxic capacity.

Family structure and substance use in 6,178 American Indian youth: a cross-sectional study.

OBJECTIVE: Adolescents from single-parent families are at significantly higher risk of substance use compared to those from mother-father families. More than half of American Indian (AI) children live in single-parent families, the second highest percentage among all groups. Given the paucity of research pertaining to the role of family structure and substance use in the AI population, we sought to examine this relationship. MATERIALS AND METHODS: Data from this study were obtained from the Substance Use Among American Indian Youth: Epidemiology and Etiology, [US], 2015-2020 study. Response variables of interest included age at first substance use, number of substances used, ever-use of substance, and substance use type (i.e., alcohol, cigarette, marijuana, etc.). RESULTS: Living in a father-only or mother-only setting showed a similar pattern of drug use. There was a significant increase in the risk of cigarette, alcohol and marijuana use. For cigarettes, the odds ratio was (OR = 2.60, 95% CI 1.80-3.75) in father-only setting compared to (OR = 1.42, 95% CI 1.13-1.78) for mother only setting. Alcohol use showed (OR = 1.72, 95% CI 1.19-2.50 and OR = 1.40, 95% CI 1.12-1.74) for father-only and mother-only respectively and marijuana use showed (OR = 1.59, 95% CI 1.10-2.30 and OR = 1.54, 95% CI -1.24-1.92) for father-only and mother-only respectively. CONCLUSIONS: Disturbed family structure is associated with increased risk of substance use among AI youth. This indicates the importance and need for policy and community level interventions to reduce youth substance exposure.

Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism.

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.

Topo2α protein expression predicts response to anthracycline combination neo-adjuvant chemotherapy in locally advanced primary breast cancer.

BACKGROUND: this study aimed to identify predictors of response to anthracycline-based chemotherapy (5-fluoro-uracil, epirubicin, cyclophosphamide (FEC)) in locally advanced primary breast cancer (LAPC). METHODS: a total of 91 LAPC patients were treated with six cycles of FEC before surgery. Protein expression of nine biomarkers (topoisomerase2α (Topo2α), ER, PR, HER2, Ki67, p53, EGFR, CK5/6 and CK14) was assessed in pre-chemotherapy core biopsies using immunohistochemistry (IHC) and results correlated with clinical and pathological response. RESULTS: clinical (cCR) and pathological (pCR) complete response were seen in 34.1% (n=31) and 20% (n=18), respectively. Pathological complete response was concordant with cCR in 14/31 cases; in four cases of cPR with palpable residual breast tumours, histology showed fibrous tissue only (pCR). On univariate analysis, pre-chemotherapy high expression of Topo2α protein (P=0.031), and negativity for ER and EGFR (P=0.001 and P=0.005, respectively) correlated with pCR. Positivity for p53 also showed significance (P=0.015), whereas basal phenotype, HER2, and all the clinicopathological variables of LAPC included in this study did not show significant correlation with response. On multivariate analysis, Topo2α expression had the strongest correlation with pCR (P=0.021) followed by EGFR (P=0.044). CONCLUSION: the study suggests that pre-chemotherapy Topo2α protein expression measured by IHC strongly correlates with pathological CR to neo-adjuvant anthracyclines in this group of LAPC studied.

Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers.

BACKGROUND: Altered DNA repair may be associated with aggressive tumour biology and impact upon response to chemotherapy and radiotherapy. We investigated whether expression of human AP endonuclease (APE1), a key multifunctional protein involved in DNA BER, would impact on clinicopathological outcomes in ovarian, gastro-oesophageal, and pancreatico-biliary cancer. METHODS: Formalin-fixed human ovarian, gastro-oesophageal, and pancreatico-biliary cancers were constructed into TMAs. Expression of APE1 was analysed by IHC and correlated to clinicopathological variables. RESULTS: In ovarian cancer, nuclear APE1 expression was seen in 71.9% (97 out of 135) of tumours and correlated with tumour type (P=0.006), optimal debulking (P=0.009), and overall survival (P=0.05). In gastro-oesophageal cancers previously exposed to neoadjuvant chemotherapy, 34.8% (16 out of 46) of tumours were positive in the nucleus and this correlated with shorter overall survival (P=0.005), whereas cytoplasmic localisation correlated with tumour dedifferentiation (P=0.034). In pancreatico-biliary cancer, nuclear staining was seen in 44% (32 out of 72) of tumours. Absence of cytoplasmic staining was associated with perineural invasion (P=0.007), vascular invasion (P=0.05), and poorly differentiated tumours (P=0.068). A trend was noticed with advanced stage (P=0.077). CONCLUSIONS: Positive clinicopathological correlations of APE1 expression suggest that APE1 is a potential drug target in ovarian, gastro-oesophageal, and pancreatico-biliary cancers.

Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases--the UK experience.

BACKGROUND: The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab. METHODS: Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented. RESULTS: Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6-24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15-27%) and median TTP was 22 weeks (95% CI: 17-27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P=0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9-39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15-28). CONCLUSIONS: Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease.

Isolation, Identification and Antimicrobial Activity of Unprecedented Lactic Acid Bacterial Isolates from Honeybees.

BACKGROUND AND OBJECTIVE: Lactic acid bacteria are generally recognized as safe that could be beneficial for several uses in food industry to get their health benefits. The present study was focused on the isolation and identification of some new lactic acid bacteria that might be naturally occurred in the honeybees stomach and tried to explore their benefits. MATERIALS AND METHODS: Twenty five isolates of lactic acid bacteria were isolated from the stomach of three different types of Egyptian bees (Apis mellifera lamarckii ), Carniolan bees (A.m. carnica) and hybrid Carniolan bees. Identification of isolates was carried out based on phenotypical tests and carbohydrate assimilation using API50 CHL and 16S rDNA sequencing. RESULTS: In the present study, the results emphasized Lactobacillus plantarum to be the predominant species (62.5%), other strains were identified as Pediococcus pentosaceus (12.5%), Lactobacillus pentosus (12.5%) and Lactobacillus sakei (12.5%). Eight of 25 isolates showed a potential antibacterial activity especially against Salmonella senftenberg strain. The novel isolates (HBMSS1, HBMSS3, HBMSS4, HBMSS5, HBMSS6 and HBMSS8) showed a significant antimicrobial activity against C. botulinum, E. coli, S. Senftenberg and S. epidermidis as food borne pathogens and P. larvae and M. plutonius as honeybee pathogens. CONCLUSION: These promising findings might be beneficial for discovering novel preservatives in food industry and substitution of antibiotic drugs used in the treatment of honeybees' infection.

Human leukocyte antigen class I expression is an independent prognostic factor in advanced ovarian cancer resistant to first-line platinum chemotherapy.

BACKGROUND: Loss of HLA class I is important in ovarian cancer prognosis but its role as a prognostic indicator in relation to therapy remains unproven. We studied the prognostic potential of this antigen and its significance in relation to platinum therapy. METHODS: A total of 157 primary ovarian cancers were assessed for HLA class I immunohistochemically and linked to a comprehensive database of clinicopathological variables, treatment details, and platinum sensitivity. RESULTS: Tumours expressing high levels of HLA class I had significantly improved survival (P=0.044). There was a 19-month difference in the median overall survival between tumours with high and low antigen expression. HLA class I antigen expression, stage, and platinum sensitivity were independently predictive of prognosis on multivariate analysis. HLA class I antigen was shown to be expressed at higher levels in patients with good overall survival in platinum-resistant patients (P=0.042). HLA class I significantly correlated with overall survival on multivariate analyses (P=0.034). CONCLUSION: Low-level HLA class I expression is an independent prognostic indicator of poor clinical outcome in ovarian cancer. The survival advantage of patients with platinum-resistant tumours expressing high levels of HLA class I suggests that immunotherapy may be of use in these ovarian cancers resistant to standard chemotherapy.

Nutritional, Physicochemical, and Sensorial Evaluation of Flat Bread Supplemented with Quinoa Flour.

The purpose of the present research was to develop novel flat bread supplemented with quinoa flour to raise its nutritional quality and functional properties. Furthermore, evaluation of the quality of developed bread was realized with blends at 5, 10, 15, 20, 25, and 30% of quinoa flour. Chemical composition of supplemented flat bread was determined. Several properties on dough (water absorption, dough development time, stability time, elasticity, and extensibility) and their corresponding characteristics (loaf specific volume, baking loss, roundness, height, baking time, hardness, cohesiveness, springiness, resilience, gumminess, and chewiness) were then evaluated. The protein content in bread-based quinoa blends was significantly increased gradually with increasing the percentage of quinoa flour from 12.12±0.63% in control to 15.85±0.065% in 30% quinoa flour. Also, the amino acids content was increased with increasing the percentage of quinoa flour. Mineral contents in 30% quinoa flour blend such as sodium, potassium, magnesium, calcium, iron, copper, manganese, and zinc were higher than other ratios and control bread (100% wheat flour). Rheological properties of supplemented bread such as specific volume, appearance, crust and crumb texture, aroma-odor, and colour were evaluated and found to be excellent. Physicosensory characteristics of the bread fortified with quinoa flour were evaluated and the most of panelists accepted and preferred the bread supplemented with quinoa flour more than control. The obtained unique nutritional, physicochemical, and organoleptic characteristics of quinoa flour-based flat bread open a new promising prospect for utilization of quinoa flour in an industrial scale for treatment and/or prevention of malnutrition in developing counties.