Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.

BACKGROUND: Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, which are CLPP activators, which inhibit OXPHOS indirectly and have demonstrated safety in patients. METHODS: We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201 and ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic efficacy in vivo in UM liver metastasis models. RESULTS: CLPP expression was detected in primary and mUM patient samples. ONC201 and 212 decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis in human UM cell lines in vitro. ONC212 inhibited OXPHOS, increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. CONCLUSIONS: Imipridones are a promising strategy for further testing and development in mUM.

Factors affecting graft healing in laryngotracheal reconstruction: a retrospective single-center experience.

PURPOSE: To examine the factors that affect graft healing after laryngotracheal reconstruction (LTR). METHODS: We conducted a retrospective chart review at King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between January-2008 and October-2023. We included all patients who underwent LTR and required anterior and/or posterior graft placement, while those who underwent procedures without graft placement and those with incomplete information were excluded. RESULTS: Forty-nine patients were analyzed. Most patients were pediatric (65.3%), male (65.3%), had no coexisting comorbidities (55.1%), and harbored grade 3-4 stenosis (59.2%). Thirty patients (61.2%) underwent open surgery. Various graft complications occurred including infection (n = 1, 2%), dehiscence (n = 3, 6.1%), scar (n = 6, 12.2%), and granulation (n = 29, 59.2%). Only 15 patients (30.65%) achieved the composite status of "healthy" graft. Among 43 patients who had postoperative cultures, positive results for Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were observed in 10 and four patients, respectively. Open surgery and double-stage procedure were significantly associated with higher rates of granulation tissue formation. Pediatric-age group had significantly higher rate of complete epithelization compared to adult-age group. A significantly greater proportion of patients who had unhealthy grafts had open surgery. The rate of double-stage LTR was significantly higher in unhealthy grafts compared to healthy grafts. Prolonged stent duration was linked to various graft-related complications. Multivariate logistic regression analyses showed no statistically significant correlations between various factors and postoperative graft-related complications. CONCLUSION: Open surgery, double-stage procedure, pediatric age group, and stent duration were not significant risk factors associated with postoperative graft-related complications during LTR in multivariate analysis.

Threat directionality modulates defensive reactions in humans: cardiac and electrodermal responses.

Features of threatening cues and the associated context influence the perceived imminence of threat and the defensive responses evoked. To provide additional knowledge about how the directionality of a threat (i.e. directed-towards or away from the viewer) might impact defensive responses in humans, participants were shown pictures of a man carrying a gun (threat) or nonlethal object (neutral) directed-away from or towards the participant. Cardiac and electrodermal responses were collected. Compared to neutral images, threatening images depicting a gun directed-towards the participant induced sustained bradycardia and an increased electrodermal response, interpreted as immobility under attack. This defensive immobility reaction is evoked by high perceived threat and inescapable situations and indicates intense action preparation. Pictures of guns directed-away from the participant induced shorter bradycardia and no significant modulation of the electrodermal response compared to neutral pictures, which might be consistent with the perception of a less threatening situation. The results show that the directionality of threat stimuli is a key factor that prompts different patterns of defensive responses.

Thematic and Demographic Analysis of Crowdsourcing Practices for Plastic Surgery.

BACKGROUND: In this study, we investigate the characterization of medical crowdsourcing on GoFundMe for plastic surgery procedures, with overall funds raised being the primary end point. HYPOTHESIS: Certain demographic factors such as sex and race mentioned in campaign narratives are associated with the effectiveness of medical crowdfunding campaigns. METHODS: Search terms were used to aggregate fundraising campaigns for plastic surgery medical procedures on GoFundMe. These studies were then stratified by demographics based on campaign text or author consensus, and were further subdivided into categories based on procedure type. RESULTS: Men were found to have higher median shares than women-raising an average of $609 more than female counterparts ( P < 0.05). Fundraising for themes such as lack of insurance, travel costs, lifesaving treatment, and end-of-life expenses were more successful than the theme of psychosocial effects of disease or social impairment. In addition, those that included a smiling picture of the recipient and those created by a friend/relative raised more funds. Although no significant difference was found in fundraising between demographics based on race, a majority (72.8%) of campaigners were White. Across ~2000 plastic surgery campaigns, a total of $10,186,687 were raised from these data. CONCLUSIONS: We identified both modifiable and nonmodifiable factors that influence success. These successful campaigns can serve as a learning opportunity for many who have been marginalized by the medical and pharmaceutical industry, and they demonstrate a promising area for demographic studies.

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats.

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

Ascorbic Acid Ameliorates Cardiac and Hepatic Toxicity Induced by Azithromycin-Etoricoxib Drug Interaction.

The complexity of prescribing safe and effective drug therapy is still challenging. Due to the increased number of medications taken by patients, the potential for drug-drug interactions has clinically important consequences. This study focuses on the potential drug-drug interaction between azithromycin and etoricoxib and the possibility of counteracting this adverse reaction by giving ascorbic acid intraperitoneally to male albino rats. Sixty adult male albino rats weighing 150-180 g were used. The rats were allocated into six equal groups. One group was a control, and the others were given azithromycin, etoricoxib, either alone or combination, with one group treated with ascorbic acid and the last group treated with the drug combination and ascorbic acid. Blood samples were collected for measuring AST, ALT, LDH, CK-MB, and troponin alongside antioxidant enzymes and histopathological examination for both liver and heart tissue. The results showed both hepatic and cardiac damage in azithromycin and etoricoxib groups represented by increasing levels of heaptoc enzymes (ALT, AST, LDH, CK-MB, and troponin) with declining antioxidant enzymes and elevation of malondialdehyde and the appearance of hepatic and cardiac toxicities. Upon administration, ascorbic acid ameliorated all the mentioned biochemical parameters. In conclusion, ascorbic acid has great antioxidant capacities and hepatic and cardiac ameliorative effects and can alleviate drug interaction toxicity.

Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells.

Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1ß, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be -370.426 Kcal/mol, while the supramolecular ternary complex alone was -38.732 Kcal/mol, with a potential energy difference of -331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.

In-silico analysis of interacting pathways through KIM-1 protein interaction in diabetic nephropathy.

BACKGROUND: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1. METHODS: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated by this protein. These genes were then further considered in pathway analysis to discover the dysregulated pathways in diabetic nephropathy. The long list of differentially expressed genes is meaningless without pathway analysis. RESULTS: Critical pathways that are dysregulated in diabetic nephropathy patients have been identified. These include Immune System (Total = 237, P < 0.05), Innate Immune System (Total = 140, P < 0.05), Cytokine Signaling Immune system (Total = 116, P < 0.05), Adaptive Immune System (Total = 85) and Neutrophil degranulation (Total = 78). CONCLUSION: The top 5 genes that are interacting directly with HIVCR1 include CASP3, CCL2, SPP1, B2M, and TIMP1 with degrees 161, 144, 108, 107, and 105 respectively for Immune system pathways (Innate Immune System, Cytokine Signaling Immune system, Adaptive Immune System and Neutrophil degranulation).

Spatial analysis of microclimatic variables in compost-bedded pack barn with evaporative tunnel cooling.

In this study, we aimed to assess the spatial variability of microclimate inside a closed compost-bedded pack barn (CBP) with a negative ventilation system during summer and winter. The research was carried out in a CBP located in the Zona da Mata region, Minas Gerais, Brazil. For each of the stations analyzed, the following environmental mean variables observed inside a CBP were measured: air dry-bulb temperature (tdb), air relative humidity (RH), and windspeed, Temperature-Humidity index, and specific enthalpy. The kriging maps showed that the most critical housing conditions in the thermal environment were found, mainly, from the central part of the CBP, close to the exhaust fans. The analyses also pointed out that the system presented temperature gradients along the length, up to 3°C. During the summer afternoon, the entire region of the CBP was in a discomfort situation (tdb>26°C; RH>75%). During the winter, the measured environmental data remained within the comfort zone throughout the facility. However, probably due to the lack of thermal insulation of the material used to close the sides of the CBP, it did not allow spatial thermal uniformity for both seasons. It was also inefficient to keep the animals within the comfort zone for lactating cattle during the critical summer period.

Impacts of sex steroids and aromatase inhibitor on performances, carcass characteristics and gonadal histology of broiler chickens slaughtered at different ages.

This experiment was established to evaluate the influence of synthetic steroid hormone and aromatase inhibitor on performance, carcass characteristics, hormonal profile and gonadal structure of broiler chickens slaughtered at two different ages. A total of 360 Cobb Avian48 chicks were sexed and distributed randomly into three groups: Tam10 group; birds received Tamoxifen10mg (Tamfen 10 mg@ ) orally at a level of 10 mg/kg body weight daily from the 3rd till the 9th day of age; BOL group: birds injected intramuscularly with Boldenone undecylenate (BOLD-GAN@ 0.1 mg/kg) at the 5th and the 9th day of age; and Control group. BOL injection or Tam supplementation improved performance traits compared with the control group. Although Tam positive effect appeared early before the 5th week of age, the BOL effect was delayed to the 6th week. BOL injection improved carcass characteristics of both sexes at both 5 and 6 weeks slaughtering ages. Regardless of treatment effect, the mortality% was higher in the late weeks of age than in the early weeks. Moreover, BOL treatment increased comb% compared with control and Tam treatments. Generally, males had significantly higher testosterone levels and lower oestrogen levels than females. Males treated with Boldenone had the highest testosterone level, although testosterone levels did not differ considerably among females of the various groups. BOL treatment females had the lowest oestrogen level. Both Tam10 and Boldenone had adverse effects on testicular and ovarian histology, affecting the typical structures. Finally, we concluded that the anabolic effect of Tam10 may be achieved in griller broilers production without changing the sex hormones assay. Although Boldenone achieved an anabolic effect without changing blood sex hormone levels, this effect is induced early with females and delayed with males, which prolongs the marketing period. The goal is to shorten this period. Therefore, this material can only be used with the possibility of separating females from males to be used with females only.

Neuroinflammation: A Potential Risk for Dementia.

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain's immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell's microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death.

Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies.

Antibacterial Activity of Dental Composite with Ciprofloxacin Loaded Silver Nanoparticles.

Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins.

Aerophagia Study in Indonesia: Prevalence and Association With Family-related Stress.

BACKGROUND: Aerophagia is a functional gastrointestinal disorder characterized by repeated air swallowing leading to chronic abdominal distension. Symptoms can be long lasting, lead to frustration, and distress. This study describes prevalence, related factors, and symptomatology of aerophagia, together with its relationship with emotional stress. MATERIALS AND METHODS: Cross-sectional study. Adolescents aged 10 to 17 years from selected state schools by convenient sampling from Jakarta, Indonesia, were recruited. Rome III self-administered questionnaire was used to compile data on gastrointestinal symptoms. Data on sociodemographic characteristics, intestinal and extraintestinal symptoms, and stressful life events were collected using a separate questionnaire. RESULTS: A total of 1796 questionnaires were included in the analysis [males 732 (40.8%), mean age 13.58 (SD 0.992) years]. There were 81 (4.5%) subjects diagnosed with aerophagia. When the criterion of belching was removed from the diagnosis of aerophagia, the prevalence drops to only 2 (0.1%). subjects. Bivariate analysis showed that sociodemographic factors have no correlation with aerophagia. In subjects with aerophagia, among the intestinal-related and extraintestinal symptoms, only loss of appetite was significantly more common in the aerophagia population (33.3%) when compared with controls (22.8%). Death of a close family member [adjusted odds ratio (OR), 2.78; 95% confidence interval (CI), 1.46-5.31; P=0.002], divorce or separation of parents (adjusted OR, 2.54; 95% CI, 1.38-4.66; P=0.003), and divorce followed by separate individual remarriage of parents (adjusted OR, 2.01; 95% CI, 1.01-3.98; P=0.046) were found to be significantly associated with aerophagia by multivariate analysis. CONCLUSIONS: The prevalence of aerophagia was found in 4.5% of Indonesian school-aged children according to Rome III criteria, but the prevalence was found only 0.1% if the belching is removed from the criteria. Besides the main symptoms, only loss of appetite was significantly more common in aerophagia among intestinal-related and extraintestinal symptoms. Family-related stress showed a significant correlation with aerophagia.

Particle composition and morphology over urban environment (New Delhi): Plausible effects on wheat leaves.

Particulate matter (PM) deposition on leaves adversely affects physical, chemical and biological nature of agricultural crops resulting in their loss of productivity and yield. Wheat being a staple food in major parts of Northern India and around the World, has been selected for research purpose by designing a study to explore the probable effects of PM deposition on wheat leaves and wheat crops to ensure the food security. PM5 (Particulate matter with aerodynamic diameter <5 µm) and Dry Deposited Particulate Matter (DDPM) on wheat leaves (Leaf_DDPM) were collected from the wheat crop field in Indian Agriculture Research Institute (IARI), New Delhi for growing and harvesting season of wheat crops (i.e. December 2014 to April 2015). The EDS (Energy Dispersive Spectroscopy) analysis was used for this study and the individual particle analysis revealed the presence of both acidic and alkaline components like C, Al, Si, Fe, Ca, K, S and Mg. The offline characterization tool i.e. SEM (Scanning Electron Microscope) was utilized for obtaining the micrographs which clearly showed the presence of some angular, sharp-edged and spherical particles consisting of both smooth and rough texture. Apart from that, prevalence of slightly non-spherical particles with aspect ratio of range (>1.20-1.40) and CIR (>0.70-0.80) for both PM5 and leaf_DDPM were observed. The size distribution of individual particles for both PM5(#194 particles) and Leaf_DDPM(#657 particles) revealed that Surface Equivalent Radius (SER) and Volume Equivalent Radius (VER) of particles observed to be 0.40-0.80 µm while surface area to be 0-1 µm2. These particles may easily block stomatal openings (with typical diameter range: 42-51 µm) of wheat leaves and damage internal leaf tissues while particle VER determines the interaction of incoming solar radiation with leaf surfaces. Average PM5 concentrations ± Standard deviations (µg/m3) were reported to be 231.05 ± 113.03. The XRF (X-Ray Fluorescence) spectrometer analysis of bulk PM5 revealed the concentrations of non-carbonaceous elements (µg/m3) as N (67.34 ± 16.09), Si (27.44 ± 11.01), Al (7.79 ± 3.37), S (3.88 ± 2.24), Na (2.29 ± 0.94), Mg (1.65 ± 0.62), K (0.51 ± 0.26), Ca (0.60 ± 0.26), Fe (0.54 ± 0.26), Cr (1.10 ± 0.70), Zn (0.05 ± 0.03), P (0.10 ± 0.03), Cu (0.07 ± 0.06). The dominant elemental oxides were calculated as SiO2, Al2O3, SO42-, Na2O, MgO, K2O, CaO, Fe2O3, Cr2O3, ZnO, P2O5, Cu2O with variable concentrations. In high humid conditions, with relative humidity (~85%) during the vegetative and flowering growth stages of wheat crops, presence of C and S rich acidic and hygroscopic particles may cause the corrosion of wheat leaves that ultimately affect the wheat crops.

The LLAMA Brazilian-Argentinian radiotelescope project: progress in Brazil and BRICS collaboration.

We present briefly the LLAMA sub-mm radiotelescope, a joint project of Argentina and Brazil, being mounted in the Andes, Argentina, at 4800 m altitude. Here we focus on the activities that are going on mostly under the responsibility of Brazil, like the high frequency receivers, parts of the back-end and electronics, the optical system of the telescope to bring the radiation to the receivers, the equipment needed for the integration and verification phase (optical telescope and holography) and the computation system.The main scientific applications that are planned are dscribed. We also report on a joint program with BRICS countries approved in 2019, which will involve the use of LLAMA for testing high-frequency receivers.

Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice.

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group; while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p < 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.

Three new species of Neoechinorhynchus (Acanthocephala: Neoechinorhynchidae) from fresh-water fish collected from Tigris River, Iraq.

Three new species of Neoechinorhynchus are described from freshwater fish of Tigris River, at Salah Al-Din province, mid Iraq, namely Neoechinorhynchus tigrisensis n. sp. from Shilik Leuciscus vorax (Heckel) and Brond-snout Chondrostoma regium (Heckel), N. planilizai n. sp. from Abu mullet Planiliza abu (Heckel) and Tigris catfish Silurus triostegus (Heckel) and N. barbi n. sp. from Mesopotamian barb Capoeta damascina (Valenciennes). The first two new species shared the para-receptacle structure (PRS) with seven nominal valid species of the genus Neoechinorhynchus but they differed in other taxonomic traits, while the third new species shared the vaginal vestibular muscles (para vaginal patch) at the end of female trunk with N. spiramuscularis Amin, Heckmann & Ha, 2014 and N. zabensis Amin, Abdullah & Mhaisen, 2003 but differed for further morphological features. Proboscis hooks of middle and posterior circles in N. barbi n. sp. are remarkably bigger than in the other two new species (N. tigrisensis and N. planilizai) while the hooks in first circle is almost similar in the three species. Furthermore, N. tigrisensis n. sp. and N. planilizai n. sp. differ from some marine species by having smallest hooks size at anterior circle, with different shape and size of hooks. The three new species reported in the present study are compared with other eight species of Neoechinorhynchus reported so far from fish in Iraq. This work contributes to increase the knowledge on the biodiversity of fish parasites all over the world, especially for acanthocephalans.

Monitoring breastfeeding indicators in high-income countries: Levels, trends and challenges.

Monitoring indicators of breastfeeding practices is important to protect and evaluate the progress of breastfeeding promotion efforts. However, high-income countries lack standardized methodology to monitor their indicators. We aimed to update and summarize nationally representative annual estimates of breastfeeding indicators in high-income countries and to describe methodological issues pertaining to the data sources used. A review was conducted through population-based surveys with nationally representative samples or health reports from nationally representative administrative data of electronic surveys or medical records. Methodological aspects and rates of all breastfeeding indicators available were summarized by country. The median and annual growth of breastfeeding in percentage points within countries with time-series data were estimated. Data from 51 out of 82 high-income countries were identified. The data were obtained through surveys (n = 32) or administrative data (n = 19). Seventy-one percent of countries have updated their indicators since 2015. Ever breastfed was the indicator most frequently reported (n = 46), with a median of 91%. By 6 months of age, the median equals 18% for exclusive and 45% for any breastfeeding. At 12 months, the median of continued breastfeeding decreased to 29%. The annual growth rate for ever breastfed, exclusive and any breastfeeding at 6 months and continued at 12 months varied from 1.5 to -2.0, 3.5 to -3.1, 5.0 to -1.0 and 5.0 to -1.9, respectively, with positive changes for most countries. Stronger interventions are needed to promote breastfeeding in high-income countries as a whole, and investments are required to monitor trends with standardized methodologies.

SUL-109 Protects Hematopoietic Stem Cells from Apoptosis Induced by Short-Term Hypothermic Preservation and Maintains Their Engraftment Potential.

The newly developed 6-hydroxychromanol derivate SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and would be particularly useful for short-term storage, such as during conditioning of patients or transport of HSC transplants. Here we cultured human CD34+ umbilical cord blood (UCB) cells and lineage-depleted (Lin-) Balb/c bone marrow (BM) cells for up to 7 days in serum-free HSC expansion medium with hematopoietic growth factors. SUL-109-containing cultures were stored at 4°C for 3 to 14 days. The UCB cells were tested for viability, cell cycle, and reactive oxygen species (ROS). DMSO-cryopreserved Lin- BM cells or Lin- BM cells maintained for 14 days at 4°C were transplanted into RAG2-/- Balb/c mice and engraftment was followed for 6 months. The addition of SUL-109 during the hypothermic storage of expanded CD34+ UCB cells provided a significant improvement in cell survival of the immature CD34+/CD38- fraction after 7 days of hypothermic storage through scavenging of hypothermia-induced ROS and was able to preserve the multilineage capacity of human CD34+ UCB cells for up to 14 days of cold storage. In addition, SUL-109 protected murine BM Lin- cells from 14 days of hypothermic preservation and maintained their engraftment potential after transplantation in immune-deficient RAG2-/- mice. Our data indicate that SUL-109 is a promising novel chemical for use as a protective agent during cold storage of human and murine HSCs to prevent hypothermia-induced apoptosis and promote cell viability.