Observation of magnet-induced star-like radiation of a plasma created from cancer cells in a laser trap.

We present a new phenomenon resulting from the interaction of magnetic beads with cancer cells in a laser trap formed on a slide containing a depression 16.5 mm in diameter and 0.78 mm of maximum depth. This phenomenon includes the apparent formation and expansion of a dark bubble that attracts and incinerates surrounding matter when it explodes, which leads to a plasma emitting intense radiation that has the appearance of a star on a microscopic scale. We have observed the star-like phenomenon for more than 4 years, and the intensity depends on the laser's power. Measuring the laser power of the dark bubble shows the entrapment of electromagnetic energy as it expands.

Quantitative and qualitative control of antineoplastic preparations: Gravimetry versus HPLC.

This article compares gravimetry vs. high-performance liquid chromatography (HPLC) as quality control (QC) methods for paclitaxel, docetaxel and oxaliplatin preparations. We aimed at assessing the preparation method reliability in our hospital, evaluating compounding accuracy and estimating the influence of personnel training and standardized homogenization on compounding accuracy. Agreement, correlation, concordance, accuracy and precision between methods were evaluated for each drug. Conforming preparation percentages (CPs) at different tolerance limits (TLs) and compounding accuracy were calculated for each method and drug. Compounding accuracy was compared before and after personnel training and standardized homogenization implantation. SPSS v 20.0 and Ene v 2.0 were used. A total of 222 samples (58 docetaxel, 95 paclitaxel and 69 oxaliplatin) were analyzed. Gravimetry and HPLC are comparable methods. Overall CP was 81% for gravimetry at 10% TL and 85% for HPLC at 15% TL. Compounding accuracy is shown to be good for all methods and drugs. Homogenization optimization and personnel training make measurements more accurate for docetaxel and paclitaxel HPLC, but seem to worsen accuracy for docetaxel gravimetry. Gravimetry has shown to be a good alternative to HPLC for routine QC. Coupling with electronic methods should be considered in the future.

Prescription drug diversion among people living with HIV: a systematic scoping review.

OBJECTIVES: Globally, people living with HIV (PLWH) are at greater risk for various infections and chronic pain, therefore, vulnerable to prescription drug diversion which might negatively impact HIV care. The study purpose is to gather evidence on prescription drug diversion among PLWH. STUDY DESIGN: This is a systematic scoping review. METHODS: Arksey and O'Malley's framework and recommendation by Levac et al. were used to guide this study. Literature was searched in PubMed, Google Scholar, EBSCOhost (Academic Search Complete, MEDLINE and Newspaper Source) and Open Access Theses and Dissertations. Studies reporting evidence of prescription drug diversion from January 1996 to July 2017 were included. Thematic content analysis was performed to summarize data on the prevalence. RESULTS: Twenty-nine studies were eligible for data synthesis. Twenty-six studies were conducted in the United States of America (USA), one study in France and two multicountry studies; one study in Kenya and Uganda and the other study in Botswana, Kenya, Malawi, South Africa; Zimbabwe, India, Thailand, Brazil and the USA. Research evidence shows high prevalence of prescription drug diversion for analgesics and antiretroviral drugs; meanwhile, stimulants and erectile dysfunction drugs were the least diverted drugs among PLWH. There is a research gap in low- to middle-income countries (LMICs) investigating prescription drug diversion among PLWH. CONCLUSION: Our findings reveal that diversion of various prescription drug classes among PWLH exists. There is lack of research in LMICs. We recommend research in LMICs where there is high HIV prevalence. PROSPERO REGISTRATION NUMBER: CRD42017074076.

Evidence of factors influencing self-medication with antibiotics in low and middle-income countries: a systematic scoping review.

OBJECTIVES: Self-medication with antibiotics (SMA) is a practice of global concern with a higher incidence within the low- and middle-income countries (LMICs). Despite worldwide efforts to control and promote the rational use of antibiotics, the continuing practice of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and a host of other antibiotic side-effects. This systematic scoping review maps evidence on the factors influencing SMA in these settings. STUDY DESIGN: Systematic scoping review. METHODS: The search strategy involved electronic databases including PubMed, Web of science, Science Direct, EBSCOhost, Google Scholar, BioMed Central, and the World Health Organization Library. PRISMA P guidelines and Arksey and O'Malley's framework were used. Thematic analysis was used to identify the factors that influence the practices of SMA in LMICs. The Mixed Method Appraisal Tool (MMAT), version 2011, was used to assess the quality of the included primary studies. RESULTS: Fifteen studies met the inclusion criteria. Studies included participants from the following LMICs: Guatemala, India, Indonesia, Kenya, Laos, Nepal, Nigeria, Pakistan, Sri Lanka, and Yemen. The findings of the review emphasized a considerable high prevalence of SMA, ranging from 8.1% to 93%, with an association with the level of education, monthly income, and gender of participants. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence SMA in LMICs. Health conditions such as a sore throat, common cold, cough, headache, toothache, flu-like symptoms, pain relief, fever, runny nose, toothache, upper respiratory tract infections, and urinary tract infection were the major complaints that led to the practices of SMA. CONCLUSIONS: There is a considerable level of research evidence predominantly in some LMICs from Asia, with less evidence from African LMICs. Sociocultural determinants of health associated with the structure and conditions of health system as well as the health-seeking behavior are the main factors influencing SMA. Contextual and comprehensive studies on the factors influencing the non-prescribed use of antibiotics are needed to enable evidence-based strategies to correctly address the utilization of antibiotics and contain the problem of antimicrobial resistance, especially within the LMICs. PROSPERO REGISTRATION: CRD42017072954.

Chronic deltoid ligament insufficiency repair with Internal Brace™ augmentation.

BACKGROUND: Patients with chronic deltoid ligament insufficiency (CDLI) present a challenging situation. Although numerous procedures have been described, optimal treatment is still a matter of debate. While the treatment armamentarium ranges from simple ligament repair to complex reconstructions with or without realignment osteotomies, direct repair augmented with an Internal Brace™ device appears to be an attractive intermediate option. We investigated functional outcomes and complications in patients with CDLI operated on using Internal Brace™ augmentation. METHODS: A prospective study was conducted. Patients were included if they presented medial ankle pain and/or giving way, exhibited asymmetric flexible hindfoot valgus, failed conservative treatment, and had a positive MRI evaluated by an independent radiologist. Patients with stage IV flatfoot deformity, neuropathy and/or inflammatory arthritis were excluded. CDLI was confirmed intraoperatively with the arthroscopic drive-through sign. Patients were evaluated preoperatively and postoperatively using FAAM, SF-36 and grade of satisfaction. Paired t-tests were used to assess FAAM and SF-36 scores variation. RESULTS: Thirteen patients met inclusion criteria. No patient was lost to follow-up, with a mean follow-up time of 13.5 months (range 6-21). Preoperative FAAM and SF-36 scores improved from 58.7 to 75.3 and from 60.2 to 84.4 postoperatively, respectively (p<.01). Two implant failures were observed, with no apparent compromise of construct stability. No patient was re-operated. CONCLUSIONS: Our results suggest that deltoid ligament repair with Internal Brace™ augmentation in patients with CDLI is a reliable option with good functional outcomes and high satisfaction grade in short term follow-up. LEVEL OF EVIDENCE: Level IV.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Impact of nutritional status on the pharmacokinetics of erlotinib in rats.

Malnourishment is a complex condition in which physiopathological changes take place in multiple systems as a result of energy, protein and nutrient deficiency. The purpose of this study was to evaluate, using an experimental animal model, the impact of nutritional status on the pharmacokinetic profile of erlotinib, a reversible, highly selective, human epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. Two groups of rats -WN (well-nourished) and UN (undernourished) - were fed with different diets for 23-26 days. Rats were assigned randomly to one of three erlotinib treatments (n = 42) consisting of a single dose administered intravenously (i.v.), via oral solution or via oral suspension. Blood samples were assayed for erlotinib concentration. A population pharmacokinetic model was developed and pharmacokinetic parameters obtained in UN rats were compared with those in WN rats. Erlotinib clearance suffered a 5% decrease in the mild-undernutrition status. Moreover, when the drug was administered orally as a suspension, the extent and rate of absorption underwent a 20% increase in UN rats. The results of this study might help to explain, at least in part, the variability of erlotinib treatment and could represent the first step towards establishing new dosage guidelines for the treatment of undernourished cancer patients. Copyright © 2015 John Wiley & Sons, Ltd.

Antiherpes simplex virus type 2 activity of the antimicrobial peptide subtilosin.

AIMS: In this study, we evaluated the antiviral activity of subtilosin, a cyclical peptide isolated from Bacillus amyloliquefaciens, against herpes simplex virus type 2 (HSV-2) in cell cultures and we investigated subtilosin mode of action. METHODS AND RESULTS: We determined, using a virus yield inhibition assay, that noncytotoxic concentrations of subtilosin inhibit HSV-2 replication in Vero cell cultures. Subtilosin strongly inhibited extracellular and total virus production even when it was added at 8 h postinfection indicating that not only virus release but also viral particle formation is impeded by the antiviral peptide. Although viral glycoprotein gD level of expression is not affected by the bacteriocin, an altered pattern of gD intracellular localization was detected by immunofluorescence assay in subtilosin-treated culture. On the other hand, at high concentrations, subtilosin displays virucidal action. CONCLUSIONS: Subtilosin displays antiviral and virucidal actions against HSV-2. The target of subtilosin inhibitory effect would be late stages of the viral replicative cycle such as viral glycoprotein intracellular transport. SIGNIFICANCE AND IMPACT OF THE STUDY: Given its antimicrobial activity and its safety for human tissues, subtilosin could represent a valuable alternative to be considered in the development of new microbicide formulations.

Comparative cost-effectiveness of bevacizumab-irinotecan-fluorouracil versus irinotecan-fluorouracil in first-line metastatic colorectal cancer.

PURPOSE: To evaluate the cost-effectiveness of the addition of bevacizumab to the irinotecan-fluorouracil (Douillard regimen-CPT-FUFA-) in first-line treatment of metastatic colorectal cancer in a single-institution population. METHODS: Controlled, nonrandomized retrospective observational study. Treatment-naïve metastatic colorectal cancer patients received CPT-FUFA (January 2000-December 2003; control group) and bevacizumab_CPT-FUFA (January 2007-December 2010; study group). Variables related to: patient, clinical response (number of disease progression or death events, progression-free survival) and treatment (antineoplastic dose reduction, incremental cost/treated patient associated with the addition of bevacizumab). STATISTICAL ANALYSIS: median progression-free survival (Kaplan-Meier method), and hazard ratio (Cox regression). Survival curves were compared (Mantel-Haenszel test). RESULTS: In all, 69 patients were included: 32 (57.2 years -95%CI: 54.0-60.5-, 65.6% men) in CPT-FUFA group and 37 (68.1 years - 95%CI: 65.5-70.7-, 78.4% men) in bevacizumab_CPT-FUFA group. The disease progression or death events were 29 (90.6%) in CPT-FUFA group and 34 (91.9%) in bevacizumab_CPT-FUFA group. Median progression-free survival was 10.1 months (95%CI: 7.1-12.2) in CPT-FUFA and 11.0 months (95%CI: 7.6-12.6) in bevacizumab_CPT-FUFA (hazard ratio = 1.22; 95%CI: 0.7-2.1). Dose reductions: irinotecan and fluorouracil 11% (range: 4-20) in 5/32 (15.6%) CPT-FUFA patients and 25% (range: 8-35) in 18/37 (48.6%) bevacizumab_CPT-FUFA patients; Bevacizumab 30% (range: 4-50) in 20/37 (54.1%) bevacizumab_CPT-FUFA patients. The incremental cost associated with the addition of bevacizumab was 12,696.5 (IC95%:10,860.8-14,532.1) euros/patient. CONCLUSION: The addition of bevacizumab to the irinotecan-fluorouracil regimen, does not improve progression-free survival in our study population but increases costs per treated patient. These results potentially compromise the cost-effectiveness of the Bevacizumab_CPT-FUFA regimen.

First Report of Bacterial Stalk Rot of Maize Caused by Dickeya zeae in Mexico.

A bacterial disease of maize, bacterial stalk and top rot, was found in the state of Morelos in February 2011, and in the state of Puebla in July 2013, Mexico. In both cases, the incidence of diseased plants was lower than 0.5%. The typical symptoms were a soft rot and darkening of the tissues affecting the stalk and the top of the plant, causing breaking of the stalk. The lesions progressed from the top to below nodes, leaf sheaths and blades, and rotten tissues emitted an unpleasant odor. Eleven diseased plants were collected, and bacterial colonies were isolated from fragments detached from the edges of symptomatic tissues after sterilization with a 0.5% solution of NaClO for 30 s, rinsing three times in sterile water. The sterilized fragments were macerated in drops of distilled sterile water for 10 min and the extract was streaked on King's medium B (agar 15 g, distilled water 1,000 ml, proteose peptone 20 g, K2HPO4 1.5 g, MgSO4·7H2O 1.5 g, glycerol 10 ml). Eight representative strains from Morelos and five from Puebla were selected for identification. All strains were gram-negative, grew at 37°C, showed pectynolitic activity on potato tubers, were positive for indole production, utilized arabinose, galactose, glucose, glycerol, lactose, mannose, melibiose, rafinose, ribose, and sucrose but did not produce acid from arabitol, adonitol, and keto-methyl-glucoside (3,4). Pathogenicity tests were conducted with each strain by inoculating with a syringe four 25-day-old maize seedlings with 107 CFU ml-1 bacterial cells in the leaf collar. Plants were incubated in the greenhouse at 30°C during the day and 24°C during the night with a 12-h photoperiod, and relative humidity of 93%. The reference strains Erwinia chrysanthemi pv zeae ATTC29942 and Dickeya zeae CFBP 2052 were used as positive controls in laboratory and greenhouses tests. Sterile water was used as negative control. Two days after inoculation, soft stalk rot symptoms developed that were identical to those observed in the field. No symptoms were observed on the negative controls. Diagnostic amplification of DNA by conventional PCR was carried out and yielded the expected amplicon size of 420 bp of the Dickeya-specific pel gene with the ADE primers set (2). PCR was used to amplify the 16S rRNA gene with the universal primers 27f and 1495r (5) for molecular identification of the 13 strains (GenBank Accession Nos. KJ438941, KJ438942, KJ438943, KJ438944, KJ438945, KJ438946, KJ438947, KJ438948, KJ438949, KJ438950, KJ438951, KJ438952, and KJ438953). The strains D. zeae CFBP 2052 and E. chrysanthemi pv. zeae ATCC 29942 were sequenced as positive controls. A BLAST search with the 13 16S rRNA gene sequences of 1.4 kb were 99% identical to the sequence of D. zeae CFBP 2052 (NR_041923). D. zeae can be a major disease of maize in tropical and subtropical countries. It is particularly severe under conditions of high temperature and high humidity, but it occurs sporadically. Control of the vector, Chilo partellus, can aid disease management (1). To our knowledge, this is the first report of D. zeae causing maize stalk rot in Mexico. References: (1) CABI. Crop Prot. Compend. CAB International, Wallingford, UK, 2014. (2) A. Nassar et al. Appl. Environ. Microbiol. 62:2228, 1996. (3) R. Samson et al. Int. J. Syst. Evol. Microbiol. 55:1415, 2005. (4) N. W. Schaad et al. Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. APS Press, St. Paul, MN, 2001. (5) W. G. Weisburg. J. Bacteriol. 173:697, 1991.

Aripiprazole as protector against COVID-19 mortality.

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice.

AIMS/HYPOTHESIS: Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα. METHODS: Wild-type (WT) and Lxrα(-/-) (Lxrα, also known as Nr1h3) mice were fed an SP diet with or without cholesterol for 28 days. The expression of LXRα target genes was measured in liver and intestine, as were hepatic lipid content and faecal bile acid concentration. Oral glucose and insulin tolerance tests were also performed. Hepatocytes were used to study the effect of isoflavones on LXR activity. RESULTS: The livers of WT and Lxrα(-/-) mice fed an SP high-cholesterol diet showed less steatosis than those fed casein. The SP diet increased the expression of the ATP-binding cassette (ABC) sub-family genes Abca1, Abcg5 and Abcg8 in the liver and intestine, as well as increasing total faecal bile acid excretion and insulin sensitivity in WT mice compared with mice fed a casein diet. However, these effects of SP were not observed in Lxrα(-/-) mice. The SP isoflavone, genistein, repressed the activation of LXRα target genes by T0901317, whereas it stimulated the activation of LXRß target genes. The AMP-activated protein kinase inhibitor, compound C, had the opposite effects to those of genistein. CONCLUSIONS/INTERPRETATION: Our results suggest that SP isoflavones stimulate the phosphorylation of LXRα or LXRß, resulting in different biological effects for each LXR isoform.

Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV and herpes simplex virus infection.

OBJECTIVES: A safe and effective topical prevention strategy will likely require sustained delivery of potent antiviral drugs and a delivery system that simultaneously maximizes drug distribution and overcomes the behavioural challenges related to adherence. Activity against HIV and herpes simplex virus (HSV) would be advantageous, given the epidemiological link between the two pathogens. We hypothesize that tenofovir disoproxil fumarate (tenofovir DF), a prodrug of tenofovir, may be more potent than tenofovir and ideal for sustained intravaginal ring (IVR) delivery. METHODS: The anti-HIV and anti-HSV activity of tenofovir and tenofovir DF were assessed in cell and explant models. Cumulative tenofovir DF release and stability from polyether urethane (PEU), ethylene-co-vinyl acetate (EVA) and silicone IVRs were compared, and the activity and safety of drug released were evaluated in cervical explants and in a polarized dual-chamber model. RESULTS: Tenofovir DF inhibited HIV and HSV at ≈ 100-fold lower concentrations than tenofovir and retained activity in the presence of semen. PEU rings delivered >1 mg/day of tenofovir DF for 30 days. Pre-treatment of cervical explants with 10 µg/mL tenofovir DF or eluants from PEU minirings resulted in >90% inhibition of HIV and reduced HSV-2 yields by 2.5 log. Tenofovir DF and eluants did not prevent cell growth or polarization, or have any deleterious effects on an epithelial barrier. CONCLUSIONS: The findings support the development of a PEU tenofovir DF ring, which may provide potent and sustained protection against HIV and HSV.

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach.

OBJECTIVE: The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity. METHODS: Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8-10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation. RESULTS: Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11-19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8 ± 4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded. CONCLUSION: The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate.

BECN1 protein expression is associated with poor survival in triple negative locally advanced breast cancer.

OBJECTIVE: The role that Beclin 1 (BECN1) plays in the development and progression of cancer mediated by autophagy, as well as its differential expression in breast cancer cell lines and mammary tumor tissue according to the molecular subtype, has been demonstrated. The objective of this study was to evaluate the association of BECN1 cytoplasmic expression with clinical and pathologic response, recurrence, disease-free survival (DFS) and overall survival (OS) in patients with locally advanced breast cancer (LABC), according to immunophenotype. PATIENTS AND METHODS: 64 patients with non-triple negative LABC and 20 patients with triple negative LABC who received preoperative chemotherapy were included in an observational, analytical and retrospective study to evaluate the cytoplasmic expression of BECN1 protein by immunohistochemistry in microarrays of breast cancer tissue obtained before treatment. Association between BECN1 and clinicopathological characteristics, clinical and pathologic response to preoperative chemotherapy and recurrence, were analyzed using Chi-square or Fisher's exact test. Postoperative DFS and OS were assessed by Kaplan-Meir curves, and the difference according to BECN1 expression was evaluated using the log-rank test. The bivariate analysis was performed using the Cox Proportional Hazards Model. A p-value of < 0.05 was considered statistically significant. RESULTS: BECN1 staining revealed positive expression in 62.5% of patients with non-triple negative and 60.0% with triple negative LABC. No association was observed between BECN1 expression and clinical or pathological response or recurrence. An association of the BECN1 expression with lower OS in triple negative breast cancer was found (HR = 5.19; 95% CI 1.12-24.02; p = 0.035). CONCLUSIONS: Results showed an association of the cytoplasmic expression of BECN1 with a lower OS, which could be a poor prognostic biomarker in triple negative LABC.

Tropospheric ozone and plants: absorption, responses, and consequences.

Ozone is now considered to be the second most important gaseous pollutant in our environment. The phytotoxic potential of O3 was first observed on grape foliage by B.L. Richards and coworkers in 1958 (Richards et al. 1958). To date, unsustainable resource utilization has turned this secondary pollutant into a major component of global climate change and a prime threat to agricultural production. The projected levels to which O3 will increase are critically alarming and have become a major issue of concern for agriculturalists, biologists, environmentalists and others plants are soft targets for O3. Ozone enters plants through stomata, where it disolves in the apoplastic fluid. O3 has several potential effects on plants: direct reaction with cell membranes; conversion into ROS and H2O2 (which alters cellular function by causing cell death); induction of premature senescence; and induction of and up- or down-regulation of responsive components such as genes , proteins and metabolites. In this review we attempt to present an overview picture of plant O3 interactions. We summarize the vast number of available reports on plant responses to O3 at the morphological, physiological, cellular, biochemical levels, and address effects on crop yield, and on genes, proteins and metabolites. it is now clear that the machinery of photosynthesis, thereby decreasing the economic yield of most plants and inducing a common morphological symptom, called the "foliar injury". The "foliar injury" symptoms can be authentically utilized for biomonitoring of O3 under natural conditions. Elevated O3 stress has been convincingly demonstrated to trigger an antioxidative defense system in plants. The past several years have seen the development and application of high-throughput omics technologies (transcriptomics, proteomics, and metabolomics) that are capable of identifying and prolifiling the O3-responsive components in model and nonmodel plants. Such studies have been carried out ans have generated an inventory of O3-Responsive components--a great resource to the scientific community. Recently, it has been shown that certain organic chemicals ans elevated CO2 levels are effective in ameliorating O3-generated stress. Both targeted and highthroughput approaches have advanced our knowledge concerning what O3-triggerred signaling and metabolic pathways exist in plants. Moreover, recently generated information, and several biomarkers for O3, may, in the future, be exploited to better screen and develop O3-tolerant plants.

Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity.

Appetite modulation in conjunction with enhancing metabolic rate with hypothalamic lesions has been widely documented in animal and even in humans. It appears these effects can be reproduced by DBS, and the titratability and reversibility of this procedure, in addition to well established safety profile, make DBS an appealing option for obesity treatment. Targeting the hypothalamus with DBS has already been shown to be feasible and potentially effective in managing patients with intractable chronic cluster headache [26]. The surgical risk however must be cautiously taken into account when targeting the hypothalamus, where some mortality cases have been reported when targeting the posterior part [34]. The development of new surgical approach will probably reduce this surgical risk. Moreover, the role of functional neurosurgery in obesity is not a new idea. In fact, LH was targeted in obese humans with electrocoagulation more than 30 years ago, resulting in significant yet transient appetite suppression and slight weight reduction [36]. All those elements have made possible the recent regain of interest in DBS for morbid obesity and open an exciting new area of research in neurosurgery and endocrinology.

Effect of germinated soybean protein hydrolysates on adipogenesis and adipolysis in 3T3-L1 cells.

Germination of soybeans increases the bioavailability of some nutrients. An evaluation was done to determine if germination increased the anti-adipogenic and lipolytic effects of soybean. Soybeans were germinated for 0 to 6 days and protein concentrates extracted from beans germinated at each period. Soy protein concentrates can retain notable amounts of phytochemicals with anti-adipogenic activity. For this reason, it was evaluated the effect of protein hydrolysates with and without phytochemicals in the adipocyte-like cells after 3T3-L1 (murine fibroblasts) cell line differentiation. Cell viability decreased with exposure to the germinated soybean protein hydrolysates during the differentiation stage, but not during the fibroblast or mature adipocyte stages. Adipogenesis and triglycerides accumulation were strongly inhibited by the hydrolysate from soybeans germinated for 2 days (with ethanol-soluble phytochemicals), when compared to ungerminated soybean. Adipolysis increased with exposure to hydrolysates from beans germinated for 2 days (with phytochemicals) and 5 days (without phytochemicals). Germinated soy protein hydrolysates had an effect on inhibition of lipid storage in adypocites and increasing lipolysis, which was improved by changes of the protein and increased phytochemical content due to germination.

Doctors' acceptance of recommendations for patients with the opportunity for pharmacotherapy improvement.

OBJECTIVE: To identify and quantify the influence of different variables on the implementation of pharmacotherapy optimisation measures in hospitalised patients. METHOD: Descriptive transversal study. PERIOD: 2000-2007. ENVIRONMENT: public university general hospital (25,000 patients admitted/year). The Programme implemented to improve pharmacotherapy quality and patient safety covers 30% of all patients. Using records from the Atefarm(®) Farmis application, we analysed pharmacotherapy recommendations (PRs) made by pharmacists to doctors. The selected variables were the following: Risk of the medication for ADE (1-high, 0-low), ADE category, (0-indication, 1-effectiveness, 2-safety), potential severity (scale of 1 to 5), impact of the PR (0-effectiveness, 1-safety, 2-efficiency) and implementation of the PR (yes/no). We calculated the frequency (%) and 95% CI for the categorical variables and performed a multivariate logistical regression analysis to identify the variables' degree of influence on implementing the PRs. RESULTS: We identified 7,920 ADEs in 4,680 patients. A PR was issued in 85% of the cases (6,762), and it was implemented in 83% (95% CI 74.2-89.8). Potential severity of the ADE ≥2 (OR 1.57; 95% CI 1.27-1.94), and ADE category for effectiveness and safety (OR 1.19; 95% CI 1.02-1.39) were shown to be determining factors for implementing the PR for the patient. CONCLUSIONS: The probability that a PR will be implemented for a patient is related to the potential severity and the category of the identified ADE. Therefore, recommendations intended to improve effectiveness of pharmacotherapy or patient safety, and those with potential clinical consequences have a greater chance of being applied to a patient.