Consecutive Cycles Of Treatment Research Articles

Efficient removal of E. coli from wastewater by novel phytofabricated nano-zinc using antibacterial potential, kinetic studies, and response surface methodology

The present investigation explores the antibacterial potential of novel ZnO-NPs synthesized from Acacia nilotica pods extract and immobilized onto sodium alginate beads to control bacterial pollution in wastewater. Phenolics and flavonoids were major phytoconstituents acting as capping, reducing, and stabilizing agents. UV–Vis analysis showed strong absorption band at 340 nm. XRD and TEM revealed hexagonal crystalline structure for zincite of average particles diameter 33.87 and 32.74 nm, respectively. FTIR demonstrated several bands with functional groups (O–H, C-H, C = O, C = C, and C–O–C) involved in ZnO-NPs synthesis. SEM images showed NPs surface completely colonized by E.coli, while EDX spectrum showed signals for zinc (52.94%) and oxygen (26.58%) confirming NPs purity. Adhesion capacity studies revealed ZnO-NPs potential (0.5 g) to remove E.coli after 120 min. Kinetic and isotherm studies indicated that pseudo-second-order model and Freundlich isotherm were best fit describing adhesion mechanism. Electrostatic attraction between negatively charged E.coli and positively charged ZnO-NPs was followed by generation of H2O2 leading to cell apoptosis. Adhesion optimization using Box–Behnken design under response surface methodology was 99.8% at disinfectant dose 30 g/L, contact time 6 h, and E.coli concentration 150 × 107 cfu/mL. For application, real wastewater was treated with removal 98.2%, 97.2%, and 96.5% for total coliform, fecal coliform, and E.coli, respectively, after 6 h. ZnO-NPs showed sustainable efficiency during four consecutive cycles of treatment. The study concluded the efficiency, eco-friendly and cost-effectiveness of phytofabricated ZnO-NPs as disinfectants for wastewater and recommended future studies on large scale for possible wastewater reuse in safe unrestricted irrigation.

Integral Use of Red Wine Pomace after Hydrostatic High Pressure: Application of Two Consecutive Cycles of Treatment.

The influence of applying hydrostatic high pressure (HHP) to red grape pomace cv. Tempranillo was studied to obtain an ingredient rich in bioactive compounds for the manufacture of food products. Four treatments were investigated: (i) 600 MPa/1 s; (ii) 600 MPa/300 s, and other two treatments with 2 cycles of HHP: (iii) 2 cycles of 600 MPa/1 s; and (iv) 1 first cycle of 400 MPa/1 s and a second cycle 600 MPa/1 s. Treated pomace was stored at different temperatures (4 and 20 °C). The application of two consecutive cycles had no effect on the microorganisms' inactivation compared to only one cycle. Immediately after HHP, the phenolic compounds content was maintained. However, HHP had no influence on the polyphenol oxidase enzyme (PPO), and so the phenolic compounds were significantly reduced during storage. Hence, the shelf-life of red grape pomace was significantly reduced at both temperatures, although phenolic compounds were better preserved under refrigeration than at room temperature.

Application of sintilimab combined with anlotinib hydrochloride in the clinical treatment of microsatellite stable colorectal cancer

BACKGROUND Microsatellite stable (MSS) colorectal cancer (CRC) is a common type of tumor with limited treatment options. Sintilimab and anlotinib hydrochloride are two extensively studied anticancer drugs. AIM To probe the clinical value of combining sintilimab with anlotinib hydrochloride in MSS CRC treatment. METHODS During the period spanning from April 2019 to April 2022, Zhejiang Provincial People’s Hospital accommodated a cohort of 92 patients diagnosed with MSS CRC who were classified into two distinct groups in our study, the observation group and the control group. The control group was administered anlotinib hydrochloride as their designated therapy, whereas the observation group received the additional treatment of sintilimab in conjunction with the therapy assigned to the control group. The administration of treatment occurred in cycles consisting of a duration of 3 wk, and the evaluation of effectiveness took place subsequent to the completion of two consecutive cycles of treatment within both groups. A comparative analysis between the two groups was conducted to assess the short-term efficacy and ascertain the incidence of adverse events transpiring throughout the duration of the treatment period. Changes in the levels of carcinoembryonic antigen, carbohydrate antigen 199 (CA199), CA125, and T cell subsets (CD4+, CD8+, CD4+/CD8+) as well as the assessment of the quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 were compared between the two groups prior to and subsequent to therapy. Finally, a 1-year follow-up was conducted for both groups of patients, and the survival status was recorded and analyzed. RESULTS The short-term effectiveness displayed by the observation group surpassed that exhibited by the control group, with a statistically significant discrepancy (76.09% vs 50.00%), reaching a significance level denoted as P < 0.05. Following the administration of treatment, the observation group manifested a considerable reduction in numerous serum indicators, which were found to be lower than the corresponding pretreatment levels within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Post-treatment, the T lymphocyte subset levels within the observation group demonstrated a remarkable amelioration, surpassing the corresponding pre-treatment levels observed within the same group as well as the post-treatment levels observed in the control group (P < 0.05). Subsequent to the therapeutic intervention, the observation group showcased a notable amelioration in the scores associated with multiple dimensions of life quality. These scores outperformed the pretreatment scores within the same group as well as the post-treatment scores observed in the control group (P < 0.05). The safety levels of drug use in the two group were comparable (19.57% vs 13.04%), and no distinct difference was observed upon comparison (P > 0.05). After the completion of treatment, both groups of patients underwent a 1-year follow-up outside the hospital. Throughout this period, 1 patient within the observation group and 2 patients within the control group became untraceable and were lost to follow-up. During the follow-up period of the observation group, 12 patients died, resulting in a survival rate of 73.33% (33/45), while in the control group, 21 patients died, resulting in a survival rate of 52.27% (23/44). The implementation of Kaplan-Meier survival analysis revealed a conspicuous contrast in survival rates exhibited by the two groups (log-rank = 4.710, P = 0.030). CONCLUSION The combination of sintilimab and anlotinib hydrochloride demonstrated favorable efficacy in the treatment of MSS CRC patients, leading to improvements in patient immunity and prognosis. Additionally, it exerted inhibitory effects on the expression of carcinoembryonic antigen, CA199, and CA125.

Synthesis & fabrication of O-linked polymeric hybrids for recovery of textile dyes: Closed loop economy

Dyes are an important resource employed for the production systems in textile, paper, paint and leather industry. An estimate of 200,000 tons of dyes are discharged as textile effluent each year worldwide. It becomes imperative to recover these dyes by treating the effluents using economically viable routes. The present research was undertaken with the objective to attain zero emission and zero waste through development of novel polymeric hybrids as adsorbents. For this purpose, metal moieties (Al3+, Si4+, Ti4+ and Zr4+) were hybridized with polyacrylic acid, and cellulose acetate for the uptake of selected dyes under optimized parameters. The structural elucidation of four synthesized hybrids (MP-Al, MP-Si, MP-Ti and MP-Zr) by FTIR, EDX and TGA confirmed O-linked grafting of metal moieties with polymers and thermally stable porous materials. SEM micrographic images displayed void spaces providing channels for effective adsorption. The batch experiments demonstrated removal of malachite green (77–96%) and congo red (70–82%) upon contact of initial 45 min on polymeric hybrids On the other hand, pristine polyacrylic acid and cellulose acetate showed remarkably low removal of dyes. The adsorption mechanism is proposed as physical in nature following type II isotherm. Further, Langmuir and Ho's pseudo second order fitness was evaluated. In order to determine the economic viability of the present research, the real textile dyes were recovered in three consecutive cycles of adsorption and chemical treatment of hybrids. The results propose a system with positive impact on economy by maximum utilization of hybrids as adsorbents and recovery of textile dyes for reuse in textile processing.

Inter-Cycle Variation in Endometrial Thickness in Fresh Embryo Transfer Cycles: Predictors and Association with Pregnancy Outcome

Background: The use of intracytoplasmic sperm injection (ICSI) has increased substantially worldwide, primarily in couples with non-male factor infertility. We recently published the results of a large randomised controlled trial (RCT) comparing ICSI and IVF showing no significant improvement of ICSI over IVF in couples with normal semen concentration and motility. Here, we assess the cost-effectiveness of ICSI in these couples, with additional attention for subgroups. Aim: To evaluate the inter-cycle variation in endometrial combined thickness (ECT) in fresh embryo transfer cycles Method: This was a retrospective cohort study in a single university affiliated fertility clinic in Chengu, China. We studied women undergoing IVF/ ICSI treatment in a fresh stimulated cycle, and measured endometrial combined thickness on the day of HCG trigger in consecutive stimulated IVF/ICSI cycles. Inter-cycle variation in ECT was the main outcome measure. Secondary outcomes were the relationship between ECT and treatment outcomes clinical pregnancy, live birth and miscarriage. Results: The mean ECT in consecutive fresh stimulated cycles was 10.28 ⊠ 2.15mm in cycle 1 (n=7038), 9.93 ⊠ 2.11mm in cycle 2 (n=1287), 9.49 ⊠ 2.22mm in cycle 3 (n=148) and 8.63 ⊠ 1.82mm in cycle 4 (n=17) (p [Formula: see text]0.01.). An incremental increase in the clinical pregnancy rate was demonstrated for each additional millimetre in ECT up to a threshold level of 12-15mm. There was no evidence of systematic bias on the visual assessment of the Bland Altman plot in women undergoing 2 consecutive cycles of treatment (mean bias 0.46, (95% limits of agreement -5.62 to 5.65)). Multivariate predictors of ECT were the number of previous treatment cycles, secondary infertility, infertility diagnoses of anovulation, endometriosis, male factor or unexplained infertility and the number of follicles greater than 14mm on the day of HCG trigger. There was a small, significant interaction between female age and ECT on the outcome clinical pregnancy. Conclusion: There is a slight decrease in mean ECT in women undergoing consecutive stimulated IVF/ICSI cycles which is potentially explained by the increased occurrence of pregnancy with thicker ECT. Each millimetre increase in late follicular ECT increases the odds ratio of clinical pregnancy to a threshold level of 12-15mm.

Assessing the Significance of the Circadian Time of Administration on the Effectiveness and Tolerability of OnabotulinumtoxinA for Chronic Migraine Prophylaxis.

We aimed to provide insights on the role of the circadian time of administration in influencing the efficacy and tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis. Methods: We retrospectively reviewed the medical files of BoNTA-naïve patients with CM who completed three consecutive cycles of treatment, according to the standard PREEMPT paradigm. Participants were classified to those scheduled to be treated in the morning hours from 8:00 to 12:00 (AM) or afternoon hours from 13:00 to 18:00 (PM). We then assessed and compared between groups the changes from baseline (T0—trimester before BoNTA’s first administration) to the period after its third administration (T3) in the following efficacy outcomes: (i) mean number of headache days/month, (ii) mean number of days/month with peak headache intensity of >4/10, (iii) mean number of days/month with consumption of any abortive treatment. Safety–tolerability was also compared between groups. Results: A total of 50 AM and 50 PM-treated patients were evaluated. The within-group analysis in both groups showed a significant decrease in all efficacy variables between T0 and T3. However, the between-group comparisons of all BoNTA-related efficacy outcomes at T3 vs. T0 documented comparable improvements between AM vs. PM-treated patients. Safety/tolerability was also similar between groups. Conclusions: We were not able to identify significant differences between patients treated in the AM vs. PM, so as to demonstrate that the circadian time of administration should be considered before initiating BoNTA in CM patients.

Subcutaneous injection of infliximab CT-P13 results in stable drug levels within 14-day treatment cycle in Crohn's disease.

CD patients in clinico-biological remission under maintenance therapy with intravenous (iv) IFX/CT-P13 were switched to CT-P13 sc 8weeks (W) after the last infusion. They were treated with CT-P13 sc, 120mg every 2W. Assessments were performed from 8W after starting CT-P13 sc and patients had to attend 6 visits on 2 consecutive cycles of treatment (cycles A and B). Visits were scheduled on days 4-6 (visit 1), days 7-9 (visit 2) and day 14 (visit 3) of each cycle, where days 1 and 14 were the days of sc injection of CT-P13. At each visit, peripheral blood was collected to measure serum IFX levels and anti-drug antibodies. Twenty patients underwent 120 evaluations. Large intra-individual variations of serum drug levels of IFX were observed. When pooling the 120 evaluations, the mean drug level was 11.3±4.9μg/ml, and the median drug level was 10.9μg/ml (IQR 7.5-15.5). During each cycle, the median drug levels were similar between visits 1 and 2 as well as between visits 1 and 3 and between visits 2 and 3. In cycle A, median drug levels were 11.1μg/ml (7.8-14.5), 12.0μg/ml (7.2-16.1) and 11.0μg/ml (7.5-15.1) at V1, V2 and V3, respectively. Similar results were obtained in cycle B, where median drug levels were 11.6μg/ml (7.9-14.9), 11.4μg/ml (8.1-15.2) and 10.9μg/ml (7.9-15.6) at V1, V2 and V3, respectively. In univariate analysis, we failed to identify factors predictive of low drug levels. IFX drug levels are quite stable within 14-day treatment cycle, without trough levels in CD patients in remission during the maintenance therapy with CT-P13 sc. In patients with inactive CD under maintenance therapy with CT-P13 sc, therapeutic drug monitoring of IFX can be performed at any time between two CT-P13 sc injections.

Elevated sperm DNA fragmentation does not predict recurrent implantation failure.

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34±3.6years and 37.3±6.6years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9-105.5] million. Overall median DFI% and HDS% was 12 [7.1-18.9] and 9.6 [6.5-14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR=1.01, 95% CI: 0.98-1.04, p=.414; HDS%: OR=0.97, 95% CI: 0.94-1.01, p=.107) or IVF success, defined as clinical pregnancy (DFI%: OR=1.00, 95% CI: 0.99-1.01, p=.641; HDS%: OR=1.01, 95% CI: 0.99-1.02, p=.565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.

1769P - High incidence of nausea during initial and repeated courses if intravenous chemotherapy in patients receiving guideline consistent antiemetic prophylaxis: A prospective, observational, real-world study

BackgroundThe development of effective anti-emetic treatments has contributed to the resolution of emesis in chemotherapy patients (pts). Current research has focused on vomiting as the primary problem of chemotherapy-induced nausea and vomiting (CINV). The incidence and impact of nausea, particularly in cancer pts undergoing chemotherapy is under-reported and remains a major unmet medical need. MethodsThe study focused on nausea in pts undergoing chemotherapy. The primary endpoint was no nausea during the 120-hours overall phase after the first 3 consecutive cycles of treatment. Secondary endpoints included no nausea during day-7 and day-10 of cycle 1. This prospective, observational single centre study enrolled 95 pts undergoing intravenous chemotherapy, receiving guideline consistent CINV prophylaxis. There were LEC = 25 pts, MEC = 24 pts and HEC (included cisplatin and doxorubicin/cyclophosphamide-based chemotherapy) = 46 pts. Patient diaries were used to collect data from day-1 to day-5, day-7 and day-10 beginning with cycle-1 for up to 3 cycles. Nausea was reported by the pts using a visual analog scale (VAS). Vomiting episodes were recorded in the patient’s diaries and data was analysed as a secondary end-point. ResultsThe incidence of nausea of the entire population was significantly higher than vomiting for cycle 1 (58% vs 14%; Chi2 22.271 p<0.0000); for cycle 2 (51% vs 14%; Chi2 26.964 p<0.0000) and for cycle 3 (46% vs 18%; Chi2 14.161 p<0.0002). Nausea was continuous in 25% of the patients in all 3 cycles. For patients with documented intermittent nausea, the mean duration was 3.8hours. The median maximum intensity of nausea was 6 (range 1-10) for all three cycles. The median time to development of first episode of nausea was 29hours (range 1 to 90). Significant variables predicted for nausea in cycle 1 included, age (OR 0.177, p<0.035) and history of morning sickness (OR 5.038, p<0.032). ConclusionsDespite the usage of guidelines consistent antiemetic prophylaxis, chemotherapy induced nausea remains a major unmet medical need in cancer pts. Further research should focus on treatment of nausea and patient’s risk factors. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Exposure to high-frequency electromagnetic field triggers rapid uptake of large nanosphere clusters by pheochromocytoma cells.

BackgroundEffects of man-made electromagnetic fields (EMF) on living organisms potentially include transient and permanent changes in cell behaviour, physiology and morphology. At present, these EMF-induced effects are poorly defined, yet their understanding may provide important insights into consequences of uncontrolled (e.g., environmental) as well as intentional (e.g., therapeutic or diagnostic) exposure of biota to EMFs. In this work, for the first time, we study mechanisms by which a high frequency (18 GHz) EMF radiation affects the physiology of membrane transport in pheochromocytoma PC 12, a convenient model system for neurotoxicological and membrane transport studies.Methods and resultsSuspensions of the PC 12 cells were subjected to three consecutive cycles of 30s EMF treatment with a specific absorption rate (SAR) of 1.17 kW kg−1, with cells cooled between exposures to reduce bulk dielectric heating. The EMF exposure resulted in a transient increase in membrane permeability for 9 min in up to 90 % of the treated cells, as demonstrated by rapid internalisation of silica nanospheres (diameter d ≈ 23.5 nm) and their clusters (d ≈ 63 nm). In contrast, the PC 12 cells that received an equivalent bulk heat treatment behaved similar to the untreated controls, showing lack to minimal nanosphere uptake of approximately 1–2 %. Morphology and growth of the EMF treated cells were not altered, indicating that the PC 12 cells were able to remain viable after the EMF exposure. The metabolic activity of EMF treated PC 12 cells was similar to that of the heat treated and control samples, with no difference in the total protein concentration and lactate dehydrogenase (LDH) release between these groups.ConclusionThese results provide new insights into the mechanisms of EMF-induced biological activity in mammalian cells, suggesting a possible use of EMFs to facilitate efficient transport of biomolecules, dyes and tracers, and genetic material across cell membrane in drug delivery and gene therapy, where permanent permeabilisation or cell death is undesirable.

Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC

IntroductionWe hypothesized that activating KRAS mutations and inactivation of the liver kinase B1 (LKB1) oncosuppressor can cooperate to sustain NSCLC aggressiveness. We also hypothesized that the growth advantage of KRAS/LKB1 co-mutated tumors could be balanced by higher sensitivity to metabolic stress conditions, such as metformin treatment, thus revealing new strategies to target this aggressive NSCLC subtype. MethodsWe retrospectively determined the frequency and prognostic value of KRAS/LKB1 co-mutations in tissue specimens from NSCLC patients enrolled in the TAILOR trial. We generated stable LKB1 knockdown and LKB1-overexpressing isogenic H1299 and A549 cell variants, respectively, to test the in vitro efficacy of metformin. We also investigated the effect of metformin on cisplatin-resistant CD133+ cells in NSCLC patient-derived xenografts. ResultsWe found a trend towards worse overall survival in patients with KRAS/LKB1 co-mutated tumors as compared to KRAS-mutated ones (hazard ratio: 2.02, 95% confidence interval: 0.94–4.35, p = 0.072). In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts. Moreover, metformin prevented the development of acquired tumor resistance to 5 consecutive cycles of cisplatin treatment (75% response rate with metformin-cisplatin as compared to 0% response rate with cisplatin), while reducing CD133+ cells. ConclusionsLKB1 mutations, especially when combined with KRAS mutations, may define a specific and more aggressive NSCLC subtype. Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells. This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC.

Photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit plants by cationic porphyrins

The studied cationic porphyrins formulation allows an effective photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit leaves under sunlight irradiation, without damaging the plant. Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative phytopathogenic bacterium responsible for canker on kiwifruit plant. Over the last decade, this bacterium dramatically affected the production of this fruit worldwide, causing significant economic losses. In general, Psa control consists in the application of copper which are toxic and persist in the environment. The application of antimicrobial photodynamic therapy (aPDT) as an alternative to inactivate Psa has already been demonstrated in recent studies that showed a 4 log Psa reduction using the cationic porphyrin Tetra-Py+-Me as photosensitizer (PS) and 3 consecutive cycles of treatment with a light irradiance of 150 mWcm-2. The present work aimed to evaluate the photodynamic efficiency of a new formulation constituted with five cationic porphyrins as PS in Psa inactivation. This new formulation was prepared to have as main component the tri-cationic porphyrin which is considered one of the most efficient photosensitizers in the photoinactivation of microorganisms. The in vitro study with a PS concentration of 5.0µM and low irradiance, showed a 7.4 log photoinactivation after 60min. Posteriorly, several assays were performed with the PS at 50µM on kiwifruit leaves (ex vivo), under different conditions of light and inoculation. The ex vivo assays with artificially contaminated leaves showed a 2.8 and 4.5 log inactivation with low irradiance and sunlight, respectively, after 90min. After a second treatment with sunlight, a 6.2 log inactivation was achieved. The photoinactivation on naturally contaminated leaves was about 2.3 log after 90min sunlight irradiation. Ten consecutive cycles of phototreatment in sub-lethal conditions showed that Psa does not develop resistance, nor recover viability. The results suggest that aPDT can be an alternative to the current methods used to control Psa, since it was possible to inactivate this bacterium under sunlight, without damaging the leaves.

Safety of Intravenous Immunoglobulin (Tegeline®), Administered at Home in Patients with Autoimmune Disease: Results of a French Study.

The efficacy of intravenous immunoglobulins (IVIg) in patients with autoimmune diseases (AID) has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8%) were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.

Sepiolite nanoplatform for the simultaneous assembly of magnetite and zinc oxide nanoparticles as photocatalyst for improving removal of organic pollutants

Novel ternary ZnO/Fe3O4-sepiolite nanostructured materials were developed in a two-step procedure based on the incorporation of ZnO nanoparticles on a substrate composed by magnetite nanoparticles previously assembled to the sepiolite fibrous silicate (Fe3O4-sepiolite). The structural and morphological characterization shows that both, ZnO and Fe3O4 nanoparticles, were homogeneously dispersed on the surface of sepiolite. Therefore, the resulting material is characterized as a multifunctional nanoplatform simultaneously providing magnetic and photoactive properties. ZnO/Fe3O4-sepiolite materials exhibit superparamagnetic properties at room temperature, which is one of the sought properties in view to facilitate their recovery from the reaction medium after application as heterogeneous catalysts. ZnO/Fe3O4-sepiolite materials were tested as photocatalysts using methylene blue dye in water as model of a pollutant molecule, showing full decolorization after 2h of UV irradiation. Moreover, the photocatalytic activity of this nanoplataform may be maintained after reuse in several consecutive cycles of treatment. Remarkably, the ZnO/magnetite-sepiolite nanostructured material displays a similar activity as ZnO/sepiolite materials, but shows the additional advantage of easier recovery by means of a magnet which facilitates its reuse.

The evolving hemostatic profile of patients with myeloma receiving treatment

Thrombosis is a well-described complication of myeloma and the drugs used to treat it. The causes are multifactorial. Traditional screening tests of coagulation, such as the prothrombin time and the activated partial thromboplastin time, are known to be poor at assessment of thrombosis risk. It has been suggested that global measures of haemostasis, such as thromboelastography, may have a role to play in the assessment of this risk. The aim of this study was to look at traditional measures of haemostasis, that measure certain parts of the coagulation cascade, as well as thromboelastography, to see if a coagulation profile of patients with myeloma could be established. Sixteen consecutive patients with symptomatic myeloma were recruited and had their coagulation parameters measured at baseline and following four consecutive cycles of treatment. IgG was the most common subtype of myeloma. Almost two thirds received an immunomodulatory agent and the majority of patients (13/16) received some form of thromboprophylaxis. The median FVIII:C level was elevated at baseline. It significantly increased after one cycle of chemotherapy (p = 0.02). This pattern was replicated with VWF:Ag (p = 0.039). Thromboelastography demonstrated a significant shortening of the mean k time (p = 0.015) and a mean increase in the alpha angle (p = 0.032) between baseline and after two cycles of treatment consistent with increasing hypercoagulability. Markers of hypercoagulability are increased in patients with myeloma and further increase when they commence treatment. There is a suggestion that after this initial increase, as the burden of myeloma decreases, so do these markers of hypercoagulability.

Effect of Photodynamic Therapy on the Virulence Factors of Staphylococcus aureus.

Staphylococcus aureus is a Gram-positive bacterium that is present in the human microbiota. Nevertheless, these bacteria can be pathogenic to the humans. Due to the increasing occurrence of antibiotic-resistant S. aureus strains, new approaches to control this pathogen are necessary. The antimicrobial photodynamic inactivation (PDI) process is based in the combined use of light, oxygen, and an intermediary agent (a photosensitizer). These three components interact to generate cytotoxic reactive oxygen species that irreversibly damage vital constituents of the microbial cells and ultimately lead to cell death. Although PDI is being shown to be a promising alternative to the antibiotic approach for the inactivation of pathogenic microorganisms, information on effects of photosensitization on particular virulence factors is strikingly scarce. The objective of this work was to evaluate the effect of PDI on virulence factors of S. aureus and to assess the potential development of resistance of this bacterium as well as the recovery of the expression of the virulence factors after successive PDI cycles. For this, the photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Tetra-Py+-Me) and six strains of S. aureus [one reference strain, one strain with one enterotoxin, two strains with three enterotoxins and two methicillin resistant strains (MRSA) – one with five enterotoxins and the other without enterotoxins] were used. The effect of photosensitization on catalase activity, beta hemolysis, lipases, thermonuclease, enterotoxins, coagulase production, and resistance/susceptibility to methicillin was tested. To assess the development of resistance after successive cycles of treatment, three strains of S. aureus (ATCC 6538, 2065 MA, and SA 3 MRSA) were used. The surviving colonies of a first cycle of PDI were collected from the solid medium and subjected to further nine consecutive cycles of PDI. The results indicate that the expression of some external virulence factors is affected by PDI and enterotoxin producing strains were more susceptible to PDI than non-toxigenic strains. The surviving bacteria did not develop resistance. PDI, contrarily to traditional antibiotics, inhibited the expression of virulence factors, efficiently inactivating either highly virulent strains and low virulent S. aureus strains, inactivating also antibiotic susceptible and resistant strains, without development of photoresistance after at least 10 consecutive cycles of treatment, and so this therapy may become a strong promising alternative to antibiotics to control pathogenic microorganisms.

Use of a carbon felt–iron oxide air-diffusion cathode for the mineralization of Malachite Green dye by heterogeneous electro-Fenton and UVA photoelectro-Fenton processes

A novel carbon felt cathode coated with iron oxides has been prepared by Fe3+ electrodeposition. The deposited iron content was analyzed by X-ray fluorescence, the composition of iron oxides formed by X-ray diffraction and the morphology of deposits by scanning electron microscopy and energy-dispersive X-ray spectroscopy. Freshly prepared electrodes were used as air-diffusion cathodes in a stirred tank reactor with a boron-doped diamond (BDD) anode to degrade solutions of Malachite Green dye at pH3.0 by heterogeneous electro-Fenton (EF) and photoelectro-Fenton (PEF) processes. Oxidizing agents were hydroxyl radicals formed at the BDD surface from water oxidation and at the cathode surface or in the bulk from Fenton's reaction between deposited or leached Fe2+ and electrogenerated H2O2 in both treatments, along with the photo-oxidation by UVA light in heterogeneous PEF. The decolorization and mineralization of dye solutions were faster for the latter process due to the photolysis of Fe(III) complexes with initial oxalate and generated carboxylic acids. TOC decay always obeyed a pseudo-first-order kinetics. The increase in dye concentration decelerated the decolorization efficiency and mineralization rate, but enhanced the mineralization current efficiency. A test of 10 consecutive cycles of heterogeneous EF treatment of 50mgL−1 of Malachite Green at 21.7mAcm−2 showed a gradual loss of iron oxides from the cathode with decreasing dye mineralization rate. An improvement of the stability of the novel cathode is then necessary for its reuse with a better keeping of the oxidation power of heterogeneous EF and PEF treatments of organic pollutants in waters.

Antitumor and antimetastasis effects of carboplatin liposomes with polyethylene glycol-2000 on SGC-7901 gastric cell-bearing nude mice.

The present study aimed to analyze the characteristics of polyethylene glycol (PEG)ylated carboplatin liposomes (PL-CBPs), including size, stability, their release, entrapping and loading efficiencies, and their antitumor and antimetastatic effects on the lymph nodes. The PL-CBPs were prepared using PEG-2000 with the thin film hydration method. The liposome size and release, entrapping and loading efficiencies were detected by ultra-violet/visible spectrophotometry. A nude mouse model was established with the SGC-7901 gastric cell line to evaluate the antitumor effect of the PL-CBP. After 7 days, the mice were randomly divided into three groups (the control, CBP, and PL-CBP groups). CBP and PL-CBP were administered at a dose of 10 mg/kg for two consecutive cycles of treatment, 5 days apart, to their respective groups. In each group, two doses of 5 mg/kg were administered every 48 h. The tumor weight and volume were detected, and the food intake and body weight were measured during the administration. Apoptosis in the tumor cells was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and platinum (Pt) accumulation was detected by atomic absorption spectroscopy. Lastly, lymph node metastasis was evaluated by hematoxylin and eosin staining. The PL-CBPs were more stable when comapred with CBP alone, and the drug release efficiency was 0.7, 22.5, 48.7 and 65.1% at 37°C for 0, 12, 24 and 48 h. The results showed that the encapsulation efficiency was 85% and the loading efficiency was 0.15 mg/mg lipid. After 35 days, PL-CBP induced potent antitumor effects compared with the control and CBP groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). PL-CBP and CBP induced a lower and the lowest body weight and level of food intake, respectively, compared with the control group (CBP vs. control, P<0.05). The apoptosis rate and lymph node metastasis in the PL-CBP group was higher than that in the CBP and control groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). Pt accumulation in the tumors was higher in the PL-CBP group than in the CBP group (PL-CBP vs. CBP, P<0.05). The PL-CBPs were more stable in the circulation and could be released more slowly at the tumor site than compared with CBP injection. The PL-CBPs showed potent antitumor and antimetastatic effects on the lymph nodes.

Prolonged Treatment with Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL),

Prolonged Treatment with Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL),

Aromatase Inhibitors in Infertility Treatment: Risks and Benefits

Ovulatory disorders (such as polycystic ovary syndrome [PCOS]) are commonly treated with clomiphene citrate (CC), with rates of ovulation ranging between 50 and 90%. However, even though the majority of pregnancies occur within the first three cycles of treatment [1], the overall pregnancy rates are disappointingly low, ranging from 20–40% [2–4], and the likelihood of miscarriage is relatively high [5]. This discrepancy between high rates of ovulation and low rates of pregnancy is believed to be a consequence of the antiestrogenic effect of CC on peripheral targets, such as the endometrium (affecting its thickness and maturation) and the endocervix (affecting the production and quality of cervical mucus). The problem is compounded by the long half-life of CC and the persistence of an isomer, zuclomiphene, both of which lead to an accumulating antiestrogenic effect with consecutive cycles of treatment [6]. In addition, due to the prolonged occupation of estrogen receptors by CC in the hypothalamus, the circulating amount of estrogen may rise to high levels from ongoing stimulation of the follicles by endogenous follicle-stimulating hormone (FSH) production. Such supraphysiological levels of estrogen may be deleterious to the developing oocyte, sperm and embryo [7]. Consequently, better methods for inducing ovulation are desirable. Studies in animals suggest that aromatase, an enzyme necessary to convert androgens to estrogen, could be a potential target for the inhibition of estrogen production. Aromatase inhibitors (AIs) increased gonadotropin levels and ovarian weight in female rats [8], and have been found to produce multiple ovarian follicles in female primates [9]. The new generation of AIs (anastrozole, letrozole and vorozole) have more specific action, fewer side effects and lower