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This work focuses on applying a combined process combining electro-Fenton (EF) pretreatment with biological degradation to mineralize the antiviral Ribavirin in an efficient, economical and ecological manner. First, the main experimental parameters affecting the efficiency of the electro-Fenton process, namely applied current intensity, Fe(II) catalyst concentration and initial Ribavirin concentration were evaluated and optimized. Indeed, the mineralization rate reaches maximum residual values of 99% after 4 hours of electrolysis applying a current of 200 mA. This mineralization is accompanied by an increase in biodegradability, evaluated from the BOD5/COD ratio, which goes from 0.04 at the beginning of treatment (1 h) to 0.45 after 2 hours of electrolysis, demonstrating the feasibility of a biological treatment. In addition, the energy efficiency decreased when the treatment time was extended due to the limitation of mass transport. Thus, the feasibility of coupling electro-Fenton and biological treatment has been successfully demonstrated on a laboratory-scale was, achieving a 96.66% removal rate by the Bio-EF process. A Box-Behnken design based on response surface methodology was applied to develop a model for predicting Rib removal rate. The interaction of factors such as Rib concentration (X1), catalyst concentration (X2) and electrolysis time (X3) was analyzed to identify optimal operating conditions. The model results obtained are statistically significant with an R2 of 0.99, indicating that the proposed model is significant and relevant. In addition, the iso-response curves obtained enabled us to determine the optimal experimental conditions required for effective mineralization of the targeted antiviral. [ABSTRACT FROM AUTHOR]

The Electro-Fenton process is an electrochemical advanced oxidation method based on electrocatalytic in situ production of hydroxyl radicals (•OH). The decontamination of water polluted by Oxytetracycline (OTC) as being a toxic and persistent organic contaminant was carried out by the Electro-Fenton process (EF). Using a platinum anode and a carbon felt, many experiments have been carried out while studying the effect of several parameters on the efficiency of EF such as the applied current, the concentration of the catalyst, and the initial concentration of OTC. The degradation kinetics were studied and monitored by HPLC during electrolysis using an OTC initial concentration of 0.03 mM, 500 mA as applied current, and 0.1 mM of Fe2+ as optimal parameters. As for the mineralization, the chemical oxygen demand COD gave a reduction rate greater than 97% for 500 mA and 0.2 mM of Fe2+. The identification of some intermediate compounds was carried out by HPLC and LC-MS/MS. [ABSTRACT FROM AUTHOR]

AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 within vitroactivity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m2twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR). Nineteen patients were accrued (7 CLL, 12 MCL). Four CLL patients achieved stable disease (SD). Two MCL patients achieved partial response (PR), and 6 had SD. One additional MCL patient with SD subsequently achieved PR 9 months after completion of AT7519M. Tumor lysis syndrome was not reported. In conclusion, AT7519M was safely administered to patients with relapsed/refractory CLL and MCL. In CLL, some patients had tumor reductions, but the ORR was low. In MCL, activity was noted with ORR of 27%. [ABSTRACT FROM PUBLISHER]

Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples.Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided.Results: Mean age was 52.1±9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin.Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin. [ABSTRACT FROM AUTHOR]

Background: Hard ticks infesting cattle are vectors of Tick-borne diseases that causes major public health problems and considerable socioeconomic losses to the livestock industry in tropical and subtropical countries. A repeated cross-sectional study was carried out by collecting ticks on cattle during the wet and dry seasons from January to August 2021 in order to determine hard tick prevalence, distribution, and abundance on cattle in Kilombero and Iringa Districts of Tanzania. The collected ticks were identified morphologically using published morphological keys under a stereomicroscope and confirmed by polymerase chain reaction (PCR) and sequencing., Results: Out of 740 examined cattle, 304, (41.08%) were infested with ticks. In total, 1,780 ticks were counted on one side of the animal's body and doubled, whereby resulting in a total of 3,560 ticks were recorded. Individual tick burden ranged from n = 2 to 82 ticks per animal, with a mean tick burden of n = 11.7 ± 0.68 per animal. A total of 1,889 ticks were collected from infected cattle including 109 additional ticks observed while collecting ticks based on the animal's posture when restrained to the ground. Out of 1,889 ticks, nine species from three genera were identified morphologically: 1,377 fit in the genus Rhipicephalus, 459 to the genus of Amblyomma, and 53 to the genus Hyalomma. Rhipicephalus microplus was the most prevalent (n = 909, 48.1%), followed by Rhipicephalus evertsi (n = 310, 16.4%), Amblyomma lepidum (n = 310, 16.4%), Rhipicephalus appendiculatus (n = 140, 7.4%), Amblyomma gemma (n = 120, 6.4%), Hyalomma rufipes (n = 50, 2.6%), Amblyomma variegatum (n = 29, 1.5%), Rhipicephalus decoloratus (n = 18, 1.0%), while the least common was Hyalomma albiparmatum (n = 3, 0.2%). Tick diversity was higher in Iringa compared to Kilombero District. Tick prevalence was higher in wet season (n = 148, 41.11%). Ticks were widely distributed in different parts of the host body, with the highest distribution on zone 4 (n = 1,060, 56.11%), which includes groin, flank, abdomen, and around inner thigh of the hind legs and the lowest distribution on zone 2 (n = 14, 0.74%), which includes the back surface of the body. Both Amblyomma lepidum and Rhipicephalus microplus species were found in all the five body zones, and with the highest proportions recorded on zone 4: A. lepidum (n = 209, 67.42%) and R. microplus (n = 714, 78.55%). The nine tick species identified morphologically were also confirmed using molecular methods. However, during sequencing, two species (Rhipicephalus appendiculatus and R. decoloratus) had poor quality sequences and were excluded from the sequence analysis. Sequencing results indicated high nucleotide identity (96-100%) with sequences available in GenBank and Barcode of Life Database (BOLD). The phylogenetic analysis of partial mitochondrial COI and 16S rRNA gene sequences of ticks were used to confirm the morphological identification., Conclusion: The results showed a high burden of tick infestation on cattle, which could reduce animal production and potentially increase the risk of tick-borne diseases. Therefore, it is necessary to explore the epidemiological and molecular aspects of various tick species in other regions of Tanzania., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ticks are vectors and reservoirs of a variety of pathogens including protozoa, bacteria and viruses which cause tick-borne diseases (TBDs) in humans and livestock. TBDs pose serious constraints to the improvement of livestock production in tropical and subtropical regions of the world. Despite their wide distribution, information on the tick and pathogen relationship is scarce in Tanzania. We used nested PCR and sequencing to screen pathogens of public and veterinary health importance in ticks collected by flagging from four districts of Tanzania. In total, 2021 ticks comprising nine species were identified. DNA from ticks was pooled according to tick species, developmental stage, and location, then screened for Babesia bigemina, Babesia bovis, Theileria parva and Coxiella burnetii. Out of 377 pools, 34.7% were positive for at least one pathogen. Theileria parva was the most abundant with a minimum infection rate (MIR) of 2.8%, followed by B. bigemina (MIR = 1.8%) and B. bovis (MIR = 0.8%). Multiple pathogens detection was observed in 7.2% of the tested pools. However, PCR screening of individual tick DNA revealed that only 0.3% of the examined pools had co-infection. DNA of C. burnetii was never detected in any tick DNA pool. The MIR of tick-borne pathogens (TBPs) differed significantly among districts, seasons, tick species, and tick developmental stages. Sequence analysis showed that B. bigemina RAP-1a, B. bovis SBP-4, and T. parva p104 genes were conserved among pathogens in the four districts. Despite the absence of C. burnetii in ticks, considering its pathogenic potential, it is essential to continue monitoring for its possible recurrence in ticks. This information adds to the knowledge of TBPs epidemiology and will contribute to the scientific basis for planning future control strategies., (© 2023. The Author(s).)

Tick-borne diseases including East Coast fever, anaplasmosis and babesiosis constitute a major constraint to improving livestock production worldwide, including Tanzania. Determination of the prevalence and factors associated with the occurrence of pathogens in cattle is important for informed decision making on the control and prevention of these diseases. However, little is known about the epidemiology of these pathogens in cattle in some regions of Tanzania. Therefore, this study aimed at establishing the prevalence of Anaplasma marginale, Babesia bigemina, Babesia bovis and Theileria parva in cattle, determine the risk factors associated with infection with these pathogens and also to assess tick control practices in Gairo and Monduli districts of Tanzania. Out of the 520 cattle sampled, the majority (82.9%) were infested with ticks of different species, predominated by Rhipicephalus decoloratus (42.7%), Amblyomma variegatum (31.3%), Rhipicephalus pulchellus (23.1%) and Rhipicephalus appendiculatus (17.7%). Other ticks that were found on cattle included Rhipicephalus microplus (15.8%), Amblyomma gema (13.8%), Rhipicephalus evertsi (12.9%), Amblyomma lepidum (8.1%), Hyalomma truncatum (2.9%) and Hyalomma albiparmatum (2.1%). On microscopy 23 (4.4%) of 520 cattle were positive for hemoparasites. Of the 23 positive cattle, 13 (2.5%), 6 (1.2%) and 3 (0.6%) were monolithically infected with A. marginale, T. parva, and B. bovis respectively, while one (0.2% %) had co-infections of T. parva and A. marginale. The number of positive cattle increased to 184 (35.4%), when they were subjected to detection with PCR. This included the 23 samples that were positive on microscopy. Based on PCR, the overall prevalence of the pathogens from the two districts was 11.5%, 11.2%, 6.2% and 2.5% for B. bigemina, A. marginale, T. parva and B. bovis, respectively. Hemoparasite co-infection occurred in 6.9% of the cattle examined. The prevalence of co-infections was 2.7%, 4%, and 0.02% for T. parva/A. marginale, B. bigemina/A. marginale and B. bigemina/A. marginale/T. parva, respectively. Cattle with co-infections had significantly lower (p < 0.005) mean packed cell volume as compared to cattle with mono-infections. The majority (96%) of cattle examined were subjected to different methods of tick control. A number of risk factors were shown to be associated with the occurrence of tick-borne pathogens in cattle. Higher prevalence of A. marginale may be due to its wide range of biological and mechanical transmission. These findings could be used to strengthen future control programs for ticks and tick-borne diseases in the study areas., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples., Methods: Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided., Results: Mean age was 52.1±9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin., Conclusions: Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)