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Zinc nanoparticles applied in the production of zinc–air batteries provide the highest specific energy among various metal–air combinations used in batteries in practice. Recent technical advances provide an opportunity to successfully solve the problems experienced during the early development of batteries of this type. For example, there is a major limitation in recharging cycles due to the massive formation of zinc oxide. In the present work, a reduction process is proposed on the basis of the use of alcohol solvent by applying microwave in-liquid plasma. The occurrence of reduction was confirmed by calculating the chemical potential of ethanol and methanol as well as spectra of plasma emission in the temperature range 1500–2000 K. Characterization of synthesized nanoparticles was carried out by energy-dispersive X-ray spectrometry and transmission electron microscopy.

Glioblastoma is a glioma characterized by highly malignant features. Numerous studies conducted on the relationship between glioblastoma and the microenvironment have indicated the significance of tumor-associated macrophages/microglia (TAMs) in glioblastoma progression. Since interleukin (IL)-1β secreted by TAMs has been suggested to promote glioblastoma growth, we attempted to elucidate the detailed mechanisms of IL-1β in glioblastoma growth in this study. A phospho-receptor tyrosine kinase array and RNA-sequencing studies indicated that IL-1β induced the activation of signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. Glioblastoma cells stimulated by IL-1β induced the production of IL-6 and CXCL8, which synergistically promoted glioblastoma growth via signal transducer and activator of transcription-3 and nuclear factor-kappa B signaling. By immunohistochemistry, IL-1β expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1β might be a useful target molecule for anti-glioblastoma therapy.

Background Carbon monoxide causes electrical, functional, and morphological changes in the heart. It is unclear, however, whether the indicators of myocardial damage can predict the patient’s prognosis after carbon monoxide poisoning. This retrospective study aimed to investigate the relationship between the carboxyhemoglobin level and electrocardiographic (ECG) changes and whether the ECG changes and troponin I levels are related to the patient’s prognosis after carbon monoxide poisoning. Methods Carboxyhemoglobin, troponin I, and ECG parameters were measured in 70 patients with carbon monoxide poisoning. The QT and RR intervals were measured for each ECG lead in all patients, and the corrected QT interval and corrected QT dispersion were calculated. Results The correlation between the maximum corrected QT interval and the carboxyhemoglobin level was significant (P = 0.0072, R2 = 0.1017), as were the relationships between QT dispersion and carboxyhemoglobin (P R2 = 0.2358) and the corrected QT dispersion and carboxyhemoglobin (P R2 = 0.2613). The multivariate logistic analysis showed that the significant predictors of sequential disability were corrected QT dispersion (P = 0.0042), and troponin I level (P = 0.0021). Conclusions Patients’ prognosis following carbon monoxide poisoning can be predicted based on corrected QT dispersion and the troponin I level. Patients with myocardial damage should be monitored not only for their cardiovascular outcome but also for their neurological outcome and their prognosis.

Pollution is affecting river Rwabakazi in the Nile basin. Its effects are reflected by high turbidity, pH, total suspended solids, (T.S.S.), electrical conductivity, metal ions concentrations, and low concentration of dissolved oxygen (DO5). In this study, we report the variations in selected physicochemical parameters of waters of the Rwabakazi river. Turbidity, pH, concentrations of selected metal ions, T.S.S., and DO5 of water sampled from three selected sites on the river in Kabale were very high. Mean DO5 fell from 96 ± 2 mg/L to 86± 1.5 mg/L downstream. The mean pH fell from 7.8 ± 0.03 to 7.6 ± 0.04, showing the removal of basic components. The turbidity dropped from370 ± 3 NTU to 305 ± 2 NTU, showing that the haziness of water decreased. The concentration of iron(II) fell from 320 ± 0.3 mg/L to 291 ± 0.2 mgL-1 indicating the fair extent of heavy metal ions downstream. The T.S.S. decreased from 330 ± 5 mg/L to 300± 5 mg/L, and concentrations of calcium and magnesium ions also decreased, providing evidence for self-purification. The available data suggests that river Rwabakazi is polluted as a result of poor agricultural practices, erosion, and flash flooding. Further studies on nutrient and pesticide pollution of this river need to be carried out, and trees should be planted on steep open surfaces to minimize erosion.

Background Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p Results Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p 3 increment). Conclusion Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

Many science-based institutions in most developing countries use heavy metal containing salts in practical teaching sessions. The commonly used chemicals are the salts of lead (II) and copper (II) and the wastes generated end up into the environment when untreated. Thus, a study was done to remove lead (II) and copper (II) ions from mono synthetic aqueous solution using bio-char from Ficus natalensis fruits (FNF). This was done at varied pH, contact time, temperature, bio-char dosage level, salinity and metal ion concentration using the batch approach. The residual metal concentrations were determined using the atomic absorption spectrophotometer. The optimum pH for the adsorption of copper (II) and lead (II) ions was found to be 4.0 and 5.0 respectively. The maximum percentage adsorption of copper (II) and lead (II) by the FNF bio-char was established at 60 minutes contact time, 47.5&degC and 0.4 g adsorbent dose. Increase in the metal ion concentration and the presence of interfering ions in the aqueous solution lead to decrease in the percentage adsorption. The highest adsorption capacity was found to be 161.29 mg/g and 1250 mg/g for copper (II) and lead (II) ions respectively. The thermodynamic parameters indicated the feasibility of the adsorption of copper (II) and lead (II) on the bio-char of FNF. Thus, bio-char from FNF may be used as an adsorbent in waste management where copper (II) and lead (II) ions are present at a concentration range of between 5 and 100 mg/l.

The potential of the Senegal date palm (Phoenix reclinata) seed bio-char to remove chromium (VI) ions from aqueous solutions by adsorption was investigated. Adsorption experiments were performed on the tannery effluent and standard aqueous solutions of chromium (VI) for varying adsorbent doses, contact times, pH, temperatures, and interfering anionic ions by batch mode. Phoenix reclinata seeds (PRS) bio-char was used in the investigation and the residual chromium (VI) was determined using the atomic absorption spectrophotometer (AAS). Results showed that the bio-char removed up to 86% of chromium (VI) ions in the effluent at pH 2. The highest percentage adsorption registered was 97% in an aqueous solution of chromium (VI) at pH 1 and this dropped to less than 10% at pH greater than 2. A general increase in adsorption with the increase in temperature was observed but reduced when the temperature was raised beyond 60°C. The presence of interfering anions caused a reduction in the adsorption of chromium (VI) ions. The adsorption process fitted both Langmuir and Freundlich adsorption models and the maximum adsorption capacity, Qo, was 0.6593 mg/g. Thus, PRS bio-char can therefore be used by industries and institutions like secondary schools to treat effluents that contain chromium (VI).

Summary 2-Methylthio-N6-isopentenyl modification of adenosine (ms2i6A) is an evolutionally conserved modification found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i6A) to ms2i6A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i6A by converting i6A to ms2i6A and protected GICs from excessive autophagy triggered by i6A. The elevated activity of CDK5RAP1 contributed to the amelioration of the tumor-suppressive effect of i6A and promoted GIC maintenance. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i6A and that GICs readily utilize this mechanism for survival., Graphical Abstract, Highlights • CDK5RAP1 is required to sustain the growth of GICs through ms2 modification of i6A • Deficit of CDK5RAP1 inhibits the growth of GIC through i6A accumulation • CDK5RAP1 detoxifies i6A by conversion into ms2i6A in the mitochondria of GICs • Mitochondria serve as antidotal machinery against i6A in GICs, Biological Sciences; Molecular Biology; Cell Biology; Stem Cells Res earch; Cancer

Most waste solvent treatment methods involve combustion; however, such methods emit carbon dioxide and are also problematic relative to energy costs. As well as reducing carbon dioxide generate, in-liquid plasma has been used to generate valuable substances and hydrogen energy from the waste solvent. As a waste solve treatment model, decomposition of acetone using 27.12 MHz in-liquid plasma was performed at atmospheric pressure. The produced gases were H2, CO, CH4, C2H2, C2H4, C2H6, and CO2, where proportion of CO2 was less than 0.25%. Two types of carbons with different properties were obtained as byproducts during the acetone decomposition. These carbons analyzed using elemental analysis and Raman spectroscopy. The analysis results revealed that the crystallinity of the carbons different significantly. Undesirable organic matter, such as benzene, was also produced during acetone decomposition. The acetone decomposition efficiency at 407 W discharge power was 0.9 μmol J−1.

Glioblastoma is one of the most devastating human malignancies for which a novel efficient treatment is urgently required. This pre–clinical study shows that eribulin, a specific inhibitor of telomerase reverse transcriptase (TERT)‐RNA‐dependent RNA polymerase, is an effective anticancer agent against glioblastoma. Eribulin inhibited the growth of 4 TERT promoter mutation‐harboring glioblastoma cell lines in vitro at subnanomolar concentrations. In addition, it suppressed the growth of glioblastoma cells transplanted subcutaneously or intracerebrally into mice, and significantly prolonged the survival of mice harboring brain tumors at a clinically equivalent dose. A pharmacokinetics study showed that eribulin quickly penetrated brain tumors and remained at a high concentration even when it was washed away from plasma, kidney or liver 24 hours after intravenous injection. Moreover, a matrix‐assisted laser desorption/ionization mass spectrometry imaging analysis revealed that intraperitoneally injected eribulin penetrated the brain tumor and was distributed evenly within the tumor mass at 1 hour after the injection whereas only very low levels of eribulin were detected in surrounding normal brain. Eribulin is an FDA‐approved drug for refractory breast cancer and can be safely repositioned for treatment of glioblastoma patients. Thus, our results suggest that eribulin may serve as a novel therapeutic option for glioblastoma. Based on these data, an investigator‐initiated registration‐directed clinical trial to evaluate the safety and efficacy of eribulin in patients with recurrent GBM (UMIN000030359) has been initiated.

Oxidation of low-density lipoproteins (LDL) causes atherosclerosis. Detection of oxidation of LDL-mimetic liposomes using an electrode might serve as a convenient tool in the search of antioxidants for the prevention of atherosclerosis. This report proposes a reaction mechanism between LDL-mimetic liposomes and an acid-treated carbon nanotube (CNT) electrode. Oxidation of the liposomes, mediated by Cu2+, was monitored by the change in electrode potential, and the fluorescence intensity generated by diphenyl-1-pyrenylphosphine (DPPP) as control. The electrode potential and fluorescence intensity increased concomitantly during oxidation, followed by a gradual decrease. Although the electrical potential peaked faster than the fluorescence intensity, addition of CNT to the DPPP reaction accelerated the latter, suggesting the role of CNT as an accelerator of liposome oxidation. Atomic force microscopy showed increased binding of liposomes to CNT along with liposomal deformation. Further, binding of Cu2+ to the liposome-bound CNT surface was observed by quartz crystal microbalance. In conclusion, the interaction of liposomes with Cu2+ and CNT surface explains the rapid response of the electrode in liposome oxidation.

Purpose: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. Experimental Design: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. Results: The probe screening identified proline-arginine–HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. Conclusions: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

Silica glass structure is simulated applying different annealing conditions that intend to imitate a fiber drawing process using molecular dynamic simulation in order to compare structural properties of differently processed glasses.

Biogas is anaerobic degradation product formed from aqueous slurry of organic waste in a digester. It can be produced from cattle dung, (cd)chicken droppings, decaying leaves, kitchen waste foods, (kwf), sewage sludge, slaughter house, goat, pig or sheep manure, Aqueous slurry of 200 g/L of mixed or single substrate of cattle dung or/and kitchen waste evolved up to 400mL of biogas at ambient temperatures. The rate of gas evolution reached 5 mL/day on the 15th day using 25 % cd mixed slurry. The overall rates of degradation attained in the mixtures were 1.42 + 0.26 mL/g for cd; 1.58+0.33 mL/g for kwf; 1.78+ 0.38 mL/g for 75 % cd mixed substrate; 1.78+ 0.29 mL/g for 50 % cd mixed substrate; 1.92+ 0.21 mL/g for 25 % cd mixed substrate slurries in the 200 g/L load. The comparative rate of biogas formation ranged from1.25 to 1.35 which was in agreement with the range published in literature of 0.8 to 5.5. Biogas can be synthesized efficiently at ambient temperature in Kampala as was done at mesophilic temperatures elsewhere. However, it may be necessary to attempt producing biogas at different pH and temperatures as well as using other substrates and inoculums.

To enhance hydrogen production efficiency by in-liquid plasma, the method inserting catalytic metal into in-liquid plasma reaction field was considered. To retain a bubble at the tip of in-liquid plasma electrode, a plate is fixed over the electrode. That plate and electrode are composed of a catalytic metal. Methanol is decomposed by in-liquid plasma, and the gas generation rate and composition rate are measured. The gas is composed of 67% H2, 30% CO, and 3% other. This rate is independent of the material of the electrode or plate. The plate enhances the hydrogen production rate. When the plate and electrode are composed of Ni (0.37 Nm3/kWh), the maximum hydrogen production rate is obtained.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

PURPOSE Fluorescence imaging is an important surgical adjunct in malignant glioma surgery. 5-aminolevulinic acid (5-ALA) has been proven effective for radical tumor resection and extended progression-free survival in a phase III randomized trial and therefore integrated into surgery for malignant glioma. Importantly, however, some limitations still exist in its use, which include false positivity and false negativity as well as inability of re-administration. In this study, we aimed to develop a novel, spray-type fluorescent probe using hydroxymethyl rhodamine green (HMRG) as a fluorescent scaffold. METHODS We have previously established a fluorescent probe library comprised of more than 320 kinds of HMRG probes. They have HMRG as a fluorescent scaffold with various types of dipeptides attached to it. Primary probe screening was performed using the homogenized tumor samples from patients with glioblastoma operated at our institution. Secondary screening followed using the selected probes and fresh tumor samples obtained from patients with glioblastoma operated from 2016 until 2018. Diced electrophoresis gel (DEG) assay, two-dimensional gel electrophoresis followed by a multi-well plate-based fluorometric assay, was performed to identify responsible enzymes for the selected probe. Further experiments with inhibitors, real-time PCR, immunohistochemistry, and western blotting were performed for confirmation. RESULTS Proline-arginine-HMRG (PR-HMRG) was selected as a candidate probe based upon the above two-step screenings. It achieved 79.4% accuracy in receiver operating characteristic curve analysis. Calpain-1 was found to be responsible to cleave PR-HMRG probe by DEG-proteome analysis. Calpain-1 protein was expressed at significantly higher level in tumors that were fluoresced by PR-HMRG than in those that were not. CONCLUSIONS Our innovative screening method was able to find PR-HMRG as a novel fluorescent probe effective for rapid detection of glioblastoma. A preclinical study is planned to assess the efficacy and safety of the selected probe.

The purpose of this study is to synthesize diamond onto Si, Cu, and Fe (SUS632J2) substrates and to analyze the effect of carbon diffusion on their surfaces. Diamond was synthesized using the in-liquid microwave plasma chemical vapor deposition (IL-MPCVD) as a novel method for synthesizing diamond on various base materials. The IL-MPCVD method is superior one due to its efficiency in terms of cost, space and speed as compared to a conventional gas phase microwave plasma CVD (MPCVD). Microwaves of 2.45 GHz generated plasma in a solution which was comprised of methanol: ethanol (M:E = 97:3). Evaluation of deposited diamond films was done by a Scanning Electron Microscope (SEM) and Raman spectroscopy. Results shows that the IL-MPCVD method can form diamond films on Cu, Si and Fe substrates. The minimum time of film formation of Cu, Si and Fe are 2.5, 3.5 and 5 min, respectively. The material that forms carbide layers such as Si is a better substrate to form diamond film by the IL-MPCVD than other metal substrates such as Cu and Fe. Synthesizing diamond directly on the Fe substrate results in poor quality layers. The effect of carbon diffusion influences diamond film nucleation and diamond growth. In order to alleviate the carbon diffusion and improve the quality of the diamond film on the Fe substrate, Si has been sputtered on the Fe substrate as an interlayer. It is found that the diamond film can be formed on a Fe substrate using a Si interlayer and that heat treatment and thickening the interlayer improve its quality.

PURPOSE: ALA is commonly used as an intraoperative tool in malignant glioma surgery, which has been proven effective for radical tumor resection and extended progression-free survival. However, there are some limitations in its use, such as false positivity, false negativity, and inability of re-administration. We aim to develop a novel fluorescent labeling system which can be repeatedly administered by spray during surgery, using hydroxymethyl rhodamine green (HMRG) as fluorescent scaffold originally designed at our university for cancer detection. [Methods]Primary probe screening was performed using the homogenized glioblastoma (GBM) samples with the fluorescent probe library comprised of more than 320 kinds of HMRG fluorescent scaffold combined with various types of dipeptides. Second probe screening was performed using fresh GBM specimens and the selected probes in primary screening. To identify the responsible enzymes, diced electrophoresis gel (DEG) assay was performed. This method utilizes the combination of two dimensional electrophoresis (isoelectric point and molecular weight) and a multiwell-plate-based fluorometric assay to find protein spots with the specified activities. [Results] The prominent probes were selected based upon the above two-step screenings. We identified two enzymes by proteome analysis and experiments using inhibitors, which was further confirmed with real-time PCR and western blotting. [Discussion] This screening methodology is innovative in that it is based on selecting probes from the probe library that respond to clinical samples rather than creating probes from the responsible enzymes. Practical fluorescent probes can be established even for low-grade gliomas, which would be a breakthrough for rapid intraoperative diagnosis in glioma surgery. [Conclusion] HMRG-based aminopeptidase fluorescent probes may be effective for GBM detection.

Mycotoxin contamination data (n=1818) in feed and food from major laboratories were categorized into hazardous and non-hazardous using contaminants regulatory limits, analyzed by logistic regression and chi-square test to identify potential health hazards. Feeds were most contaminated, with 64% and 39% having total aflatoxin (AFT) levels above Kenyan and American standards respectively. Peanuts, the most contaminated food, had 61% and 47% of samples failing Kenyan and American AFT standards respectively. By European standards, wheat had highest AFT contamination rate of 84%. Half of baby foods sampled had AFT level above Kenyan and European standards. Maize had failure rates of 20% (Kenyan standard), 14% (American standard) and 25% (European standard) for AFT. We observed high frequency of mycotoxins (AFT, aflatoxin M1, zearalenone, T-2 toxin, ochratoxin A, fumonisins, deoxynivalenol) and AFT hazards with significantly (pppppppppppppppp

BACKGROUND: If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS: Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged

Background. Artisanal and small-scale gold mining is a human health concern, especially in low-income countries like Uganda due to the use of mercury (Hg) in the mining process. Objective. The aim of the present study was to assess Hg exposure among artisanal and small-scale gold miners in Uganda through biologic monitoring parameters and Hg-related clinical manifestations. Methods. A cross-sectional study was conducted from June to July 2018 among 183 miners from Ibanda (Western region), Mubende (Central region), Amudat (Karamoja region) and Busia (Eastern region) in Uganda. An interviewer-administered questionnaire and health assessment were used to collect socio-demographic, exposure and self-reported Hg poisoning symptoms. In addition, 41 urine, 41 blood and 26 environment samples were assessed. Descriptive statistics, Kruskal-Wallis test and Wilcoxon signed-rank test for comparison of Hg levels in urine and blood among miners were performed while logistic regression was used to assess associations between exposure and Hg poisoning-related symptoms. Results: The miners ranged from 15 to 65 years old and were primarily male (72.6%). The majority (73.3%) had worked directly with Hg for an average duration of 5.3 years. Symptoms associated with working directly with Hg included chest pain (odds ratio (OR)=9.0, confidence interval (CI)=3.3 to 24.6), numbness (OR=8.5, CI=2.1 to 34.4), back pain (OR=6.2, CI= 2.2 to 17.5), fatigue and stress (OR=5.4, 2.0 to CI=14.9), headache (OR=4.7, CI=1.9 to 11.3), dizziness (OR=3.8, CI=1.5 to 9.7) joint pain (OR=3.2, CI=1.3 to 8.3) and respiratory problems (3.2, 1.0 to 10.1). Statistically significant differences in Hg levels with p-values less than 0.05 were observed across district, gender and type of work. Mubende had the highest blood and urine levels (136 μg/l and 105.5 μg/l) in comparison with Busia (60 μg/l and 70.6 μg/l) and Ibanda (43 μg/l and 58 μg/l). Females (84.7 μg/l), panners (109 μg/l) and those with knowledge of occupational health and safety measures (95.6 μg/l) reported higher levels of Hg in urine. The average levels of Hg in water and soil samples were 23.79 μg/l and 0.21 μg/l, respectively. Conclusions. Variation in Hg levels were attributed to varied duration of exposure across geographical sites. There was considerable exposure to Hg as indicated by both clinical manifestations and biologic parameters among miners in Uganda with Hg in urine exceeding the recommended thresholds. Participant Consent. Obtained Ethics Approval. Ethical approval was obtained from the Makerere University School of Health Science Institutional Review Board (reference number SHSREC REF 2018–2019) and Uganda National Council for Science and Technology (reference number SS 4577) Competing Interests. The authors declare no competing financial interests.

Glioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C‐terminal lysine residues. Our results suggest that SIRT2‐mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may be a promising molecular target for the therapy of glioblastoma.

Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. In this study, we investigated whether brain exposure of Pg-LPS induced systemic organ dysfunction in a model of AD mouse. We employed 6 (young) and 13 (middle-aged) months-old 5XFAD mice and 6 months-old littermate (LT) mice, and treated with intracerebroventricular (ICV) injection of 2 μg Pg-LPS or saline (vehicle). The animals were monitored cognitive functions (Y maze, nest building, and Morris water maze tests), motor functions (wire hang and rotarod tests), physical condition (symptom score), and blood pressure (BP). Twenty-eight days later, their organs were weighted and the organ damages were examined. Continuous ICV injection of 2 μg/day Pg-LPS increased ionized calcium binding adapter molecule-1 (Iba-1) and cluster of differentiation 3 (CD3) positive cells in periventricular area of 5XFAD mice without enhancement of cognitive impairment, amyloid β protein deposition, expressions of phosphorylated nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (COX-2). In addition, the Pg-LPS lowered the latency of rotarod test in young 5XAD mice and also reduced symptom score and weight of gastrocnemius muscle in the middle-aged animals. Moreover, the Pg-LPS induced cardiac atrophy in both young and middle-aged 5XFAD mice, and increased Iba-1 positive cells in left ventricle of the young animals. On the other hand, single ICV injection of 2 μg Pg-LPS in 5XFAD and continuous injection of 2 μg/day Pg-LPS in LT mice did not show any positive findings. Our present results demonstrated that continuous brain exposure of Pg-LPS started sarcopenia and cardiac injury without enhancing cognitive impairment in AD model mice.

Bleaching of edible oils is known to alter the composition of oils as it removes impurities and certain food nutrients. The characteristics of bleached oil are strongly related to type bleaching medium, temperature at which bleaching is done and other factors. In this study, we compare peroxide, free fatty acid, acid and iodine values, copper and iron content of bleached and crude oils to establish the characteristics of edible oils bleached using smectite and kaolinite-rich clays. Oil industries spend large sums of money purchasing bleaching earths yet no country lacks natural clays which can be developed to bleach oils. In Uganda alone more than US$ 700,000 is spent every month yet many clay deposits are unexploited. In this study, we have documented trace metal composition, peroxide values, acid values, iodine values and free fatty acid content of bleached and unbleached cotton-seed and sunflower seed oils. The bleached oils were found to be fit for human use. Clays are either kaolinites or smectites, but the clays used to bleach edible oils are montmorillonites or bentonites. The decrease in content of iron in the bleached oils was highest for all oils bleached. The content of copper showed the smallest change. The content of copper in cotton oils decreased from 0.5 ppm to 0.15 ppm using Kajansi clay leached in 20% acid yet when Chelel clay leached under similar conditions was used decrease was from 0.5 to 0.1 ppm. The content of iron in sunflower oils bleached using Kajansi clay leached in 20% acid decreased from 1.6 to 0.2 ppm yet that bleached with Chelel clay under similar conditions decreased to 0.1 ppm. The acid values showed that the acidity in sunflower oils is largely due to oleic acid as the average value for acids is in the range close to oleic acid, cotton-seed oil corresponded to linoleic acid. The levels of free fatty acid were found to lie in range from 3.8 - 3.2 for all clays used showing no significant rise. The peroxide values of bleached oils lay between 1.2 and 0.8.

Background Brain radiation necrosis (BRN) can be a complication of radiotherapy for primary and secondary brain tumors, as well as head and neck tumors. Since vascular endothelial growth factor (VEGF) is also a vascular permeability factor in the brain, bevacizumab, a humanized antibody that inhibits VEGF, would be expected to reduce perilesional edema that often accompanies BRN. Methods Patients with surgically untreatable, symptomatic BRN refractory to conventional medical treatments (eg, corticosteroid, anticoagulants, or hyperbaric oxygen therapy) were enrolled. We judged that a major cause of perilesional edema with a lesion-to-normal brain ratio ≤1.8 on 11C-methionine or ≤2.5 on 18F-boronophenylalanine PET was BRN, not tumor recurrence, and 6 cycles of biweekly bevacizumab (5 mg/kg) were administered. The primary endpoint was a ≥30% reduction from the patients' registration for perilesional edema continuing for ≥1 month. Results Of the 41 patients enrolled, 38 were fully eligible for the response assessment. The primary endpoint was achieved in 30 of the 38 (78.9%) patients at 3.0 months (median) after enrollment. Sixteen patients (42.1%) experienced improvement of their Karnofsy Performance Score. Corticosteroid use could be reduced in 29 patients (76.3%). Adverse events at grade ≥3 occurred in 10 patients (24.4%). Conclusions Bevacizumab treatment offers certain clinical benefits for patients with surgically untreatable, symptomatic BRN. The determination of BRN using amino-acid PET, not biopsy, is adequate and less invasive for determining eligibility to receive bevacizumab.

This research involves two in-liquid plasma methods of methane hydrate decomposition, one using radio frequency wave (RF) irradiation and the other microwave radiation (MW). The ultimate goal of this research is to develop a practical process for decomposition of methane hydrate directly at the subsea site for fuel gas production. The mechanism for methane hydrate decomposition begins with the dissociation process of methane hydrate formed by CH4 and water. The process continues with the simultaneously occurring steam methane reforming process and methane cracking reaction, during which the methane hydrate is decomposed releasing CH4 into H2, CO and other by-products. It was found that methane hydrate can be decomposed with a faster rate of CH4 release using microwave irradiation over that using radio frequency irradiation. However, the radio frequency plasma method produces hydrogen with a purity of 63.1% and a CH conversion ratio of 99.1%, which is higher than using microwave plasma method which produces hydrogen with a purity of 42.1% and CH4 conversion ratio of 85.5%.

Hydrogen is a very attractive source of highly efficient and environmentally friendly energy. Investigation into hydrogen production from glucose decomposition by 27.12 MHz radio-frequency in-liquid plasma with and without ultrasonic vibrations was carried out utilizing 29 kHz and 1.6 MHz ultrasonic transducers to determine the effects of agitation and acoustic streaming. In-liquid plasma is generated inside a bubble, resulting in a high temperature chemical reaction field within the liquid which is then irradiated by ultrasonic vibration. The dependence of hydrogen production rate, hydrogen yield, hydrogen purity and hydrogen production efficiency on the types of ultrasonic vibration applied was investigated. Higher intensities of active C atoms species were observed in the emission spectrum of RF in-liquid plasma when irradiated with ultrasonic vibration and it is believed that these species function as precursors or intermediaries for other components in the gas product. Hydrogen production rate was enhanced by 30% when RF in-liquid plasma was irradiated by the 1.6 MHz piezoelectric transducer. The highest hydrogen yield was 72% for RF in-liquid plasma with the 29 kHz ultrasonic transducer at an initial concentration 1.0%. The hydrogen purity was enhanced by 5% for the highest initial concentration when applying the 29 kHz ultrasonic transducer to the RF in-liquid plasma. Thus the acoustic streaming effect by 1.6 MHz piezoelectric vibration enhanced the hydrogen production rate, while on the other hand, the agitation effect by 29 kHz ultrasonic vibration enhanced hydrogen yield and hydrogen purity. Though the hydrogen production efficiency of RF in-liquid plasma with ultrasonic vibration applied was lower overall when compared to that without ultrasonic vibration except for decomposition of glucose 20 wt% by RF in-liquid plasma with 1.6 MHz ultrasonic transducer which was 7% higher than that without ultrasonic vibrations, this remains a process that could be considered as a promising future technique for hydrogen production.

The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was established. Cell viability after MTX treatment with LV rescue was evaluated using sodium butyrate (NaBu), a histone-deacetylase inhibitor that induces polyglutamylation by elevating FPGS expression. The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p

At present, pharmaceutical researchers are focusing on instantaneous intraoral dispersible technologies as novel drug delivery systems because; they have outstanding advantages over the traditional oral and parenteral routes of drug administration. Some essential natural drugs have low oral bioavailability due to extensive first pass metabolism and pre systemic degradation in the gastrointestinal tract. Now, a cheap rice paper Intraoral Dispersible Film (IDF) has been developed. In this study, formulation was optimized using the experimental factorial design. The IDFs were loaded with model, natural, anti-cancer drugs, Resveratrol and Curcumin with low oral bioavailability. They were evaluated for thickness, folding endurance, swelling behaviour, among others. These related to their drug release properties. Permeation was evaluated using the pig mucosal membrane mounted on a Franz diffusion cell. Taste testing was done to determine acceptability using a taste panel. Sixteen formulations showed variations in their profiles. Formulation 16 proved optimal. The dissolution rate at steady state concentrations of Resveratrol was 29 mg per second and the Permeability coefficient was 389 mg/sec.cm2. Curcumin dissolution rate at steady state concentrations was 0.25 mg per second and the Permeability coefficient was 42.71 mg/sec.cm2. Resveratrol permeability rate was 0.42 mg/sec. And that of Curcumin was 0.14 mg/sec. Resveratrol Flux was 0.21 mg/sec./cm2. Curcumin Flux was 0.14 mg/sec. / cm2. Drug entrapment was 80% for both molecules. The 20 mg of Resveratrol and Curcumin dissolved in 47.6 sec. and 71.4 sec. respectively. In this study, after permeation, a concentration of 6.73 mg/ml of Resveratrol and 0.061 mg/ml of Curcumin were detected after 2 hours of the experiment on administering only 20 mg of each of the drugs suggesting that Curcumin is 100 times less permeable than Resveratrol. The release profile was a burst release. On contrast, Curcumin oral dose of 2 g/kg to rats yielded 1.35 ± 0.23 μg/ml in 0.83 hours and in humans, given the same dose yielded either undetectable or extremely low (0.006 ± 0.005 μg/ml after 1 hour in blood. Two separate monoglucuronide metabolites yielded a Cmax of ~7.5 μm following a single 5.0 g oral dosage of Resveratrol. The key finding was, ex vivo release profiles of the optimized formulation revealed first order release and later zero order. Therefore, it is evident that rice paper IDF could efficiently deliver natural drugs into the systemic circulation intraorally. However, further studies using human subjects need to be performed to prove increased bioavailability in human subjects (Graphical Abstract).

The Langmuir isotherms of 1-aminobutane in isohexane slurries showed increase in clay acidity with increase in concentration of mineral acid used to leach the clay as well as the temperature at which the clay was thermally activated prior to experimentation involving adsorption of 1-aminobutane. The values of acidity for Central Uganda were low ranging from 0.07 mol/g to 0.32 mol/g yet those for clays from Eastern Uganda were high ranging from 0.1 mol/g to 1.85 mol/g. Based on acidity, pH, elemental and mineral compositions, the clays from Central Uganda were found to be kaolinites or halloysites, yet Eastern Uganda clays were resolved to contain nontronite and kaolinite.

The available data have shown that acid-leached clays had sites for adsorption of impurities in oils. Data obtained on residual impurities in cotton and sunflower-seed oils bleached with the same clay materials produced linear Langmuir and Freundlich isotherms. The increase in constant, k with increase in both temperature of thermal activation and concentration of acid used to leach the clay, suggests that bleaching efficiency increased. The value of n decreased with increase in temperature of activation and concentration of acid used to leach the clay suggesting that bleaching capacity increased. The mineral compositions of the clays influenced their surface, structural and bleaching properties.

Methimazole (MMI) is usually used at an initial dose of 30 mg/day for severe Graves' disease (GD) hyperthyroidism, but adverse effects are more frequent at this dose than at MMI 15 mg/day.We designed a regimen to address the lack of a primary therapeutic effect of the MMI 15 mg/day by combining it with inorganic iodine at 38.2 mg/day. Our aim was to compare the two regimens (MMI 15 mg+inorganic iodine at 38.2 mg/day (M15+I) vs. MMI 30 mg/day (M30)) in terms of therapeutic effect, adverse effects, and remission rate.In a prospective study, 310 patients with untreated GD (serum free thyroxine (fT4) ≥5 ng/dL) were assigned to one of the two regimens. Potassium iodide was discontinued in the M15+I group as soon as the serum fT4 level was within the reference range (0.8-1.6 ng/dL).Percentages of patients achieving an fT4 level within reference range in ≤30, ≤60, or 90 days on the study treatment regimens were 45.3%, 73.9%, and 82.0% respectively for the M15+I group, and 24.8%, 63.1%, and 75.2% respectively for the M30 group. Hence, the proportions of patients achieving this goal in ≤30 or ≤60 days were significantly larger in the M15+I group. Adverse effects that required discontinuation of MMI were more frequent in the M30-treated than in the M15+I-treated group (14.8% vs. 7.5%; p=0.0387). The remission rates in the M15+I and M30 groups were 19.9% and 14.8%-higher in the former, but the difference did not reach statistical significance.The results of this study raise the possibility that M15+I is superior to M30 as a primary treatment for moderate to severe hyperthyroidism caused by GD.

The results on the elemental and mineralogical compositions of clays from Central Uganda differed from those from the volcanic sediments of the Mt. Elgon in Eastern Uganda. Utilisation of the two types of clays should be strict after understanding their structural differences. Whereas elemental, mineralogical, DTA, IR, XRD and pH data on selected clays from Kumi, Nakawa, Seeta, Kajansi, Kawuku, Lwanda, Chodah and Umatengah indicated that they were kaolinites. Similar data on clays from Mutufu, Budadiri, Chelel and Siron indicated that they were largely smectites. The IR data accumulated on Kawuku, Kajansi, Lwada, Seeta, Chodah, Umatengah, Kumi and Nakawa clays revealed they were largely kaolinites yet that on Mutufu, Chelel, Budadiri and Siron clays indicated they were smectite-rich.

Cellulose is a kind of saccharide that is the main component in cell walls of plants and therefore is the organic compound that exists in the largest amount in nature. The purpose of this experiment is to convert cellulose to a fuel. Radio frequency (RF) in-liquid plasma is generated in a cellulose distributed solution and a glucose solution, and the generation gas rate is measured. While hydrogen is the main gas generated by the plasma breakdown, carbon monoxide, carbon dioxide, and low-grade flammable gases are also produced. In the glucose water solution or the glucose distributed solution, the solution itself evaporates and decomposes inside the plasma but since the saccharides are non-volatile, they cannot penetrate into the plasma and are not decomposition. However, when the cellulose is at concentrations of 30 wt% or more, it becomes granular and can directly enter the plasma as a solid, where the plasma decomposes the cellulose itself, significantly increasing the amount of gas generated. In addition, the spectrometry of the plasma emission shows the solution after the creation of plasma has the ability to absorb ultraviolet light.

Despite of recent intense investigations, no effective molecular targeting therapy has been successfully developed in patients with glioblastomas (GBMs). Approximately 60–80% of GBM harbor mutations in the promoter region of telomerase reverse transcriptase (TERT), which leads to its upregulation. It has been reported recently that TERT has an RNA-dependent RNA polymerase (RdRP) activity and TERT-RdRP activity controls cell cycle and maintains stem cell phenotype, suggesting that TERT can be directly targeted to suppress tumor cell proliferation. We have previously identified eribulin mesylate, which is an FDA-approved drug used to treat breast cancer and liposarcoma, as a specific inhibitor of RdRP activity of TERT and investigated the antitumor efficacy of eribulin using multiple human GBM cell lines in preclinical mouse brain tumor models. All GBM cell lines tested in vitro that harbored TERT promoter mutations were highly sensitive to eribulin with IC50 below 1nM. Intraperitoneal administration of eribulin (0.5 mg/kg), which was equivalent to the dose used in human (1.4 mg/m2), significantly prolonged the survival of multiple mouse brain tumor models established with U87MG or LN229 (p

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non-taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M-phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation-induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient-derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas.