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Antiviral drugs are a class of medications used for treating viral infections. Due to their widespread use, especially in cases of pandemics and limited human metabolism, antivirals have been detected in multiple environmental matrices. This study aims to evaluate the chronic effects of acyclovir, efavirenz, lamivudine and zidovudine using Ceriodaphnia dubia and Raphidocelis subcapitata. The results with R. subcapitata showed the following toxicities: zidovudine (IC50 = 5.442 mg L−1) < acyclovir (IC50 = 3.612 mg L−1) < lamivudine (IC50 = 3.013 mg L−1) < efavirenz (IC50 = 0.034 mg L−1). The results of the chronic bioassay with C. dubia demonstrated that zidovudine is the least toxic (EC50 = 5.671 mg L−1), followed by acyclovir (EC50 = 3.062 mg L−1), lamivudine (EC50 = 1.345 mg L−1) and efavirenz (EC50 = 0.026 mg L−1). Both species have been shown to be sensitive to efavirenz. A risk quotient (RQ) was calculated, and efavirenz had an RQ greater than 1 for both species, and lamivudine had an RQ greater than 1 for C. dubia, representing a high ecological risk for these organisms. Antivirals pose a significant environmental risk to aquatic organisms and should be taken into consideration in future monitoring of water sources.

The wastewater from food-processing industries is generally heavily charged with lipids and proteins. Flotation process is commonly applied to separate the hydrophobic material phase, producing flotation froth, a waste that has high levels of fats and proteins. Enzymatic hydrolysis may be used to overcome the difficulty of fat biotransformation in a subsequent anaerobic digestion. In the present work, wastes from the flotation process of two industries (dairy and poultry slaughterhouse) were hydrolyzed with a commercial lipase and without enzyme addition (control). The effect of adjusting the pH at the beginning of the hydrolytic assays was also investigated. The long chain free fatty acids (LCFAs) released were identified and quantified and 5-d digestion assays were conducted with the hydrolyzed material. The results indicated that the hydrolysis assays conducted with initial pH adjusted to 7.0 and the utilization of a commercial enzyme promoted a higher increase in amounts of LCFAs, particularly of unsaturated acids. In most anaerobic digestion assays, the specific methane production showed a decreasing trend with the increase of unsaturated fatty acids in the medium. In general, the utilization of a commercial enzyme (lipase) in the hydrolysis process did not contribute to enhancing methane production in 5-d anaerobic digestion assays.

The industrial wastewater from a carbon monoxide production unit was treated by physico-chemical processes in order to achieve a quality level appropriate for reuse. In preliminary tests, coagulation/flocculation (CF), sand filtration and activated carbon adsorption were investigated in order to select the materials and the process conditions. Based on the results a combined treatment was proposed: CF followed by down-flow filtration in a combined medium (sand and granular activated carbon). The results obtained in a bench-scale treatment unit showed that the combined treatment removed wastewater turbidity (95%), total suspended solids (97%), volatile suspended solids (81%), chemical oxygen demand (74%) and dissolved organic carbon (65%). Polycyclic aromatic hydrocarbons (PAHs) were removed to non-detectable levels. The residual conductivity of the treated wastewater is a matter of concern, and considering the water characteristics of this industrial process, a reuse scheme was proposed based on on-line monitoring and control of conductivity and partial reuse of the treated wastewater.

T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed.

In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. European Myeloma Network and Janssen Research and Development.

Soil organic carbon (SOC) is a key indicator for assessing pasture degradation. This study presents an integrated, field-based approach to analyzing SOC dynamics in pastures of Rio de Janeiro state (Brazil). Unlike methods based exclusively on remote sensing or modeling, our analysis is based on 350 georeferenced soil samples collected by Embrapa Solos and complemented by historical land use data, providing robust and reliable empirical evidence. Statistical methods (ANOVA, Tukey test), geostatistical interpolation (kriging), and unsupervised clustering (k-means) were used to characterize the spatiotemporal distribution of SOC. The results revealed patterns linked to both topographic and anthropogenic drivers, enabling the objective delineation of degraded versus non-degraded pastures. SOC levels below 40 g/kg in areas under 300 m elevation were strongly associated with degradation due to intensive use. In contrast, degradation at higher altitudes was primarily linked to sloping terrain more prone to water erosion. This methodological approach demonstrates the potential of combining field data with data mining tools to detect degradation patterns and inform targeted land management. The findings reaffirm SOC as a vital indicator of soil quality and highlight the importance of sustainable pasture practices in conserving carbon stocks and mitigating climate change. The proposed threshold-based method offers a practical foundation for diagnosing degraded pastures and identifying priority areas for restoration.

Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. Of 457 patients screened for eligibility, 402 were randomly allocated—195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group—and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2–19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4–19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73–not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11–10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53–0·93], p=0·0075). The most frequent grade 3–4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32–0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. Karyopharm Therapeutics.

Background Mobile health is gradually revolutionizing the way medical care is delivered worldwide. In Mozambique, a country with a high human immunodeficiency virus prevalence, where antiretroviral treatment coverage is 77% accompanied by a 67% of retention rate, the use of mobile health technology may boost the antiretroviral treatment, by delivering care beyond health facilities and reaching underrepresented groups. Leveraging new technologies is crucial to reach the 95–95-95 United Nations target by 2030. The design, development, implementation, and evaluation of a mobile health platform called Infomóvel were covered in this article. Its intended use involves collaboration with community health workers and aims to increase human immunodeficiency virus patient access, adherence, and retention to care. Methods Using the Design Science Research Methodology, Infomóvel was created, as well as this publication. The explanation of various actions includes everything from problem description to observational study and goal-following for a solution, which results in the design and development of a platform proposal. Before the utility assessment of Infomóvel was conducted to make adjustments, a demonstration phase was conducted in one region of Mozambique. Results The initial subjects of the Infomóvel flowchart and physical process design were patients receiving antiretroviral medication who were enrolled in the patients tracking system and who had consented to home visits. The case manager examines the file before importing it into the Infomóvel database stored on a cloud server using the website www.commcarehq.org . The case manager application synchronises with the Infomóvel server database, enabling the import of latest data and access to the lists of new patients and community health workers. The community health worker uses his phone to access his application, which allows him to record the geographic coordinates and sort the list of patients by priority and type of visit. Conclusion Results from Infomóvel add to the growing body of data showing that mobile health techniques are beneficial for managing stable individuals with chronic conditions in Mozambique. These approaches can be scaled up and better utilised. However, additional studies should be conducted to quantify the resources needed to implement on a larger scale.

The ability of dermatophytes to live in communities and resist antifungal drugs may explain treatment recurrence, especially in onychomycosis. Therefore, new molecules with reduced toxicity that target dermatophyte biofilms should be investigated. This study evaluated nonyl 3,4-dihydroxybenzoate (nonyl) susceptibility and mechanism of action on planktonic cells and biofilms of T. rubrum and T. mentagrophytes. Metabolic activities, ergosterol, and reactive oxygen species (ROS) were quantified, and the expression of genes encoding ergosterol was determined by real-time PCR. The effects on the biofilm structure were visualized using confocal electron microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). T. rubrum and T. mentagrophytes biofilms were susceptible to nonyl and resistant to fluconazole, griseofulvin (all strains), and terbinafine (two strains). The SEM results revealed that nonyl groups seriously damaged the biofilms, whereas synthetic drugs caused little or no damage and, in some cases, stimulated the development of resistance structures. Confocal microscopy showed a drastic reduction in biofilm thickness, and transmission electron microscopy results indicated that the compound promoted the derangement and formation of pores in the plasma membrane. Biochemical and molecular assays indicated that fungal membrane ergosterol is a nonyl target. These findings show that nonyl 3,4-dihydroxybenzoate is a promising antifungal compound.

IntroductionTypical Western diet, rich in salt, contributes to autoimmune disease development. However, conflicting reports exist about the effect of salt on neutrophil effector functions, also in the context of arthritis.MethodsWe investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions in vitro , and in vivo employing the murine K/BxN-serum transfer arthritis (STA) model.Results and discussionThe effects of NaCl and external reactive oxygen species (H2O2) were further examined on osteoclasts in vitro. Hypertonic sodium-rich media caused primary/secondary cell necrosis, altered the nuclear morphology, inhibited phagocytosis, degranulation, myeloperoxidase (MPO) peroxidation activity and neutrophil extracellular trap (NET) formation, while increasing total ROS production, mitochondrial ROS production, and neutrophil elastase (NE) activity. High salt diet (HSD) aggravated arthritis by increasing inflammation, bone erosion, and osteoclast differentiation, accompanied by increased NE expression and activity. Osteoclast differentiation was decreased with 25 mM NaCl or 100 nM H2O2 addition to isotonic media. In contrast to NaCl, external H2O2 had pro-resorptive effects in vitro . We postulate that in arthritis under HSD, increased bone erosion can be attributed to an enhanced oxidative milieu maintained by infiltrating neutrophils, rather than a direct effect of NaCl.