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Scientific Reports Nov 2023Nitrate pollution in surface water has become a significant environmental concern. Sulfur autotrophic denitrification (SAD) technology is gaining attention for its...
Nitrate pollution in surface water has become a significant environmental concern. Sulfur autotrophic denitrification (SAD) technology is gaining attention for its cost-effectiveness and efficiency in nitrate removal. This study aimed to investigate the structure and function of sulfur autotrophic denitrification microbial communities in systems using sodium thiosulfate (Group A) and elemental sulfur (Group B) as the sole electron donors. Metagenomic amplicon sequencing and physicochemical analysis were performed to examine the microbial communities. The results revealed that on day 13, the nitrate nitrogen removal rate in Group A was significantly higher (89.2%) compared to Group B (74.4%). The dominant genus in both Groups was Thiobacillus, with average abundances of 34.15% and 16.34% in Groups A and B, respectively. β-diversity analysis based on species level showed significant differences in bacterial community structure between the two Groups (P < 0.001). Group A exhibited a greater potential for nitrate reduction and utilized both thiosulfate and elemental sulfur (P < 0.01) compared to Group B. This study provides a sufficient experimental basis for improving the start-up time and operating cost of SAD system through sulfur source switching and offers new prospects for in-depth mechanistic analysis.
Topics: Denitrification; Nitrates; Sulfur; Bacteria; Thiobacillus
PubMed: 37938235
DOI: 10.1038/s41598-023-46829-y -
JCI Insight Dec 2023The widely used chemotherapy cisplatin causes permanent hearing loss in 40%-60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in...
The widely used chemotherapy cisplatin causes permanent hearing loss in 40%-60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multidose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cell counts. Toxicity of the drug cotreatment was evaluated, and levels of phosphorylated ERK were measured. A dabrafenib dose of 3 mg/kg BW, twice daily, in mice, was determined to be the minimum effective dose, and it is equivalent to one-tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20-25 dB at the 3 frequencies tested, in both female and male mice, persisted for 4 months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), protected hearing in 2 mouse strains, and diminished cisplatin-induced weight loss. This study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss.
Topics: Humans; Male; Female; Child; Mice; Animals; Cisplatin; Hearing Loss; Antineoplastic Agents; Imidazoles; Neoplasms; Deafness
PubMed: 37934596
DOI: 10.1172/jci.insight.171140 -
BioRxiv : the Preprint Server For... Jun 2024Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin...
Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancies, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin and UPR-modulating drugs, and UPR marker gene expression and cell death measured. Treatment with ISRIB, a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested in an in vivo mouse model of cisplatin ototoxicity and well as a head and neck squamous cell carcinoma (HNSCC) cell-based assay of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose-response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact the cytotoxic effects of cisplatin on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.
PubMed: 37905009
DOI: 10.1101/2023.10.17.562797 -
Plants (Basel, Switzerland) Sep 2023Female hemp plants are desired in floral hemp operations due to their higher cannabinoid contents. To produce feminized seeds, a critical step of inducing fertile male...
Female hemp plants are desired in floral hemp operations due to their higher cannabinoid contents. To produce feminized seeds, a critical step of inducing fertile male flowers on female plants is performed. In feminized seed production, freshly mixed STS (silver thiosulfate + sodium thiosulfate) is applied to female plants as an ethylene inhibitor to induce male flowers. However, the short-shelf stability of the STS buffer can cause difficulty in the application and inconsistent results. Alternative methods with improved accessibility and stable buffers will be beneficial for the hemp industry and hemp breeders. A commercially available floriculture product, Chrysal ALESCO, contains silver nitrate, the same active ingredient as STS but with increased shelf stability. This study compares Chrysal ALESCO to the traditional STS standard methods for male flower induction on female plants and their pollen quality. The two treatments were applied to six female hemp accessions with three replicates investigated, and the male flower counts and pollen quality were compared. No statistically significant difference was discovered in their male flower counts; the STS-treated plant produced an average of 478.18 male flowers, and the Chrysal ALESCO-treated plant produced an average of 498.24 male flowers per plant. Fluorescein diacetate (FDA) and acetocarmine stains were used to investigate the pollen quality (non-aborted rate) of two chosen genotypes. FDA-stained pollen of Chrysal ALESCO showed a significantly higher non-aborted rate than the pollen of traditional STS-treated plants ( < 0.001); however, only a marginally higher non-aborted rate was discovered by acetocarmine staining ( = 0.0892). In summary, Chrysal ALESCO performed equally to traditional STS treatment at male flower counts and better or equally in pollen quality. With better shelf stability and easy application, ALESCO can be a viable alternative option for stimulating male flowers on female hemp plants.
PubMed: 37836111
DOI: 10.3390/plants12193371 -
Annals of Medicine and Surgery (2012) Oct 2023Calciphylaxis manifests clinically by skin ischemia and necrosis and histologically by calcification of dermal arterioles. Usually, it occurs in patients with end-stage...
INTRODUCTION AND IMPORTANCE
Calciphylaxis manifests clinically by skin ischemia and necrosis and histologically by calcification of dermal arterioles. Usually, it occurs in patients with end-stage renal disease on dialysis or in patients who had a kidney transplant. Here, the authors present a case of calciphylaxis occurring in a patient with psoriasis and psoriatic arthritis.
CASE PRESENTATION
A 66-year-old Syrian male with a history of psoriatic arthritis presented for evaluation of 2-month nonpainful ulcers on his feet and hands that were treated with warfarin. Biopsies confirmed the diagnosis of calciphylaxis. The patient received sodium thiosulfate, zoledronic acid, intralesional sodium thiosulfate injections, and an intravenous infusion of vitamin K with dramatic improvement. At the 3-month follow-up, his wounds had been completely remitted.
DISCUSSION
Nonuremic calciphylaxis occurs in many cases, like vitamin D administration, vitamin K antagonists' administration, chronic inflammation, and others. The association between calciphylaxis and psoriasis was reported only in four cases in the literature; meanwhile, this was the first case that described calciphylaxis in the setting of psoriatic arthritis.
CONCLUSION
A suspicion of calciphylaxis should be maintained in patients with underlying inflammatory mechanism diseases.
PubMed: 37811033
DOI: 10.1097/MS9.0000000000001281 -
Renal Failure 2023Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had... (Review)
Review
Sailing between scylla and charybdis-anticoagulation dilemma in a patient with calciphylaxis and mechanical cardiac valve replacement: a case report and literature review.
Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.
Topics: Aged; Female; Humans; Anticoagulants; Atrial Fibrillation; Calciphylaxis; Heart Valves; Kidney Failure, Chronic
PubMed: 37799073
DOI: 10.1080/0886022X.2023.2264401 -
Ecotoxicology and Environmental Safety Oct 2023Chemical reduction combined with microbial stabilization is a green and efficient method for the remediation of hexavalent chromium (Cr(VI)) contaminated soil. In this...
Effective Cr(VI) reduction and immobilization in chromite ore processing residue (COPR) contaminated soils by ferrous sulfate and digestate: A comparative investigation with typical reducing agents.
Chemical reduction combined with microbial stabilization is a green and efficient method for the remediation of hexavalent chromium (Cr(VI)) contaminated soil. In this study, the combination of ferrous sulfate with kitchen waste digestate was applied to reduce and immobilize Cr(VI) in chromite ore processing residue (COPR) contaminated soils, and systematically evaluated the remediation performance of Cr(VI) compared with several typical reducing agents (i.e., ferrous sulfate, zero valent iron, sodium thiosulfate, ferrous sulfide, and calcium polysulfide). The results showed that the combination of ferrous sulfate and digestate had superior advantages of a lower dosage of reducing agent and a long-term remediation effect compared to other single chemical reductants. Under an Fe(II):Cr(VI) molar ratio of 3:1% and 4% digestate (wt), the content of Cr(VI) in the soil decreased to 5.07 mg/kg after 60 days of remediation. Meanwhile, the leaching concentrations of Cr(VI) were below detection limit, which can meet the hazardous waste toxicity leaching standard. The risk level of Cr pollution was decreased from very high risk to low risk. The X-ray photoelectron spectroscopy (XPS) results further demonstrated that the combined treatments were beneficial to Cr(VI) reduction and stabilization. The abundance of bacteria with Cr(VI) reducing ability was higher than other treatments. Moreover, the high abundance of carbon and nitrogen metabolism in the combined treatments demonstrated that the addition of digestate was beneficial to the recovery and flourishing of Cr(VI)-reducing related microorganisms in COPR contaminated soils. This work provided an alternative way on Cr(VI) remediation in COPR contaminated soils.
PubMed: 37769582
DOI: 10.1016/j.ecoenv.2023.115522 -
Renal Failure 2023Coronary artery calcification (CAC) is common in dialysis patients and is associated with a higher risk of future cardiovascular events. Sodium thiosulfate (STS) is... (Meta-Analysis)
Meta-Analysis
Coronary artery calcification (CAC) is common in dialysis patients and is associated with a higher risk of future cardiovascular events. Sodium thiosulfate (STS) is effective for calciphylaxis in dialysis patients; however, the influence of STS on CAC in dialysis patients remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of STS on CAC in patients undergoing dialysis. PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched from inception to 22 March 2023 for controlled studies comparing the influence of STS versus usual care without STS on CAC scores in dialysis patients. A random effects model incorporating the potential influence of heterogeneity was used to pool the results. Nine studies, including two non-randomized studies and seven randomized controlled trials, were included in the meta-analysis. Among these, 365 patients on dialysis were included in the study. Compared with usual care without STS, intravenous STS for 3-6 months was associated with significantly reduced CAC scores (mean difference [MD] = -180.17, 95% confidence interval [CI]: -276.64 to -83.70, < 0.001, I = 0%). Sensitivity analysis limited to studies of patients on hemodialysis showed similar results (MD: -167.33, 95% CI: -266.57 to -68.09, = 0.001; I = 0%). Subgroup analyses according to study design, sample size, mean age, sex, dialysis vintage of the patients, and treatment duration of STS also showed consistent results (p for subgroup differences all > 0.05). In conclusion, intravenous STS may be effective in attenuating CAC in dialysis patients.
Topics: Humans; Coronary Artery Disease; Renal Dialysis; Thiosulfates; Vascular Calcification
PubMed: 37755153
DOI: 10.1080/0886022X.2023.2254569 -
Renal Failure 2023A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report...
A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients ( = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes ( = 11), calcium-based phosphate binders use ( = 10), warfarin use ( = 9), obesity ( = 7), female gender ( = 8) and intravenous iron use ( = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.
Topics: Humans; Female; Calciphylaxis; Retrospective Studies; Kidney Failure, Chronic; Calcium
PubMed: 37724534
DOI: 10.1080/0886022X.2023.2256413 -
Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161