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Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
Nanoscale Jun 2024This work reports temperature-dependent shape-changeable two-dimensional (2D) nanostructures by crystallization-driven self-assembly (CDSA) from a chromophore-conjugated...
This work reports temperature-dependent shape-changeable two-dimensional (2D) nanostructures by crystallization-driven self-assembly (CDSA) from a chromophore-conjugated poly(L-lactide) (PLLA) homopolymer (PTZ-P1) that contained a polar dye, phenothiazine (PTZ), at the chain-end of the crystallizable PLLA. The CDSA of PTZ-P1 in a polar solvent, isopropanol (iPrOH), by an uncontrolled heating-cooling process, majorly generates lozenge-shaped 2D platelets chain-folding-mediated crystallization of the PLLA core, leading to the display of the phenothiazines on the 2D surface that confers colloidal stability and orange-emitting luminescent properties to the crystal lamellae. Isothermal crystallization at 60 °C causes a morphological change in PTZ-P1 platelets from lozenge to truncated-lozenge to perfect hexagon under different annealing times, while no shape change was noticed in the structurally similar PTZ-P2 polymer with a longer PLLA chain under similar conditions. This study unveils the complex link between the 2D platelet morphologies and degree of polymerization (DP) of PLLA and the corona-forming dye character. Further, the co-assembly potential of PTZ-P1 with hydrophobic pyrene-terminated PLLAs of varying chain lengths (PY-P1, PY-P2, and PY-P3) was examined, as these two dyes could form a Förster Resonance Energy Transfer (FRET) pair on the 2D surface. The impact of the length of the crystallizable PLLA on the photophysical properties of the surface-occupied chromophores revealed crucial insights into interchromophoric interactions on the platelet surface. A reduction in the propensity for π-stacking with increasing chain-folding in longer PLLAs is manifested in the chain-length-dependent FRET efficiencies and excimer emission lifetimes within the resultant monolayered 2D assemblies. The unconventional "butterfly-shaped" molecular architecture of the tested phenothiazine, combined with its varied functional features and polar character, adds a distinctive dimension to the underdeveloped field of CDSA of chromophore-conjugated poly(L-lactides), opening future avenues for the development of advanced nanostructured biodegradable 2D materials with programmable morphology and optical functions.
PubMed: 38894626
DOI: 10.1039/d4nr01683a -
International Journal of Molecular... May 2024For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of... (Review)
Review
For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling and antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there has been limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal senescence, brain volume loss, the attenuation of gamma oscillations in electroencephalograms, and the oxidation of lipids in the plasma and mitochondrial membranes. We surmise that the aberrant activation of the aryl hydrocarbon receptor by toxins derived from gut microbes or the environment drives premature cellular and neuronal senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including the impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: (1) to summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders, and (2) to discuss novel strategies for improving long-term outcomes in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor antagonists.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Animals; Brain; Cellular Senescence
PubMed: 38892092
DOI: 10.3390/ijms25115904 -
Journal of Medical Case Reports Jun 2024Hiccups are among the rare complications of COVID-19 infections. There are several published reports of persistent hiccups presenting during the acute COVID-19 period....
INTRODUCTION
Hiccups are among the rare complications of COVID-19 infections. There are several published reports of persistent hiccups presenting during the acute COVID-19 period. However, there are very few published reports of persistent hiccups occurring in the post-acute COVID-19 period. Consequently, most clinicians may not be aware of this rare presentation. This case highlights an atypical presentation of persistent hiccups that manifested during the post-acute COVID -19 period that clinicians need to be aware of. The caseadds to the ever increasing body of knowledge about symptoms and signs associated with Severe Acute Respiratory Syndrome Corona Virus type 2 (SARS CoV-2) infection.
CASE PRESENTATION
A 27 year old male black Zambian patient presented to the emergency department of our hospital with persistent hiccup, 35 days after the initial acute episode of COVID-19. This was associated with breathlessness. There were no other symptoms. He had no history of pulmonary, gastrointestinal, neurological disease or malignancy. He did not take any alcohol or smoke. He had never used any recreational drugs. He was employed as a monitoring and evaluation officer at one of the main COVID centres in the capital. On examination, the patient was anxious. Blood pressure was 141/82, pulse rate was 95 beats per minute, respiratory rate was 26 breaths per minute, temperature was 36.8C and oxygen saturation was 97% on room air. Systemic examination was normal. Chest X-ray and abdominal ultrasonography were normal. A rapid COVID-19 antigen test, and COVID-19 Polymerase Chain Reaction (PCR) test that were done the following day were negative. All other haematological and biochemical tests, including D-dimer and C-reactive protein (CRP), were also normal. A diagnosis of post-acute COVID-19 associated hiccups was made. The patient responded well to treatment with chlorpromazine 25 mg 8 hourly. The hiccups disappeared completely after the fourth dose of chlorpromazine.
CONCLUSION
This is one of the few published cases of COVID-19 associated persistent hiccups, occurring more than a month after the initial presentation. Most of the published cases report hiccups occurring in the acute COVID-19 period. Consequently, hiccups occurring in the post-acute COVID-19 period may not be attributable to COVID-19. This case has highlighted the need to consider post-acute COVID-19 in the differential diagnosis of persistent hiccup.
Topics: Humans; Hiccup; Male; Chlorpromazine; Adult; COVID-19; SARS-CoV-2; COVID-19 Drug Treatment; Post-Acute COVID-19 Syndrome; Treatment Outcome
PubMed: 38890624
DOI: 10.1186/s13256-024-04500-8 -
BMC Medical Imaging Jun 2024Leishmaniasis is a vector-born neglected parasitic disease belonging to the genus Leishmania. Out of the 30 Leishmania species, 21 species cause human infection that...
BACKGROUND
Leishmaniasis is a vector-born neglected parasitic disease belonging to the genus Leishmania. Out of the 30 Leishmania species, 21 species cause human infection that affect the skin and the internal organs. Around, 700,000 to 1,000,000 of the newly infected cases and 26,000 to 65,000 deaths are reported worldwide annually. The disease exhibits three clinical presentations, namely, the cutaneous, muco-cutaneous and visceral Leishmaniasis which affects the skin, mucosal membrane and the internal organs, respectively. The relapsing behavior of the disease limits its diagnosis and treatment efficiency. The common diagnostic approaches follow subjective, error-prone, repetitive processes. Despite, an ever pressing need for an accurate detection of Leishmaniasis, the research conducted so far is scarce. In this regard, the main aim of the current research is to develop an artificial intelligence based detection tool for the Leishmaniasis from the Geimsa-stained microscopic images using deep learning method.
METHODS
Stained microscopic images were acquired locally and labeled by experts. The images were augmented using different methods to prevent overfitting and improve the generalizability of the system. Fine-tuned Faster RCNN, SSD, and YOLOV5 models were used for object detection. Mean average precision (MAP), precision, and Recall were calculated to evaluate and compare the performance of the models.
RESULTS
The fine-tuned YOLOV5 outperformed the other models such as Faster RCNN and SSD, with the MAP scores, of 73%, 54% and 57%, respectively.
CONCLUSION
The currently developed YOLOV5 model can be tested in the clinics to assist the laboratorists in diagnosing Leishmaniasis from the microscopic images. Particularly, in low-resourced healthcare facilities, with fewer qualified medical professionals or hematologists, our AI support system can assist in reducing the diagnosing time, workload, and misdiagnosis. Furthermore, the dataset collected by us will be shared with other researchers who seek to improve upon the detection system of the parasite. The current model detects the parasites even in the presence of the monocyte cells, but sometimes, the accuracy decreases due to the differences in the sizes of the parasite cells alongside the blood cells. The incorporation of cascaded networks in future and the quantification of the parasite load, shall overcome the limitations of the currently developed system.
Topics: Deep Learning; Humans; Microscopy; Azure Stains; Leishmaniasis; Leishmania
PubMed: 38890604
DOI: 10.1186/s12880-024-01333-1 -
Scientific Reports Jun 2024A composite of Zinc oxide loaded with 5-weight % silver decorated on carbon nanotubes (Ag-loaded ZnO: CNT) was synthesized using a simple refluxed chemical method. The...
A composite of Zinc oxide loaded with 5-weight % silver decorated on carbon nanotubes (Ag-loaded ZnO: CNT) was synthesized using a simple refluxed chemical method. The influence of deviation in the weight % of carbon nanotube loading on photocatalytic dye degradation (methylene blue and rose bengal) and antibiotic (antimicrobial and antifungal) performance was investigated in this study. The light capture ability of Ag-loaded ZnO:CNT in the visible region was higher in photocatalytic activity than that of Ag-loaded ZnO and ZnO:CNT. The bandgap of the Ag-loaded ZnO: CNT was tuned owing to the surface plasmon resonance effect. The photocatalytic degradation investigations were optimized by varying the wt% in CNTs, pH of dye solution, concentration of the dye solution, and amount of catalytic dose. Around 100% photocatalytic efficiency in 2 min against MB dye was observed for Ag doped ZnO with 10 wt% CNT composite at pH 9, at a rate constant 1.48 min. Bipolaris sorokiniana fungus was first time tested against a composite material, which demonstrated optimum fungal inhibition efficiency of 48%. They were also tested against the bacterial strains Staphylococcus aureus, Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium, which showed promising antibacterial activity compared to commercially available drugs. The composite of Ag doped ZnO with 5 wt% CNT has shown competitive zone inhibition efficacy of 21.66 ± 0.57, 15.66 ± 0.57, 13.66 ± 0.57 against bacterial strains Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium which were tested for the first time against Ag-loaded ZnO:CNT.
Topics: Zinc Oxide; Silver; Nanotubes, Carbon; Anti-Bacterial Agents; Catalysis; Antifungal Agents; Staphylococcus aureus; Methylene Blue; Coloring Agents; Rose Bengal; Microbial Sensitivity Tests; Salmonella typhimurium; Hydrogen-Ion Concentration; Photolysis; Photochemical Processes
PubMed: 38890495
DOI: 10.1038/s41598-024-64746-6 -
Journal of Fluorescence Jun 2024Two novel naphthalimide derivatives PTZNI-Cz and PTZNI-TPA were successfully designed and synthesized, in which phenothiazine, triphenylamine and carbazole were used as...
Two novel naphthalimide derivatives PTZNI-Cz and PTZNI-TPA were successfully designed and synthesized, in which phenothiazine, triphenylamine and carbazole were used as electron donors and naphthalimide was used as the electron acceptor. Their photophysical, electrochemical, and thermal properties were investigated. These derivatives showed remarkable aggregation-induced emission (AIE) effect. Furthermore, the maximum emission peaks of PTZNI-Cz and PTZNI-TPA in the thin film state are at 610 nm and 623 nm respectively, which is typical of red fluorescent materials.
PubMed: 38884826
DOI: 10.1007/s10895-024-03800-y -
National Science Review Jul 2024Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived...
Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct -type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The -type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (HO). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable HO synthesis rate of 3324 μmol g h, which makes the PTZ-COF one of the best crystalline porous photocatalysts in HO production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.
PubMed: 38883289
DOI: 10.1093/nsr/nwae177 -
Analytical Methods : Advancing Methods... Jun 2024This study proposes a strategy using a microfluidic ratiometric electrochemical aptasensor to detect PCB77 with excellent sensitivity and specificity. This sensing...
This study proposes a strategy using a microfluidic ratiometric electrochemical aptasensor to detect PCB77 with excellent sensitivity and specificity. This sensing platform combines a microfluidic chip, a wireless integrated circuit system for aptamer-based electrochemical detection, and a mobile phone control terminal for parameter configuration, identification, observation, and wireless data transfer. The sensing method utilizes a cDNA (MB-COOH-cDNA-SH) that is labelled with the redox probe Methylene Blue (MB) at the 5' end and has a thiol group at the 3' end. Additionally, it utilizes a single strand PCB aptamer that has been modified with ferrocenes at the 3' end (aptamer-Fc). Through gold-thiol binding, the labelled probe of MB-COOH-cDNA-SH was self-assembled onto the surface of an Au/NbCT/GO modified electrode. On exposure to aptamer-Fc, it will hybridize with MB-COOH-cDNA-SH to form a stable double-stranded structure on the electrode surface. When PCB77 is present, aptamer-Fc binds specifically to the target, enabling the double-stranded DNA to unwind. Such variation caused changes in the differential pulse voltammetry (DPV) peak currents of both MB and Fc. A substantial improvement is observed in the ratio between the two DPV peaks. Under the optimum experimental conditions, this assay has a response that covers the 0.0001 to 1000 ng mL PCB77 concentration range, and the detection limit is 1.56 × 10 ng mL. The integration of a ratiometric electrochemical aptasensor with designed microfluidic and integrated devices in this work is an innovative and promising approach that offers an efficient platform for on-site applications.
Topics: Aptamers, Nucleotide; Polychlorinated Biphenyls; Electrochemical Techniques; Biosensing Techniques; Limit of Detection; Microfluidic Analytical Techniques; Gold; Methylene Blue; Ferrous Compounds; Electrodes
PubMed: 38874006
DOI: 10.1039/d4ay00830h -
Angewandte Chemie (International Ed. in... Jun 2024Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis...
Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis and characterization. Herein, we present the synthesis of a polyradical cation cage 14•+ through post-synthetic oxidation of a redox-active phenothiazine-based Pd2L4-type coordination cage 1. It's worth noting that 1 exhibits excellent reversible electrochemical and chemical redox activity due to the introduction of a bulky 3,5-di-tert-butyl-4-methoxyphenyl substituent. The generation of 14•+ through reversible electrochemical oxidation is investigated by in situ UV-vis-NIR and EPR spectroelectrochemistry. Meanwhile, chemical oxidation of 1 can also produce 14•+ which can be reversibly reduced back to the original cage 1, and the process is monitored by EPR and NMR spectroscopies. Eventually, we succeed in the isolation and single crystal X-ray diffraction analysis of 14•+, whose electronic structure and conformation are distinct to original 1. The magnetic susceptibility measurements indicate the predominantly antiferromagnetic interactions between the four phenothiazine radical cations in 14•+. We believe that our study including the facile synthesis methodology and in situ spectroelectrochemistry will shed some light on the synthesis and characterization of novel polyradical systems, opening more perspectives for developing functional supramolecular cages.
PubMed: 38872356
DOI: 10.1002/anie.202407279