[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Bacteriophage therapy for drug-resistant Staphylococcus aureus infections.

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.

Bioactive Compounds from Plant Origin as Natural Antimicrobial Agents for the Treatment of Wound Infections.

The rising prevalence of drug-resistant bacteria underscores the need to search for innovative and nature-based solutions. One of the approaches may be the use of plants that constitute a rich source of miscellaneous compounds with a wide range of biological properties. This review explores the antimicrobial activity of seven bioactives and their possible molecular mechanisms of action. Special attention was focused on the antibacterial properties of berberine, catechin, chelerythrine, cinnamaldehyde, ellagic acid, proanthocyanidin, and sanguinarine against Staphylococcus aureus, Enterococcus spp., Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa. The growing interest in novel therapeutic strategies based on new plant-derived formulations was confirmed by the growing number of articles. Natural products are one of the most promising and intensively examined agents to combat the consequences of the overuse and misuse of classical antibiotics.

Herbal Products-Powered Thermosensitive Hydrogel with Phototherapy and Microenvironment Reconstruction for Accelerating Multidrug-Resistant Bacteria-Infected Wound Healing.

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum ß-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.

Adherence and discontinuation of prescription cannabidiol for the management of seizure disorders at an integrated care center.

OBJECTIVE: Evaluate adherence, discontinuation rates, and reasons for non-adherence and discontinuation of prescription CBD during the 12-months post-initiation period at an integrated care center. METHODS: This was a prospective study of patients prescribed CBD by a neurology clinic provider with initial prescription fulfillment through the center's specialty pharmacy from January 2019 through April 2020. Baseline demographics and reasons for non-adherence and/or discontinuation were collected from the electronic health record and pharmacy claims history was used to calculate adherence using proportion of days covered (PDC). Patients were included in the PDC analysis if they had at least 3 fills during the study period. Non-adherence was defined as a PDC < 0.8. Descriptive statistics were used to summarize data with categorical variables represented as frequencies and percentages and continuous variables as medians and interquartile ranges (IQRs). RESULTS: We included 136 patients with a median age of 14 years (IQR 9 - 21). Most patients were white (n = 115, 85%), with a diagnosis of intractable epilepsy (n = 100, 74%). Among the 128 patients with 3 or more fills, the median PDC was 0.99 (IQR 0.95 - 1.00) with non-adherence seen in 6% (n = 8) of patients. The most common reason for non-adherence was side effects (n = 2, 25%). Prescription CBD was discontinued by 23% (n = 31) of patients with a median time to discontinuation of 117 days (IQR 68 - 216). The most common reason for discontinuation was major side effects (n = 12, 39%). The most common side effects leading to discontinuation were agitation/irritability (n = 4), mood changes (n = 4), aggressive behavior (n = 3), and increased seizure frequency (n = 3). CONCLUSION: Adherence to prescription CBD at an integrated care center was high with approximately 94% of patients considered adherent. Providers and pharmacists may improve adherence and discontinuation rates by educating patients on the timeline of response, potential side effects, and potential for dose adjustments.

Drug resistant epilepsy and associated factors among children with epilepsies in tanzania: a cross-sectional study.

BACKGROUND: Epilepsy contributes to high morbidity among children and adolescents in developing countries. A quarter of all children with epilepsy will be resistant to anti-seizure medications (ASMs), with associated neurocognitive impairments and risk of higher mortality. This study aimed to estimate and characterize drug-resistant epilepsy (DRE) (defined as failure to achieve sustained remission after adequate trials of two tolerated and appropriately chosen ASMs) and its associated factors among children and adolescents with epilepsies attending the pediatric neurology clinic at Muhimbili National Hospital (MNH), Dar es Salaam Tanzania. METHODS: This cross-sectional study was conducted from June 2020 to June 2021. Children with epilepsies and who had been treated with ASMs for at least 3 months were eligible for inclusion. Exclusion criteria included children whose caregivers denied consent and those who exhibited acute medical conditions necessitating admission on the scheduled visit day. Data on demographic characteristics, perinatal history, detailed history of the seizures semiology, drug history, magnetic resonance imaging (MRI), and electroencephalography (EEG) results were obtained from caregivers and medical records available during recruitment. Seizures and epilepsies were classified using the 2017 International League Against Epilepsy (ILAE) classification. Logistic regression was used to determine factors associated with DRE. RESULTS: A total of 236 children and adolescents aged between 4 months and 15 years (Median age 72 months (IQR = 42-78)) were enrolled in this study. We found the proportion of DRE to be 14.8% in this cohort. Of the thirty-five patients with DRE, 60% had generalized epilepsy and almost 25% had a diagnosis of an epilepsy syndrome, the most common being Lennox-Gastaut syndrome (LGS). Structural abnormalities on brain MRI were seen in almost 80% of all patients with DRE, the most prevalent being cystic encephalomalacia, which was observed in 34% of patients. Patients using both ASMs and alternative therapies accounted for 9% of this cohort. The onset of seizures during the first month of life (aOR = 1.99; 95%CI 1.7-4.6; p = 0.031) and high initial seizure frequency (aOR = 3.6; 95%CI 1.6-8;p = 0.002) were found to be independently associated with DRE. CONCLUSION: The proportion of DRE in Tanzania is high. Patients with neonatal onset seizures and high initial seizure frequency should be followed up closely to ensure early diagnosis of DRE.

The potential usage of Caatinga natural products against multi-drug-resistant bacteria.

New sources of antibacterial drugs have become urgent with increasing bacterial resistance. Medicinal plants are attractive sources for antimicrobial compounds with fewer side effects and cheaper obtention. Brazil contains six biomes, including Caatinga, a semi-arid tropical vegetation exclusively from Brazil that contains over thousand vascular plant species. This review presents the potential of using Caatinga plant products to treat multidrug-resistant bacteria. This review used the keywords of antimicrobial resistance, resistance profile, multidrug resistance, Caatinga biome, and pathogenic bacteria to search in Scientific Electronic Library Online, the U.S. National Library of Medicine, and Google Scholar. Plant species as Schinopsis brasiliensis Engl., Annona vepretorum Mart., Croton pulegioides Baill., Myracrondruon urundeuva Allemo, Cereus jamacaru DC., Opuntia ficus-indica L., Bauhinia forficata L., Eucalyptus globulus, Croton sonderianus Muell. Arg., Campomanesia pubescens, and Abarema cochliacarpos showed bacteriostatic activity. Encholirium spectabile Mart., Hymenaea courbaril L., Neoglaziovia variegata Mez, Selaginella convoluta Spring, Encholirium spectabile Mart., Bromelia laciniosa Mart., Hymenaea martiana, Commiphora leptophloeos, and Mimosa tenuiflora presented bactericidal activity. Those extracts inhibited clinical-importance bacteria, such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Therefore, Caatinga biome plants are a valuable source of active biomolecules against pathogenic bacteria, and their therapeutic potential must be further explored.

Revealing active constituents within traditional Chinese Medicine used for treating bacterial pneumonia, with emphasis on the mechanism of baicalein against multi-drug resistant Klebsiella pneumoniae.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence of antibiotic-resistant bacteria has rendered it more challenging to treat bacterial pneumonia. Traditional Chinese medicine (TCM) has superior efficacy in the treatment of pneumonia, and it has the unique advantage of antibacterial resistance against multi-drug resistant (MDR) bacteria, but the medication rule and pharmacological mechanism of its antibacterial activity are not clear. AIM OF THE STUDY: This study aims to reveal Chinese medication patterns in treating bacterial pneumonia to select bioactive constituents in core herbs, predict their pharmacological mechanisms and further explore their antibacterial ability against clinically isolated MDR Klebsiella pneumoniae (KP) and their antibacterial mechanisms. MATERIALS AND METHODS: The high-frequency medicinal herbs to treat lung diseases were first screened from Pharmacopoeia of the People's Republic of China (ChP.), and then bioactive compounds in core herbs and targets for compounds and disease were collected. Potential targets, signaling pathways, and drugs' core components were determined by constructing protein-protein interaction network, enrichment analysis and "component-target-pathway-disease" network were mapped by Cytoscape 3.8.2, and the potential therapeutic value of selected core components was verified by comparing the disease targets in the GEO database with the herbal component targets in the ITCM database. The clinically isolated KP were screened by drug sensitivity tests with meropenem (MEM), polymyxin E (PE), and tigecycline and biofilm-forming assay; broth microdilution, chessboard methods and biofilm morphology and permeability experiments were employed to determine the antibacterial, bactericidal and biofilm inhibition ability of selected bioactive constituents alone and in combination with antibiotics; The mechanism of bioactive components on quorum sensing (QS) genes LuxS and LuxR was predicted by molecular docking and tested by RT-PCR. RESULTS: The 13 core Chinese medicines were obtained by mining ChP., and 615 potential targets of core herbal medicine were screened, and the PI3K-Akt signaling pathway might play crucial roles in the therapeutic process. In-vitro experiments revealed that the selected core compounds, including forsythoside B, baicalin, baicalein, and forsythin, all have antibacterial activity, in which baicalein had the strongest ability and a synergistic effect in combination with MEM or PE. Their synergy exhibited a stronger effect on biofilms of MDR KP, inhibiting biofilm formation, disrupting formed biofilms, and removing the residual structures of dead bacteria. Baicalein was predicted to have stable binding capacity to LuxS and LuxR genes by molecular docking, and RT-PCR results verified that the combination of baicalein with MEM or PE was effective in inhibiting the expression of QS genes (LuxS and LuxR) and consequently suppressing biofilm formation. CONCLUSION: The core Chinese herbal medicine in the ChP. to treat lung diseases has a multi-component, multi-target, and multi-pathway synergy to improve bacterial pneumonia. Experimental studies have confirmed that the bioactive compound baicalein was able to combat MDR KP alone and synergistic with MEM or PE, inhibited and disrupted biofilms via regulating LuxS and LuxR genes, and further disturbed quorum sensing system to promote the therapeutic efficacy, which provides a new pathway and rationale for treating MDR KP-induced bacterial pneumonia.

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

PURPOSE: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. METHODS: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. RESULTS: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. CONCLUSION: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Low serum vitamin D in North Indian multi-drug resistant pulmonary tuberculosis patients: the role of diet and sunlight.

Background: Tuberculosis (TB) and malnutrition are major global health problems, with multidrug-resistant (MDR) TB complicating international efforts. The role of vitamin D in susceptibility to and as an adjunctive treatment for TB is being studied extensively, although no study has included MDR-TB patients in context to dietary profile with vitamin D levels and sunlight exposure.Objective: This study aimed to estimate vitamin D serum levels and examine their association with dietary intake of vitamin D and sun exposure in patients with MDR-TB.Methods: North Indian participants were enrolled in three groups: MDR-TB, drug-susceptible pulmonary TB (DS-PTB), and healthy controls. All consenting participants underwent the estimation of macro- and micronutrient intake and sunlight exposure using structured questionnaires. Serum biochemistry, including 25-hydroxyvitamin D and calcium levels, was measured, and the correlation between variables was determined.Results: 747 participants were enrolled. Significant differences among the three groups were found in mean serum 25-hydroxyvitamin D levels, body mass index, macronutrient intake, dietary vitamin D and calcium content, and sun exposure index (SEI). All except sun exposure (SEI was highest in DS-PTB patients) were found to follow the trend: MDR-TB < DS-PTB < healthy controls. The mean serum vitamin D levels of all groups were deficient and correlated positively with dietary intake and SEI.Conclusion: In this study's we found significant association of serum vitamin D concentrations, dietary intake and sunlight exposure in MDR-TB, DS-PTB patients and healthy controls. Dietary intake may be more important than sun exposure in determining serum levels. However, the significance of this finding is uncertain. Further studies are required to confirm the association, direction, and potential for vitamin D supplementation to treat or prevent MDR-TB infection.

Evaluating the therapeutic potential of Indian traditional medicine against multidrug-resistant pathogens: a comprehensive approach with MALDI-TOF-MS and gc-MS analysis.

Multidrug-resistant pathogens pose a significant and pressing global health threat. This study explores the therapeutic potential of Indian Traditional Medicine, particularly Yagya, as an innovative antimicrobial strategy rooted in the ancient Rig Veda traditions dating back to 7500 B.C. Our research uses advanced analytical techniques like GC-MS and MALDI-TOF to investigate Yagya's antimicrobial properties against challenging Gram-positive and Gram-negative bacteria. Our study reveals proteomic insights into bacterial responses, including Glutamate Decarboxylase, EF-Tu, and Alpha-Hemolysin. Altered expression levels suggest significant impacts on bacterial survival, shedding light on the multifaceted mechanisms. By showcasing Yagya's remarkable antimicrobial properties, it provides valuable proteomic insights into its mode of action. This study sets stage for future research to harness Indian Traditional Medicine in combatting microbial infections, especially those driven by multidrug-resistant pathogens. This research emphasises the importance of exploring alternative and complementary approaches in modern medicine to combat the global health crisis of antibiotic resistance.

Stimulation of the pulvinar nucleus of the thalamus in epilepsy: A systematic review and individual patient data (IPD) analysis.

Emerging neuromodulatory treatments, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have shown promise in reducing drug-resistant seizures. While centromedian thalamic nucleus and anterior thalamic nucleus stimulation have been effective in certain types of seizures, limited research has explored pulvinar nucleus stimulation for epilepsy. To address this gap, we conducted a systematic review and individual patient data analysis. Of 78 resultant articles, 5 studies with transient stimulation and chronic stimulation of the pulvinar nucleus were included. Of the 20 patients reviewed, 65% of patients had temporal lobe seizures, while 20% had temporooccipital/occipital lobe seizures. Transient stimulation studies via stereoelectroencephalography (SEEG) showed pulvinar evoked potential response rates of 80% in the mesial temporal region, 76% in the temporal neocortex, and 67% in the TP junction. Another study reported clinically less severe seizures in 62.5% of patients with pulvinar stimulation. In chronic stimulation studies, 80% of patients responded to RNS or DBS, and 2 of 4 patients experienced > 90% seizure reduction. The pulvinar nucleus of the thalamus emerges as a potential target for chronic stimulation in drug-resistant epilepsy. However, knowledge regarding pulvinar connectivity and chronic stimulation remains limited. Further research should investigate specific subregions of the pulvinar for epilepsy treatment. Understanding the role of pulvinar stimulation and its cortical connectivity will advance therapeutic interventions for epilepsy patients.

Advanced drug delivery and therapeutic strategies for tuberculosis treatment.

Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance.

Advancing the frontiers of thalamic neuromodulation: A review of emerging targets and paradigms.

The thalamus is a key structure that plays a crucial role in initiating and propagating seizures. Recent advancements in neuroimaging and neurophysiology have identified the thalamus as a promising target for neuromodulation in drug-resistant epilepsies. This review article presents the latest innovations in thalamic targets and neuromodulation paradigms being explored in pilot or pivotal clinical trials. Multifocal temporal plus or posterior quadrant epilepsies are evaluated with pulvinar thalamus neuromodulation, while centromedian thalamus is explored in generalized epilepsies and Lennox Gastaut syndrome. Multinodal thalamocortical neuromodulation with novel stimulation paradigms such as long bursting or low-frequency stimulation is being investigated to quench the epileptic network excitability. Beyond seizure control, thalamic neuromodulation to restore consciousness is being studied. This review highlights the promising potential of thalamic neuromodulation in epilepsy treatment, offering hope to patients who have not responded to conventional medical therapies. However, it also emphasizes the need for larger randomized controlled trials and personalized stimulation paradigms to improve patient outcomes further.

Red light enhances the antibacterial properties, biofabrication, and stability of Fagonia indica callus-based silver nanoparticles.

Plant-based nanoparticles can be tuned through the frequency of light for efficient synthesis, structural properties, and antibacterial applications. This research assessed the effect of material type (callus and whole-plant extract) and the interaction with a specific range of light wavelength on AgNP synthesis. All types of AgNPs were characterized by their size, shape, associated functional groups, and surface charge. Interestingly, the size of red light and callus-based AgNPs (RC-AgNPs) was smaller (6.32 nm) compared to 14.59 nm for Ultraviolet light and callus-based AgNPs (UV-C-AgNPs). Zeta potential analysis showed that RC-AgNPs had higher stability (-29.2 mV) compared to UV-C-AgNPs (-16.7 mV). Similarly, red light-based AgNPs had higher Oxidation reduction potential in both whole-plant-based and callus-based AgNPs, indicating a more oxidizing nature compared to those synthesized under UV light. This was confirmed by the lower total phenolic and flavonoid content associated with them and their lower antioxidant activity. The higher antibacterial activities and lower minimum inhibitory concentrations of red light-based AgNPs against highly resistant pathogenic bacteria demonstrated the role of red light in enhancing antibacterial activity. These results indicate that AgNPs synthesized in red light and callus extract are more active compared to those synthesized under other wavelengths and/or in whole-plant extracts.

The burden of chronic drug-refractory focal onset epilepsy: Can it be prevented?

Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL). The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE-including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition.

Biocompatible Gallium Nanodots against Drug-Resistant Bacterial Pneumonia and Liver Abscess.

Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.

Effects of high-dose docosahexaenoic acid supplementation as an add-on therapy for canine idiopathic epilepsy: A pilot study.

Background: The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial. The dosage and efficacy of DHA were various in the previous reports. Aim: The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated. Methods: An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal fluid examination (median: 2.0 years before the trial). They had 5-45 seizures and/or auras (median: 9.0) in the month before starting DHA supplementation. DHA was adjunctively administered at doses of 69-166 mg/kg/day without changing other prescriptions. Results: Four of the six patients completed the 6-month observation period. All the patients showed a decrease in seizure frequency of 50% or more within 2-3 months after the start of the administration, and three patients decreased to a frequency of 0-1 per month after 5-6 months. No clear adverse events were observed in the general condition or blood test results in any patients. Conclusion: Although the sample size was small and the study was not a randomized controlled trial, the data suggest that add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy.