Addition Of Agents Research Articles

Comparative safety and efficacy of a hybrid intravenous and oral diltiazem protocol for acute rate control in the emergency department

Study objectiveIntravenous diltiazem has experienced numerous supply shortages over the past few years. The purpose of this study was to compare the safety and efficacy of a traditional diltiazem intravenous bolus and continuous infusion protocol to a diltiazem intravenous bolus and oral maintenance protocol for acute rate control in the emergency department. MethodsPatients who received intravenous diltiazem in the emergency department between January 1, 2018 and May 31, 2019 were screened. Patients were included if they received the diltiazem intravenous bolus and continuous infusion protocol (IV + infusion group) or the hybrid diltiazem intravenous bolus and oral maintenance protocol (IV + PO group). The primary outcome was the proportion of patients with rate control, without need for additional rate control agents or additional boluses during the maintenance phase. ResultsA total of 106 patients were matched with 53 patients in each group. For the primary outcome of rate control at four hours, 62.3% of patients in the intravenous bolus + infusion group versus 75.5% of patients in the IV bolus + PO group (p = 0.142) achieved rate control. There was no difference in rates of hypotension or bradycardia between groups. ConclusionResults of this study demonstrated no difference in acute rate control when using a hybrid IV and oral diltiazem protocol, compared to a traditional IV bolus and infusion strategy. This information supports the further use of a hybrid diltiazem IV and oral protocol, which provides increased flexibility during shortages of either medication.

Broadening the Scope of Sapofection: Cationic Peptide-Saponin Conjugates Improve Gene Delivery In Vitro and In Vivo.

Gene therapies represent promising new therapeutic options for a variety of indications. However, despite several approved drugs, its potential remains untapped. For polymeric gene delivery, endosomal escape represents a bottleneck. SO1861, a naturally occurring triterpene saponin with endosomal escape properties isolated from Saponaria officinalis L., has been described as additive agent to enhance transfection efficiency (sapofection). However, the challenge to synchronize the saponin and gene delivery system in vivo imposes limitations. Herein, we address this issue by conjugating SO1861 to a peptide-based gene vector using a pH-sensitive hydrazone linker programmed to release SO1861 at the acidic pH of the endosome. Nanoplexes formulated with SO1861-equipped peptides were investigated for transfection efficiency and tolerability in vitro and in vivo. In all investigated cell lines, SO1861-conjugated nanoplexes have shown superior transfection efficiency and cell viability over supplementation of transfection medium with free SO1861. Targeted SO1861-equipped nanoplexes incorporating a targeting peptide were tested in vitro and in vivo in an aggressively growing neuroblastoma allograft model in mice. Using a suicide gene vector encoding the cytotoxic protein saporin, a slowed tumor growth and improved survival rate were observed for targeted SO1861-equipped nanoplexes compared to vehicle control.

Stimuli Responsive Molecular Exchange of Structure Directing Agents on Gold Nanobipyramids: Cancer Cell Detection and Synergistic Therapeutics.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Remendable Cross-Linked Alginate/Gelatin Hydrogels Incorporating Nanofibers for Wound Repair and Regeneration.

Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness in vivo wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.

Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: a retrospective analysis

Steroid-refractory chronic graft-versus-host disease (cGvHD) is associated with significant morbidity and mortality, with ruxolitinib being the first drug approved for its treatment. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of cGvHD at our center between 07/2015 and 12/2022 and identified 48 patients receiving ruxolitinib as second (18/48) or advanced (30/48) treatment line. Ruxolitinib was started on median day 340 (range 119–595) after cGvHD onset; median duration of administration was 176 (range, 79–294) days with 16/48 patients continuing treatment at last follow-up. National Institutes of Health organ grading and the intensity of immunosuppression were assessed at the start of ruxolitinib treatment and repeated after 1, 3, 6, and 12 months. Response assessment was terminated at the start of any additional new immunosuppressant treatment. The median time of follow-up was 582 (range, 104–1161) days. At the primary analysis after six months on ruxolitinib treatment, the overall response rate was 33%, and failure-free survival was 58%. Infectious adverse events ≥ CTCAE grade III were observed in 10/48 patients. The response rate was not associated with the severity of cGvHD, number of previous treatment lines, or number of additional agents combined with ruxolitinib applying a univariate regression model. At the time of the 12-month follow-up, four patients experienced recurrence of the underlying malignancy and two patients had experienced non-relapse-related mortality. Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population.

Dissociation and Loss: a Challenge for Sustainable and Inclusive Conservation

ABSTRACT The agents of deterioration (AoD) offer a structured categorization of hazards to collections: they are a basis for risk-informed preservation management. In drawing up the AoD their creators were not ignorant of wider societal issues of concern to conservators, but they envisaged them to be part of a broader institutional activity located beyond the scope of preventive conservation. Within conservation, there have been discussions about additional agents: social, cultural, or political causes of loss. Their continued exclusion from the AoD may mistakenly be interpreted as a lack of consideration of such concerns. There are reasons to limit the scope of an institution’s preventive conservation system but not everyone agrees that those reasons are sufficient to justify this limitation. This paper is a discussion and disagreement by two authors. Henderson argues that dissociation should capture any loss of meaning resulting from any aspect of conservation practice, including cleaning, documentation, failure to respect beliefs, etc. She argues that dissociation from context may stop preventive conservators from identifying and respecting optimal traditional sustainable methods and techniques. Waller argues that the threat of losing context information about collection items should be managed as part of the wider cultural heritage institution’s role and resolved through its engagement with the community. He acknowledges that preventive conservation can contribute to understanding and mitigating this form of loss, but advocates that primary responsibility must be situated at a higher level than the preventive conservation remit.

Development and thermal property analysis of biobased binary composite heat storage materials

Natural aliphatic dibasic acids are a type of bio-based material that shows promising potential as green phase change thermal storage materials due to their favorable thermophysical properties. However, these materials have been found to have issues with subcooling, low thermal conductivity, and poor temperature matching. In this study, three aliphatic dibasic acids, namely adipic acid (AA), sebacic acid (SA), and azelaic acid (ZA), were selected for further investigation. Three biobased eutectic systems, AA-SA (melting point: 118.3 °C), ZA-SA (melting point: 96.2 °C), and AA-ZA (melting point: 98.4 °C), were then prepared based on the calculation of Schrader's equation and experimental screening. The eutectic systems were thoroughly characterized, revealing thermal conductivities ranging from 0.4 to 0.5 W·m−1·K−1, with all systems exhibiting a subcooling of around 20 °C. Based on the principle of optimal overall performance, the AA-SA system was selected for modification. By incorporating Expanded graphite (EG) as a highly thermally conductive additive and nucleating agent, the AA-SA/EG composite phase change material (CPCM) was successfully prepared. This modification effectively reduced the supercooling degree of the bio-based phase change materials (PCM) and significantly improved its thermal conductivity by a factor of four. The resulting AA-SA/EG CPCM demonstrated excellent temperature suitability and has the potential to contribute to the application of bio-based phase change materials in waste heat recovery and solar energy systems. This study provides valuable insights into the development and optimization of bio-based phase change materials, contributing to the sustainable utilization of renewable resources for thermal energy storage applications.

Formation and health risk assessment of trihalomethanes in coastal wells impacted by seawater intrusion

The formation of trihalomethanes (THMs) in coastal wells impacted by seawater intrusion (SWI) is relatively understudied. Coastal wells, unlike typical groundwater sources, frequently exhibit elevated levels of chloride and bromide ions, potentially influencing the formation and speciation of THMs. The current study investigated the THM formation in coastal well water from a location affected by SWI. Samples were chlorinated with 2.5 mg L−1 and 5 mg L−1 chlorine doses to replicate field conditions. The THM concentration in the samples exceeded the maximum permissible limit for drinking water. The well with the highest chloride-to-bromide (Cl/Br) ratio (Cl/Br = 645) exhibited the highest total THM concentration (503.2 μg L−1). Samples with high bromide concentration had more brominated THMs over the 5-day reaction period. The bromine substitution factors for wells after 24 h with a chlorine dose of 2.5 mg L−1 were 1.89, 2.21, and 2.78, corresponding to bromide concentrations of 0.098, 0.109, and 1.275 mM, respectively. The average cancer risk associated with the well water was estimated to be 20.9 × 10−06 through dermal contact and 6.84 × 10−04 through inhalation. The study area had an estimated average cancer risk of 705 cases per million population. The study area's common diseases and cancer incidence data for the past four decades indicated a decreasing trend for waterborne diseases and a steep increase in cancers. While several factors may contribute to increasing cancer cases, our study highlights chlorinated coastal well water as an additional potential cancer risk agent.

Quantitative Single‐Cell Comparison of Sensitization to Radiation and a Radiomimetic Drug for Diverse Gold Nanoparticle Coatings

Metal‐based nanoparticles (NPs) have entered clinical use for enhancing radiotherapy, but the underlying mechanisms remain ambiguous. Herein, single‐cell analysis of two cell lines in response to megavolt irradiation and a radiomimetic drug, neocarzinostatin (NCS) after coculture with gold NPs with different surface coatings, polyethylene glycol (AuPEG), PEG, and transferrin (AuT) or silica (AuSiO2), is reported. Different surface chemistry presents a major challenge for objective comparison between the biological impacts where major differences in cell‐uptake exist. AuSiO2 NPs are the most efficient for promoting radiosensitization despite being associated with cells 10 times less than the actively targeted AuT NPs. Conversely, for cells exposed to NCS, AuSiO2 NPs impede the radiomimetic action and promote cell survival. AuT NPs enhance death of cells in combination with NCS showing that NPs can sensitize against cytotoxic agents in addition to radiation. While NPs contribute to radiosensitization (or enhancing/impeding chemotherapeutic drug activity), due to cell and cell line heterogeneity, the ultimate radiosensitivity of a cell appears to be dominated by its inherent radiosensitivity and how this cell‐regulated response is manipulated by NPs. This is evidenced through comparison of radiobiological response of cells with equivalent NP association rather than equivalent coculture conditions.

Successive ionic layer adsorption and reaction grown silver nanoflowers as an efficient flexible SERS substrate

The detection limitations of surface-enhanced Raman spectroscopy (SERS) sensors largely depend on the nano tip structure, yet the methods for constructing it are often overly complex. Here, we introduce a method using successive ionic layer adsorption and reaction (SILAR) to synthesize silver nanoflowers (AgNFs) within and on the surface of soft cellulose filter paper. This synthesis relies on a redox reaction involving silver nitrate (AgNO3) and ascorbic acid (AA), with no surfactants or additional agents utilized. Key synthesis parameters were investigated, such as the molar concentration of reactants and the number of synthesis cycles performed. As a result, the detection limit for rhodamine 6G (R6G) using SERS approached 10−11 M when deposited on the optimally synthesized AgNFs sample, yielding a corresponding enhancement factor of 8.9 × 108. The growth mechanism of AgNFs was analyzed by examining morphological changes over the initial five reaction cycles, and differences in X-ray diffraction (XRD) peak intensity ratios of (111) and (200) among the samples were considered. These findings pave a way for the development of high performance, Ag-based flexible SERS substrates.

Tailoring interlayer spacing of Ti3C2Tx MXene with organic acid doped polyaniline and polypyrrole for more stable supercapacitors

Polyaniline (PANI) and polypyrrole (PPy) are promising for use as spacers materials to prevent re-stacking of MXene layers and to increase their electrochemical properties. However, these conducting polymers (CPs) may undergo hydrolysis during long charge-discharge cycles. The use of organic acids to dope CPs may lead to better polymer cyclic stability. However, PANI and PPy used as spacers in MXene are mainly doped with inorganic acids. Herein, we applied dodecylbenzenesulfonic acid (DBSA) doped PANI and PPy as effective spacers and additional pseudocapacitance agents for Ti3C2Tx MXene. Taking advantage of the favored dispersibility of the functional inks in water, we easily prepared the electrodes by drop casting. X-ray diffractograms confirmed that the CPs are effectively allocated among MXenes sheets. Spectroscopic analyses showed that the functional groups of Ti3C2Tx may work as effective dopants for PANI and PPy. The enhanced interlayer spacing of MXenes and increased high conductivity of CPs boosted capacitance from 175 F g−1 (Ti3C2Tx) to 255 F g−1 and 270 F g−1 at 1 A g−1 after addition of 10 wt% of PANI and PPy, respectively, at a three-electrode setup. The Dunn’s and Trasatti’s methods showed greater pseudocapacitive contribution after addition of PPy and greater double layer capacitance contribution after addition of PANI. Similarly, symmetric solid-state SCs exhibited enhancement of 72 % in specific capacitance for Ti3C2Tx/PANI and 208 % for Ti3C2Tx/PPy, when compared to pristine Ti3C2Tx. SCs based on Ti3C2Tx/CPs also yielded outstanding capacitance retentions (>98 %) after 5000 cycles against only 88 % of the Ti3C2Tx pristine device. These results indicate that the organic doped-CPs modulated interlayer spacing of MXene sheets, preventing their re-stacking during the charge and discharge cycles. Finally, the aqueous Ti3C2Tx/CPs based inks is an eco-friendly and low-cost alternative to fabricate SCs with enhanced capacitance and stability.

Envisioning how to advance the MASH field.

Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has ledto, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.

Evaluation of Polyethylene Glycol Dosing for Functional Constipation in Children.

Objective: The goal of this study was to evaluate the current use of polyethylene glycol (PEG) in a pediatric gastroenterology outpatient clinic. The primary endpoint was to determine the current weight-based PEG dosing schedules used for home cleanouts and maintenance treatment for functional constipation. The secondary endpoint was to assess the dosing efficacy for home cleanouts. Methods: This study was a retrospective cohort analysis of electronic medical records documenting new patient visits at our pediatric gastroenterology clinic between September 2017 and October 2018. Patients included in the study were 13 months to 18 years of age and prescribed PEG for an at-home cleanout and/or maintenance therapy for functional or slow transit constipation. Study participants given a clean-out regimen were divided into those who received treatment for less than 2 days or more. Cleanouts were considered successful if documented as such by the prescriber in the follow-up note or if there was documentation of clear flow. Results: Of the 201 new patients included, 112 (55.7%) received a recommendation for a home cleanout. Of these, 111 patients (99%) underwent PEG-based therapy with or without additional agents. The median weight-based PEG dose was 5.3 ± 2.4 and 4.6 ± 1.9 g/kg/day for 1- and 2-day cleanouts, respectively (P = 0.124). Of the 38 patients with documented outcomes, 28 (73.7%) were successful. We observed no statistically significant differences in the number of successful versus unsuccessful outcomes based on PEG dosing (P = 0.3) or cumulative dose exposures (P = 0.388). Similarly, we observed no significant differences when comparing those on 1-day versus 2-or-more-day cleanouts, (P = 0.17). The median weight-based maintenance PEG dose was 0.74 g/kg/day (interquartile range [IQR], 0.55, 0.96). Conclusions: While the PEG doses used by this clinic for 1-day bowel cleanouts align with the NASPGHAN best practices for colonoscopy report, patients who underwent a 2-day cleanout were provided more than double the weight-based doses. The doses were nearly 3-fold higher than the recommended doses for functional constipation home cleanouts. More information will be needed to determine if these higher doses for home cleanouts are needed for the successful management of patients with functional constipation.

Pulp carbon fixation via pyrolysis using ammonium dihydrogen phosphate as an additive

In recent years, waste pulp incineration has become a problem due to the large amount of carbon dioxide emissions. The effect of ammonium dihydrogen phosphate (ADP) as an additive agent was investigated by pyrolyzing ADP-supplemented pulp, and the yields of carbon fixation, phosphorus recovery, and nitrogen recovery were calculated. An ADP/pulp ratio of 0.01 mol/g was found to be the optimal amount of ADP addition according to the pyrolysis profile, N fixation, carbon yield, and surface properties. The addition of ADP significantly increased the carbon fixation yield from approximately 30 % to over 80 %. The product activated carbon with ADP possessed surface area of 730 m2/g, which was a 2.4-fold increase compared to 300 m2/g without ADP. In addition, the effect of ADP on intramolecular dehydration of pulp was quantitatively discussed by identifying the amount of water, which was about three water molecules from a 2-unit repetition of pulp structure.

Use of Infliximab in the Treatment of Immune Checkpoint Inhibitors-Related Myocarditis: A Systematic Review of Case Reports

Immune-mediated myocarditis is uncommon, progresses rapidly and has high mortality rate. Infliximab has been used in practice, particularly in steroid refractory cases, but evidence supporting the use is still lacking. This review aims to provide an overview of infliximab use in managing immune-related myocarditis. A systematic search was conducted using the PubMed and Cochrane Library databases as well as manual searching of bibliographies, from inception to 1 October 2021. Eligible studies were selected by the inclusion criteria. All the included studies were assessed for methodological quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports. There were 13 articles with total 14 reported cases of immune-related myocarditis treated with infliximab. Most patients developed myocarditis with high severity grade, concurrent immune-related adverse events (irAEs), particularly neuromuscular irAEs and multiple potentially fatal complications. Most patients received single dose of infliximab, whereas few received multiple doses. Four patients improved clinically or biochemically, but 10 patients did not improve or deteriorated clinically with the addition of infliximab. Half of the reported cases did not survive due to myocarditis and its complications. Conflicting results were observed when infliximab was used in patients with heart failure and higher dose did not appear to be beneficial in these patients. Concomitant irAEs, high severity grade and occurrence of potentially fatal complications indicate the need to escalate the treatment by using additional immunosuppressive agents such as infliximab. However, there is no standardisation on the infliximab treatment regimen, outcomes have been inconsistent and safety data is limited.

Preparation and Characterization of Ferulic Acid Hydrogel and Its Application as a Local Drug Delivery Agent in Periodontitis.

Introduction Periodontitis, a persistent inflammatory condition, impacts the tissues supporting teeth. Beyond mechanically eradicating the biofilm, additional host-modulating agents can aid in the treatment of periodontitis. Among these, gels are a very popular choice for use in the field of dentistry as these systems boast high biocompatibility and bioadhesiveness. These qualities make them easily administered and fabricated. They aretypically placed into the periodontal site via wide-port needle syringes. Many investigations have demonstrated that hydrogels possess the ability for controlled drug release and aid in periodontal wound healing. Hence, this study aimed to develop a ferulic acid hydrogel and assess its effectiveness for managing periodontitis. Materials and methods Ferulic acid hydrogel was prepared followed by haemolysis assay and biocompatibility assay. After the in vitro analysis, a clinical trial was conducted: 20 patients were divided into Group A (comprising patients in whom scaling and root planing (SRP) was done) and Group B (comprising patients in whom SRP along with hydrogel application was done). Each patient's pocket depth (PD), clinical attachment loss (CAL), gingival index (GI), and plaque index (PI) were recorded at baseline and at three months. Intergroup and intragroup comparisons of the parameters were made. Results Ferulic acid hydrogels exhibit a minimal ratio of red blood cell destruction, indicating their low haemolytic activity. Beyond 94 hours, ferulic acid hydrogel demonstrates minimal toxicity towards human fibroblasts, suggesting it has good biocompatibility. When clinical parameters were compared after three months of treatment with SRP alone, significant reductions were observed in all parameters. However, when hydrogel application was done along with SRP, greater reduction was seen in terms of all clinical parameters indicating the efficacy of the ferulic acid hydrogel as an adjunct. Conclusion Ferulic acid has distinct haemolytic activity as well as good biocompatibility. Its use also led to a considerable reduction in all clinical parameters, necessitating its role as a local drug delivery agent in the treatment of periodontitis.

Severe Mpox Among People With Advanced Human Immunodeficiency Virus Receiving Prolonged Tecovirimat in New York City.

Severe mpox has been observed in people with advanced human immunodeficiency virus (HIV). We describe clinical outcomes of 13 patients with advanced HIV (CD4 <200 cells/μL), severe mpox, and multiorgan involvement. Despite extended tecovirimat courses and additional agents, including vaccinia immune globulin, cidofovir, and brincidofovir, this group experienced prolonged hospitalizations and high mortality.

Initial Despair and Current Hope of Identifying a Clinically Useful Treatment of Myocardial Reperfusion Injury: Insights Derived from Studies of Platelet P2Y12 Antagonists and Interference with Inflammation and NLRP3 Assembly

Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y12 receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y12 antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y12 antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y12 antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.

Electron Reservoir MoO3–x‐Driven Cu+ Doped Nanozyme with Enhanced Antibacterial Activity via Disrupting Redox Homeostasis

Comprehensive SummaryRedox nanozymes offer an appealing reactive oxygen species (ROS)‐based antibacterial strategy via disrupting intracellular homeostasis, however, they still face many obstacles such as low enzymic activity and irreversible loss of catalytic active center. Meanwhile, the antioxidant glutathione (GSH) overexpressed in infected sites would limit the therapy efficiency. Herein, we develop a multifunctional nanozyme based on copper(I) (Cu+) ion doped MoO3–x (Cu+‐MoO3–x) by a simple yet efficient oxygen vacancy‐reduced strategy without any pretreatment or additional agents. The resultant Cu+‐MoO3–x hybrid possesses enhanced peroxidase‐like (POD‐like) activity, rapid GSH‐depleting function and biodegradable ability. It can achieve highly efficient elimination of Pseudomonas aeruginosa (P. aeruginosa) via disrupting cellular redox balance. More intriguingly, GSH‐depleting redox reaction between Cu+‐MoO3–x and GSH could translate Mo6+ into Mo5+, thereby leading to partial recovery of POD‐like activity of Cu+‐MoO3–x hybrid for continuous ∙OH generation. In vitro and in vivo experiments demonstrated that Cu+‐MoO3–x hybrid had stronger antibacterial property compared to MoO3–x by rapid GSH consumption and plentiful ∙OH generation without providing extra H2O2, as well as neglective toxicity to healthy organs. In view of its remarkable enzymic activity and good biosafety, the developed Cu+‐MoO3–x redox nanozyme can be used as a promising antimicrobial for P. aeruginosa infection.