Safe Approach Research Articles

Combined Laparoscopic Cholecystectomy and Transcystic Common Bile Duct Exploration for Choledocholithiasis

Abstract Background: There is no consensus on the ideal approach for managing patients with common bile duct (CBD) stones. The combined approach is less popular, possibly due to the complexity of the surgical technique and the availability of choledochoscope. Aim: We aim to assess the safety and feasibility of transcystic (TC) CBD exploration using the flexible bronchoscope for choledocholithiasis. Methods: Forty patients with symptomatic calculus gallbladder with concomitant CBD stones were randomized into two groups. Single-session laparoscopic cholecystectomy (LC) and laparoscopic TC CBD exploration were performed for one group using the flexible bronchoscope. Endoscopic retrograde cholangiopancreatography followed by LC after 4–6 weeks was conducted for the other group. Results: Twenty patients were randomized to each group. The clearance rate of CBD stones was significantly higher in the single-session Group A (95%) than in the two-session Group B (70%). Group B was associated with a significantly prolonged operative (P = 0.01). The total hospital stay and operative time were significantly longer in Group B than in Group A (P = 0.004). There was no significant difference between both groups regarding the intraoperative or postoperative complications. Conclusion: Combined LC and TC CBD exploration is a safe and feasible approach and is associated with significantly shorter operative time and length of hospital stay.

A Novel Cell- and Virus-Free SARS-CoV-2 Neutralizing Antibody ELISA Based on Site-Specific Labeling Technology.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the global spread of coronavirus disease 2019 (COVID-19), creating an urgent need for updated methods to evaluate immune responses to vaccines and therapeutic strategies. In this study, we introduce a novel cell-free, virus-free SARS-CoV-2 neutralizing antibody ELISA (NAb-ELISA), which is based on competitive inhibition of the receptor binding domain (RBD) of spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. In this method, site-specific biotinylated hACE2-Fc-Avi recombinant protein is immobilized onto a 96-well plate for capture, and the RBD-Fc-vHRP recombinant proteins serve as detection probes. Evaluation of sera from wild type (WT) or Delta RBD-immunized mice using the NAb-ELISA and pseudovirus neutralization tests (pVNTs) demonstrated strong correlations between assays (R2 = 0.91 and 0.90 for the WT and Delta groups, respectively). Additionally, the NAb-ELISA successfully detected cross-neutralizing activity in sera, though with slightly lower correlation to pVNT (R2 = 0.70-0.83). By employing NAb-ELISA instead of an indirect ELISA for hybridoma screening, five monoclonal antibodies (mAbs) with neutralizing activities against WT, Delta, and BA.2 pseudoviruses were obtained. This assay offers a straightforward, rapid, and safe approach to characterizing vaccine-induced antibody responses and mAb neutralization activity. Notably, the NAb-ELISA platform can be quickly adapted to assess neutralizing antibody responses against emerging mutant strains, addressing the rapid mutation of the virus.

Analysis of Children's Road Crashes in Hungary

In the EU, more than 6,000 children died in road accidents between 2011 and 2020. Children are particularly vulnerable road users, and they need to be protected. This underlines the importance of the Safe System approach. The Safe System approach is a holistic view of road safety, which integrates the different elements of the traffic system and takes human vulnerability and fallibility into account. Children are still in the phase of developing the cognitive and physical skills necessary to travel safely in traffic. Because of their small size, children are less visible than other road users and less experienced; they can easily become innocent victims in collisions. Despite significant improvements in vehicle safety in recent years, almost half of all child road deaths occur while traveling in cars. Limited data is available on the correct use of child seats in cars across the EU, but studies have shown that misuse remains a significant problem. Several measures have been taken in recent years to make it safer for children to travel on the roads, but many more interventions are needed to further improve their safety. Our research aimed to examine the characteristics of child accidents in Hungary and to highlight the main road safety problems affecting children in Hungary.

Numerical Modelling and Experimental Validation of Selective Laser Melting Processes Using a Custom Argon Chamber Setup for 316L Stainless Steel and Ti6AI4V

Selective Laser Melting (SLM) is an advanced additive manufacturing technique that demands meticulous control over thermal dynamics to maintain the integrity and performance of manufactured parts. This study presents the development and validation of a thermal model designed to enhance the SLM process for 316L stainless steel (316L SS) and titanium alloy Ti6Al4V. A specially constructed Argon Chamber Setup, equipped with a 200 W continuous-wave (CW) fibre laser system, was used to create an SLM-representative environment for 316L SS, enabling precise experimental validation of the model. This validation serves as a robust baseline, facilitating the model’s extension to more complex materials like Ti6Al4V, thereby supporting a cost-efficient and safe approach to initial testing. The rigorously validated thermal model offers a comprehensive link between experimental data and numerical simulations in SLM. It supports process optimisation by accurately predicting thermal behaviours, contributing significantly to additive manufacturing advancements. By fine-tuning processing parameters, this model enhances material characteristics, thereby providing practical insights applicable to industrial production and improving the consistency and quality of SLM-manufactured parts.

“They talk about it like it's an overdose crisis when in fact it's basically genocide”: The experiences of Indigenous peoples who use illicit drugs in Vancouver's Downtown Eastside neighbourhood

Indigenous Peoples who use illicit drugs (IPWUID) are disproportionately represented among toxic drug poisoning deaths in Canada. These drug-related harms are framed by the historical and ongoing trauma related to settler colonialism and are acutely visible in Vancouver, Canada's Downtown Eastside - a low-income neighbourhood that is an epicenter of the drug poisoning crisis and characterized by entrenched poverty, substance use, violence, and homelessness. This study was undertaken to examine the experiences and perspectives of IPWUID in the Downtown Eastside regarding the drug poisoning crisis and the responsiveness of harm reduction programs within the context of settler colonialism. Indigenous-led qualitative interviews were conducted with 16 IPWUID recruited by Indigenous peer researchers. Indigenous ways of knowing were embedded throughout the entire research design to ensure research was culturally congruent. Interview transcripts were analyzed thematically and interpreted by drawing on concepts of social violence and racial capitalism. Our analysis reviewed three key themes that centered the experiences of IPWUID in Vancouver's Downtown Eastside in relation to the drug poisoning crisis: (1) that the drug poisoning crisis is understood as a form of genocide toward Indigenous Peoples; (2) that the crisis is experienced within the context of pervasive distrust and adversarial relationships with police rooted in structurally racist experiences of place-based policing practices; and (3) that there is a desire for culturally-safe harm reduction care with Indigenous representation, cultural integration, and that addresses inequities and injustice stemming from colonialism and structural racism. Findings demonstrate how responses to the drug poisoning crisis among IPWUID need to respond to social and materials conditions perpetuated by colonialism and racial capitalism, while also centering IPWUID through the development and implementation of Indigenous-led and culturally safe harm reduction approaches.

Research on coal rock parameter calibration based on discrete element method

To ensure that the discrete element model of the coal wall accurately reflects the actual cutting process of coal and rock during virtual prototype simulation of mining equipment, this study aims to expedite the development of intelligent mining machinery. Using coal samples from the 4602 working face of Yangcun Coal Mine, operated by Yanzhou Coal Mining Group, we conducted coal rock packing experiments and uniaxial compression tests to obtain the packing angle and compressive strength of the coal samples. Based on the experimental results, we designed Plackett–Burman experiments (PB experiments), steepest ascent experiments, and Box-Behnken experiments to study the influence of particle contact mechanics parameters and bonding mechanics parameters on the packing angle and compressive strength, using the packing angle and compressive strength as response variables. Our objective is to minimize the relative error between the simulated packing angle and the measured packing angle. We solved and optimized the parameter calibration model and conducted simulation calibration experiments based on the optimization results. A comparative analysis with the actual test results revealed that the maximum relative errors between the simulated and measured values for the packing angle and compressive strength were only 2.9% and 5.0%, respectively. Additionally, a discrete element model of a typical working face coal wall was established based on the parameters obtained from this calibration method. A bidirectional coupling model of the cutting process between the coal and rock was created using EDEM-RecurDyn to simulate the rigid-flexible coupling of the coal cutter. An experimental coal wall model was constructed based on similarity theory, and both simulation and physical experiments were conducted. The evaluation metrics for comparison were the time-domain and frequency-domain characteristics of the drum’s vibration signals. The maximum relative error for the time-domain signal characteristics between the two experimental setups was only 4.19%, while the maximum relative error for the frequency-domain signal characteristics was 3.75%. This validates the feasibility of the proposed calibration method for the discrete element coal wall model and the accuracy of the calibration results. Furthermore, it demonstrates that the constructed discrete element coal wall accurately represents the actual coal and rock properties. The virtual simulation based on this model effectively replicates the interaction process between mining machinery and coal, providing a safe, efficient, and low-cost technological approach for performance analysis of mining equipment and intelligent control of supporting devices.

Resurgence of vaginal route of hysterectomy: Comparison based outcomes of abdominal and vaginal hysterectomy.

Objective: To determine the preferable route of hysterectomy by comparing the intra-operative and post-operative complications of non descent vaginal hysterectomy with abdominal hysterectomy. Study Design: Randomized Control Trial. Setting: Madina Teaching Hospital, Faisalabad, Pakistan. Period: January 2022 to December 2022. Methods: Forty cases of each vaginal and abdominal hysterectomy were enrolled for study. Outcome was measured by recording intra-operative and post-operative complications in both groups. Results: Time of surgery, postoperative pain, postoperative blood transfusion, wound infection, febrile morbidity and duration of hospital stay were significantly less (p value 0.0001) in the non descent vaginal hysterectomy compared to abdominal hysterectomy. Conclusion: Non descent vaginal hysterectomy is a safe and cost effective approach when compared to abdominal rout due to less intra and post operative morbidity particularly in settings where facilities and expertise for laparoscopic surgery are lacking.

Ultrasound-guided percutaneous biopsy for challenging perihilar focal liver lesions: diagnostic accuracy and safety assessment.

In cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions. We included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023. All samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported. US-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.

Effective method of pedicle screw fixation in patients with neurologically intact thoracolumbar burst fractures: a systematic review of studies published over the last 20 years

ObjectiveTo conduct a systematic review of studies on various posterior pedicle screw fixation (PSF) methods used for treating neurologically intact thoracolumbar burst fractures and to identify the most effective and safe approaches. MethodsWe conducted a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the study registered in PROSPERO (CRD42024531093). The inclusion criteria were: (1) publication dates from January 1, 2004, to December 31, 2023; (2) availability of full-text articles in English; (3) thoracolumbar burst fractures without neurological deficits; (4) patients aged over 18; (5) reports on treatment outcomes or complications; (6) a mean follow-up period of at least 12 months. ResultsA total of 69 articles covering 116 patient groups were included. Our analysis highlighted the advantages of short-segment fixation without fusion over monosegmental, short-segment and long-segment fusion in terms of shorter operation times and reduced intraoperative blood loss (p = 0.001 and p < 0.001, respectively). Extensive fusion was associated with a significantly higher frequency of deep surgical site infections compared to other PSF methods (p = 0.043). Percutaneous pedicle screw fixation, applied to patients with lower body compression rates and kyphotic deformities, led to less potential for correction (p = 0.004), yet significantly decreased blood loss (p = 0.011), operation duration (p < 0.0001), and hospitalization duration (p < 0.0001). No significant benefits were observed with the use of additional intermediate screws in short-segment PSF. ConclusionsShort-segment pedicle screw fixation could be the optimal surgical treatment method for neurologically intact thoracolumbar burst fractures. The use of posterior lateral fusion in this context may increase the deep surgical site infection rate without reducing the frequency of implant-related complications or improving long-term treatment outcomes. The percutaneous approach remains the preferred technique; however, its limited reduction capabilities should be carefully considered during surgical planning for patients with severe kyphotic deformities. The application of intermediate screws in such patients has not demonstrated significant advantages. Removing the fixation system has not led to a significant decrease in implant-related complications or improvement in quality of life. The data obtained from the systematic review may assist surgeons in selecting the most appropriate surgical treatment method for patients with neurologically intact thoracolumbar burst fractures, thereby avoiding ineffective procedures and improving both short-term and long-term outcomes.

Direct Colour Printing on Zirconia Using 222nm UV-C Photons

ObjectivesTo proof the feasibility of direct colour printing on 3Y-TZP using 222nm UV-C, investigate the degree and durability of the colour changes and testify whether other properties are influenced by the treatment. Methods222nm UV-C light (Irradiance: 1.870mW/cm2) was used to treat 3Y-TZP for durations from 15minutes to 24hours. ΔE*, TP, crystalline structure, surface morphology, Sa, BFS and biological activities were investigated before and after irradiation. SPSS 28.0 was used for statistical analysis (α = 0.05). Results222nm UV-C irradiation was capable of shading white 3Y-TZP into tooth colours. With the increase of ΔE*, TP decreased, such that the longer the irradiation, the higher the ΔE* (logarithmic relationship) and the lower the TP. Despite the induced optical changes being prone to fade, the process can be predicted by inversely proportional relationships between ΔE*, TP and the testing points. The treated surface exhibited enhanced hydrophilicity, while the recovery phenomenon was observed. Other properties were not altered by the treatment. SignificanceThis is the seminal study demonstrating the feasibility of direct colour printing on 3Y-TZP using 222nm UV-C. The new relationship between the colour centre and Eg of 3Y-TZP was established, whereas the induced optical changes were stabilised after a certain period and were highly predictable by controlling irradiation periods. The irradiation was only related to the electron excitation and oxygen vacancies, and would not lead to changes of other properties. A simple, safe and promising approach to achieve satisfactory colours on 3Y-TZP in clinical practice can be developed.

Anatomical-guided third-generation laser balloon ablation for the treatment of paroxysmal atrial fibrillation assessed by continuous rhythm monitoring: results from a multicentre prospective study

Abstract Aims The third-generation laser balloon (LB3) is an established ablation device for pulmonary vein isolation (PVI) that allows direct visualization of the anatomical target. Equipped with an automatic circumferential laser delivery modality, it aims at continuous circumferential PVI, improving both acute and clinical outcomes. We sought to evaluate the clinical efficacy of LB3 ablation using an anatomical-based approach without verifying electrical isolation. Methods and results Among 257 paroxysmal AF patients undergoing LB3 ablation across four Italian centres, 204 (72% male, mean age 60.4 ± 11.1 years) were included. The primary endpoint was freedom from any atrial tachyarrhythmia (ATa) recurrence after the blanking period (BP), assessed with implantable cardiac monitors (ICMs). All pulmonary veins (PVs) were targeted using the LB3, with the RAPID mode used on an average of 96 ± 8, 86 ± 19, 98 ± 11, and 84 ± 15% for the left superior, left inferior, right superior, right inferior PV, and left common ostium, respectively. Freedom from arrhythmia recurrences was 84.8% at 1, 80.4% at 2, and 76.0% at 3 years. An ATa burden ≥ 5% was documented in 2.5, 4.4, and 5.4% at 1, 2, and 3 years, respectively. Relapses during the BP [hazard ratio (HR) = 2.182, P = 0.032] and left atrial dilation (HR = 1.964, P = 0.048) were independent predictors of recurrences. Conclusion Anatomical-guided LB3 ablation for paroxysmal AF is a safe and effective approach, providing excellent clinical outcomes as assessed by ICM over nearly 3 years of follow-up.

Airway management in infants with Robin sequence in the United Kingdom and Ireland: A prospective population-based study.

There is currently no consensus about managing upper airway obstruction (UAO) in infants with Robin sequence (RS), in terms of treatment efficacy or clinical outcomes. This study describes UAO management in UK/Ireland, and explores relationships between patient characteristics, UAO management, and clinical outcomes in the first 2 years of life. Active surveillance of RS throughout UK/Ireland via the British Paediatric Surveillance Unit and nationally commissioned cleft services. Clinical data were collected at initial notification and 12-month follow-up. 173 infants with RS were identified, of which 47% had additional congenital anomalies or an underlying syndrome (non-isolated RS). Two-thirds (n = 119) required an airway intervention other than prone positioning: non-surgical in 84% and surgical (tracheostomy) in 16%. Nasopharyngeal airway (NPA) was the most common intervention, used in 83% (n = 99) for median 90 days (IQR 136). Surgical UAO management was associated with prolonged hospital admission, higher prevalence of neurodevelopmental delay (NDD), lower weight-for-age z-scores, and delayed oral feeding. These findings were not attributable to a higher prevalence of non-isolated RS in this group. Although more commonly associated with non-isolated RS, growth faltering was also identified in 48%, and NDD in 18%, of cases of isolated RS. In UK/Ireland, most infants with RS are managed with NPA, and tracheostomy is reserved for refractory severe UAO. Clinical outcomes and duration of use indicate that NPA is a safe and feasible first-line approach to UAO. Longitudinal assessment of neurodevelopment and growth is imperative, including in children with isolated RS. Current variations in practice reinforce the need for evidence-based treatment guidelines.

SafeMD: Ownership-Based Safe Memory Deallocation for C Programs

Rust is a relatively new programming language that aims to provide memory safety at compile time. It introduces a novel ownership system that enforces the automatic deallocation of unused resources without using a garbage collector. In light of Rust’s promise of safety, a natural question arises about the possible benefits of exploiting ownership to ensure the memory safety of C programs. In our previous work, we developed a formal ownership checker to verify whether a C program satisfies exclusive ownership constraints. In this paper, we further propose an ownership-based safe memory deallocation approach, named SafeMD, to fix memory leaks in the C programs that satisfy exclusive ownership defined in the prior formal ownership checker. Benefiting from the C programs satisfying exclusive ownership, SafeMD obviates alias and inter-procedural analysis. Also, the patches generated by SafeMD make the input C programs still satisfy exclusive ownership. Usually, a C program that satisfies the exclusive ownership constraints is safer than its normal version. Our evaluation shows that SafeMD is effective in fixing memory leaks of C programs that satisfy exclusive ownership.

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

Relational Lorentzian Asymptotically Safe Quantum Gravity: Showcase Model

In a recent contribution, we identified possible points of contact between the asymptotically safe and canonical approaches to quantum gravity. The idea is to start from the reduced phase space (often called relational) formulation of canonical quantum gravity, which provides a reduced (or physical) Hamiltonian for the true (observable) degrees of freedom. The resulting reduced phase space is then canonically quantized, and one can construct the generating functional of time-ordered Wightman (i.e., Feynman) or Schwinger distributions, respectively, from the corresponding time-translation unitary group or contraction semigroup, respectively, as a path integral. For the unitary choice, that path integral can be rewritten in terms of the Lorentzian Einstein–Hilbert action plus observable matter action and a ghost action. The ghost action depends on the Hilbert space representation chosen for the canonical quantization and a reduction term that encodes the reduction of the full phase space to the phase space of observables. This path integral can then be treated with the methods of asymptotically safe quantum gravity in its Lorentzian version. We also exemplified the procedure using a concrete, minimalistic example, namely Einstein–Klein–Gordon theory, with as many neutral and massless scalar fields as there are spacetime dimensions. However, no explicit calculations were performed. In this paper, we fill in the missing steps. Particular care is needed due to the necessary switch to Lorentzian signature, which has a strong impact on the convergence of “heat” kernel time integrals in the heat kernel expansion of the trace involved in the Wetterich equation and which requires different cut-off functions than in the Euclidian version. As usual we truncate at relatively low order and derive and solve the resulting flow equations in that approximation.

Optimizing CAR-NK Cell Transduction and Expansion: Leveraging Cytokine Modulation for Enhanced Performance.

Cellular immunotherapy has emerged as one of the most potent approaches to treating cancer patients. Adoptive transfer of chimeric antigen receptor (CAR) T cells as well as the use of haploidentical natural killer (NK) cells can induce remission in patients with lymphoma and leukemia. Although the use of CAR T cells has been established, this approach is currently limited for wider use by the risk of severe adverse events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Moreover, the risk of triggering graft vs host reactions in settings of allogeneic T cell infusion limits the use to autologous CAR T cells if advanced CRISPR engineering is not applied. In contrast, NK cell-based cancer immunotherapy has emerged as a safe approach even in allogeneic settings. However, efficient transduction of primary blood NK cells with vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped lentivirus commonly used for T cell modification remains challenging. This article presents a detailed method that significantly enhances the transduction efficiency of NK cells by utilizing a short-term culture in cytokine-supplemented medium. It also encompasses the preparation of high-titer and high-quality lentiviral particles for optimal NK cell transduction. Overall, this protocol details the step-by-step culture of NK cells in cytokine-supplemented medium, their transduction with VSV-G lentiviral vectors, and subsequent expansion for functional assays. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Isolation of NK cells from human peripheral blood mononuclear cells (PBMCs) Basic Protocol 2: NK cell expansion and transduction with lentivirus for generating CAR-NK cells Support Protocol 1: Plasmid amplification Support Protocol 2: Lentivirus preparation Support Protocol 3: Lentivirus titration.

Enhancing Ras cheese safety: antifungal effects of nisin and its nanoparticles against Aspergillus flavus

BackgroundDue to the adverse effects of industrial chemicals and their carcinogenicity and toxicity for humans, the debates have increased on using natural preservatives. This study was conducted to investigate the inhibitory effect of pure nisin and nisin nanoparticles (nisin NPs) against Aspergillus flavus in vivo by inoculation in laboratory-manufactured Ras cheese. A novel, safe, and natural approach of nanoprecipitation using acetic acid was employed to prepare nisin nanoparticles. The prepared NPs were characterized using zeta-sizer, FTIR, and transmission electron microscopy (TEM). Furthermore, the cytotoxicity of nisin NPs on Vero cells was assessed. The minimum inhibitory concentrations (MICs) of nisin and its nanoparticles were determined in vitro against A. flavus isolates using the agar well-diffusion method. The sensory evaluation of manufactured Ras cheese was conducted over a 60-day storage period.ResultsThe obtained results showed a strong antifungal activity of nisin NPs (0.0625 mg/mL) against A. flavus strain in comparison with pure nisin (0.5 mg/mL). Notably, the count decreased gradually by time from 2 × 108 at zero time and could not be detected at the 7th week. The count with pure nisin decreased from 2 × 108 at zero time and could not be detected at the 10th week where it’s enough time to produce aflatoxins in cheese. The MICs of nisin and nisin NPs were 0.25 and 0.0313 mg/mL, respectively. Nisin NPs used in our experiment had good biocompatibility and safety for food preservation. Additionally, the sensory parameters of the manufactured Ras cheese inoculated with nisin and nisin NPs were of high overall acceptability (OAA).ConclusionsOverall, the results of this study suggested that adding more concentration (˃0.0625 mg/mL) from nisin nanoparticles during the production of Ras cheese may be a helpful strategy for food preservation against A. flavus in the dairy industry.

Shortened versus standard duration of dual antiplatelet treatment after percutaneous coronary intervention in patients with and without chronic kidney disease: a systematic review and meta-analysis

Abstract Background Impaired renal function is an established risk factor for recurrent cardiac events. The severity of chronic kidney disease (CKD) is related with an increased risk for both ischemic and bleeding complications. As a result, the clinical implications of antithrombotic therapies may be different in patients with CKD as compared to those without. Recently, shortened duration of DAPT, namely one to three months, after percutaneous coronary intervention (PCI) has been proven as a safe and feasible strategy in various different clinical scenarios, like in high-bleeding risk patients, in acute coronary syndromes and complex PCI. However, it remains debatable whether DAPT should be shortened in patients with high ischemic and bleeding risk, such as those with CKD. Purpose The aim of our systematic review and meta-analysis is to explore the safety and efficacy of shortened therapy (1-3 months; S–DAPT) in patients without and without CKD undergoing PCI. Methods Three major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) were screened for eligible randomized – controlled trials, or subgroup or post – hoc analyses of them. The studies should compare shortened (S–DAPT) with longer (&amp;gt;3 months) DAPT (L–DAPT) in patients undergoing PCI, and include data on CKD presence. The endpoints were Net Adverse Clinical Events (NACE) and Major Adverse Cardiac Events (MACE) and should be evaluated at 12 months. NACE and MACE were used as per trial defined. The effect of different DAPT regimens was assessed by calculating the risk ratio (RR) with 95% confidence interval (CI) using random-effects model (Mantel-Haenzel). Results A total of eight studies and 56,660 patients were included in our analysis; a notable proportion of patients (9.7%, N=5,466) suffered from CKD. Our analysis showed an overall benefit of S-DAPT in NACE (RR: 0.88, 95%CI: 0.81 – 0.95), which was consistent in patients with and without CKD (p-interaction=0.58). (Figure 1) No significant difference regarding MACE was observed between S-DAPT and L-DAPT (RR: 0.98, 95%CI: 0.90 – 1.06) in both patients with and without CKD (p-interaction=0.19). (Figure 2) Conclusions Our analysis showed an overall benefit of S-DAPT in NACE without any difference in MACE, with similar findings among patients with and without CKD. Thus, DAPT shortening could be a feasible and safe approach when it is required, even in patients with impaired renal function. Further randomized controlled trials focusing on patients with CKD are required for validating the previous results and exploring further benefits of abbreviated duration of DAPT.Net adverse clinical eventsMajor adverse cardiac events

An epigenetic editor targeting human PCSK9 efficiently and durably lowers Low Density Lipoprotein Cholesterol (LDL-C) in non-human primates

Abstract Background Reducing the risk of atherosclerotic cardiovascular disease is dependent on both the magnitude and cumulative duration of LDL-C lowering. However, in clinical practice achieving treatment goals is often hampered by low adherence to standard of care. Although PCSK9 inhibitors represent an effective option for LDL-C lowering, they require chronic life-long treatment. Epigenetic editing is a new therapeutic approach designed to durably silence genes by leveraging nature’s endogenous cellular mechanism for gene regulation via CpG methylation without the inherent genotoxic risks of genome editing approaches that nick or cut the DNA. We are developing a PCSK9 epigenetic editor (PCSK9-EE) to durably silence PCSK9, with the promise of lifelong reduction in LDL-C. Methods Here, we describe the development of an epigenetic editor targeting human PCSK9. This epigenetic editor consists of a DNA targeting component fused to a transcriptional repressor domain and a DNA methyltransferase domain. PCSK9-EE was first screened and evaluated for specificity and efficacy in primary human hepatocytes (PHH). In vivo efficacy and durability were then evaluated in a transgenic mouse carrying the human PCSK9 genomic locus (hPCSK9-Tg mouse) and non-human primates (NHP). Results Our initial screen of PCSK9-EEs identified several hits that efficiently suppressed secreted PCSK9 levels in immortalized liver cells. We confirmed that our top PCSK9-EE candidates robustly decreased PCSK9 secretion in PHH and were found to be highly specific at targeting PCSK9 as assessed by RNA-seq, methylation array, and whole-genome methylation sequencing. To examine in vivo activity, we treated hPCSK9-Tg mice with a single administration of a lipid nanoparticle delivering mRNA encoding our PCSK9-EE and observed &amp;gt;97% reduction in liver PCSK9 mRNA, and &amp;gt;98% reduction in plasma PCSK9 for the duration of the study (one year). We then delivered PCSK9-EE in NHP and observed a robust reduction in plasma PCSK9 with a concomitant reduction in LDL-C. These effects were found to be durable for at least 6 months following a single administration of PCSK9-EE in NHP. To establish a mechanistic relationship between PCSK9-EE’s molecular action and durable PCSK9 silencing, we performed serial liver biopsies in each NHP approximately 2 months apart. Robust CpG methylation at the PCSK9 genomic locus was observed in the first liver biopsy and was comparable to that observed in the second liver biopsy suggesting that PCSK9-EE induced stable CpG methylation in NHP livers. Conclusions We believe PCSK9-EE may offer an effective, safe, and durable approach to suppress hepatic PCSK9 expression and achieve long-lasting reduction in LDL-C. Furthermore, epigenetic editing may hold promise for one-and-done approaches for the treatment of atherosclerotic cardiovascular disease without cutting, nicking, or altering the DNA sequence.

Analysis of the Emergency Rescue Nursing Intervention Effect and Rescue Success Rate for Patients with Traumatic Hemorrhagic Shock

Objective: To analyze the value of emergency rescue nursing intervention in the care of patients with traumatic hemorrhagic shock and its impact on the success rate of rescue efforts. Methods: A total of 80 patients with traumatic hemorrhagic shock were selected as samples, with the timeframe from July 2022 to July 2023. The patients were randomly divided into two groups using a random number table method. Group A received emergency rescue nursing, while Group B received routine nursing care. The success rate of rescue, rescue indicators, complication rates, and family satisfaction with nursing care were compared between the two groups. Results: The rescue success rate in Group A was higher than in Group B (P &lt; 0.05); the total blood loss in Group A was less, and the rescue time, full transportation time, and hospitalization time were shorter than in Group B (P &lt; 0.05); the complication rate of patients with traumatic hemorrhagic shock in Group A was lower than in Group B (P &lt; 0.05); the family satisfaction with emergency nursing care in Group A was higher than in Group B (P &lt; 0.05). Conclusion: Emergency rescue interventions for patients with traumatic hemorrhagic shock can reduce blood loss, shorten rescue times, and improve the success rate of shock rescue, providing a safe and effective approach.