Safe Approach Research Articles

Stimulation of inactivated Metschnikowia bicuspidata promotes the growth, and immunity of Eriocheir sinensis larvae

The Chinese mitten crab (Eriocheir sinensis) is an economically essential crustacean specie in China. The outbreak of disease caused by Metschnikowia bicuspidata has resulted in high mortality and huge economic loss in the E. sinensis aquaculture industry. Immune priming can protect invertebrates against pathogens in the second exposure, which has been reported in adult E. sinensis and provides a novel approach for disease control. This study evaluated the effects of treatment with formalin-killed M. bicuspidata on the growth, development, and immunity of E. sinensis embryos and larvae. Stimulation of E. sinensis embryos with inactivated M. bicuspidata (Mb group) did not significantly affect the mass and size of embryos. While the carapace width, abdominal length, and tail length of larvae in the Mb group were significantly longer than those of control group in most stages. At 120 h and 144 h after embryo hatching, the metamorphosis rate of larvae in the Mb group was 24.59-fold (p < 0.05) and 16.07-fold (p < 0.001) higher than that in the control group. Moreover, after the larvae suffered alive M. bicuspidata challenge, the mortality in the Mb group significantly decreased (0.48-fold, p < 0.05) compared with that in the control group, and the mRNA expression levels of genes related to immunity (MAPK, Toll2, and STAT), growth (ATGL, Chi, Chymotrypsin, and mTOR), and development (Ubx) were significantly increased in the Mb group. These results suggested that stimulation of E. sinensis embryos with inactivated M. bicuspidata significantly promoted the growth and development of larvae and endowed them with stronger resistant capacity to M. bicuspidate. This finding may provide a novel and safe approach for preventing disease and improving larvae quality in E. sinensis aquaculture.

Online Mindfulness-Based Intervention (eMBI) in management of dyspnea in patients with interstitial lung disease: A randomized clinical trial

Dyspnea and cough are frequent symptoms in ILD patients. The management of these symptoms is challenging, and evidence-based therapies are lacking. To evaluate the effect of an online Mindfulness-Based Intervention (eMBI) on reducing dyspnea in patients affected by different ILDs. This study was a prospective, open-label, controlled trial that included patients ≥18 years and a modified Medical Research Council (mMRC) dyspnea scale score of ≥ 1. Patients were randomized into either the eMBI or the control group (CG) for 8 weeks. The primary outcome was the change in the dyspnea mMRC scale. The Leicester Cough Questionnaire (LCQ), King's Brief Interstitial Lung Disease (K-BILD) questionnaire, and Depression, Anxiety, and Stress Scale (DASS-21) were performed before and after the eight weeks. All analyses were conducted on an intention-to-treat basis. The study was registered at the Brazilian Registry of Clinical Trials (ReBEC), RBR-3s4mf9y. 24 patients in the eMBI and 25 in the CG completed the intervention. In the eMBI group, compared to the control group, there was a greater proportion of patients with a reduction in dyspnea according to the mMRC scale score (48.9% versus 15.4%, p = 0.001). There was no significant difference between the groups in the LCQ (p = 0.666), or in the K-BILD (p = 0.108), depression (p = 0.08), or anxiety (p = 0.869 or stress (p = 0.789). No moderate or severe adverse events were observed in either group. Eight weeks eMBI is a potentially viable and safe approach, that can help manage dyspnea in ILD patients.

Laparoscopic adrenalectomy performed with the Endo GIA™ Stapler as an easy and safe approach.

The purpose of this study was to determine whether the application of the Endo GIA™ Stapler (Medtronic, Dublin, Ireland) could be helpful in the dissection of adrenal tumors in complicated cases. We retrospectively reviewed the records of patients who underwent laparoscopic adrenalectomy between 2012 and 2022 at the College of Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea (Seoul, Republic of Korea). We adopted the Endo GIA™ Stapler (Medtronic) to seal vessels around adrenal gland and separate adrenal gland completely when it was difficult to perform meticulous dissection and isolation with laparoscopic instruments. Thirteen patients who underwent laparoscopic adrenalectomy with Endo GIA™ staplers were reviewed and compared with 45 other patients who underwent laparoscopic adrenalectomy without Endo GIA™ staplers. There were no statistical differences between the two groups in demographic, tumor-related, and diagnostic variables. Surgical outcomes such as margin involvement, bleeding, operation duration, rate of conversion to open surgery, blood transfusion, complications, and recurrence were not different between the two groups. In our experience, applying of the Endo GIA™ Stapler (Medtronic) in laparoscopic adrenalectomy is a feasible and acceptable approach.

Surgical Technique for Repair of Tegmen Dehiscence with Encephalocele: A Retrospective Study

Tegmen dehiscence with encephalocele presents certain surgical challenges, necessitating innovative approaches to improve patient outcomes and minimize complications. Here we aim to evaluate the safety and efficacy of a novel middle cranial fossa craniotomy technique. Nineteen adult patients with radiographically confirmed tegmen dehiscence with encephalocele were included. Patients underwent a middle cranial fossa craniotomy technique for tegmen dehiscence repair, utilizing a split thickness bone graft, pedicled pericranial flap, and hydroxyapatite for extradural repair and with an inlay graft for the intradural repair. The primary outcome measured was major perioperative complications or need for revision surgery while secondary outcome measured was the resolution or improvement of preoperative symptoms associated with tegmen dehiscence. Our series encompassed tegmen dehiscence repairs in 19 patients, with an average age at surgery of 51 years (range 24 to 82). The average follow-up time was 8.80 months (range 0.43 to 27.62 months). Patients commonly presented with symptoms such as hearing loss (n=8), otorrhea (n=8), fullness or ear pressure (n=6), dizziness or imbalance (n=6), or a history of meningitis (n=4), among others. Postoperatively, symptoms resolved completely in 42% of patients (n=8) and partially in 58% of patients (n=11). Notably, no patients required revision surgery or developed new dehiscences in the follow-up period. Our middle cranial fossa craniotomy technique for tegmen dehiscence with encephalocele repair demonstrated promising postoperative outcomes, with complete or partial symptom resolution in all patients and no major complications. Our findings suggest that this technique is a safe and effective approach for tegmen dehiscence repair.

Transoral approach for hilo-parenchymal submandibular stones: outcomes and predictors of success

ObjectiveTo evaluate the efficacy and safety of transoral surgical management for complex submandibular gland (SMG) stones. Study DesignA retrospective cohort study of 240 patients treated for sialolithiasis between 2015 and 2018, focusing on 57 cases of submandibular gland stones that underwent stone removal procedures. Treatment methods, success rates, and complications were analyzed using Kaplan-Meier analysis, Cox proportional hazards regression, and multiple logistic regression. ResultsTransoral surgical release was successful in 72.9% of cases. The overall complication rate was 10%. Stone size (HR = 0.85, p = 0.004) and hilar location (HR = 0.72, p = 0.036) were associated with longer symptom resolution time. Multivariate analysis revealed that stone size (OR = 0.78, p = 0.009) and hilar location (OR = 0.45, p = 0.029) decreased the odds of successful removal. ConclusionTransoral surgical management of hilo-parenchymal SMG stones appears to be a safe and effective approach, potentially reducing the need for sialoadenectomy.

Accelerated Return To Sport Following Hip Arthroscopy For Femoroacetabular Impingement Syndrome: A Safe And Effective Approach

Accelerated Return To Sport Following Hip Arthroscopy For Femoroacetabular Impingement Syndrome: A Safe And Effective Approach

Controllable H2S supply via membrane contactors for safe and efficient arsenic precipitation from acidic wastewater

Sulfide precipitation is a popular technique for the treatment and resource recovery of arsenic-containing dirty acid wastewater. However, this approach frequently suffers from toxic hydrogen sulfide (H2S) escape and agent wastage issues. Herein, a safe and efficient technique is proposed based on a polytetrafluoroethylene membrane contactor wherein the mass transfer resistance of the gas, membrane, and liquid phases can be easily and independently regulated to control the H2S supply. Additionally, H2S is transferred in bubble-free form, fundamentally avoiding the issue of gas escape, and uniform membrane distribution contributes to evenly distributed H2S delivery. The results demonstrated that 99.3% arsenic precipitation could be achieved and the H2S emission ratio was limited to <0.12%, which was significantly better than traditional methods. Thus, highly efficient separation and resource recovery of heavy metals in wastewater can be achieved using this unique and controllable low-dose H2S supply method. The separation factor between copper and arsenic was as high as 7490.9. This study provides a safe, reliable, and promising new approach for the treatment of arsenic-containing acidic wastewater.

The demonstrated step-by-step RATS 1ˢᵗ rib resection has shown to be a safe and effective approach for 1ˢᵗ rib resection in thoracic outlet syndrome.

The demonstrated step-by-step RATS 1ˢᵗ rib resection has shown to be a safe and effective approach for 1ˢᵗ rib resection in thoracic outlet syndrome.

Uterus Didelphys with Hematocervix in the Unilateral Obstructed Hemivagina and Ipsilateral Renal Agenesis: A Case Report of Herlyn–Werner–Wunderlich Syndrome

Background: Mullerian duct anomalies include a broad spectrum of genital tract defects that arise from developmental abnormalities of the genital tract. Herlyn–Werner–Wunderlich syndrome (HWWS) refers to the combination of uterus didelphys, blind hemivagina and ipsilateral renal agenesis. In the literature, the syndrome often appears as a few sporadic case reports. Case: We report a case of symptomatic Herlyn–Werner–Wunderlich syndrome diagnosed by transavaginal scan and MRI and successfully treated with a laparoscopic-assisted hysteroscopic vaginal septum resection. The postoperative course was without complications, and clinical symptoms completely resolved the surgery. Summary and Conclusions: Combination of laparoscopy and hysteroscopy was found to be an easy, safe, effective and appropriate approach for patients with HWWS.

Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.

Effective and safe pharmacological approaches for atrial defibrillation offer several potential advantages over techniques like ablation. Pharmacological therapy is noninvasive, involving no risk associated with the procedure or resulting complications. Moreover, acute drug intervention with existing drugs is likely to be low cost and broadly accessible, thereby addressing a central tenet of health equity. This study aims to investigate ibutilide-mediated action potential prolongation to promote use-dependent effects of flecainide on Na+ channels by reducing the diastolic interval and, consequently, drug unbinding to reduce action potential excitability in atrial tissue and terminate re-entrant arrhythmia. Here we utilize a modeling and simulation approach to predict the specific combinations of sodium- and potassium-channel blocking drugs to chemically terminate atrial re-entry. Computational modeling and simulation show that acute application of flecainide and ibutilide is a promising example of drug repurposing that may constitute a promising combination for chemical atrial defibrillation. We predict the drug concentrations that promote efficacy of flecainide and ibutilide used in combination for atrial chemical defibrillation. We also predict the potential safety pharmacology impact of this drugcombination on ventricular electrophysiology.

Public Support for a Safe System Approach to Reducing Motor Vehicle Crashes Deaths in the United States

Conventional road safety strategies are yielding diminishing returns. The Safe System approach is based on the premise that human errors will occur on the roadway and that the system should be designed to accommodate these errors, so they do not result in death or serious injury. Elements of the system include the roadway infrastructure, vehicle engineering, and speed management.Political support for U.S. Safe System implementation gained momentum with $5 billion in appropriated funds in the 2021 Bipartisan Infrastructure Law. The purpose of this study was to measure public support for Safe System implementation. We fielded a nationally representative survey of US adults from May 4 to June 10, 2022 (N=2,274). We measured whether respondents considered individual- or systems-oriented approaches as the most effective way to prevent traffic deaths. We also assessed support for various roadway interventions and vehicle safety technologies. Most respondents agreed that system-level changes were the most effective way to prevent traffic deaths. Endorsement for system-level changes was significantly higher among younger age groups. Support for roadway improvements and vehicle safety technologies varied according to the type of intervention that was proposed. Public support for a Safe System approach is high, particularly among younger adults, which suggests that the momentum for the movement can be sustained over the long term.

An Advanced Hydrogel Dressing System with Progressive Delivery and Layer-to-Layer Response for Diabetic Wound Healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of SignificanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

An adapted taxonomy and framework for monitoring road safety strategies: a case study of Morocco.

Traditional approaches to monitoring road safety have primarily focused on measuring outcomes such as the number of fatalities and injuries. While effective in capturing overall trends, this macroscopic approach often overlooks the underlying causes of unsafe conditions. Recognizing these limitations, many countries now embrace a safe system-based approach, which emphasizes a holistic view of road safety, considering various elements and their interactions. In response to this shift, this study introduces a five-step framework designed to provide comprehensive coverage and tailored assistance in selecting and utilizing appropriate Road Safety Indicators (RSIs) for more effective performance monitoring. The framework integrates a novel RSIs taxonomy aligned with critical elements of the safe system. It also incorporates an MCDA-based approach to account for decision-makers' preferences when selecting suitable RSIs. A case study demonstrates the practical application of the proposed steps, including the identification, classification, selection, and development of descriptive sheets for each selected RSI, as well as the continuous updating of the RSIs set. The findings offered valuable insights into the commonly used indicators in international road safety reports, while also revealing the limitations of currents metrics and data in fully capturing critical elements and hierarchical level within the road safety management system.

A Simple and Forgiving Automatic Docking System for Under-Actuated USVs

Abstract This article presents the development and testing of an automatic docking system, tailored to smaller, under-actuated, and uncrewed vessels. The system integrates a vessel control system for safe and repeatable dock approaches, and a mooring system capable of handling significant trajectory and pose offsets. The developed system features a shore-focused, floating structure with vertically mounted flat funnels for mooring. Testing involved various on-water experiments, validating the system’s reliability in correcting yaw and lateral offsets under challenging conditions. Later development and testing included the integration of automatic mooring control, a vessel charging concept, as well as a capable vessel approach controller. The final test demonstrated the system’s ability to achieve automatic docking in 33 out of 36 attempts despite varying wind conditions. The system’s performance highlights its potential to enhance docking safety and efficiency for under-actuated vessels. Combining automatic approach and automatic mooring, the presented system has the potential to enable routine under-actuated USV operations with minimal human effort.

Asymptotically safe — canonical quantum gravity junction

The canonical (CQG) and asymptotically safe (ASQG) approach to quantum gravity share to be both non-perturbative programmes. However, apart from that they seem to differ in several aspects such as: 1. Signature: CQG is Lorentzian while ASQG is mostly Euclidian. 2. Background Independence (BI): CQG is manifesly BI while ASQG is apparently not. 3. Truncations: CQG is apparently free of truncations while ASQG makes heavy use of them.The purpose of the present work is to either overcome actual differences or to explain why apparent differences are actually absent. Thereby we intend to enhance the contact and communication between the two communities. The focus of this contribution is on conceptual issues rather than deep technical details such has high order truncations. On the other hand the paper tries to be self-contained in order to be useful to researchers from both communities.The point of contact is the path integral formulation of Lorentzian CQG in its reduced phase space formulation which yields the formal generating functional of physical (i.e. gauge invariant) either Schwinger or Feynman N-point functions for (relational) observables. The corresponding effective actions of these generating functionals can then be subjected to the ASQG Wetterich type flow equations which serve in particular to find the rigorous generating fuctionals via the inverse Legendre transform of the fixed pointed effective action.

Posterior Cruciate Ligament Reconstruction Using a Trans-septal Approach With Preserved Hamstrings Tibial Insertion

Posterior cruciate ligament reconstruction is a challenging procedure and requires a safe approach that provides a proper visualization of the tibial footprint while avoiding neurovascular damage and facilitating graft passage. Recent studies have shown that the preservation of the hamstring tibial attachment improves fixation and vascularization in the setting of anterior cruciate ligament reconstruction. This Technical Note reports an effective and reproducible arthroscopic single-bundle posterior cruciate ligament reconstruction through a trans-septal approach wit preserved hamstring tibial insertion.

A simplified and safe approach to percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis (ALS) patients

A simplified and safe approach to percutaneous endoscopic gastrostomy tube placement in amyotrophic lateral sclerosis (ALS) patients

Digoxin Discontinuation in Patients with HFrEF on Beta-Blockers: Implication for Future “Knock-Out Trials” in Heart Failure

Background: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers. Methods: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated. Results: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85–1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85–1.25) or death (HR, 0.91; 95% CI, 0.72–1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25–2.04), 1.62 (1.18–2.22) and 1.43 (1.08–1.89). Conclusions: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy.

Triple-targeted therapy of dabrafenib, trametinib, and osimertinib for the treatment of the acquired BRAF V600E mutation after progression on EGFR-tyrosine kinase inhibitors in advanced EGFR-mutated non-small cell lung cancer patients.

The B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation is responsible for approximately 3% of acquired resistance mechanisms to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant non-small cell lung cancer (NSCLC). This study investigated the efficacy and safety of a triple-targeted therapy combining EGFR/BRAF/mitogen-activated protein kinase kinase (MEK) inhibitors of dabrafenib, trametinib, and osimertinib in NSCLC patients with acquired BRAF V600E mutation after EGFR-TKI treatment. A multi-center retrospective review of medical records was performed to analyze EGFR-mutated advanced Chinese NSCLC patients who acquired the BRAF V600E mutation following EGFR-TKI treatment. All patients subsequently received dabrafenib, trametinib, and osimertinib. The clinical characteristics, progression-free survival (PFS), and adverse events (AEs) were documented. The in-vivo drug response of patient-derived organoids (PDOs) was observed. Next-generation sequencing (NGS) was performed upon progression to triple-targeted therapy. Thirteen patients with BRAF V600E mutations were included. Following triple-targeted therapy, the corresponding objective response rate and disease control rate were 61.5% and 92.3%, respectively. The median PFS was 13.5 months (95% confidence interval: 6.6-20.4). PDOs derived from one patient's tumor sample were established, revealing that the triple-targeted therapy had a significantly lower half-maximal inhibitory concentration (IC50) value compared to other regimens. The tumor growth inhibitory rate was 99.36% for dabrafenib, trametinib, and osimertinib; 99.25% for osimertinib plus vemurafenib; 98.92% for osimertinib, encorafenib, and cetuximab; and 62.83% for pemetrexed plus carboplatin. NGS analysis identified major resistance mechanisms following the triple-targeted therapy, including the EGFR-dependent pathway, EGFR and BRAF V600E-dependent pathway, and an off-target mechanism. EGFR/BRAF/MEK triple-targeted therapy is an effective and safe approach for treating EGFR-mutated NSCLC patients resistant to EGFR-TKIs with acquired BRAF V600E mutations.

Multifunctional HxMoO3-y-MoO2/Carbon Composite Particles for Water Remediation.

Solving a scarcity of freshwater resources is an urgent global challenge by a safe and sustainable approach using renewable energy. We demonstrate the multifunctional catalyst of HxMoO3-y-MoO2/carbon composite particles toward highly efficient water remediation. A one-step mechanochemical reaction successfully upgraded the composites from commercially available MoO3-polypropylene (PP) powders without introducing hydrogen gas. The composite particles exhibited broad light absorption in the UV-visible (Vis)-near-infrared (NIR) region (200-2000 nm), with an optical band-gap narrowing to 1.03 eV. The plasmonic properties of HxMoO3-y-MoO2 allowed a fast water evaporation rate (3.29 kg m-2 h-1) with a photothermal conversion efficiency of 88.8%. In addition, the HxMoO3-y-MoO2 heterojunction dominated wide-spectrum activity under Vis and NIR light irradiation, up to 3 orders of magnitude higher than pristine MoO3 in the photocatalytic degradation of azo-dye pollutants. Furthermore, the byproduct carbon with abundant oxygen-containing groups efficiently eliminated water pollutants as a Brønsted acid catalyst and performed exceptional adsorption capacities of heavy metal ions in the dark.