Educational impact and recommendations from implementation of student-led clinical trial recruitment: a mixed-methods study.

Medical students have an essential role in medical research, yet often lack opportunities for involvement within randomised trials. This study aimed to understand the educational impact of clinical trial recruitment for medical students. Tracking wound infection with smartphone technology (TWIST) was a randomised controlled trial that included adult patients undergoing emergency abdominal surgery across two university teaching hospitals. All recruiters underwent prerecruitment training based on 'Generating Student Recruiters for Randomised Trials' principles, and completed prerecruitment and postrecruitment surveys. Respondent agreement with statements were assessed using 5-point Likert scales (from 1 ('strongly disagree') to 5 ('strongly agree')). Quantitative data were analysed using paired t-tests to compare differences pre-involvement and post-involvement. Thematic content analysis was performed on free-text data to generate recommendations for future student research involvement. Of 492 patients recruited to TWIST between 26 July 2016 and 4 March 2020, 86.0% (n=423) were recruited by medical students. Following introduction of student co-investigators (n=31), the overall monthly recruitment rate tripled (4.8-15.7 patients). 96.8% of recruiters (n=30/31) completed both surveys, and all respondents reported significant improvement in clinical and academic competencies. Three higher-level thematic domains emerged from the qualitative analysis: (1) engagement, (2) preparation and (3) ongoing support. Student recruitment in clinical trials is feasible and accelerates recruitment to clinical trials. Students demonstrated novel clinical research competencies and increased their likelihood of future involvement. Adequate training, support and selection of suitable trials are essential for future student involvement in randomised trials.

Oncological and clinical outcomes after conventional right hemicolectomy.

PURPOSE: Complete mesocolic excision (CME) has been proposed for better local control of colon cancer and to improve cancer-specific survival (CSS). However, CME may be associated with increased morbidity from bleeding during central vascular ligation. This study aimed to investigate the outcome of conventional right hemicolectomy, a traditional anatomical dissection along anatomical planes with radical excision of the central lymph nodes at the level of the origin of colic artery but without exposure of superior mesenteric vein and artery (SMV/SMA). METHOD: This was a retrospective review of a cohort of all elective right hemicolectomies performed at a specialist tertiary unit during a five-year period (2011-2015). RESULTS: Five-hundred-nineteen patients (271 female, a median age of 73.0 years (interquartile range (IQR) 65.0-80.0)) were included (Stage I disease: 2.7%, stage II: 53.2%, stage III: 33.3%, stage IV: 10.8%). At the latest follow-up (a median 47 months (IQR 29-67)), local recurrence occurred in 34 patients (6.6%). Three-year overall survival was 74.4% and 3-year CSS was 85.9%. Subgroup analysis for stage I-III showed local recurrence in 6.0%, sole distant recurrence in 7.6% while 19 patients (4.1%) suffered concomitant local and distant recurrence. The anastomotic leak rate was 1.0% and perioperative bleeding occurred in 1.2%. CONCLUSIONS: Oncological outcomes comparable to those of CME can be achieved by conventional surgery but with low rates of bleeding complications and anastomotic leakage. The proposed advantages of CME should be carefully considered and balanced against patients' co-morbidities and potential complications.

Validation of the Waterless Empirical Taste Test (WETT®).

The sense of taste is rarely assessed quantitatively outside of a limited number of academic and industrial laboratories, despite its role in influencing nutrition, the flavor of foods and beverages, and protection against ingestion of spoiled and toxic foodstuffs. This dearth reflects, in part, practical limitations of most taste tests, most notably their reliance on liquid stimuli for stimulus presentation or rinsing. In this study, a novel portable taste test that requires neither liquid tastants nor liquid rinses is described and validated within a clinic population. This test, termed the Waterless Empirical Taste Test (WETT®), uses stimuli that are embedded in pads of monometer cellulose located on disposable plastic strips applied to the tongue's surface. The test-retest and split-half reliability coefficients of the WETT® were 0.92 and 0.88, respectively. These respective coefficients for sucrose, NaCl, citric acid, caffeine, and MSG were 0.82 and 0.80, 0.78 and 0.77, 0.56 and 0.73, and 0.84 and 0.84. The WETT® exhibited comparable, in some cases higher, sensitivity than two comparison taste tests, the Whole Mouth Taste Test and the Taste Quadrant Taste Test, to age, sex, etiology (head trauma vs. upper respiratory infections), and phenylthiocarbamide (PTC) taste ability. This study demonstrates that a taste test that does not require liquids can be as reliable and sensitive as more traditional liquid-based taste tests to clinical alterations in taste function.

Simple fluorescent reagents for monitoring disulfide reductase and S-nitroso reductase activities in vitro and in live cells in culture.

This study describes the theoretical basis and the methods for the facile synthesis and characterization of four fluorogenic probes, N-amido-O-aminobenzoyl-S-nitrosoglutathione (AOASNOG), N-thioamido-fluoresceinyl-S-nitroso-glutathione (TFSNOG), N,N-di(thioamido-fluoresceinyl)-cystine (DTFCys2) and N,N-di(thioamido-fluoresceinyl)-homocystine (DTFHCys2). In addition, the study describes the methodology for the application of these reagents for measuring and imaging of free thiols on cell surfaces as well as their use as pseudo substrates for the thiol reductase and S-nitrosothioldenitrosylase activities of protein disulfide isomerase (PDI) and S-nitrosothiol reductase activity of S-nitrosoglutathione reductase (GSNOR) in vitro and on live cells in culture.

In vivo validation of a miniaturized electrochemical oxygen sensor for measuring intestinal oxygen tension.

Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O2 tension (PTo2) by means of an implantable sensor is potentially useful in many clinical situations, including the perioperative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients. This study describes the in vivo validation of a novel, miniaturized electrochemical O2 sensor to provide real-time data on intestinal PTo2. A single O2 sensor was placed onto the serosal surface of the small intestine of anesthetized rats that were exposed to ischemic (superior mesenteric artery occlusion) and hypoxemic (alterations in inspired fractional O2 concentrations) insults. Control experiments demonstrated that the sensors can function and remain stable in an in vivo environment. Intestinal PTo2 decreased following superior mesenteric artery occlusion and with reductions in inspired O2 concentrations. These results were reversible after reinstating blood flow or by increasing inspired O2 concentrations. We have successfully developed an anesthetized rat intestinal ischemic and hypoxic model for validation of a miniaturized O2 sensor to provide real-time measurement of intestinal PTo2. Our results support further validation of the sensors in physiological conditions using a large animal model to provide evidence of their use in clinical applications where monitoring visceral surface tissue O2 tension is important.NEW & NOTEWORTHY This is the first report of real-time continuous measurements of intestinal oxygen tension made using a microfabricated O2 sensor. Using a developed rodent model, we have validated this sensor's ability to accurately measure dynamic and reversible changes in intestinal oxygenation that occur through ischemic and hypoxemic insults. Continuous monitoring of local intestinal oxygenation could have value in the postoperative monitoring of patients having undergone intestinal surgery.

Atomic structure of a rationally engineered gene delivery vector, AAV2.5.

AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Šusing cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.

Electrochemically decoupled reduction of CO2 to formate over a dispersed heterogeneous bismuth catalyst enabled via redox mediators.

Electrochemical CO2 reduction is a topic of major interest in contemporary research as an approach to use renewably-derived electricity to synthesise useful hydrocarbons from waste CO2. Various strategies have been developed to optimise this challenging reaction at electrode interfaces, but to-date, decoupled electrolysis has not been demonstrated for the reduction of CO2. Decoupled electrolysis aims to use electrochemically-derived charged redox mediators - electrical charge and potential vectors - to separate catalytic product formation from the electrode surface. Utilising an electrochemically generated highly reducing redox mediator; chromium propanediamine tetraacetate, we report the first successful application of decoupled electrolysis to electrochemical CO2 reduction. A study of metals and metal composites found formate to be the most accessible product, with bismuth metal giving the highest selectivity. Copper, tin, gold, nickel and molybdenum carbide heterogeneous catalysts were also investigated, in which cases H2 was found to be the major product, with minor yields of two-electron CO2 reduction products. Subsequent optimisation of the bismuth catalyst achieved a high formate selectivity of 85%. This method represents a radical new approach to CO2 electrolysis, which may be coupled directly with renewable energy storage technology and green electricity.

Structural insight into the unique properties of adeno-associated virus serotype 9.

Adeno-associated virus serotype 9 (AAV9) has enhanced capsid-associated tropism for cardiac muscle and the ability to cross the blood-brain barrier compared to other AAV serotypes. To help identify the structural features facilitating these properties, we have used cryo-electron microscopy (cryo-EM) and three-dimensional image reconstruction (cryo-reconstruction) and X-ray crystallography to determine the structure of the AAV9 capsid at 9.7- and 2.8-Å resolutions, respectively. The AAV9 capsid exhibits the surface topology conserved in all AAVs: depressions at each icosahedral two-fold symmetry axis and surrounding each five-fold axis, three separate protrusions surrounding each three-fold axis, and a channel at each five-fold axis. The AAV9 viral protein (VP) has a conserved core structure, consisting of an eight-stranded, ß-barrel motif and the αA helix, which are present in all parvovirus structures. The AAV9 VP differs in nine variable surface regions (VR-I to -IX) compared to AAV4, but at only three (VR-I, VR-II, and VR-IV) compared to AAV2 and AAV8. VR-I differences modify the raised region of the capsid surface between the two-fold and five-fold depressions. The VR-IV difference produces smaller three-fold protrusions in AAV9 that are less "pointed" than AAV2 and AAV8. Significantly, residues in the AAV9 VRs have been identified as important determinants of cellular tropism and transduction and dictate its antigenic diversity from AAV2. Hence, the AAV9 VRs likely confer the unique infection phenotypes of this serotype.

An Azomethine-H-Based Fluorogenic Sensor for Formic Acid.

Formic acid (FA) is an important C1-containing feedstock that serves as a masked source of dihydrogen gas (H2). To encourage the adoption of cleaner (noncarbonaceous) energy sources, FA detection and sensing is thus of considerable interest. Here, we examine the use of a commercially available dye, azomethine-H (Az-H), for FA sensing. Solution studies confirm that FA quenches both the absorbance and the luminescence properties of Az-H. FA was additionally found to attenuate a known Az-H (E)-to-(Z) conformational change, suggesting an Az-H/FA interaction, possibly through hydrogen bonding; this phenomenon was probed using 1H NMR spectroscopy. Moving toward a solid-state sensor, the Az-H probe was incorporated into a gelatin-based matrix. On exposure to FA, the luminescence of this system was found to increase in a FA-dependent manner, attributed to the formation of stable hydrogen-bonded structures, facilitating a (Z)-to-(E) isomerization via imine protonation, allowing for production of the more luminescent (E)-isomer. This fluorogenic signal was used as a FA sensor with an estimated detection limit of ca. 0.4 ppb FA vapor. This work constitutes an important step toward a highly sensitive FA sensor in both the solution and solid state, opening new space for the detection of organic acids in differing chemical environments.

Evaluation of remote digital postoperative wound monitoring in routine surgical practice.

Remote digital postoperative wound monitoring provides an opportunity to strengthen postoperative community care and minimise the burden of surgical-site infection (SSI). This study aimed to pilot a remote digital postoperative wound monitoring service and evaluate the readiness for implementation in routine clinical practice. This was a single-arm pilot implementational study of remote digital postoperative wound monitoring across two tertiary care hospitals in the UK (IDEAL stage 2b, clinicaltrials.gov: NCT05069103). Adults undergoing abdominal surgery were recruited and received a smartphone-delivered wound assessment tool for 30-days postoperatively. Patients received 30-day postoperative follow-up, including the Telehealth Usability Questionnaire (TUQ). A thematic mixed-methods approach was used, according to the WHO framework for monitoring and evaluating digital health interventions. 200 patients were enroled, of whom 115 (57.5%) underwent emergency surgical procedures. Overall, the 30-day SSI rate was 16.5% (n = 33/200), with 72.7% (n = 24) diagnosed post-discharge. Usage of the intervention was 83.0% (n = 166/200), with subsequently 74.1% (n = 123/166) TUQ completion. There were no issues reported with feasibility of the technology, with the reliability (3.87, 95% CI: 3.73-4.00) and quality of the interface rated highly (4.18, 95%: 4.06-4.30). Patient acceptance was similarly high with regards to ease of use (4.51, 95% CI: 4.41-4.62), satisfaction (4.27, 95% CI: 4.13-4.41), and usefulness (4.07, 95% CI: 3.92-4.23). Despite the desire for more frequent and personalised interactions, the majority viewed the intervention as providing meaningful benefit over routine postoperative care. Remote digital postoperative wound monitoring successfully demonstrated readiness for implementation with regards to the technology, usability, and healthcare process improvement.

Readiness for implementation of novel digital health interventions for postoperative monitoring: a systematic review and clinical innovation network analysis.

An increasing number of digital health interventions (DHIs) for remote postoperative monitoring have been developed and evaluated. This systematic review identifies DHIs for postoperative monitoring and evaluates their readiness for implementation into routine health care. Studies were defined according to idea, development, exploration, assessment, and long-term follow-up (IDEAL) stages of innovation. A novel clinical innovation network analysis used coauthorship and citations to examine collaboration and progression within the field. 126 DHIs were identified, with 101 (80%) being early stage innovations (IDEAL stage 1 and 2a). None of the DHIs identified had large-scale routine implementation. There is little evidence of collaboration, and there are clear omissions in the evaluation of feasibility, accessibility, and the health-care impact. Use of DHIs for postoperative monitoring remains at an early stage of innovation, with promising but generally low-quality supporting evidence. Comprehensive evaluation within high-quality, large-scale trials and real-world data are required to definitively establish readiness for routine implementation.

Structural studies of adeno-associated virus serotype 8 capsid transitions associated with endosomal trafficking.

The single-stranded DNA (ssDNA) parvoviruses enter host cells through receptor-mediated endocytosis, and infection depends on processing in the early to late endosome as well as in the lysosome prior to nuclear entry for replication. However, the mechanisms of capsid endosomal processing, including the effects of low pH, are poorly understood. To gain insight into the structural transitions required for this essential step in infection, the crystal structures of empty and green fluorescent protein (GFP) gene-packaged adeno-associated virus serotype 8 (AAV8) have been determined at pH values of 6.0, 5.5, and 4.0 and then at pH 7.5 after incubation at pH 4.0, mimicking the conditions encountered during endocytic trafficking. While the capsid viral protein (VP) topologies of all the structures were similar, significant amino acid side chain conformational rearrangements were observed on (i) the interior surface of the capsid under the icosahedral 3-fold axis near ordered nucleic acid density that was lost concomitant with the conformational change as pH was reduced and (ii) the exterior capsid surface close to the icosahedral 2-fold depression. The 3-fold change is consistent with DNA release from an ordering interaction on the inside surface of the capsid at low pH values and suggests transitions that likely trigger the capsid for genome uncoating. The surface change results in disruption of VP-VP interface interactions and a decrease in buried surface area between VP monomers. This disruption points to capsid destabilization which may (i) release VP1 amino acids for its phospholipase A2 function for endosomal escape and nuclear localization signals for nuclear targeting and (ii) trigger genome uncoating.

An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery.

BACKGROUND: The appropriate tropism of adeno-associated virus (AAV) vectors that are systemically injected is crucial for successful gene therapy when local injection is not practical. Acidic oligopeptides have been shown to enhance drug delivery to bones. METHODS: In this study six-L aspartic acids (D6) were inserted into the AAV2 capsid protein sequence between amino acid residues 587 and 588. 129SVE mice were injected with double-stranded wild-type- (WT-) or D6-AAV2 mCherry expression vectors (3.24 x 1010 vg per animal) via the superficial temporal vein within 24 hours of birth. RESULTS: Fluorescence microscopy and quantitative polymerase chain reaction confirmed higher levels of mCherry expression in the paraspinal and gluteus muscles in the D6-AAV2 injected mice. The results revealed that although D6-AAV2 was less efficient in the transduction of immortalized cells stronger mCherry signals were detected over the spine and pelvis by live imaging in the D6-AAV2-injected mice than were detected in the WT-AAV2-injected mice. In addition, D6-AAV2 lost the liver tropism observed for WT-AAV2. CONCLUSIONS: An acidic oligopeptide displayed on AAV2 improves axial muscle tropism and decreases liver tropism after systemic delivery. This modification should be useful in creating AAV vectors that are suitable for gene therapy for diseases involving the proximal muscles.

Fluorescein isothiocyanate, a platform for the selective and sensitive detection of S-Nitrosothiols and hydrogen sulfide.

Here we show that the fluorescence of fluorescein isothiocyanate (FITC) is not altered by its reaction with primary amines. However, the fluorescence is rapidly quenched upon reaction with small molecular weight thiols including cysteine, glutathione, homocysteine, dithiothreitol, and sulfide. We have taken advantage of the thiol-dependent quenching of FITC to devise a sulfide specific assay by utilizing polydimethylsiloxane (PDMS) membranes that are permeable to hydrogen sulfide but not to larger charged thiols. In addition, we have discovered that the fluorescein dithiocarbamate (FDTC) formed by the reaction with sulfide can specifically react with S-nitrosothiols (RSNO) to regenerate FITC, thus serving as a specific, fluorogenic reagent to detect picomol levels of RSNO. FDTC was tested as an intracellular RSNO-sensor in germinating tomato seedlings (Solanum lycopersicum) via epifluorescence microscopy. Control plant roots exposed to FDTC showed low intracellular fluorescence which increased ∼3-fold upon exposure to extracellular S-nitrosoglutathione and ∼4-fold in the presence of N6022, a S-nitrosoglutathione reductase (GSNOR) inhibitor, demonstrating that FDTC can be used to visualize intracellular RSNO levels.

Conjugated Polymer Nanoparticles as a Universal High-Affinity Probe for the Selective Detection of Microplastics.

Microplastic (MP) pollution is a global challenge that requires immediate mitigation practices. Monitoring is crucial for quantifying MPs, but their mitigation remains very challenging due to several factors, including the lack of selective materials to specific polymers, and the low sensitivity of the current detection techniques. In this work, we introduce a novel design for the selective detection of MPs through fluorescence spectroscopy by exploiting conjugated polymer nanoparticles (CPNs). Fluorescent diketopyrrolopyrrole nanoparticles were prepared by nanoprecipitation to incorporate peripheral hyaluronic acid to increase their affinity for various plastics. The affinity of the new ligand for various types of MPs was examined through several characterization techniques, including fluorescence spectroscopy and microscopy, nanoparticle tracking analysis and computational studies. The new CPN were shown to be highly fluorescent in the presence of typically abundant MPs, achieving very strong binding constants in the picomolar range. This very strong affinity for a broad family of plastics was found to be the results of cooperative supramolecular effects and topographical affinity, as probed by advanced microscopy and in silico studies. Furthermore, the new affinity probes were shown to be highly selective for MPs, allowing for their detection in heterogeneous samples, including soil debris and other organic contaminants. The new materials design introduced in this work constitute a promising platform for the development of novel MP detection devices directly useable at the point of collection. Moreover, it opens new avenue for the mitigation of this environmental hazard through tailorable materials.

Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter.

In the context of T-cell depletion, failing to achieve full donor chimerism (FDC) entails higher risk of graft loss and disease relapse. Donor lymphocyte infusion (DLI) is an adoptive immunotherapy for mixed chimerism (MC) or relapsed disease after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, little is known of factors associated with attaining FDC or disease remission. We carried out a retrospective study with 100 adult patients to identify patient and donor factors that can predict achievement of FDC and disease remission and describe complications after DLI. Indications for DLI were T-cell MC in 61 patients and relapsed disease in 39 patients. Forty patients (65.6%) with MC attained T-full donor chimerism (T-FDC), with higher responses seen in patients whose donors were female (81.5% versus 52.9%, P = .004) and cytomegalovirus negative (76.5% versus 52%, P = .004). However, only patients with younger donors (<30 years old) compared to older donors (94.4% versus 53.5%, P = .013) and those attaining unfractionated whole blood (UWB) FDC after DLI (76.6% versus 28.6%, P < .001) had a survival benefit and subsequently a better graft-versus-host disease (GvHD)-free/relapse-free survival. Nineteen of 39 patients (48.7%) with relapsed disease achieved remission after DLI. In this cohort, attaining T-FDC impacted favorably in disease control (76.7% versus 12.5%, P = .012) and improved survival (45.5% versus 12.5%, P = .007). In the whole population, the cumulative incidence of acute GvHD (aGvHD) at day 100 after DLI was 23%, and chronic GvHD (cGvHD) at 1 year after DLI was 22%. In the whole population, donor age was also a determining factor for aGvHD, because patients with younger donors had a lower incidence of aGvHD (8% versus 36%, P = .021). The cGvHD was more likely to occur in patients who converted to T-FDC (34% versus 10.3%, P = .025). Donor characteristics are increasingly considered when deciding approaches for HSCT. Donor age should be considered when planning HSCT, as well as doses and scheduling of DLI. As per our experience, this should be done alongside T/UWB chimerism to achieve the maximal clinical benefit with less associated toxicity. Selection of younger male donors from stem cell registries can minimize the risk of GvHD and improve survival.

Exploring the Electrochemistry of Iron Dithiolene and Its Potential for Electrochemical Homogeneous Carbon Dioxide Reduction.

In this work, the dithiolene complex iron(III) bis-maleonitriledithiolene [Fe(mnt)2] is characterised and evaluated as a homogeneous CO2 reduction catalyst. Electrochemically the Fe(mnt)2 is reduced twice to the trianionic Fe(mnt)2 3- state, which is correspondingly found to be active towards CO2. Interestingly, the first reduction event appears to comprise overlapping reversible couples, attributed to the presence of both a dimeric and monomeric form of the dithiolene complex. In acetonitrile Fe(mnt)2 demonstrates a catalytic response to CO2 yielding typical two-electron reduction products: H2, CO and CHOOH. The product distribution and yield were governed by the proton source. Operating with H2O as the proton source gave only H2 and CO as products, whereas using 2,2,2-trifluoroethanol gave 38 % CHOOH faradaic efficiency with H2 and CO as minor products.

Predictive and Diagnostic Biomarkers of Anastomotic Leakage: A Precision Medicine Approach for Colorectal Cancer Patients.

Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient's post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.

NaCl and KCl mediate log increase in AAV vector particles and infectious titers in a specific/timely manner with the HSV platform.

The increasing demand for adeno-associated virus (AAV) vectors, a result from the surging interest for their potential to cure human genetic diseases by gene transfer, tumbled on low-performing production systems. Innovative improvements to increase both yield and quality of the vector produced have become a priority undertaking in the field. In a previous study, we showed that adding a specific concentration of sodium chloride (NaCl) to the production medium resulted in a dramatic increase of AAV vector particle and infectious titers when using the herpes simplex virus (HSV) production system, both in adherent or suspension platforms. In this work, we studied additional salts and their impact on AAV vector production. We found that potassium chloride (KCl), or a combination of KCl and NaCl, resulted in the highest increase in AAV vector production. We determined that the salt-mediated effect was the most impactful when the salt was present between 8 and approximately 16 h post-infection, with the highest rate increase occurring within the first 24 h of the production cycle. We showed that the AAV vector yield increase did not result from an increase in cell growth, size, or viability. Furthermore, we demonstrated that the impact on AAV vector production was specifically mediated by NaCl and KCl independently of their impact on the osmolality of the production media. Our findings convincingly showed that NaCl and KCl were uniquely efficacious to promote up to a 10-fold increase in the production of highly infectious AAV vectors when produced in the presence of HSV. We think that this study will provide unique and important new insights in AAV biology toward the establishment of more successful production protocols.