Short Retention Research Articles

Pericardial Delivery of Sodium Alginate-Infusible Extracellular Matrix Composite Hydrogel Promotes Angiogenesis and Intercellular Electrical Conduction after Myocardial Infarction.

Injectable extracellular matrix (iECM) is a versatile biological material with beneficial properties such as good degradability, promotion of cell survival, immunomodulation, and facilitation of vascular formation. However, intravenous injection of iECM faces challenges like a short retention time in vivo and low concentration at the lesion site. To address these issues, we prepared a composite hydrogel composed of sodium alginate and iECM and administered it via intrapericardial injection, forming a structure akin to cardiac patches within the pericardium. Compared with intramyocardial injection, intrapericardial injection avoids direct myocardial injury and ectopic tumor formation, offering less invasiveness and better biocompatibility. This study demonstrates that the sodium alginate/infusible extracellular matrix (SA/iECM) composite hydrogel can effectively prolong the local retention time of iECM in the heart, enhance electrical conduction between cardiomyocytes, promote angiogenesis at ischemic myocardial sites, inhibit apoptosis in the infarcted region, mitigate left ventricular remodeling postmyocardial infarction (MI), and improve cardiac function after infarction. Precise coordination of cardiomyocyte contraction and relaxation depends on the rhythmic occurrence of calcium-dependent action potentials. Cardiac dysfunction is partially attributed to the disruption of the excitation-contraction coupling (ECC) mechanism, which is associated with prolonged intracellular Ca2+ transients and alterations in contraction and relaxation Ca2+ levels. Our results show that the SA/iECM composite hydrogel improves electrical conduction, as evidenced by increased Cx43 expression and enhanced intercellular electrical connectivity. This research establishes that intrapericardial injection of a SA/iECM composite hydrogel is a safe and effective treatment modality, providing a theoretical basis for the use of biomaterials in MI therapy.

A visual management and augmented-reality-based training module for the enhancement of short and long-term procedural knowledge retention in complex machinery setup

Proper training for operators is essential, given the complexity of modern manufacturing and the challenges posed by diverse worker demographics and high workforce turnover. Since conventional training methods are inadequate when considering the mentioned challenges, digital technologies and assistive devices can be used to improve information management. This work studies how the combination of Augmented Reality (AR) and Visual Management (VM) supports worker training by considering short- and long-term efficacy. The literature gaps on researching the training and knowledge retention of manufacturing workers using combined lean tools and digital technologies indicate that current studies focus on short-term training performed in laboratories, overlooking the integration of VM and AR for industrial training. Thus, the authors developed and validated in practice a VMAR-based training module for the setup of complex machinery in the process industry. To assess its efficacy, a comparison between a test group and a confirmation group of company’s workers has been performed. The number and types of setup error have been collected and analysed to evaluate and compare short- and long-term procedural knowledge retention. The results reveal that the VMAR-based training module better supports workers both in the short- and long-period compared with traditional working procedures. Furthermore, the analysis demonstrates the inefficacy of traditional approaches in properly supporting the training of complex machinery setups considering the study’s application. Future works should address the assessment of knowledge retention by considering a longer period, as well as on physiological data collection to better understand which elements of the training module are most crucial to the transfer of knowledge.

Quercetin-Loaded Zeolitic Imidazolate Framework-8 (ZIF-8) Nanoparticles Attenuate Osteoarthritis by Activating Autophagy via the Pi3k/Akt Signaling.

Osteoarthritis treatment remains a significant clinical challenge. Quercetin, a natural flavonoid with anti-inflammatory and antiapoptotic properties, might be utilized to treat OA. However, poor water solubility and short joint retention duration limit its bioavailability and translation to clinical applications. A one-step self-assembly method was utilized to fabricate quercetin-loaded zeolitic imidazolate framework-8 (Qu@ZIF-8) nanoparticles using zinc ions, 2-methylimidazole, and quercetin. In vitro tests showed that Qu@ZIF-8 nanoparticles released pH-responsive agents into chondrocytes, effectively protecting them from interleukin (IL)-induced inflammation and apoptosis, thereby promoting cartilage anabolic activities. These underlying mechanisms revealed a remarkable increase of autophagy in IL-β-treated chondrocytes, followed by the inhibition of the Pi3k/Akt signaling pathway, which contributed to the protective effect of Qu @ZIF-8. By the establishment of medial meniscus instability (DMM) in OA mice, Qu@ZIF-8 substantially improved cartilage structural integrity and chondrocyte status, as well as attenuated OA progression. Importantly, Qu@ZIF-8 outperformed quercetin alone in the treatment of OA due to its control release. The combined research findings indicate that Qu@ZIF-8 shields chondrocytes from inflammation and apoptosis by activating autophagy and repressing the Pi3k/Akt pathway. This investigation may provide new insights for clinically extending the therapy of OA.

Matrix metalloproteinase 2-responsive dual-drug-loaded self-assembling peptides suppress tumor growth and enhance breast cancer therapy.

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self-assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP-2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP-2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor-associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.

Engineered Exosomes Biopotentiated Hydrogel Promote Hair Follicle Growth via Reprogramming the Perifollicular Microenvironment.

Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.

Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·（m3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

A thiolated oxidized guar gum and sodium alginate dual-network microspheres with enhanced gastric acid resistance and mucoadhesion for delivery of probiotics

Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca2+ to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.

The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.

Enhancement of skin localization of β-carotene from red fruit (Pandanus conoideus Lam.) using solid dispersion-thermoresponsive gel delivered via polymeric solid microneedles

Red fruit (Pandanus conoideus Lam.) boasts high β-carotene (BC) content, often consumed orally. However, absorption issues and low bioavailability due to food matrix interaction have led to transdermal delivery exploration. Nevertheless, BC has a short skin retention time. To address these limitations, this study formulates a β-carotene solid dispersion (SD-BC) loaded thermoresponsive gel combined with polymeric solid microneedles (PSM) to enhance in vivo skin bioavailability. Characterization of SD-BC includes saturation solubility, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and in vitro release. Characterization of SD-BC thermoresponsive gel includes gelation temperature, viscosity, rheological behaviour, pH, bio-adhesiveness, spreadability, and extrudability. PSM’s mechanical properties and insertion capability were assessed. Ex vivo and in vivo dermato-pharmacokinetic studies, drug content, hemolysis, and skin irritation assessments were conducted to evaluate overall performance. Results confirm amorphous SD-BC formation, enhancing solubility. Both SD-BC thermoresponsive gel and PSM exhibit favourable characteristics, including rheological properties and mechanical strength. In vitro release studies showed a seven-fold increase in BC release compared to plain hydrogel. SD-BC thermoresponsive gel combined with PSM achieves superior ex vivo permeation (Cmax = 305.43 ± 32.07 µg.mL−1) and enhances in vivo dermato-pharmacokinetic parameters by 200–400 %. Drug content, hemolysis, and skin irritation studies confirmed its safety and non-toxicity.

FESTIVAL ISLAMIC GOOD CHILD SEBAGAI SARANA PENANAMAN NILAI RELIGIUS

Festival Islamic good child is a single work program coordinated by one of the students of Islamic University 45 Bekasi held in the village of Sirnajati. The purpose of organizing the Festival Islamic Good Child program is to enhance the enthusiasm for seeking knowledge about Islam, and cultivate interest and ability in the field of religion, and foster self-confidence in the children of Sirnajati Village. In the implementation of the Festival Islamic Good Child, there are 3 competition classes: adhan rivalry, short surah retention rivalry, and calligraphy shading. The technique of conducting training is by examining the needs of early childhood, organizing, implementing, evaluating, and following up on the training that has been conducted. The consequence of this Festival Islamic Good Child program is that the children of the Madrasah Diniyah Takmiliyah Awaliyah (MDTA) Jamiatul Khoir in Sirnajati Village will be more enthusiastic in learning and practicing the teachings of Islam, and then the children of Sirnajati Village will also be more courageous in demonstrating their abilities and their self-confidence will increase after participating in the Festival Islamic Good Child program. This is evidenced by several youths from Sirnajati Village who initially did not want to perform the adhan, but after the Festival Islamic Good Child was held, they became fearless to perform the adhan.

Why aphid virus retention needs more attention: modelling aphid behaviour and virus manipulation in non-persistent plant virus transmission.

Abstract Plant viruses threaten food security and are often transmitted by insect vectors. Non-persistently transmitted (NPT) plant viruses are transmitted almost exclusively by aphids. Because virions attach to the aphid's stylet (mouthparts) and are acquired and inoculated via brief epidermal probes, the aphid-virus interaction is highly transient, with a very short aphid virus retention time. Many NPT viruses manipulate their host plant's phenotype to change aphid behaviour to optimise virus transmission. Epidemiological models of this have overlooked a key feature of aphid NPT virus retention: probing or feeding on a plant causes aphids to lose the virus. Additionally, experimental studies suggest aphids could possibly inoculate multiple healthy plants within one infective period. However, consequences of this for virus manipulation of host plant phenotype have not been explored. Our new compartmental epidemiological model includes both behaviour-based aphid dispersal and infectivity loss rates, and the ability of infective aphids to probe more than one plant before virus loss. We use our model to explore how NPT virus-induced host phenotypes affect epidemic outcomes, comparing these results to representative previous models. We find that previous models behave fundamentally differently and underestimate the benefit of an 'attract-and-deter' phenotype, where the virus induces increased aphid attraction to infected plants but deters them from prolonged feeding. Our results also highlight the importance of characterising NPT virus retention upon the aphid during probing. Allowing for multiple infective probes increases disease incidence and the effectiveness of virus manipulation, with implications for epidemic prediction and control.

Exploring a Lux® i-Amylose-3 column in normal phase and polar-organic mode for chiral separation of cathinone derivatives and pyrovalerones using high-performance liquid chromatography.

Each year, new psychoactive substances appear on the global drug market leading to constant changes. Most of these compounds with stimulating effect possess a chiral center, thus leading to two enantiomers with presumably different pharmacological properties. Among them, synthetic cathinones, often misleadingly traded as "bath salts," play an important role. There is little knowledge about the distinct effect of the enantiomers. The aim of this study was to test a commercially available Lux® i-Amylose-3 column by HPLC-UV for enantiorecognition of cathinone derivatives. Overall, 80 compounds were tested in normal phase mode, where 75 substances were separated under initial conditions. After method optimization, at least partial separation was achieved for the remaining compounds. The same set of substances was measured in polar-organic mode, where 63 analytes were resolved into their enantiomers under initial conditions with very short retention times. Both modes showed complementary results for the individual compounds. Furthermore, the tested methods proved to be suitable for differentiation of positional isomers, which can be useful for drug checking programs. All measurements were carried out under isocratic conditions, and intraday and interday repeatability tests were performed.

Superior mainstream partial nitritation in an acidic membrane-aerated biofilm reactor

Shortcut nitrogen removal holds significant economic appeal for mainstream wastewater treatment. Nevertheless, it is too difficult to achieve the stable suppression of nitrite-oxidizing bacteria (NOB), and simultaneously maintain the activity of ammonia-oxidizing bacteria (AOB). This study proposes to overcome this challenge by employing the novel acid-tolerant AOB, namely “Candidatus Nitrosoglobus”, in a membrane-aerated biofilm reactor (MABR). Superior partial nitritation was demonstrated in low-strength wastewater from two aspects. First, the long-term operation (256 days) under the acidic pH range of 5.0 to 5.2 showed the successful NOB washout by the in situ free nitrous acid (FNA) of approximately 1 mg N/L. This was evidenced by the stable nitrite accumulation ratio (NAR) close to 100 % and the disappearance of NOB shown by 16S rRNA gene amplicon sequencing and fluorescence in situ hybridization. Second, oxygen was sufficiently supplied in the MABR, leading to an unprecedentedly high ammonia oxidation rate (AOR) at 2.4 ± 0.1 kg N/(m3 d) at a short hydraulic retention time (HRT) of a mere 30 min. Due to the counter diffusion of substrates, the present acidic MABR displayed a significantly higher apparent oxygen affinity (0.36 ± 0.03 mg O2/L), a marginally lower apparent ammonia affinity (14.9 ± 1.9 mg N/L), and a heightened sensitivity to FNA and pH variations, compared with counterparts determined by flocculant acid-tolerant AOB. Beyond supporting the potential application of shortcut nitrogen removal in mainstream wastewater, this study also offers the attractive prospect of intensifying wastewater treatment by markedly reducing the HRT of the aerobic unit.

Downflow sponge biofilm reactors for polluted raw water treatment: Performance optimisation, kinetics, and microbial community

Water outages caused by elevated ammonium (NH4+-N) levels are a prevalent problem faced by conventional raw water treatment plants in developing countries. A treatment solution requires a short hydraulic retention time (HRT) to overcome nitrification rate limitation in oligotrophic conditions. In this study, the performance of polluted raw water treatment using a green downflow sponge biofilm (DSB) technology was evaluated. We operated two DSB reactors, DSB-1 and DSB-2 under different NH4+-N concentration ranges (DSB-1: 3.2–5.0 mg L−1; DSB-2: 1.7–2.6 mg L−1) over 360 days and monitored their performance under short HRT (60 min, 30 min, 20 min, and 15 min). The experimental results revealed vertical segregation of organic removal in the upper reactor depths and nitrification in the lower depths. Under the shortest HRT of 15 min, both DSB reactors achieved stable NH4+-N and chemical oxygen demand removal (≥95%) and produced minimal effluent nitrite (NO2−-N). DSB system could facilitate complete NH4+-N oxidation to nitrate (NO3−-N) without external aeration energy requirement. The 16S rRNA sequencing data revealed that nitrifying bacteria Nitrosomonas and Nitrospira in the reactor were stratified. Putative comammox bacteria with high ammonia affinity was successfully enriched in DSB-2 operating at a lower NH4+-N loading rate, which is advantageous in oligotrophic treatment. This study suggests that a high hydraulic rate DSB system with efficient ammonia removal could incorporate ammonia treatment capability into polluted raw water treatment process and ensure safe water supply in many developing countries.

A sterilizable platform based on crosslinked xanthan gum for controlled-release of polymeric micelles: Ocular application for the delivery of neuroprotective compounds to the posterior eye segment

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release. The system was loaded with melatonin and cyclosporin A, neuroprotective compounds to be delivered to the posterior eye segment. Citric acid and heating at different times and temperatures were exploited as crosslinking approach, giving the possibility to tune swelling, micelles release and drug release. The biocompatibility of the platform was confirmed by HET-CAM assay. Ex vivo studies on isolated porcine ocular tissues, conducted using Franz cells and two-photon microscopy, demonstrated the potential of the xanthan gum-based platform and enlightened micelles penetration mechanism. Finally, the sterilization step was approached, and a process to simultaneously crosslink and sterilize the platform was developed.

A Rapid Self-Assembling Peptide Hydrogel for Delivery of TFF3 to Promote Gastric Mucosal Injury Repair.

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable β-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.

Use of carbonyldiimidazole as a derivatization agent for the detection of pinacolyl alcohol, a forensic marker for Soman, by EI-GC-MS and LC-HRMS in official OPCW proficiency test matrices.

Pinacolyl alcohol (PA), a key forensic marker for the nerve agent Soman (GD), is a particularly difficult analyte to detect by various analytical methods. In this work, we have explored the reaction between PA and 1,1'-carbonyldiimidazole (CDI) to yield pinacolyl 1H-imidazole-1-carboxylate (PIC), a product that can be conveniently detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Regarding its GC-MS profile, this new carbamate derivative of PA possesses favorable chromatographic features such as a sharp peak and a longer retention time (RT = 16.62 min) relative to PA (broad peak and short retention time, RT = 4.1 min). The derivative can also be detected by LC-HRMS, providing an avenue for the analysis of this chemical using this technique where PA is virtually undetectable unless present in large concentrations. From a forensic science standpoint, detection of this low molecular weight alcohol signals the past or latent presence of the nerve agent Soman (GD) in a given matrix (i.e., environmental or biological). The efficiency of the protocol was tested separately in the analysis and detection of PA by EI-GC-MS and LC-HRMS when present at a 10 μg/mL in a soil matrix featured in the 44th PT and in a glycerol-rich liquid matrix featured in the 48th Official Organization for the Prohibition of Chemical Weapons (OPCW) Proficiency Test when present at a 5 μg/mL concentration. In both scenarios, PA was successfully transformed into PIC, establishing the protocol as an additional tool for the analysis of this unnatural and unique nerve agent marker by GC-MS and LC-HRMS.

Single-Cell Oral Delivery Platform for Enhanced Acid Resistance and Intestinal Adhesion.

Oral delivery of cells, such as probiotics and vaccines, has proved to be inefficient since cells are generally damaged in an acidic stomach prior to arrival at the intestine to exert their health benefits. In addition, short retention in the intestine is another obstacle which affects inefficiency. To overcome these obstacles, a cell-in-shell structure was designed with pH-responsive and mucoadhesive properties. The pH-responsive shell consisting of three cationic layers of chitosan and three anionic layers of trans-cinnamic acid (t-CA) was made via layer-by-layer (LbL) assembly. t-CA layers are hydrophobic and impermeable to protons in acid, thus enhancing cell gastric resistance in the stomach, while chitosan layers endow strong interaction between the cell surface and the mucosal wall which facilitates cell mucoadhesion in the intestine. Two model cells, probiotic L. rhamnosus GG and dead Streptococcus iniae, which serve as inactivated whole-cell vaccine were chosen to test the design. Increased survival and retention during oral administration were observed for coated cells as compared with naked cells. Partial removal of the coating (20-60% removal) after acid treatment indicates that the coated vaccine can expose its surface immunogenic protein after passage through the stomach, thus facilitating vaccine immune stimulation in the intestine. As a smart oral delivery platform, this design can be extended to various macromolecules, thus providing a promising strategy to formulate oral macromolecules in the prevention and treatment of diseases at a cellular level.

Post-Pandemic Changes to Employment and Employment Satisfaction in Early Career and Career Advancing Athletic Trainers.

The labor market suffered a mass exodus of employees, including healthcare workers, due to the COVID-19 pandemic. Previous research highlights the vulnerability of young professional athletic trainers (YPATs) to attrition. Investigating pandemic-related employment changes and their impact is essential for developing strategies to improve the retention of YPATs. to determine impact of COVID-19 on YPATs' employment and effect of COVID-19 and employment setting migration on outcome measures of personal and financial well-being, job and career satisfaction, and optimism about staying in the profession. Cross-sectional, descriptive study. Web-based survey. 1,111 participants responded to survey for an 11.5% response rate (n=1,111/12,810). Partial responses were included; thus, number of respondents varied by question. A web-based survey comprised of 34 closed-ended questions was disseminated to NATA members in November 2022. Descriptive statistics including counts and frequencies for each surveyed item in addition to chi-square tests were used to analyze responses. 30.2% (n=335/1,111) of YPATs changed employers and 25.7% (n=286/1,111) reported a change in employment setting. Notably, YPATs migrated from high school, collegiate, and professional athletics to clinic, industrial, or sales settings. Overall, the pandemic decreased job satisfaction, career satisfaction, and optimism about professional longevity. Changes in employment had a positive impact on personal well-being in addition to job and career satisfaction, but not optimism regarding staying in profession. Salary and work-life balance were reported as important predictors of short and long-term retention for YPATs. The pandemic brought changes to employers and employment settings for many YPATs. To reduce turnover and attrition, administrators must begin to prioritize employee well-being and satisfaction. In addition to increasing salary and reducing workload, employers should recognize the importance of administrative support in promoting well-being together with satisfaction and professional optimism in early professional and career-advancing athletic trainers.

Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery.

Ocular drug delivery poses unique challenges due to the complex anatomical and physiological barriers of the eye. Conventional dosage forms often fail to achieve optimal therapeutic outcomes due to poor bioavailability, short retention time, and off-target effects. In recent years, vesicular drug delivery systems have emerged as promising solutions to address these challenges. Vesicular systems, such as liposome, niosome, ethosome, transfersome, and others (bilosome, transethosome, cubosome, proniosome, chitosome, terpesome, phytosome, discome, and spanlastics), offer several advantages for ocular drug delivery. These include improved drug bioavailability, prolonged retention time on the ocular surface, reduced systemic side effects, and protection of drugs from enzymatic degradation and dilution by tears. Moreover, vesicular formulations can be engineered for targeted delivery to specific ocular tissues or cells, enhancing therapeutic efficacy while minimizing off-target effects. They also enable the encapsulation of a wide range of drug molecules, including hydrophilic, hydrophobic, and macromolecular drugs, and the possibility of combination therapy by facilitating the co-delivery of multiple drugs. This review examines vesicular drug delivery systems, their advantages over conventional drug delivery systems, production techniques, and their applications in management of ocular diseases.