Enis Ben Bnina, Jihen Missaoui, Mohamed Firas Gannouni
et al.
Food safety and control are fundamental public health issues that maintain consumer confidence and protection. This design (management) requires monitoring production, processing, and conservation processes while limiting microbiological, chemical, and physical risks. In this context, clove essential oil, a bioactive essence with a broad spectrum of biological activities, is increasingly studied as a natural biopreservative in innovative food safety strategies. This study reports the encapsulation of this oil into a nanoemulsion at concentrations of 10 mg/mL, 1 mg/mL, and 0.1 mg/mL. Dynamic light scattering, zeta potential, polydispersity index, and particle size all demonstrated optimal morphology and a stable system.The nanoformulation significantly improves the antioxidant activity of clove essential oil, even at high dilutions, while protecting the degradation of natural active ingredients and ensuring controlled release. This nanoemulsion exhibits a moderate antimicrobial effect against various resistant pathogenic bacteria and fungi. However, at a concentration of 10 mg/mL, it showed a 100 % antibiofilm effect against both Gram-positive and Gram-negative bacteria. This nanoemulsion demonstrated significant potential to prevent surface adhesion against all bacteria tested, except L. monocytogenes.This research reveals crucial information about an innovative natural nanoemulsion for food safety and control, unveiling its antioxidant, anti-adhesive, and anti-biofilm potential against resistant pathogens. These results represent a promising step forward in reducing contamination risks and extending shelf life without altering organoleptic properties, offering environmental benefits and hygiene practices while targeting sustainable industrial applications to increase food safety.
Jennifer W. Leiding, Clayton E. Mathews, Danielle E. Arnold
et al.
NADPH oxidase (NOX) family members are major resources of intracellular reactive oxygen species (ROS). In the immune system, ROS derived from phagocytic NOX (NOX2) participate in both pathogen clearance and signaling transduction. The role of NOX2 in neutrophils and macrophages has been well studied as mutations in NOX2 subunits cause chronic granulomas disease (CGD). NOX2 is expressed across a wide range of immune cells and recent reports have demonstrated that NOX2-derived ROS play important roles in other immune cells during an immune response. In this review, we summarize current knowledge of functions of NADPH oxidase 2 in each subset of leukocytes, as well as associations of NOX2 deficiency with diseases associated specifically with autoimmunity and immune deficiency. We also discuss important knowledge gaps as well as potential future directions for NOX2 research.
Background:The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA).Methods:A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL was estimated using probit regression.Results:The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5–50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups.Conclusion:The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5–50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.
Maurice Kanyoni, Lena N. Wikmar, Joliana Philips
et al.
Background: Traumatic spinal cord injury (TSCI) survivors are confronted by both physical and psychosocial barriers when returning to their communities. Therefore, reintegration is an important aspect of their journey back into social life.
Objectives: To assess psychosocial reintegration after TSCI in Rwanda.
Method: All community-dwelling adults who were registered in the previous epidemiological study were recruited and injury characteristics questionnaire and the Sydney Psychosocial Reintegration Scale version 2 (SPRS-2) were used to collect data through a telephone interview.
Results: The study traced 58 participants, 77.6% (n = 45) were male and 56.9% (n = 33) were categorised with paraplegia. Overall, the results show poor community reintegration. The SPRS-2 and domain mean (SD) scores were: overall SPRS-2 of 20.95 (11.56), occupational activity (OA) of 3.68 (4.31), interpersonal relationship (IR) of 7.11(4.31) and living skills (LS) of 7.43 (5.32). Gender significantly influenced overall SPRS-2 (p = 0.011) and two domains: OA (p = 0.005) and LS (p = 0.012). Level of injury was significantly associated with an OA domain score of SPRS-2 (p = 0.002). Gender explained 29% of the variance in the LS domain of SPRS-2, with males reporting better psychosocial reintegration.
Conclusion: Gender strongly predicted psychosocial reintegration following a TSCI, which is an indication of the role of social support.
Clinical Implications: Traumatic SCI rehabilitation should be holistic to help prepare the person to return to the community. There should be an assessment of an individual’s readiness to return to the community before discharge from the hospital.
Photodynamic Therapy (PDT), as a minimally invasive treatment method, has demonstrated its distinct advantages in the management of skin malignant tumors. This article examines the current application status of PDT, assesses its successful cases and challenges in clinical treatment, and anticipates its future development trends. PDT utilizes photosensitizers to interact with light of specific wavelengths to generate reactive oxygen species that selectively eradicate cancer cells. Despite PDT’s exceptional performance in enhancing patients’ quality of life and prognosis, the limitation of treatment depth and the side effects of photosensitizers remain unresolved issues. With the advancement of novel photosensitizers and innovative treatment technology, the application prospects of PDT are increasingly expansive. This article delves into the mechanism of PDT, its application in various skin malignancies, its advantages and limitations, and envisions its future development. We believe that through continuous technological enhancements and integration with other treatment technologies, PDT has the potential to assume a more pivotal role in the treatment of skin malignancies.
Ariel A. Hippen, Dalia K. Omran, Lukas M. Weber
et al.
Abstract Background Single-cell gene expression profiling provides unique opportunities to understand tumor heterogeneity and the tumor microenvironment. Because of cost and feasibility, profiling bulk tumors remains the primary population-scale analytical strategy. Many algorithms can deconvolve these tumors using single-cell profiles to infer their composition. While experimental choices do not change the true underlying composition of the tumor, they can affect the measurements produced by the assay. Results We generated a dataset of high-grade serous ovarian tumors with paired expression profiles from using multiple strategies to examine the extent to which experimental factors impact the results of downstream tumor deconvolution methods. We find that pooling samples for single-cell sequencing and subsequent demultiplexing has a minimal effect. We identify dissociation-induced differences that affect cell composition, leading to changes that may compromise the assumptions underlying some deconvolution algorithms. We also observe differences across mRNA enrichment methods that introduce additional discrepancies between the two data types. We also find that experimental factors change cell composition estimates and that the impact differs by method. Conclusions Previous benchmarks of deconvolution methods have largely ignored experimental factors. We find that methods vary in their robustness to experimental factors. We provide recommendations for methods developers seeking to produce the next generation of deconvolution approaches and for scientists designing experiments using deconvolution to study tumor heterogeneity.
Flavio Polito, Florinda Fratianni, Filomena Nazzaro
et al.
<i>Eucalyptus</i> species have been widely employed in the projects of reforestation in Tunisia. Although their ecological functions are controversial, these plants are indeed important to counteract soil erosion, and represent a fast-growing source of fuelwood and charcoal wood. In the present study, we considered five <i>Eucalyptus</i> species, namely <i>Eucalyptus alba</i>, <i>E. eugenioides</i>, <i>E. fasciculosa</i>, <i>E. robusta</i>, and <i>E. stoatei</i> cultivated in the Tunisian <i>Arboreta</i>. The aim was to carry out the micromorphological and anatomical characterization of the leaves, the extraction and phytochemical profile of the essential oils (EOs), and the evaluation of their biological properties. Four of the EOs showed the prevalence of eucalyptol (1,8-cineole) varying from 64.4 to 95.9%, whereas <i>a</i>-pinene predominated in <i>E. alba</i> EO (54.1%). These EOs showed in vitro antioxidant activity, and reduced the oxidative cellular stress as shown by their activity on reactive oxygen species (ROS) production, and modulation of the expression of antioxidant enzymes, such as glutamate-cysteine ligase (GCL) and heme oxygenase-1 (Hmox-1). Moreover, the EOs inhibited the production of nitric oxide (NO), showing anti-inflammatory activity. The data collected suggest that these EOs may be considered a promising therapeutic strategy for inflammation-based diseases and may represent an additional value for the economy of Tunisia.
Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent progress in the field of drug receptors, focusing on cryo-EM of two protein families with established therapeutic value, the γ-aminobutyric acid A receptors (GABAARs) and G protein-coupled receptors (GPCRs). GABAARs are pentameric ion channels, and cryo-EM structures of physiological heteromeric receptors in a lipid environment have uncovered the molecular basis of receptor modulation by drugs such as diazepam. The structures of ten GPCR-G protein complexes from three different classes of GPCRs have now been determined by cryo-EM. These structures give detailed insights into molecular interactions with drugs, GPCR-G protein selectivity, how accessory membrane proteins alter receptor-ligand pharmacology, and the mechanism by which HIV uses GPCRs to enter host cells. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 60 is January 9, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Microsurgery is a minimally invasive procedure that uses a surgical microscope, specially designed equipment, and suture materials. Even though this equipment and expertise of numerous surgeries are required to meet patient esthetic reckoning, doctors must be ready to invest time and effort into becoming familiar with novel surgical methods and devices. The ambition of this case series is to compare conventional macro surgery and microsurgery in terms of clinical approach. This study included four cases, two flap surgery, and two root coverage. Clinical parameters for root coverage, increase in keratinized tissue (KT), gain in clinical attachment level (CAL) and complete root coverage (CRC), dentin hypersensitivity index-Schiff's index and for flap surgery, probing depth, clinical attachment level. Healing and pain analysis were done. There was no significant difference seen between conventional and clinical outcomes of a microsurgical technique such as clinical attachment level, probing depth, increase in KT, gain in clinical attachment level (CAG), and CRC, dentin hypersensitivity index-Schiff's index. When patient-based outcomes such as healing index and Visual Analog Scale, a significant difference was seen. If a microsurgical method is used instead of a traditional macroscopic approach, the early healing index can be significantly improved and there will be less postoperative pain.
Therapeutics. Pharmacology, Pharmacy and materia medica
Since TND could be an appropriate method to assess vaccine effectiveness, we want to know whether it may be used for the estimation of vaccine immunological surrogate endpoints, like case-control study. We conducted two study designs (test-negative design (TND) VS matched case-control design (MCC)) to evaluate immunological surrogate endpoint against EV71-associated diseases. We calculated sensitivity (proportion of participants with EV71-associated disease who have a titer less than the cutoff at day 56), specificity (proportion of matched controls who have a titer equal or greater than the cutoff at day 56), and corresponding Youden index ([sensitivity + specificity] − 1). Then, we compared them between TND and MCC. In test-negative design, we totally enrolled 7029 subjects, 49 tested positive as cases and 6980 tested negative as controls in per-protocol population. In matched case-control design, we totally enrolled 305 subjects, 51 as cases, and 254 as controls in whole cohort. In sensitivity and specificity comparison, TND and MCC’s results were similar to each other, except for a titer of 1:4. Nonetheless, in Youden index comparison, MCC’s results were slightly higher than the TND’s, except for a titer of 1:4. EV71 vaccine immunological surrogate endpoints derived from TND was similar to MCC’s. Our results supported that TND could become an alternative research design with the progress of surveillance.
Metallo-β-lactamases (MBLs) are a significant clinical problem because they hydrolyze and inactivate nearly all β-lactam-containing antibiotics. These 'lifesaving drugs' constitute >50% of the available contemporary antibiotic arsenal. Despite the global spread of MBLs, MBL inhibitors have not yet appeared in clinical trials. Most MBL inhibitors target active site zinc ions and vary in mechanism from ternary complex formation to metal ion stripping. Importantly, differences in mechanism can impact pharmacology in terms of reversibility, target selectivity, and structure-activity relationship interpretation. This review surveys the mechanisms of MBL inhibitors and describes methods that determine the mechanism of inhibition to guide development of future therapeutics.
Claudia Vales-Villamarín, Olaya de Dios, Iris Pérez-Nadador
et al.
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.
Alexander McQuiston, Alexander McQuiston, Amir Emtiazjoo
et al.
Lung transplant patients have the lowest long-term survival rates compared to other solid organ transplants. The complications after lung transplantation such as primary graft dysfunction (PGD) and ultimately chronic lung allograft dysfunction (CLAD) are the main reasons for this limited survival. In recent years, lung-specific autoantibodies that recognize non-HLA antigens have been hypothesized to contribute to graft injury and have been correlated with PGD, CLAD, and survival. Mounting evidence suggests that autoantibodies can develop during pulmonary disease progression before lung transplant, termed pre-existing autoantibodies, and may participate in allograft injury after transplantation. In this review, we summarize what is known about pulmonary disease autoantibodies, the relationship between pre-existing autoantibodies and lung transplantation, and potential mechanisms through which pre-existing autoantibodies contribute to graft injury and rejection.
Satoshi Nakamura, Takashi Arima, Ryoichi Tashiro
et al.
Abstract Background Antimicrobial stewardship (AS) is defined as coordinated interventions to improve and measure the appropriate use of antimicrobial agents. However, available resources for AS differ depending on the size of the clinical setting. Therefore, AS programs based on guidelines need to be selected in order to implement AS in small- to medium-sized hospitals. The present study compared the impact of AS in a 126-bed community hospital between pre- and post-AS periods. Methods The present study was retrospectively performed by selecting data on eligible patients from electronic medical records stored in the central database of the hospital. The roles of the AS team included weekly rounds and recommendations on the appropriate use of antimicrobials, and pharmacists working on post-prescription audits and pharmaceutical care at the bedside closely communicated with the AS team to assist with its implementation. As process measurements, the order rate of culture examinations, the conducting rate of de-escalation, antimicrobial use density (AUD), days of therapy (DOT), and the AUD/DOT ratio of carbapenems and tazobactam-piperacillin (TAZ/PIPC) were measured. Thirty-day mortality and recurrence rates were examined as clinical outcomes. Results A total of 535 patients (288 in the pre-AS period and 247 in the post-AS period) were enrolled in the present study. The recommendation rate to prescribers significantly increased (p < 0.01) from 10.4% in the pre-AS period to 21.1% in the post-AS period. The order rate of culture examinations increased from 56.3 to 73.3% (p < 0.01). The conducting rate of de-escalation increased from 10.2 to 30.8% (p < 0.05). The AUD of carbapenems and TAZ/PIPC significantly decreased (p < 0.05). The DOT of carbapenems (p < 0.01) and TAZ/PIPC (p < 0.05) also significantly decreased. The AUD/DOT ratio of carbapenem significantly increased from 0.37 to 0.60 (p < 0.01). Thirty-day mortality rates were 11.2 and 14.2%, respectively, and were not significantly different. The 30-day recurrence rate significantly decreased (p < 0.05) from 14.7 to 7.5%. Conclusions The implementation of AS in this hospital improved the appropriate use of antimicrobials without negatively affecting clinical outcomes. These results may be attributed to close communication between pharmacists working on post-prescription audits and pharmaceutical care at the bedside and the AS team.
Therapeutics. Pharmacology, Pharmacy and materia medica