Catheters linked thrombosis in neonates: a single center observational study.

BACKGROUND: Central venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors. METHODS: This observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study's eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed. RESULTS: Seventeen patients with catheter's thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs' days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters' days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013-32.836). CONCLUSION: Many factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.

Green nanobiocatalysts: enhancing enzyme immobilization for industrial and biomedical applications.

Nanobiocatalysts (NBCs), which merge enzymes with nanomaterials, provide a potent method for improving enzyme durability, efficiency, and recyclability. This review highlights the use of eco-friendly synthesis methods to create sustainable nanomaterials for enzyme transport. We investigate different methods of immobilization, such as adsorption, ionic and covalent bonding, entrapment, and cross-linking, examining their pros and cons. The decreased environmental impact of green-synthesized nanomaterials from plants, bacteria, and fungi is emphasized. The review exhibits the various uses of NBCs in food industry, biofuel production, and bioremediation, showing how they can enhance effectiveness and eco-friendliness. Furthermore, we explore the potential impact of NBCs in biomedicine. In general, green nanobiocatalysts are a notable progression in enzyme technology, leading to environmentally-friendly and effective biocatalytic methods that have important impacts on industrial and biomedical fields.

Unveiling the ecotoxicological effects of azoxystrobin-based fungicides at realistic concentrations on the land snail, Theba pisana.

The ecotoxicological consequences of azoxystrobin on land snails have not yet been addressed. Therefore, the present study aims to provide novel data on the threat of a commercial grade azoxystrobin (AMISTAR) at two environmentally relevant concentrations (0.3 µg/ml) and tenfold (3 µg/ml) on the model species, Theba pisana by physiological, biochemical, and histopathological markers for 28 days. Our results showed a reduction in animal food consumption and growth due to exposure to both azoxystrobin concentrations. It also induced oxidative stress and led to a significant decrease in lipid peroxidation (LPO) levels after 7 days of exposure, while the opposite effect occurred after 28 days. Except for the 7-day exposure, all treated snails had significantly reduced glutathione (GSH) content and increased catalase (CAT) activity at all-time intervals. Glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and protein content (PC) were elevated in treated snails at all-time intervals. Moreover, alterations in acetylcholinesterase (AChE) activity between a decrease and an increase were noticed. Additionally, azoxystrobin exerted changes in T. pisana hepatopancreas architecture. Our study suggests that azoxystrobin may have negative ecological consequences for T. pisana and highlights its potential risks to the natural environment.

Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.

Influence of computerized intraosseous anesthesia compared with traditional mandibular nerve block on children's behavior: A randomized clinical trial.

BACKGROUND: Effective pain management is crucial for the successful completion of dental procedures in children. Research has examined whether computerized intraosseous anesthesia (CIOA) could serve as a safe and viable substitute for the conventional inferior alveolar nerve block (IANB) technique in pediatric patients. This study investigates the efficacy of CIOA, aiming to determine its effectiveness as an alternative anesthesia method. AIM: This study compared the efficacy of local intraosseous anesthesia using a computerized device (QuickSleeper 5) to conventional IANB anesthesia on cooperation and pain perception in children, using a randomized controlled trial design. DESIGN: The study included 88 healthy children, aged between 6 and 9 years, who required pulpotomy for their mandibular second primary molars. The study was approved by the local research ethics committee and registered at clinicaltrials.gov (NCT05193487). The heart rate and Venham behavior rating scale were recorded and analyzed. Categorical data were analyzed using Fisher's exact test. Age and heart rate were compared using an independent t-test for intergroup comparison. The intragroup comparison was carried out using repeated measures ANOVA, followed by the Bonferroni post hoc test. The Mann-Whitney U-test was used to analyze the Venham scale scores. The significance level was set at p < .05 RESULTS: The mean Venham score was slightly higher in the IANB group than in the CIOA group, but was not statistically significant (p = .852). One minute after anesthesia administration, the heart rate (beats per minute [BPM]) was significantly higher in the IANB group (92.30 ± 13.45) than in the CIOA group (83.20 ± 10.40) (p < .001). Additionally, there was a significant difference in heart rate values measured at different intervals within the IANB group. CONCLUSION: The QuickSleeper 5 device was found to be a feasible alternative for IANB in children over 6 years old.

Trueness of vat-photopolymerization printing technology of interim fixed partial denture with different building orientation: A Microcomputed tomography study.

Background: The aim was to assess the consequence of different printing orientation on the marginal misfit and internal gap of 3-unit interim fixed partial denture manufactured by two different additive manufacturing technologies compared to milling technique. Material and Methods: Three-unit interim fixed partial denture (FPD) was designed by using exocad software (Dental CAD 3.0 Galway) in the format of standard tessellation language (STL) , which was transferred to a nesting software (PreForm) and printed by A Next Dent C&B resin liquid (NextDent; Soesterberg, Neitherland) by using two printing technologies; stereolithography (SLA, n=30) and digital light processing (DLP, n=30) with 3 different orientations (occlusal direction [0°] ,buccal direction [90°] & lingual direction [270°]) for each technology (n=10). Additionally, a control group was milled (CAD/Milling, n=10) from DC PMMA A1 Disc (White peaks dental solutions; Gmbh& co., Germany). A Microcomputed tomography was used to measure the marginal misfit and internal gap for each specimen in 12 different points. The average value of the marginal and internal gaps measurements was calculated, and one-way ANOVA was used for the comparison between groups. Results: SLA printing technology showed a similar result to CAD/Milling with all different printing orientations tested. DLP printing technology showed the highest gap values within all the printing orientations with significant difference (p< 0.001) with the CAD/Milling and SLA. Conclusions: Regarding the trueness of the interim FPDs, SLA was a promising technology for its superior adaptation. Marginal misfit and Internal gap for DLP printing technology limiting the use of that technology as it exceeded the acceptable clinical range. Key words:3D Printing, Microcomputed topography, Marginal Gap, Internal Misfit.

Reproducibility of MRI Diagnosis of Female Genital Anomalies.

Purpose: To assess and compare intrareader and interreader reproducibility of magnetic resonance imaging (MRI) diagnosis of female genital anomalies (FGAs) using the American Society for Reproductive Medicine-Mullerian anomalies classification 2021 (ASRM-MAC 2021) and European Society of Human Reproduction and Embryology-European Society for Gynecological Endoscopy (ESHRE-ESGE) 2016 classification. Methods: In this retrospective study, we searched our electronic MRI database from April 2021 to September 2023, selecting MRI studies with FGAs. Seventy-six consecutive studies were included and reviewed by 4 independent radiologists using both classifications. Studies were re-evaluated after 1 month. Reproducibility was assessed using kappa (κ) scores with 95% confidence intervals (CI). Results: Intrareader agreement for MRI diagnosis of FGAs was substantial to excellent, with κ scores ranging from 0.684 (95% CI, 0.534-0.834) to 0.985 (95% CI, 0.963-1.01) using the ASRM-MAC 2021 and from 0.743 (95% CI, 0.621-0.865) to 0.846 (95% CI, 0.719-0.973) using the ESHRE-ESGE 2016 classification. Pairwise interreader agreement was higher with the ASRM-MAC 2021, ranging from moderate (κ = 0.491; 95% CI, 0.341-0.642) to substantial (κ = 0.709; 95% CI, 0.597-0.821), compared to the ESHRE-ESGE 2016 classification, with weak (κ = 0.080; 95% CI, 0.068-0.228) to moderate (κ = 0.511; 95% CI, 0.344-0.678) agreement. Overall interreader agreement was moderate for both classifications (κ = 0.599; 95% CI, 0.562-0.638 for ASRM-MAC 2021 and κ = 0.429; 95% CI, 0.396-0.463 for ESHRE-ESGE 2016 classification), but with significant differences (non-overlapping CIs). Conclusion: The intrareader reproducibility was high for both classifications, whereas the interreader reproducibility was higher using the ASRM-MAC 2021, highlighting the impact of classification criteria on the reproducibility of MRI diagnosis of FGAs.

Transcriptional and Translational Regulation of Differentially Expressed Genes in Yucatan Miniswine Brain Tissues following Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of morbidity, disability, and mortality worldwide. Motor and cognitive deficits and emotional disturbances are long-term consequences of TBI. A lack of effective treatment for TBI-induced neural damage, functional impairments, and cognitive deficits makes it challenging in the recovery following TBI. One of the reasons may be the lack of knowledge underlying the complex pathophysiology of TBI and the regulatory factors involved in the cellular and molecular mechanisms of inflammation, neural regeneration, and injury repair. These mechanisms involve a change in the expression of various proteins encoded by genes whose expression is regulated by transcription factors (TFs) at the transcriptional level and microRNA (miRs) at the mRNA level. In this pilot study, we performed the RNA sequencing of injured tissues and non-injured tissues from the brain of Yucatan miniswine and analyzed the sequencing data for differentially expressed genes (DEGs) and the TFs and miRs regulating the expression of DEGs using in-silico analysis. We also compared the effect of the electromagnetic field (EMF) applied to the injured miniswine on the expression profile of various DEGs. The results of this pilot study revealed a few DEGs that were significantly upregulated in the injured brain tissue and the EMF stimulation showed effect on their expression profile.

The impact of incorporating dried cafeteria leftover food on growing APRI rabbits productivity, profitability and meat quality.

This study was conducted to investigate the effect of dried cafeteria leftover food (DCLF) incorporation in growing APRI rabbit diets on nutrient digestibility, live body weight, body weight gain, carcass traits, meat quality, blood parameters, and economic efficiency. Thirty-six APRI rabbits (6 weeks of age), after weaning, were randomly divided into three groups (12 rabbits/group, 613 ± 5 g). During the experiment, rabbits aged 6-14 weeks participated in the experiment. An approximate isocaloric and isonitrogenous composition was achieved in three pelleted experimental diets. For the rabbit groups D1 (as the control), D2, and D3, DCLF was added at doses of 0%, 17.5%, and 35%, respectively. Digestibility trails were carried out at the end of the feeding experiment to evaluate the nutritional and feeding values of the experimental diets. To examine the characteristics of the carcasses, the quality of the meat, the histopathological analysis, and the blood plasma parameters, three rabbits were slaughtered from each group. The results showed that the feeding values (TDN and DE), which had the greatest values, as well as the digesting coefficients for dry matter, organic matter, crude fiber, and ether extract between the D1 and D3 groups were significantly different (p < 0.05). On the contrary, the curde protein, nitrogen-free extract, and digestible crude protein of the examined diets showed no signifcant differences compared with the control diet. The level of DCLF incorporation in diets significantly (p < 0.05) increased the live body weight at 14 weeks; with D3 recording the highest values (2130.9 g) when compared to the D1 and D2 groups. A similar pattern was observed for both daily increase and total body gain (6-14 weeks). Feed conversion recorded insignificant differences among the experimental diets respecting the period 6-14 weeks of age. DCLF levels had a significant effect on dressing and giblet percentages. The chemical composition and color parameters of rabbit meat were similar (p > 0.05), except for fat%, which had the highest value in the D3 group (p < 0.05) compared to the D1 and D2 groups. Economic efficiency was improved by using DLCF up to 35% in terms of gross margin and feed cost/kg gain. In conclusion, using DCLF in the feeding system of rabbits could enhance productive performance, carcass traits, meat quality, and physiological function, as well as improve economic efficiency.

Insights Into MRI Neuroimaging Patterns of COVID-19 in Children: A Retrospective Comprehensive Analysis.

RATIONALE AND OBJECTIVES: Neurological complications associated with coronavirus disease (COVID-19) have been reported in children; however, data on neuroimaging findings remain limited. This study aimed to comprehensively examine neuroimaging patterns of COVID-19 in children and their relationship with clinical outcomes. MATERIALS AND METHODS: This retrospective cross-sectional study involved reviewing the medical records and MRI scans of 95 children who developed new neurological symptoms within 2-4 weeks of clinical and laboratory confirmation of COVID-19. Patients were categorized into four groups based on guidelines approved by the Centers for Disease Control and Prevention (CDC). Initial brain/spinal MRI was performed. Images were reviewed by three blinded radiologists, and the findings were analyzed and categorized based on the observed patterns in the brain and spinal cord. Follow-up MRI was performed and analyzed to track lesion progression. RESULTS: Encephalopathy was the most common neurological symptom (50.5%). The most common initial MRI involvement patterns were non-confluent multifocal hyperintense white matter (WM) lesions (36.8%) and ischemia (18.9%). Most patients who underwent follow-up MRI (n = 56) showed complete resolution (69.9%); however, some patients developed encephalomalacia and myelomalacia (23.2% and 7.1%, respectively). Non-confluent hyperintense WM lesions were associated with good outcomes (45.9%, P = 0.014), whereas ischemia and hemorrhage were associated with poor outcomes (44.1%, P < 0.001). CONCLUSION: This study revealed diverse neuroimaging patterns in pediatric COVID-19 patients. Non-confluent WM lesions were associated with good outcomes, whereas ischemia and hemorrhage were associated with poorer prognoses. Understanding these patterns is crucial for their early detection, accurate diagnosis, and appropriate management.

Does commercial indoxacarb pose ecotoxicological consequences? Employing a multi-marker approach in the model species Theba pisana.

Indoxacarb is one of the most extensively used oxadiazine insecticides worldwide, but it may exert detrimental effects on ecosystems, population dynamics, and health. Due to the lack of knowledge on the ecotoxicity of indoxacarb, it is still challenging to assess whether this insecticide poses an ecotoxicological impact on terrestrial environments. Therefore, our study aims to provide novel data on the toxic effects of 28-day dietary exposure to commercial grade indoxacarb at two environmentally relevant concentrations, 0.02 µg/mL and tenfold (0.2 µg/mL) on the model species, Theba pisana. Their effects were studied using a multiple biomarker approach by evaluating physiological, biochemical, and histopathological responses. After 28 days of treatment, indoxacarb at both concentrations significantly reduced the food intake and growth of the treated snails. Also, it caused decreases in lipid peroxidation (LPO)  levels after 7 and 14 days of exposure, whereas an opposite effect occurred after 21 and 28 days. All treated snails were found to exhibit a lower content of glutathione (GSH) after all times of exposure. Moreover, catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) activities, as well as protein content (PC), were elevated in the treated snails after all time intervals. Post exposure to both realistic indoxacarb concentrations, changes in acetylcholinesterase (AChE) activity between a decrease and an increase were observed. Furthermore, indoxacarb caused histo-architectural changes in the hepatopancreas of T. pisana. Our results demonstrate that, at environmentally relevant concentrations, indoxacarb poses negative consequences for T. pisana, indicating its ecotoxicological impacts.

Chemistry and Pharmacology of Delta-8-Tetrahydrocannabinol.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern hemisphere, its use has moved and flourished in the Western nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis, with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. The passing of the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents, as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

Transcriptomic Analysis of Gene Expression and Effect of Electromagnetic Field in Brain Tissue after Traumatic Brain Injury.

Traumatic brain injury (TBI) due to a direct blow or penetrating injury to the head damages the brain tissue and affects brain function. Primary and secondary damage to the brain tissue increases disability, morbidity, and mortality and costs millions of dollars in treatment. Injury to the brain tissue results in the activation of various inflammatory and repair pathways involving many cellular and molecular factors. Increased infiltration of immune cells to clear the debris and lesion healing, activation of Schwann cells, myelination, oligodendrocyte formation, and axonal regeneration occur after TBI to regenerate the tissue. However, secondary damage to brain tissue results in behavioral symptoms. Repair and regeneration are regulated by a complex cascade involving various cells, hormones, and proteins. A change in the expression of various proteins due to altered gene expression may be the cause of impaired repair and the sequelae in TBI. In this pilot study, we used a Yucatan miniswine model of TBI with and without electromagnetic field (EMF) stimulation and investigated the differential gene expression between injured and non-injured cortex tissues. We found several differentially expressed genes including INSC, TTR, CFAP126, SEMA3F, CALB1, CDH19, and SERPINE1. These genes are associated with immune cell infiltration, myelination, reactive oxygen species regulation, thyroid hormone transportation, cell proliferation, and cell migration. There was a time-dependent effect of EMF stimulation on the gene and protein expression. The findings support the beneficial effect of EMF stimulation in the repair process following TBI.

Ligand-based design and synthesis of new trityl histamine and trityl cysteamine derivatives as SIRT2 inhibitors for cancer therapy.

The relentless pursuit of novel therapeutic agents against cancer has led to the identification of multiple molecular targets, among which Sirtuin 2 (SIRT2) has garnered significant attention. This study presents an extensive SAR study of our reported trityl scaffold-based SIRT2 inhibitors. This study encompasses a range of different medicinal chemistry approaches to improve the activity of the lead compounds TH-3 and STCY1. The rationally designed and synthesized structures were confirmed using NMR and high-resolution mass spectroscopy before performing SIRT2 inhibition assay, NCI60 cytotoxicity test, and cell cycle analysis. Indeed, our strategies afforded hitherto unreported SIRT2 inhibitors with high activity, particularly 2a, 4a, 7c, and 7f. Remarkably, the presence of a lipophilic para substitution on the phenyl group of a freely rotating or a locked trityl moiety enhanced activity SIRT2 inhibition. Concomitantly, the synthesized compounds showed prominent activity against different cancer lines from the NCI60 assay. Of interest, compound 7c stands out as a potent and highly selective antiproliferative agent against leukemia and colon cancer panels. Furthermore, 7c treatment resulted in cell cycle arrest in MCF-7 cells at G2 phase and did not cause in vitro DNA cleavage.

Evaluation of dispensaries' cannabis flowers for accuracy of labeling of cannabinoids content.

BACKGROUND: Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis products are marketed in dispensaries in different forms, most abundantly as flowers intended for smoking and sometimes vaping. All samples used in this study were obtained directly from law enforcement. The sample collection process was facilitated and funded by the National Marijuana Initiative (NMI), part of the High-Intensity Drug Trafficking Area (HIDTA) program. This initial report focuses on cannabis flowers. Similar studies with other cannabis products will be the subject of a future report. METHODS: A total of 107 Δ9-THC cannabis flower samples were collected by law enforcement from adult commercial use cannabis dispensaries, located in three different states (Colorado, Oregon, and California) and analyzed in this study for cannabinoid concentration. Samples were analyzed by GC-FID following our previously published procedure. DISCUSSION: The label claims for total Δ9-THC content ranged from 12.04 to 58.20% w/w, while GC-FID results showed a concentration ranging from 12.95 to 36.55% w/w. Of the evaluated 107 products, only 32 samples have Δ9-THC content within ± 20% of the labeled content. However, the remaining 75 samples were found to be out of the ± 20% acceptance criteria. The degree of agreement for the tested samples using ± 20% tolerance with label claims was only 30%. The results of this study indicate that there is a need for more stringent regulations to ensure that product labeling is accurate, as 70% of the evaluated products did not meet the ± 20% acceptance criteria. This highlights the importance of healthcare professionals and patients being vigilant about the Δ9-THC content, as inaccurate labeling of cannabis products could potentially result in adverse health effects. Furthermore, there is a pressing need for more rigorous regulation of commercial cannabis products in the United States.

Redirecting pantoprazole as a metallo-beta-lactamase inhibitor in carbapenem-resistant Klebsiella pneumoniae.

The development of resistance to carbapenems in Klebsiella pneumoniae due to the production of metallo-ß-lactamases (MBLs) is a critical public health problem because carbapenems are the last-resort drugs used for treating severe infections of extended-spectrum ß-lactamases (ESBLs) producing K. pneumoniae. Restoring the activity of carbapenems by the inhibition of metallo-ß-lactamases is a valuable approach to combat carbapenem resistance. In this study, two well-characterized clinical multidrug and carbapenem-resistant K. pneumoniae isolates were used. The sub-inhibitory concentrations of pantoprazole and the well-reported metallo-ß-lactamase inhibitor captopril inhibited the hydrolytic activities of metallo-ß-lactamases, with pantoprazole having more inhibiting activities. Both drugs, when used in combination with meropenem, exhibited synergistic activities. Pantoprazole could also downregulate the expression of the metallo-ß-lactamase genes bla NDM and bla VIM. A docking study revealed that pantoprazole could bind to and chelate zinc ions of New Delhi and Verona integron-encoded MBL (VIM) enzymes with higher affinity than the control drug captopril and with comparable affinity to the natural ligand meropenem, indicating the significant inhibitory activity of pantoprazole against metallo-ß-lactamases. In conclusion, pantoprazole can be used in combination with meropenem as a new strategy for treating serious infections caused by metallo-ß-lactamases producing K. pneumoniae.

Modulation of Inflammatory Response by Electromagnetic Field Stimulation in Traumatic Brain Injury in Yucatan Swine.

Traumatic brain injury is a leading cause of disability and death worldwide and represents a high economic burden for families and national health systems. After mechanical impact to the head, the first stage of the damage comprising edema, physical damage, and cell loss gives rise to a second phase characterized by glial activation, increased oxidative stress and excitotoxicity, mitochondrial damage, and exacerbated neuroinflammatory state, among other molecular calamities. Inflammation strongly influences the molecular events involved in the pathogenesis of TBI. Therefore, several components of the inflammatory cascade have been targeted in experimental therapies. Application of Electromagnetic Field (EMF) stimulation has been found to be effective in some inflammatory conditions. However, its effect in the neuronal recovery after TBI is not known. In this pilot study, Yucatan miniswine were subjected to TBI using controlled cortical impact approach. EMF stimulation via a helmet was applied immediately or two days after mechanical impact. Three weeks later, inflammatory markers were assessed in the brain tissues of injured and contralateral non-injured areas of control and EMF-treated animals by histomorphometry, immunohistochemistry, RT-qPCR, Western blot, and ELISA. Our results revealed that EMF stimulation induced beneficial effect with the preservation of neuronal tissue morphology as well as the reduction of inflammatory markers at the transcriptional and translational levels. Immediate EMF application showed better resolution of inflammation. Although further studies are warranted, our findings contribute to the notion that EMF stimulation could be an effective therapeutic approach in TBI patients.

Autoantibodies profile in autoimmune liver diseases and chronic viral hepatitis.

Despite their low prevalence, autoimmune liver diseases (AILD) cause liver cirrhosis, progress and leads to mortality from liver failure. Autoantibodies are confirmed to have significance in the early screening of AILD patients, especially in those who are asymptomatic before onset of clinical signs. This study aimed to assess levels of liver autoantibodies and their association with clinical manifestations of autoimmune liver diseases and chronic viral hepatitis (CVH) patients. This case-control study included 50 patients (case group of 25 patients with AILD and control group of 25 patients with CVH). They were investigated for presence of antibodies against LKM-1, AMA-M2, PML, M2-3E (BPO), gp210, Sp100, LC-1, Ro52 and SLA/LP using the line immune blot technique, and for the presence of antinuclear antibodies (ANA), as non-organ specific autoantibodies, using indirect immunofluorescence technique. Specific autoantibodies were detected in all AILD cases and some of their levels were significantly higher when compared with CVH group. Among AILD patients, 52% were positive for ANA, whereas 61.1% of chronic hepatitis C and 28.6% of chronic hepatitis B patients were positive for ANA with no significant difference (p=0.3). In conclusion, early diagnosis of autoimmune liver diseases has been linked to assessment of autoantibodies, allowing for prompt therapeutic intervention to stop the progression of liver cirrhosis and the accompanying complications.

Curcuma longa essential oils: toxicity and repellency against imported fire ants (Formicidae: Hymenoptera).

Curcuma longa L. (Zingiberales: Zingiberaceae) leaf and rhizome essential oils were evaluated for their toxicity and repellency against invasive fire ants: red imported fire ants (RIFA), Solenopsis invicta Buren, black imported fire ants (BIFA), Solenopsis richteri Forel, and a reproductively functional hybrid (HIFA). Ar-turmerone was the major constituent of leaf (42.4%) and rhizome (40.4%) essential oils. A range of concentrations starting from 156 µg/g until the failure of treatment were used. Removal of treated sand in digging bioassay was used as a criterion for repellency. Leaf essential oil showed significantly higher repellency at concentrations of 19.5, 9.8, and 4.9 µg/g against RIFA, BIFA, and HIFA workers, respectively, as compared with control whereas rhizome essential oil was active at 39, 19.5, and 4.9 µg/g against BIFA, RIFA, and HIFA, respectively. Ar-turmerone exhibited repellency at 19.5 µg/g against HIFA workers whereas DEET (N,N-diethyl-meta-toluamide) failed at 39 µg/g. Leaf essential oil showed LC50 values of 85.8, 97.7, and 182.7µg/g against RIFA, BIFA and HIFA workers, whereas the rhizome essential oil had LC50 values of 127, 109.9, and 151.2 µg/g against these species, respectively. Ar-turmerone, tested only against HIFA, with LC50 value of 57.2 was the most active compound. Bifenthrin, a commonly used pyrethroid, with LC50 of 0.03, 0.32, and 0.018 µg/g was toxic against RIFA, BIFA, and HIFA workers, respectively. Both the essential oils and ar-turmerone showed toxicity and repellency against imported fire ants. Different formulations of these natural products will be tested to explore the use potential of these natural products under field conditions.

HIV-1 Gag MA domain binds to cardiolipin in a binding mode distinct from virus assemble mediator PI(4,5)P2.

The human immunodeficiency virus type 1 (HIV-1) Gag protein is responsible for facilitating HIV-1 virion assembly and budding. Our study demonstrates that cardiolipin (CL), a component found in the inner mitochondrial membrane, exhibits the highest binding affinity to the N-terminal MA domain of the HIV-1 Gag protein within the lipid group of host cells. To assess this binding interaction, we synthesized short acyl chain derivatives of CL and employed surface plasmon resonance (SPR) analysis to determine the dissociation constants (Kd) for CL and the MA domain. Simultaneously, we examined the Kd of D-myo-phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) derivatives, known to play a crucial role in virion formation. Among all the derivatives, Tetra-C7 -CL exhibited the lowest Kd value (Kd = 30.8 ± 6.9 µM) for MA binding on the CL analog-immobilized sensorchip, indicating a higher affinity. Similarly, the Kd value of Di-C7 -PIP2 (Kd = 36.6 ± 4.7 µM) was the lowest on the PI(4,5)P2 analog-immobilized sensorchip. Thus, Tetra-C7 -CL binds to the MA domain using a distinct binding mode while displaying a comparable binding affinity to Di-C7 -PIP2. This discovery holds significant implications for comprehending the virological importance of CL-MA domain binding, such as its subcellular distribution, including mitochondrial translocation, and involvement in viral particle formation in concert with PI(4,5)P2 . Furthermore, this study has the potential to contribute to the development of drugs in the future.