Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.

Therapeutic small interfering RNA (siRNA) requires sugar and backbone modifications to inhibit nuclease degradation. However, metabolic stabilization by phosphorothioate (PS), the only backbone chemistry used clinically, may be insufficient for targeting extrahepatic tissues. To improve oligonucleotide stabilization, we report the discovery, synthesis and characterization of extended nucleic acid (exNA) consisting of a methylene insertion between the 5'-C and 5'-OH of a nucleoside. exNA incorporation is compatible with common oligonucleotide synthetic protocols and the PS backbone, provides stabilization against 3' and 5' exonucleases and is tolerated at multiple oligonucleotide positions. A combined exNA-PS backbone enhances resistance to 3' exonuclease by ~32-fold over the conventional PS backbone and by >1,000-fold over the natural phosphodiester backbone, improving tissue exposure, tissue accumulation and efficacy in mice, both systemically and in the brain. The improved efficacy and durability imparted by exNA may enable therapeutic interventions in extrahepatic tissues, both with siRNA and with other oligonucleotides such as CRISPR guide RNA, antisense oligonucleotides, mRNA and tRNA.

Proton Pump Inhibitor Induced Hypomagnesemia Causing Seizures: A Rare Adverse Effect of a Commonly Used Medication.

Hypomagnesemia is defined as serum magnesium levels less than 0.7mmol/L and can result in a plethora of symptoms ranging from mild gastrointestinal symptoms to serious conditions such as cardiac arrhythmias and neurological complications. When considering the etiological factors, drug-induced hypomagnesemia is highlighted because commonly used medications such as proton pump inhibitors (PPIs), aminoglycoside antibiotics, and loop and thiazide diuretics can cause low magnesium levels. A 49-year-old male presented to the emergency department with severe vomiting worsening over three days complicated with generalized tonic-clonic seizures. He was an averagely built male, a non-smoker, and a non-alcoholic with no significant co-morbidities. He had a history of chronic over-the-counter pantoprazole intake over the last one year, and apart from that, his medication history was unremarkable. Initial investigations revealed severe hypomagnesemia (with serum magnesium level of 0.1mmol/L), with marginal hypokalemia, hypophosphatemia, and hypocalcemia. Following the initial resuscitation and magnesium supplementation, the patient's clinical condition significantly improved. Due to the lack of proper knowledge, the patient continued to take omeprazole 20mg tablets after discharge, and up until proper education and total cessation of PPIs, marginal hypomagnesemia, with serum magnesium level of 0.5mmol/L, persisted without any significant overt clinical manifestations. In this case report, we intend to highlight the importance of assessing for all possible electrolyte abnormalities in a patient presenting with neurological symptoms, relevance of taking a thorough drug history including all undocumented over-the-counter medications, and importance of patient education in the prevention of further episodes.

Clinical Evaluation of Different Designs of Fixed Space Maintainer: A Randomized Clinical Trial.

Purpose: Evaluation of survival rates for three space maintainers (SMs) of different designs compared to the standard one. Materials and methods: A total of 52 extraction sites in children aged 4-7 years with prematurely lost primary molars were selected for this study. The whole sample was divided into four groups of 13 each. In group I, Band and Loop (B&L); group II, single-sided Band and Loop (Ss B&L); group III, Direct Bonded Wire (DBW); and group IV, Tube and Loop (T&L). Children were recalled at 3, 6, 9, 12, and 15 months. Cumulative survival rates of SMs were estimated using the Kaplan-Meier method with a logrank test. Results: Although there was a nonsignificant difference in the number of failed cases among all groups, the overall survival rate for group I was 69.2%, group II was 53.8%, group III was 38.5%, and group IV was 30.8% at the end of the study. The failure types for B&L were solder breakage (75% of the total failure rate) and cement dissolution (25%); for Ss B&L, they were solder breakage with lost loop (50%), soft tissue impingement (33%), and dislodgment (17%); for DBW, they were composite-wire interface debonding (75%) and enamel-composite interface debonding (25%); and finally, for T&L, they were lost T&L (56%), soft tissue impingement (22%), and total loss (22%). Conclusion: Banded SMs survived for a longer time than bonded ones, with superior performance for B&L compared to Ss B&L. In addition, bonded SMs required strict isolation conditions. DBW could be used in the maxilla rather than the mandible and was preferable for older children. How to cite this article: Hemdan ME, H El Kalla IHH, El Agamy RA. Clinical Evaluation of Different Designs of Fixed Space Maintainer: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2024;17(4):442-450.

Anxiolytic treatment of a trapped rat reduces helping and anxiogenic treatment increases helping: Evidence for emotional contagion in altruism.

The present experiment used the trapped rat model to explore whether pharmacological manipulation of distress affects the likelihood of helping behavior. 120 Sprague-Dawley rats (30 male pairs and 30 female pairs) completed 12 consecutive, daily trials assessing helping behavior. During an individual trial, a trapped rat was placed in a restrainer in the center of an open field, while its cagemate could move around freely and possibly open the restrainer by lifting a door. Trapped rats received an intraperitoneal injection of either 1) physiological saline, 2) the anxiolytic midazolam (1.5 mg/kg), or 3) the anxiogenic yohimbine (2.5 mg/kg) 30 min prior to the start of each trial. Dependent variables measured were: 1) door opening latency (sec), 2) percentage of trials in which a door opening occurred, and 3) the number of free rats classified as "openers." Based on emotional contagion theory, we predicted that 1) free rats paired with midazolam-subjects would show attenuated helping behavior (e.g., higher door opening latency) compared to controls, and conversely 2) free rats paired with yohimbine-subjects would show enhanced helping behavior. First, a significant sex-difference was observed, in that more females were classified as openers than males. This supports previous evidence that females express higher altruistic motivation and experience stronger emotional contagion than males. Second, midazolam-treatment significantly attenuated helping behavior. From trials 4-12, free rats paired with midazolam-subjects expressed slower door opening latencies compared to controls. Third, yohimbine-treatment significantly increased helping behavior (e.g., reduced door opening latencies) - but only on trials 1-3; by trials 9-12, this pattern was reversed. These results are consistent with emotional contagion theory and indicate that intensity of distress directly modulates altruistic motivation through vicarious state-matching.

Biomedical properties, characterization of seaweeds species and antimicrobial activity.

Marine organisms produce a variety of compounds with pharmacological activities. In order to better comprehend the medicinal value of five particular seaweed orders Ulvales (Ulva intestinalis), Bryopsidales (Codium decorticatum), Ectocarpales (Iyengaria stellata), Dictyotales (Spatoglossum aspermum) and Gigartinales (Hypnea musciformis), a bioactive analysis including the screening of phytochemical components, antioxidant and antimicrobial activities was the aim of the investigation. The species include U. intestinalis was collected from Sandspit, while C. decorticatum, I. stellata, S. aspermum, and H. musciformis were gathered from Buleji. These species evaluated for their ability to inhibit human infectious gram positive pathogens Staphylococcus aureus, Staphylococcus epidermidis as well as gram negative bacteria Escherichia coli. Additionally vegetable pathogen Fusarium oxysporum, and fruit pathogens (Aspergillus niger and Aspergillus flavus) were evaluated to determine the zone of inhibition. Two organic solvents, ethanol and methanol, were used to prepare seaweed extract. The disc diffusion method was utilized to quantify the zone of inhibition and the DPPH method was employed to measure the antioxidant activity. The study unveiled various phyto-constituents in the tested seaweeds, with flavonoids, tannins, and proteins found in all selected species, while saponins, terpenoids, and carbohydrates were absent in I. stellata and S. aspermum. Notably, ethanolic extracts of I. stellata and S. aspermum demonstrated superior higher antioxidant activity, with increasing percentages of inhibition from 1 to 6 mg/ml. Furthermore, the findings indicated that the ethanolic extract of U. intestinalis displayed the highest resistance against F. oxysporum and A. flavous among other seaweeds. Meanwhile, the ethanolic extract of C. decorticatum exhibited the highest resistance against A. Niger. Additionally, the ethanolic extract of I. stellata and H. musciformis displayed the highest resistance against the gram-negative bacteria E. coli and the gram-positive bacteria S. epidermidis, whereas the methanolic extract of U. intestinalis demonstrated the highest resistance against the gram-positive bacteria S. aureus. The findings of this investigation show that a range of bioactive compounds with antioxidant properties are involved in the antimicrobial activities of disease-causing pathogens.

Functional chitosan surfactants for corrosion inhibition in petroleum industry.

Chitosan is a natural biodegradable biopolymer, and the structure of its unit is 2-amino-d-glucopyranose that has been it more attractive to applied as natural corrosion inhibitor of metals for different area. Functionalization chitosan by surfactant is necessary to improve some of its properties such as solubility, surface activity, and corrosion inhibition efficiency. Corrosion of metals is a global problem particularly in petroleum industry field needs to favorably inhibition process using environmentally friendly inhibitors such chitosan. In this work, it was presented on researches which taken chitosan functionalized by different types of surfactants as green corrosion inhibitor of metals in petroleum field. It was concluded from displayed researches data that functionalization of chitosan by surfactant could be on three categories; cationic, anionic and nonionic form. Otherwise, the unsaturated chain, benzene rings, and quaternary ammonium groups greatly increase the inhibition efficiency compared to hydrophobic chains. Furthermore, the nanoparticles of chitosan nonionic surfactant or those assembled on silver nanoparticles exhibited high inhibition efficiency. The inhibition performance of chitosan surfactant categories are more effective even at lower concentrations, and form a protective film onto metal surface, as well as and the inhibitor adsorption mechanism is mostly mixed type and obey Langmuir model.

Enhanced photocatalytic activity of green synthesized zinc oxide nanoparticles using low-cost plant extracts.

Developing stable and highly efficient metal oxide photocatalysts remains a significant challenge in managing organic pollutants. In this study, zinc oxide nanoparticles (ZnO NPs) were successfully synthesized using various plant extracts, pomegranate (P.M), beetroot roots (B.S), and seder, along with a chemical process. The produced ZnO NPs were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), Field Emission Scanning Electron Microscope (FESEM), High-Resolution Transmission Electron Microscopy (HRTEM), and Surface Area. For all prepared samples, the results indicated that the composition of the plant extract affects several characteristics of the produced particles, such as their photocatalytic properties, energy bandgap (Eg), particle size, and the ratio of the two intensity (0 0 2) and (1 0 0) crystalline planes. The particle size of the produced NPs varies between 20 and 30 nm. To examine NPs' photocatalytic activity in the presence of UV light, Methyl Orange (MO) was utilized. The Eg of  ZnO synthesized by the chemical method was 3.16 e. V, whereas it was 2.84, 2.63, and 2.59 for P.M, Seder, and B.S extracts, respectively. The most effective ZnO NPs, synthesized using Beetroots, exhibited a degradation efficiency of 87 ± 0.5% with a kinetic rate constant of 0.007 min-1. The ratio of the two intensity (0 0 2) and (1 0 0) crystalline planes was also examined to determine a specific orientation in (0 0 2) that is linked to the production of oxygen vacancies in ZnO, which enhances their photocatalytic efficiency. Furthermore, the increase in photocatalytic effectiveness can be attributed to the improved light absorption by the inter-band gap states and effective charge transfer.

Experimental and Computational Anticorrosion Behaviors of Pyrazole s-Triazine/anilino-morpholino Derivatives for Steel in Acidic Solutions.

The corrosion inhibition of C-steel by two s-triazine/morpholino-anilino-pyrazole derivatives, namely, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-N-phenyl-1,3,5-triazin-2-amine (1) and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine (2) was investigated by impedimetric and potentiometric studies. It was found that (1) and (2) acted as cathodic-type corrosion inhibitors that retard the hydrogen evolution reaction. The percent corrosion inhibition, 98.5% for compound (2) (with bromo substituent) at 80 ppm, was slightly higher than 97.8% for (1) at 100 ppm. Thus, the replacement of a -H with -Br substituent increased the corrosion inhibition properties. Compound (2) exhibited Temkin isotherm adsorption, whereas compound (1) exhibited Langmuir adsorption. Scanning electron microscopy (SEM) analysis of the steel surface indicated that the inhibitors caused protection of the surface. The weight loss experiment also proved the decrease in the corrosion rate when inhibitors were added. The difference in inhibitory efficiency between compounds (1) and (2) was investigated by density functional theory (DFT) to study neutral and protonated species in gaseous and aqueous phases. The theoretical analysis demonstrated that compound (2) exhibited higher inhibitory activity on a metal surface compared to compound (1), aligning with the experimental results. The energy associated with the metal/adsorbate arrangement, represented by dE ads/dNi , was higher for (2) (-380.91 kcal mol-1) compared to (1) (-371.64 kcal mol-1). This indicated better adsorption of (2) over (1).

Burden of obstructive sleep apnea and CPAP use on patients with chronic rhinosinusitis.

OBJECTIVE: To evaluate the impact of obstructive sleep apnea (OSA) on the quality-of-life (QoL) of patients with chronic rhinosinusitis (CRS). METHODS: Retrospective cohort study of all adult patients with CRS presenting to our rhinology clinic between August 2020 and February 2023 was performed. OSA was established based on positive polysomnography. Patients' characteristics, apnea-hypopnea index, comorbidities, endoscopy scores, and SNOT-22 scores were collected. RESULTS: A total of 513 patients with CRS were included, 127 patients with OSA and 386 without OSA. CRS patients with OSA were older (p < 0.001), had higher BMI (p < 0.001), more likely to be males (p = 0.07), more likely to have asthma (p < 0.001), and more likely to have COPD (p = 0.001). Presence of nasal polyps did not differ between the two groups. Baseline SNOT-22 scores were worse in the OSA cohort (44.4 vs 40.5, p = 0.064) secondary to worse sleep (13.4 vs 11.1; p = 0.002) and psychological (14.2 vs 11.5; p = 0.002) domains. Worse SNOT scores were strongly associated with presence of OSA after adjusting for confounding variables, including age, gender, asthma, allergic rhinitis, nasal septal deviation, and smoking status. CONCLUSION: OSA is an independent negative contributor to the disease specific QoL in patients with CRS. CPAP use does not seem to affect the QoL in CRS patients with OSA. Further research is warranted to explore the impact of OSA in the outcome of medical and surgical treatment of CRS patients.

Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of ß-Cyclodextrin and Hydroxypropyl ß-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib.

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with ß-cyclodextrin (ßCD) and hydroxy propyl ß-cyclodextrin (HPßCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with ßCD and HPßCD. This study identified the most soluble complex (ALB-HPßCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPßCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPßCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

Evaluation of time to sputum smear conversion and its association with treatment outcomes among drug-resistant tuberculosis patients: a retrospective record-reviewing study.

Background: This study examined the time to sputum smear and culture conversion and determinants of conversion, as well as variables associated with treatment outcomes among drug-resistant pulmonary tuberculosis (DR-PTB) cases. Methods: The electronic database and written medical records of patients were utilized to assess the sociodemographic, clinical, microbiological, and treatment characteristics and outcomes of study participants. Results: Among 736 patients with pulmonary tuberculosis (PTB), the mean age was 36.5 ± 16.5 years, with males comprising 53.4% and a mean weight of 47.76 ± 11.97 kg. The median time period for sputum smear conversion and sputum culture conversion was a month. The first-month culture conversion (p < 0.001, aOR = 5.817, and 95% CI = 3.703-9.138) was the determinant of sputum smear conversion and receiver operating curve analysis with AUC = 0.881, 95% CI = 0.855-0.907, and p < 0.001, which showed a high level of predictive ability for the regression model for the initial sputum smear conversion. However, the first-month sputum conversion (p < 0.001, aOR = 7.446, and 95% CI = 4.869-11.388) was attributed to sputum culture conversion, and the model has shown excellent predictive ability for regression with ROC curve analysis demonstrating AUC = 0.862, 95% CI = 0.835-0.889, and p < 0.001. A total of 63.2% of patients showed favorable treatment outcomes, with 63.1% of cases achieving treatment-cured status. The previous use of SLD, history of smoking, duration of illness ≤ 1 year, extensively drug-resistant tuberculosis, and first-month sputum conversion were the variables attributed to favorable treatment outcomes observed in drug-resistant pulmonary tuberculosis cases. ROC curve analysis with AUC = 0.902, 95% CI = 0.877-0.927, and p < 0.001) has shown outstanding ability for regression model prediction for the variables influencing treatment outcomes. Conclusions: Within 2 months of treatment, most patients had converted their sputum cultures and sputum smears. The determinants of early sputum smear and sputum culture conversion, as well as favorable treatment outcomes, were identified. These factors should be considered during the design and implementation of effective strategies for drug-resistant tuberculosis control programs.

Bis(dimethylpyrazolyl)-aniline-s-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies.

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

Unsolved Controversies in Management of Infective Endocarditis.

Infective endocarditis (IE) is defined as an infection in the cardiac endothelium. It is triggered by both bacteremia and endothelial dysfunction and poses many risks to the health of the patient. Many organisms can cause IE with Staphylococcus aureus being the major cause. Signs and symptoms may vary according to age and agent but almost all cases are presented with fever, fatigue, and a maculopapular rash. Although pediatric IE is very rare, risk factors such as congenital heart defects have been identified, with some of the cases remaining a mystery. We present a case of a 19-year-old patient, previously healthy and developing subacute IE with sepsis and septic embolic showers in multiple organs. IE cannot be taken for granted as mortality is high, hence a multidisciplinary approach is prompt and necessary for the survival of the patient.

Impact of allergic rhinitis on quality of life in patients with chronic rhinosinusitis.

OBJECTIVES: To evaluate the impact of allergic rhinitis (AR) on the quality of life (QoL) in patients with chronic rhinosinusitis (CRS). METHODS: Retrospective cross-sectional study of adult patients with CRS presenting to our clinic between August 2020 and February 2023 was performed. AR was diagnosed based on a positive skin or blood allergy test. Patients' characteristics, AR status, comorbidities, endoscopy scores, and SNOT-22 scores were collected. RESULTS: A total of 514 CRS patients were included, with 265 (51.6 %) patients with AR. CRS patients with AR were younger (p = 0.004), more likely to be female (p < 0.001), and more likely to have asthma (p < 0.001). Polyp status and endoscopy scores did not differ between patients with and without AR. Baseline SNOT-22 scores were slightly worse in the AR cohort (43.6 vs 38.7, p = 0.007), which was mainly secondary to rhinologic (p = 0.002), extrarhinologic (p = 0.007), and ear/facial (p = 0.007) subdomains. Worse rhinologic and extrarhinologic scores were associated with the presence of AR after adjusting for confounding variables (Coef = 1.55, p = 0.011; and Coef = 0.83, p = 0.021 respectively). CONCLUSION: The impact of allergic rhinitis on QoL is mainly on the nasal symptoms. Further studies should look at the role of AR on the QoL of different CRS endotypes; and at the role of AR-specific treatment, such as immunotherapy, on the QoL of patients with CRS.

Green synthesized silver nanoparticles of Terminalia bellirica leaves extract: synthesis, characterization, in-silico studies, and antimalarial activity.

Malaria is a mosquito-borne infectious disease that is caused by the Plasmodium parasite. Most of the available medication are losing their efficacy. Therefore, it is crucial to create fresh leads to combat malaria. Green silver nanoparticles (AgNPs) have recently attracted a lot of attention in biomedical research. As a result, green mediated AgNPs from leaves of Terminalia bellirica, a medicinal plant with purported antimalarial effects, were used in this investigation. Initially, cysteine-rich proteins from Plasmodium species were studied in silico as potential therapeutic targets. With docking scores between -9.93 and -11.25 kcal/mol, four leaf constituents of Terminalia bellirica were identified. The green mediated silver nanoparticles were afterward produced using leaf extract and were further examined using UV-vis spectrophotometer, DLS, Zeta potential, FTIR, XRD, and FESEM. The size of synthesized TBL-AgNPs was validated by the FESEM results; the average size of TBL-AgNPs was around 44.05 nm. The zeta potential study also supported green mediated AgNPs stability. Additionally, Plasmodium falciparum (3D7) cultures were used to assess the antimalarial efficacy, and green mediated AgNPs could effectively inhibit the parasitized red blood cells (pRBCs). In conclusion, this novel class of AgNPs may be used as a potential therapeutic replacement for the treatment of malaria.

Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo.

Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides-antisense oligonucleotides and small-interfering RNAs-are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.

Green hydrogen generation in alkaline solution using electrodeposited Ni-Co-nano-graphene thin film cathode.

Green hydrogen generation technologies are currently the most pressing worldwide issues, offering promising alternatives to existing fossil fuels that endanger the globe with growing global warming. The current research focuses on the creation of green hydrogen in alkaline electrolytes utilizing a Ni-Co-nano-graphene thin film cathode with a low overvoltage. The recommended conditions for creating the target cathode were studied by electrodepositing a thin Ni-Co-nano-graphene film in a glycinate bath over an iron surface coated with a thin copper interlayer. Using a scanning electron microscope (SEM) and energy-dispersive X-ray (EDX) mapping analysis, the obtained electrode is physically and chemically characterized. These tests confirm that Ni, Co, and nano-graphene are homogeneously dispersed, resulting in a lower electrolysis voltage in green hydrogen generation. Tafel plots obtained to analyze electrode stability revealed that the Ni-Co-nano-graphene cathode was directed to the noble direction, with the lowest corrosion rate. The Ni-Co-nano-graphene generated was used to generate green hydrogen in a 25% KOH solution. For the production of 1 kg of green hydrogen utilizing Ni-Co-nano-graphene electrode, the electrolysis efficiency was 95.6% with a power consumption of 52 kwt h-1, whereas it was 56.212. kwt h-1 for pure nickel thin film cathode and 54. kwt h-1 for nickel cobalt thin film cathode, respectively.

Correlation of patient reported outcome measures with endoscopic findings in pediatric chronic adenoiditis and chronic rhinosinusitis.

BACKGROUND: Studies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS. METHODS: Cross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size. RESULTS: 124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma. CONCLUSION: There is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.

Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation.

Nucleic acid-based therapies have become the third major drug class after small molecules and antibodies. The role of nucleic acid-based therapies has been strengthened by recent regulatory approvals and tremendous clinical success. In this review, we look at the major obstacles that have hindered the field, the historical milestones that have been achieved, and what is yet to be resolved and anticipated soon. This review provides a view of the key innovations that are expanding nucleic acid capabilities, setting the stage for the future of nucleic acid therapeutics.

Role of Sinonasal Anatomic Variants in Recurrent Acute Rhinosinusitis.

OBJECTIVES: Prior studies evaluating the role of sinonasal anatomic variants with recurrent acute rhinosinusitis (RARS) are limited by inconsistent results. The goal of this study is to evaluate the association between sinonasal anatomic variants and RARS. METHODS: A 1:2 retrospective case-control study was conducted using patients presenting to the rhinology clinic from August 2020 to January 2023. A total of 60 patients with RARS were compared to 120 control patients. RARS was diagnosed based on the International Consensus Statement on Allergy and Rhinology criteria of four or more independent episodes of acute rhinosinusitis per year with at least one episode documented by objective findings, with complete resolution of the infection in-between episodes. Sinonasal anatomic variants included nasal septal deviation (NSD), concha bullosa (CB), infraorbital (Haller) cells, nasal septal spur in the middle meatus, and frontal sinus cells (supra-agger, supra-agger frontal, and suprabullar frontal cells). RESULTS: Age was similar in RARS and control patients (47.4 ± 16.5 vs. 49.3 ± 14.5, p = 0.432). Both the RARS group and control group were more likely to be female (78.3% vs. 77.5%, p = 0.899). There was no significant association between NSD and RARS compared to the control group (OR = 0.97, p = 0.916), and no significant association between any of the anatomic variants and RARS [infraorbital cells (OR = 0.64, p = 0.167), CB (OR = 0.84, p = 0.596), spur in the middle meatus (OR = 1.28, p = 0.514), supra-agger (OR = 0.88, p = 0.708), supra-agger frontal cells (OR = 0.97, p = 0.939), or suprabullar frontal cells (OR = 1.13, p = 0.766)]. CONCLUSION: Our findings suggest no association between nasal septal deviation or any of the anatomic variants studied and RARS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3489-3492, 2024.