Specific Formulation Research Articles

A comprehensive and systematic review on Curcumin as a promising candidate for the inhibition of melanoma growth: From pre-clinical evidence to molecular mechanisms of action

BackgroundMelanoma, a highly malignant skin tumor, can develop systemic metastases during the early stage. Several studies of melanoma animal models indicate that curcumin, a natural plant extract, inhibits melanoma growth through various mechanisms. To evaluate the relationships among different experimental conditions, curcumin itself, its derivatives, and special formulations, it is necessary to conduct a systematic review and meta-analysis. PurposeThis meta-analysis aims to evaluate the potential of Curcumin as a drug for inhibiting the growth of melanoma and to determine the optimal dosage range and treatment duration for Curcumin administration. MethodsA systematic search of studies published from inception to December 2023 was conducted across six databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP). Methodological quality was assessed using SYRCLE's RoB tool. Study heterogeneity was assessed using Cochran's Q test and I2 statistics. Publication bias risk was evaluated using a funnel plot. All analyses were performed using R (version 4.3.3). Additionally, three-dimensional effect analysis and machine learning techniques were utilized to determine the optimal dosage range and treatment duration for Curcumin administration. ResultsForty studies involving 989 animals were included. The results demonstrated that, relative to the control group, administration of Curcumin resulted in a significant reduction in tumor volume. [SMD=−3.44; 95 % CI (−4.25, −2.63); P<0.01; I2 = 79 %] and tumor weight [SMD=−1.93; 95 % CI (−2.41, −1.45); P<0.01; I2 = 75 %]. Additionally, Curcumin demonstrated a significant capacity to decrease the number of lung tumor nodules and microangiogenesis, as well as to extend survival time, in animal models. The results from three-dimensional effect analysis and machine learning emphasize that the optimal dosage range for Curcumin is 25–50 mg/kg, with an intervention duration of 10–20 days. ConclusionCurcumin can inhibit the growth of melanoma, and the dose-response relationship is not linear. However, further large-scale animal and clinical studies are required to confirm these conclusions.

Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis.

Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD). We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values. Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD. FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.

ОБ УТОЧНЕНИИ ПОДСЛЕДСТВЕННОСТИ ПО УГОЛОВНЫМ ДЕЛАМ ЗА УНИЧТОЖЕНИЕ ИЛИ ПОВРЕЖДЕНИЕ ИМУЩЕСТВА ПО НЕОСТОРОЖНОСТИ

The article considers the actual problems of forming a correct legal conceptual and categorical apparatus used in Russian legislation regulating responsibility for activities that create increased danger to others. The methodological basis of the analysis carried out by the authors is the dialectic of legislative and law enforcement activities in their contradictory unity and the desire to achieve maximum meaningful purity of legal categories introduced into circulation, using the example of article 168 of the Criminal code of the Russian Federation. The authors propose specific formulations of the criminal law norm prescribed in article 168 of the Criminal code of the Russian Federation and their justification, which makes it possible to clarify the jurisdiction attributed to the competence of the investigators of the state fire supervision of the federal fire service of the State fire service of EMERCOM of Russia in criminal cases for the destruction or damage of property by negligence.

Ranking Magnetic Colloid Performance for Magnetic Particle Imaging and Magnetic Particle Hyperthermia

AbstractMagnetic particle imaging (MPI) is an emerging modality that can address longstanding technological challenges encountered with magnetic particle hyperthermia (MPH) cancer therapy. MPI is a tracer technology compatible with MPH for which magnetic nanoparticles (MNPs) provide signal for MPI and heat for MPH. Identifying whether a specific MNP formulation is suitable for both modalities is essential for clinical implementation. Current models predict that functional requirements of each modality impose conflicting demands on nanoparticle magnetic properties. This objective here is to develop a measurement and ranking scheme based on end‐use performance to streamline evaluation of candidate MNP formulations. The measured MPI point‐spread function (PSF) and specific loss power (SLP) is combined to generate a single numerical value for comparison on a relative ranking scale, or figure of merit (FoM). 12 aqueous iron‐containing formulations are evaluated, including FDA‐approved (parenteral) iron‐containing colloids. MNPs with high (Synomag‐D70: 123.4), medium (Synomag‐D50: 63.2), and low (NanoXact: 0.147) FoM values are selected for in vivo validation of the selection scheme in subcutaneous 4T1 tumors. Results demonstrate that the proposed ranking accurately assessed the relative performance of MNPs for MPI and MPH. Data demonstrated that image quality and tumor temperature rise increased with FoM ranking, validating predictions. It isshown that the MPI signal correlated with MNP concentration in tissue. Computational heat transfer models anchored on tumor MPI data harmonized with experimental results to within an average of 2 °C when MNP content estimated from MPI data is included. Computational studies emphasized the importance of post‐injection MNP quantitation and MPI spatial resolution.

Lyotropic liquid crystal and self-emulsifying drug delivery systems nanoparticles as artesunic acid and praziquantel carriers: An innovative approach for formulation of anti-malaria and schistosomicidal drugs

Praziquantel (PZQ) is the drug of choice for treating cestode and trematode infections, and it is currently the only option against schistosomiasis. Artesunic acid (AcART) is effective against several parasites and has emerged as an alternative for schistosomiasis treatment. However, AcART and PZQ have limited bioavailability due to poor water solubility, low permeability, and rapid cell clearance. To address these challenges, this study aimed to develop self-emulsifying drug delivery systems to develop SEDDS and NPs-LLC to overcome the low water solubility affecting AcART and PZQ bioavailability. The study involved validating the HPLC analytical methodology for AcART, SEDDS, and NPs-LLC formulations, and conducting physicochemical characterization and ex-vivo intestinal permeation assays. The composition of formulations was determined by the solubility balance of AcART and PZQ. The drug content ranged between 83 and 90 %. The anionic zeta potential was attributed to Myverol®, and the particle diameter increased slightly after the drug incorporation, while the polydispersity index indicated the relatively narrow particle size distribution. Additionally, the DSC thermogram confirmed that PZQ and AcART are in solution within SEDDS and NPs-LLC. The FTIR analysis suggests that components of SEDDS and NPs-LLC and drugs do not react to form new chemical species. The selection of specific compound formulations was based on achieving the best solubility balance. The nanostructures were stable and exhibited a surface charge favorable to mucosal permeation, with slightly superior performance for SEDDS. The innovative formulations, SEDDS and NPs-LLC, are suitable and effective carriers for AcART and PZQ.

Targeted nanoliposomes of oncogenic protein degraders: Significant inhibition of tumor in lung-cancer bearing mice

With 60 % of non-small cell lung cancer (NSCLC) expressing epidermal growth factor receptor (EGFR), it has been explored as an important therapeutic target for lung tumors. However, even the well-established EGFR inhibitors tend to promptly develop resistance over time. Moreover, strategies that could impede resistance development and be advantageous for both EGFR-Tyrosine kinase inhibitor (TKI)-sensitive and mutant NSCLC patients are constrained. Based on the critical relationship between EGFR, c-MYC, and Kirsten rat sarcoma virus (K-Ras), simultaneous degradation of EGFR and Bromodomain-containing protein 4 (BRD4) using “Proteolysis Targeting Chimeras (PROTACs)” could be a promising approach. PROTACs are emerging class of oncoprotein degraders but very challanging to deliver in vivo. Compared to individual IC50s, strong synergism was observed at 1:1 ratio of BPRO and EPRO in NSCLC cell lines with diverse mutation. Significant inhibition of cell growth with higher cellular apoptosis was observed in 2D and 3D-based cell assays in nanomolar concentrations. EGFR activation assay revealed 47.60 % EGFR non-expressing cells confirming EGFR-degrading potential of EPRO. A lung cancer specific nanoliposomal formulation of EGFR and BRD4-degrading PROTACs (EPRO and BPRO) was prepared and characetrized. Successful encapsulation of the two highly lipophilic molecules was achieved in EGFR-targeting nanoliposomal carriers (T-BEPRO) using a modified hydration technique. T-BEPRO revealed a particle size of 109.22 ± 0.266 nm with enhanced cellular uptake and activity. Remarkably, parenterally delivered T-BEPRO in tumor-bearing mice showed a substantially higher % tumor growth inhibition (TGI) of 77.6 % with long-lasting tumor inhibitory potential as opposed to individual drugs.

The metamorphosis of definition of punishment in international criminal law

The article is devoted to an attempt to generalise and systematise the preliminary considerations regarding the outline of the initial contours of the so-called “interdependence” of the internal content and specific formulations and expressions which are currently commonly used to refer to the concept of “punishment in international criminal law”. An assumption is suggested concerning the evolving nature of the definition of the notion of punishment in international criminal law, given the wide terminological variety of concepts and constructs present in scientific usage, which are as a rule either “located alongside” or “used instead”. At least eighteen, to a certain extent, unique and original phrases designed to describe phenomena similar to “punishment in international criminal law” are identified, among which a special emphasis is traditionally assigned to such specific syntactic units as “international punishment” and “international criminal punishment”, the use of which is quite typical and fairly evident in the modern scientific and information discourse. An assertion is made about the potential existence of a fundamental difference in the definition of the concept of punishment in international criminal law depending on the approaches to its perception, in view of the underlying method depicted in specific terms and categories: 1) through the prism of the imposition of punishment on specific individuals (“punishment of international criminals”); 2) by understanding punishment through the category of “incredible atrocities” (“punishment for international crimes”); 3) by “reading” its content from the perspective of international and national criminal justice bodies (“punishment in the law and practice of international criminal tribunals and courts, national and local institutions”); 4) comprehending its essence by inserting it into a certain setting (“punishment in international, transitional and transitional contexts”); 5) either from the standpoint and perspectives of legal norms (“punishment and international law, punishment and international criminal law”) or their violation (“punishment for violations of international criminal and international humanitarian law”). It is emphasized that further scientific investigations aimed at establishing the essence of each of the currently existing terms with a view to clarifying their content in order to develop a unified definition of the concept of punishment in international criminal law are expedient.

Comparative efficacy of probiotic mixture Bifidobacterium longum KABP042 plus Pediococcus pentosaceus KABP041 vs. Limosilactobacillus reuteri DSM17938 in the management of infant colic: a randomized clinical trial

We aimed to compare the efficacy of Bifidobacterium longum KABP042 + Pediococcus pentosaceus KABP041 (BL + PP) vs. Limosilactobacillus reuteri DSM17938 (LR) in alleviating the symptoms of infant colic, as commercially available formulations. A randomized, multicenter, parallel, single-blind (investigator) trial was conducted in 112 colicky infants diagnosed as per Rome IV criteria and randomly allocated to receive BL + PP orally (109 colony-forming units [CFU]/day, n = 55) or LR (108 CFU/day, n = 57) for 21 days. Primary study outcomes were percentage of responders (≥ 50% reduction in crying and fussing time from baseline, as reported by parents in a structured diary) and daily crying and fussing time (minutes/day) on days 7, 14, and 21 after randomization. Study groups were comparable at baseline. Responder rate was significantly higher in BP + PP group vs. LR group at days 7 (61.1% vs. 37.5%, p = 0.013) and 14 (84.6% vs. 59.3%, p = 0.004). Crying and fussing time (median [IQR]) became significantly lower in BL + PP group vs. LR group on day 7 (119 [60–210] vs. 180 [110–270]; p = 0.028), day 14 (60.0 [30–105] vs. 120 [60–180]; p = 0.017), and day 21 (29 [0–85] vs. 67 [30–165]; p = 0.011). No significant differences were found in the number of adverse events between the groups. Conclusion: The specific formulation of B. longum KABP042 and P. pentosaceus KABP041 achieved a higher response rate and a larger reduction in crying and fussing time in colicky infants. Both probiotic interventions were well tolerated.Trial registration: The study was retrospectively registered as NCT05271747 on February 28th, 2022.What is Known:• L. reuteri DSM17938 (LR) is the most researched probiotic strain for infant colic against placebo in randomized, controlled clinical trials, and is recommended in various guidelines. A novel probiotic combining strains B. longum KABP042 and P. pentosaceus KABP041 (BL + PP) has also demonstrated efficacy in infant colic against placebo.What is New:• This randomized study provides the first direct comparison of two probiotics for infant colic. BL + PP seems to be superior to LR in reducing crying time.

Urban Air Logistics with Unmanned Aerial Vehicles (UAVs): Double-Chromosome Genetic Task Scheduling with Safe Route Planning

In an efficient aerial package delivery scenario carried out by multiple Unmanned Aerial Vehicles (UAVs), a task allocation problem has to be formulated and solved in order to select the most suitable assignment for each delivery task. This paper presents the development methodology of an evolutionary-based optimization framework designed to tackle a specific formulation of a Drone Delivery Problem (DDP) with charging hubs. The proposed evolutionary-based optimization framework is based on a double-chromosome task encoding logic. The goal of the algorithm is to find optimal (and feasible) UAV task assignments such that (i) the tasks’ due dates are met, (ii) an energy consumption model is minimized, (iii) re-charge tasks are allocated to ensure service persistency, (iv) risk-aware flyable paths are included in the paradigm. Hard and soft constraints are defined such that the optimizer can also tackle very demanding instances of the DDP, such as tens of package delivery tasks with random temporal deadlines. Simulation results show how the algorithm’s development methodology influences the capability of the UAVs to be assigned to different tasks with different temporal constraints. Monte Carlo simulations corroborate the results for two different realistic scenarios in the city of Turin, Italy.

7966 Long-Term Safety and Efficacy of a Hydrocortisone Oral Granules in a Young Child with Congenital Adrenal Hypertrophy

Abstract Disclosure: M. Bertossi: None. C. Lowe: None. Q.L. Van Meter: Consulting Fee; Self; Eton Pharmaceuticals. Speaker; Self; Eton Pharmaceuticals. Introduction: Congenital adrenal hyperplasia (CAH) is the most common cause of pediatric adrenal insufficiency. Children diagnosed with CAH need exogenous glucocorticoid therapy throughout their lifetime. Because low dose hydrocortisone (HC) tablets are not available, patients and their caregivers must either split/crush hydrocortisone tablets or rely on HC that has been compounded from adult medications. In late 2020, a pediatric specific HC formulation, an oral granule, became available with doses as low as 0.5 mg. There are minimal data concerning the long-term use of this novel HC formulation. Subject and Method: This case study is a girl (DOB 11/2016) with CAH who has been administered the HC oral granule formulation for over 3 years. Results: The subject is a 7-year-old female who was diagnosed at birth with CAH. At an outside institution, she administered 6.25 mg HC, divided into three doses of 2.5 mg in the morning, 1.25 mg in the afternoon, and 2.5 mg in the evening (2.5/1.25/2.5; 9 mg/m2). She was also administered 0.15 mg fludrocortisone qd. Her dose was increased to a total dose of 7.5 mg, administered 2.5 mg three times/day (10 mg/m2) because of a high 17-OHP concentration, 1048 mg/dL. Other hormone levels were unremarkable. Her 17-OHP levels increased to 2662 mg/dL after 3 months of the increased dose. Because of the development of Cushing’s symptoms, she was switched to the 7.0 mg HC granules (2.5/2.0/2.5; 9.5 mg/m2 total dose). After the switch to the HC granules, her 17-OHP levels was 293 ng/dL. Because of rising 17-OHP levels, her dose needed to be increased twice over the past 2 yrs. Her current dose is 12 mg HC granules (4/4/4; 11 mg/m2 total dose), and her three most recent 17-OHP levels were 73, 101, and 89 ng/dL, respectively. She is also taking 0.2 mg fludrocortisone po, q am. Throughout HC granule therapy, she had no incidence of adrenal crisis. Her most recent calculated bone age was 8 yr 10 mo, with her chronological age was 6 yr, 8 mo with no evidence of virilization. Growth curves suggest that she is neither under- nor over-dosed on her HC therapy. Conclusion: This case may be the longest, continuous administration of the novel HC granules in US for a child with CAH. The results show the potential to better titrate HC dosing, especially with the narrow therapeutic window of HC in children with CAH. Her daily dose was adjusted by titrating in small increments to result in good outcomes, such as better hormonal control, the lack of virilization and continuous growth. Further evaluations of the long-term use of HC granules are needed to occur to establish the long-term risks and benefits of this novel HC granule. Presentation: 6/3/2024

Comparison of Omega-3 polyunsaturated fatty acids bioavailability in fish oil and krill oil: Network Meta-analyses

Background and Aims: Fish oil and krill oil are primary sources of Omega-3 polyunsaturated fatty acids (PUFAs), differing in their molecular forms and bioavailability. Understanding these differences can optimize their therapeutic use. This study aims to compare the bioavailability of Omega-3 PUFAs in fish oil and krill oil using a network meta-analysis approach. By evaluating various molecular forms and dosages, the study seeks to identify the most effective Omega-3 sources and dosing regimens to maximize health benefits.Methods: The study adhered to the explanation of the PRISMA network meta-analysis 2015 (registered PROSPERO ID: CRD42024532536). The risk of bias was evaluated using the PEDro scale. This network meta-analysis incorporated data from studies published between 2003 and 2023, sourced from five databases: ClinicalTrials.gov, PubMed, Cochrane CENTRAL, the International Clinical Trials Registry Platform-World Health Organization, and Embase. Statistical analysis was conducted using advanced models in R software to ensure a rigorous evaluation of bioavailability.Results: Out of 26 high-quality studies, findings reveal superior bioavailability of krill oil compared to fish oil. Specifically, fish oil above 3000 mg, in re-esterified triacylglycerol or ethyl ester formulations (100–2900 mg), and krill oil (100–1900 mg) significantly enhanced the Omega-3 index. At lower dosages (under 2000 mg), krill oil shows superior Omega-3 absorption compared to fish oil. Using fish oil ethyl ester at doses between 2000 and 2900 mg may be the most effective for reducing Tmax. However, this finding should be interpreted with caution due to high heterogeneity and limited statistical significance. The highest AUC values were observed in krill oil phospholipid/free fatty acid formulation. Emulsion forms of fish oil are more effective in increasing Cmax than other formulations. These results were supported by robust statistical evidence (Egger's test, p > 0.05), highlighting the effectiveness of specific formulations and doses in optimizing Omega-3 absorption.Conclusion: The research highlights the importance of understanding the bioavailability of Omega-3 PUFAs from fish oil and krill oil. The findings suggest that low-dose krill oil and fish oil emulsions (under 2000 mg) are effective and potentially safer alternatives to high-dose fish oil, potentially minimizing the risk of adverse effects.

An Organic Mineral Adhesive Bone Graft: A Preclinical Study.

The development of a successful bone grafting technology with cohesive and adhesive properties has been an elusive goal for dental and orthopedic researchers. Tetracalcium phosphate combined with phosphoserine (TTCP-PS) is a synthetic, injectable, cohesive, self-setting, mineral-organic wet-field adhesive. The objective of this study was to evaluate four formulations of TTCP-PS in comparison to the conventional grafting materials, Bioglass and deproteinized cancellous bovine bone with a bioresorbable collagen membrane in standardized defects created in the angle of the rat mandible. Microcomputed tomography and histomorphometry were utilized to evaluate bone replacement with each of these materials after in vivo residence of either 4 or 12 weeks. The results of this study demonstrate that specific TTCP-PS formulations can form bone comparable to conventional materials in an osteopromotive mechanism but with the advantage of having cohesive and adhesive properties.

Real-World Effectiveness of Menopausal Hormone Therapy in Preventing Relapse in Women With Schizophrenia or Schizoaffective Disorder.

Antipsychotic effectiveness in preventing relapse declines around menopausal age in women with schizophrenia or schizoaffective disorder (SSD). It is not known whether systemic menopausal hormone therapy (MHT) can help to prevent psychosis relapse. A within-subject study design was used to study the effectiveness of MHT in preventing relapse in a Finnish nationwide cohort of women with SSD between 40 and 62 years of age who used MHT during follow-up (1994-2017). Hazard ratios adjusted for age and psychotropic drug use were calculated for psychosis relapse as main outcome and any psychiatric hospitalization as secondary outcome. The study population comprised 3,488 women using MHT. Use of MHT was associated with a 16% lower relapse risk (adjusted hazard ratio [aHR]=0.84, 95% CI=0.78-0.90) when compared to non-use. Stratified by age, MHT was associated with decreased relapse risks when used between ages 40-49 (aHR=0.86, 95% CI=0.78-0.95) and ages 50-55 (aHR=0.74, 95% CI=0.66-0.83), but not between ages 56-62 (aHR=1.11, 95% CI=0.91-1.37). Similar effectiveness was found for estrogen alone or combined with fixed or sequential progestogens (aHRs between 0.79 and 0.86), transdermal and oral formulations (aHRs 0.75-0.87), and for most specific formulations (aHRs 0.75-0.85), except tibolone (aHR=1.04, 95% CI=0.75-1.44) and formulations with dydrogesterone (aHR=1.05, 95% CI=0.85-1.30). Similar results were observed with any psychiatric hospitalization as outcome measure. The findings underscore the potential value of MHT in preventing psychosis relapse among women with SSD of menopausal age. These findings translate clinical evidence on the neuroprotective effects of estrogens to real-world settings, encompassing a group of women for whom current antipsychotic treatment options may be insufficient.

Risk of infections among persons treated with opioids for chronic pain: a systematic review and meta-analysis protocol

IntroductionMillions of persons with chronic pain across North America and Europe use opioids. While the immunosuppressive properties of opioids are associated with risks of infections, these outcomes could be mitigated...

Constraints of the teleparallel equivalent of general relativity in a gauge

We consider a specific Hamiltonian formulation of the Teleparallel Equivalent of General Relativity, where the canonical variables are expressed by means of differential forms. We show that some “position” variables of this formulation can be always gauge-transformed to zero. In this gauge the constraints of the theory become simpler, and the other “position” variables acquire a nice geometric interpretation that allows for an alternative, clearer form of the constraints. Based on these results we derive some exact solutions to the constraints.

Nicotine and cannabis routes of administration and dual use among U.S. young adults who identify as Hispanic, non-Hispanic Black, and non-Hispanic White

BackgroundUse of cannabis and nicotine is at record levels among young adults, and health consequences vary by route of administration. However, there is a paucity of research characterizing use of both substances, especially among individuals of racial/ethnic minoritized identities. MethodParticipants (N = 1,032; age 18–25 years) completed a cross-sectional survey administered through an online panel in 2021 in eight U.S. states where cannabis was legal for both recreational and medical use and eight states where cannabis was not legal for medical or recreational purposes. Sampling was stratified by race/ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White) and gender (male, female). Survey weighting was based on state-level gender and race/ethnicity data in the 2021 U.S. Census Bureau. ResultsOver one third (37.9%) of respondents reported current use of both cannabis and tobacco, more than double the proportion using tobacco (12.1%) or cannabis (4.1%) only. Vaporization was the most common method for using nicotine (40.2%). Disposable nicotine vape products were used more than any other method (27.1%). Smoking was the most common route of administration for cannabis (35.7%). Simultaneous use of tobacco and cannabis was common (27.0%) overall and greater among those who identify as non-Hispanic Black than non-Hispanic White. There were few differences in product use by gender or state legality. DiscussionDual cannabis and tobacco use is prevalent among young adults. Given the dynamic regulatory landscape, continued monitoring of specific cannabis formulations and tobacco products is recommended. Trends in simultaneous use of cannabis and tobacco and associated adverse effects warrant continued assessment.

Calibration of the UBC3D-PLM soil model from Dilatometer Marchetti Test (DMT) for the liquefaction behaviour and cyclic resistance ratio (CRR) of sandy soils

Seismic liquefaction is one of the most devastating natural hazards that can cause significant damage to structures and infrastructure. The liquefaction behaviour is simulated in the finite element code PLAXIS by the UBC3D-PLM constitutive model that is 3-D generalized formulation of the 2-D UBCSAND model developed at the University of British Colombia. The UBC3D-PLM model used in this work was successfully employed in many recent studies, e.g. to evaluate the liquefaction effects on the seismic soil–structure interaction, to assess the dynamic behaviour of earthen embankments built on liquefiable soil and to investigate the seismic performance of offshore foundations. Moreover, UBC3D-PLM model involves many input parameters to model the onset of the liquefaction phenomenon. Therefore, their determination becomes a crucial concern. Previous studies elaborated a specific formulation that requires the corrected Standard Penetration Test (SPT) blow counts as input. However, the Dilatometer Marchetti Test (DMT), compared to the SPT, is more sensitive to several factors that affect the liquefaction resistance such as aging, stress history, overconsolidation and horizontal earth pressure. For this reason, a new parameter selection procedure, which uses the horizontal stress index derived from DMT, was developed in this study.The new relationships were applied for determining the initial parameters of the UBC3D-PLM model to describe the behavior of several liquefiable deposits located in eastern Sicily (Italy) that experienced destructive earthquakes in the past. For each site, the model was calibrated to the DMT-based liquefaction triggering curve, developed by combining DMT correlations with the current method based on SPT test, by the simulation of cyclic direct simple shear tests (CDSS). Finally, CDSS tests were performed by means of the CDSS device at the Soil Dynamics and Geotechnical Engineering Laboratory of the University “Kore” of Enna (Italy). This allowed to validate the applicability of the proposed procedure in simulating the liquefaction behavior of sandy soils.

THE ROLE OF BASTI IN AGNIDEEPANA.

Ayurveda, being the science of life, believes that for the ‘Swastha’ state of the individual, Dosha, Dhatu, Mala and Agni should be in ‘Sama’ Avastha along with harmony in Indriyas, Atma and Mana. Agni is considered the most crucial entity in our body as it is the origin of our lives and maintaining health. Any abnormality in Agni may cause a diseased condition, which in turn may be responsible for the death of an individual. To perform chikitsa of any vyadhi, Vaidya should initiate with correction of Agni. There are many ways Agni Deepana is explained in Ayurvedic classical texts, and Panchakarma is one of them. Basti karma, in particular,is praised as the Best and Ardha Chikitsa. Basti karma plays an essential role in Agnideepana by acting on multiple factors affecting Agni. Also, some specific basti formulations are explained in samhitas for Agni Deepana. This study is an effort to understand the least considered Agni Deepana karma among all karmas of Basti, highlighting the urgency of maintaining balance in Agni.

Highly efficient nucleic acid encapsulation method for targeted gene therapy using antibody conjugation system

Gene therapy has surfaced as a promising avenue for treating cancers, offering the advantage of deliberate adjustment of targeted genes. Nonetheless, the swift degradation of nucleic acids in the bloodstream necessitates an effective and secure delivery system. The widespread utilization of poly lactic-co-glycolic acid (PLGA) nanoparticles as drug delivery systems has highlighted challenges in controlling particle size and release properties. Moreover, the encapsulation of nucleic acids exacerbates these difficulties due to the negatively charged surface of PLGA nanoparticles. In this study, we aimed to improve the encapsulation efficiency of nucleic acids by employing negatively charged microbeads and optimizing the timing of the specific formulation steps. Furthermore, by conjugating PSMA-617, a ligand for the prostate-specific membrane antigen (PSMA), with PLGA nanoparticles, we assessed the antitumor effects and the efficacy of a nucleic acid delivery system on prostate cancer model. The employed technique within the nucleic acid encapsulation system represents a novel approach that could be adapted to encapsulate various kinds of nucleic acids. Moreover, it enables the attachment of targeting moieties to different cell membrane proteins, thereby unveiling new prospects for precise therapeutics in cancer therapy.

Chemical timescale analysis of the Partially Stirred Reactor model for a hydrogen-fuelled scramjet

Scramjet engines offer a promising option for powering hypersonic vehicles, although the unique characteristics of supersonic combustion present numerous challenges. Notably, turbulence-chemistry interactions are significant in supersonic flows, demanding specific combustion formulations in numerical simulations due to their dissimilarity from traditional combustion systems. This work evaluates the performance of the Partially Stirred Reactor (PaSR) closure of the mean chemical source term by performing Reynolds-Averaged Navier-Stokes (RANS) simulations of the German Aerospace Centre (DLR) scramjet. The PaSR approach requires defining a chemical timescale, and this study assesses several formulations. Among them, the Fastest Formation Rate (FFR) does not provide stable combustion, while the Slowest Formation Rate (SFR) achieve fairly good predictions. Moreover, the sensitivity to species selection in calculating the chemical timescale is investigated, as well as the impact of two PaSR residence time formulations. A newly proposed Batchelor-based mixing timescale performs well with both the SFR and FFR formulations and guarantees a coupling between chemical and mixing times. It also accounts for species diffusivity, which can have important effects on hydrogen-based fuel combustion.