Hasil untuk "Pharmacy and materia medica"

Sujin Lee, Dagyeong Guk, Youngdo Jeong et al.

<b>Background/Objectives:</b> Microbe-derived extracellular vesicles (MEVs) provide a biocompatible, naturally derived platform for drug delivery. <b>Methods:</b> We encapsulated doxorubicin in <i>Lactobacillus plantarum</i>-derived EVs and evaluated their ability at delivering doxorubicin to colorectal cancer cells in vitro. Endocytosis inhibitors were used to investigate the mechanisms by which the MEVs entered the cells. <b>Results:</b> The MEVs maintained structural stability under physiological conditions. Cellular internalization of doxorubicin-loaded MEVs involve clathrin/caveolae-dependent endocytosis, and dynamin- and clathrin-mediated pathways. <b>Conclusions:</b> These findings highlight the role of the microbe–cancer cell biointerface in mediating drug uptake and enabling intracellular delivery. The study supports the potential of MEVs as nanocarriers for anticancer drugs and provides mechanistic insights into the intracellular trafficking pathways that influence drug activity.

Ali Muhammad, Imtiaz Khan, Tianjun Li et al.

Driven by the growing agreement between the experimentally measured muon anomalous magnetic moment and its SM prediction, we reexamine phenomenological consequences of the MSSM, which is embedded in the supersymmetric $SU(4)_C \times SU(2)_L \times SU(2)_R$ Pati-Salam model. In contrast to earlier studies that predominantly favored a specific sign for the Higgsino mass parameter, our analysis systematically explores both $μ> 0$, and $μ< 0$ scenarios in light of current collider, cosmological, and DM constraints. Within this framework, we identify viable parameter space regions where the observed DM relic density is reproduced through multiple mechanisms: co-annihilations involving sbottom-neutralino, gluino-neutralino, stop-neutralino, stau-neutralino, and chargino-neutralino coannihilation, as well as resonant s-annihilation channel via the pseudoscalar Higgs boson. We demonstrate that all such scenarios are consistent with present bounds from LHC supersymmetry searches, the Planck~2018 DM relic density bound, and current limits from DD DM searches. Our results reveal characteristic mass spectra associated with these mechanisms. In particular, sbottom-neutralino coannihilation typically requires sbottom masses near $2.8~\text{TeV}$, while gluino-neutralino and stop-neutralino coannihilation scenarios allow gluino masses in the range $1$--$3~\text{TeV}$ and stop masses between $1$ and $3.5~\text{TeV}$. In coannihilation-dominated regions, the stau and chargino masses may reach values as high as $3.8~\text{TeV}$, whereas viable $A$ resonance solutions are realized for pseudoscalar Higgs masses spanning approximately $1.6$--$3.8~\text{TeV}$. We anticipate that a portion of the parameter space will be accessible to supersymmetry searches in LHC Run-3 and future runs.

Truong-Thanh Le, Hoang-Loc La, Amir Taherkordi et al.

We present PM2Lat, a fast and generalized framework for accurately predicting the latency of deep neural network models on GPUs, with special focus on NVIDIA. Unlike prior methods that rely on deep learning models or handcrafted heuristics, PM2Lat leverages the Single-Instruction-Multiple-Thread architecture of GPUs to model execution time of DNN models. First, we dive into fine-grained GPU operation modeling by studying computational behavior and memory access patterns. After identifying these characteristics, we found that different GPU kernels exhibit significant performance disparities, even when serving the same purpose. Hence, the core idea of PM2Lat is to differentiate kernels based on their configurations and analyze them accordingly. This kernel-aware modeling enables PM2Lat to achieve consistently low prediction error across diverse data types and hardware platforms. In addition, PM2Lat generalizes beyond standard matrix multiplication to support complex GPU kernels such as Triton, Flash Attention, and Cutlass Attention. Experimental results show that PM2Lat consistently achieves error rates below 10% across different data types and hardware platforms on Transformer models, outperforming the state-of-the-art NeuSight by 10-20% for FP32 and by at least 50% for BF16. When applying to diverse kernels, the error rate is maintained at 3-8%.

Eimear Byrne, Giovanni Longobardi, and Rocco Trombetti

In this article, we study polymatroids that are representable by means of linear restricted rank-metric codes, namely, by subspaces of the space of alternating, symmetric, or Hermitian square matrices endowed with the rank metric. More precisely, we characterize the rank function defining these polymatroids and establish sufficient conditions on the relevant parameters under which it is fully determined. We show that there are several differences in compared to the behaviour of $q$-polymatroids of unrestricted matrix codes.

Claude Carlet, and Alexander Kholosha

Much work has been devoted to bent functions in odd characteristic, but a gap remains between our knowledge of binary and nonbinary bent functions. In the first part of this paper, we attempt to partially bridge this gap by generalizing to any characteristic important properties known in characteristic 2 concerning the Walsh transform of derivatives of bent functions. Some of these properties generalize to all bent functions, while others appear to apply only to weakly regular bent functions. We deduce a method to obtain a bent function by adding a quadratic function to a weakly regular bent function. We also identify a particular class of bent functions possessing the property that every first-order derivative in a nonzero direction has a derivative (which is then a second-order derivative of the function) equal to a nonzero constant. We show that this property implies bentness and is shared in particular by all cubic bent functions. It generalizes the notion of cubic-like bent function, that was introduced and studied for binary functions by Irene Villa and the first author. In the second part of the paper, we provide (for the first time) a primary construction leading to an infinite class of cubic bent functions that are not weakly regular. We show the bentness of the functions by two approaches: by calculating the Walsh transform directly and by considering the second-order derivatives (and applying the results from the first part of the paper).

Fahad Alfhaid, Mansour Khater Alzahrani, Mohammed Zaid Aljulifi et al.

Objective: This study was carried out to assess the prevalence and perception of human papilloma virus (HPV) vaccination in health science students in Majmaah University, Saudi Arabia. Methodology: A descriptive cross-sectional study was conducted at different health science colleges of Majmaah University on female students. The knowledge of the participants regarding HPV was assessed using a pre-tested questionnaire. The history of vaccination of these female participants was also enquired. Results: More than three-fifth of the participants had heard about HPV. Of these, 83 participants, 59 (71.1%), were aware that it is a disease of women and how to diagnose it. Most participants (86.7%) knew that it can cause cervical cancer, while only 57.8% knew it could be asymptomatic. There were 18% of such participants who thought that HPV and human immunodeficiency virus are the same and that there is no vaccine for the prevention of HPV. Only 14.5% (n = 12) were vaccinated against HPV. Conclusion: A clear gap between knowledge and practice of HPV vaccination was observed, and health education should be planned to educate health professionals to avoid misconceptions.

Rajeev K Jaiswal, Deepti Chandra, Md Arif Khan et al.

Aim: To evaluate “coronally advanced flap” with or without “a platelet-rich fibrin membrane for the root coverage.” Materials and Methods: All the clinical parameters were assessed at different time intervals (at baseline, 1, 3, and 6 months) in both experimental and control group. Following “clinical parameters” were recorded using “UNC-15” “Probe-Plaque Index (PI)” (Silness and Loe, 1964), “Gingival Index” (GI) (Loe and Silness, 1963), “Recession depth (RD),” “Recession width (RW),” “Clinical attachment level (CAL),” and “Width of keratinized gingiva (WKG)”. Results: At final evaluation (i.e., mean change from baseline to 6 months), “the decrease in Plaque Index was 2.5% higher in Group B (66.0%) as compared to Group A (63.5%). The decrease in Gingival Index was 6.1% higher in Group B (91.4%) as compared to Group A (85.3%), and the decrease in recession width was 4.0% higher in Group B (75.2%) as compared to Group A (71.2%). The decrease in clinical attachment level was 4.4% higher in Group B (53.2%) as compared to Group A (48.4%). The increase in width of keratinized gingiva was 1.9% higher in Group A (28.8%) as compared to Group B (26.9%).” Conclusion: The controlled, randomized, split mouth design showed that CAF surgery, either by alone or in combination with PRF, is an efficient treatment method for covering denuded roots. “This design was used to treat bilateral isolated Miller's class I and II recessions in gingival part. When compared to the CAF approach, the results from a combination of CAF and PRF after a 6-month period showed additional advantages in addition to mean root coverage in the treatment of Miller's classes I and II recessions in gingival part.”

Harry V. M. Spiers, Lukas K. J. Stadler, Hugo Smith et al.

Extracellular vesicles are lipid bilayer-delimited nanoparticles excreted into the extracellular space by all cells. They carry a cargo rich in proteins, lipids and DNA, as well as a full complement of RNA species, which they deliver to recipient cells to induce downstream signalling, and they play a key role in many physiological and pathological processes. There is evidence that native and hybrid EVs may be used as effective drug delivery systems, with their intrinsic ability to protect and deliver a functional cargo by utilising endogenous cellular mechanisms making them attractive as therapeutics. Organ transplantation is the gold standard for treatment for suitable patients with end-stage organ failure. However, significant challenges still remain in organ transplantation; prevention of graft rejection requires heavy immunosuppression and the lack of donor organs results in a failure to meet demand, as manifested by growing waiting lists. Pre-clinical studies have demonstrated the ability of EVs to prevent rejection in transplantation and mitigate ischemia reperfusion injury in several disease models. The findings of this work have made clinical translation of EVs possible, with several clinical trials actively recruiting patients. However, there is much to be uncovered, and it is essential to understand the mechanisms behind the therapeutic benefits of EVs. Machine perfusion of isolated organs provides an unparalleled platform for the investigation of EV biology and the testing of the pharmacokinetic and pharmacodynamic properties of EVs. This review classifies EVs and their biogenesis routes, and discusses the isolation and characterisation methods adopted by the international EV research community, before delving into what is known about EVs as drug delivery systems and why organ transplantation represents an ideal platform for their development as drug delivery systems.

Francesco Coccia, Angelo Pietrobelli, Thomas Zoller et al.

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.

Verdi Vanreusel, Alessia Gasparini, Federica Galante et al.

Radiotherapy is part of the treatment of over 50% of cancer patients. Its efficacy is limited by the radiotoxicity to the healthy tissue. FLASH-RT is based on the biological effect that ultra-high dose rates (UHDR) and very short treatment times strongly reduce normal tissue toxicity, while preserving the anti-tumoral effect. Despite many positive preclinical results, the translation of FLASH-RT to the clinic is hampered by the lack of accurate dosimetry for UHDR beams. To date radiochromic film is commonly used for dose assessment but has the drawback of lengthy and cumbersome read out procedures. In this work, we investigate the equivalence of a 2D OSL system to radiochromic film dosimetry in terms of dose rate independency. The comparison of both systems was done using the ElectronFlash linac. We investigated the dose rate dependence by variation of the 1) modality, 2) pulse repetition frequency, 3) pulse length and 4) source to surface distance. Additionally, we compared the 2D characteristics by field size measurements. The OSL calibration showed transferable between conventional and UHDR modality. Both systems are equally independent of average dose rate, pulse length and instantaneous dose rate. The OSL system showed equivalent in field size determination within 3 sigma. We show the promising nature of the 2D OSL system to serve as alternative for radiochromic film in UHDR electron beams. However, more in depth characterization is needed to assess its full potential.

Jia-Nan Wu, Bingsuo Zou, and Yongyou Zhang

Manipulating photon states serves as a primary requirement for various optical devices and is of high relevance for quantum information technology. Nevertheless, the fundamental theoretical framework for tens-of-photon states has not been established. This study successfully establishes the matrix-product-state theory to explore the statistics of the tens-of-photon states scattered by optical cavities (OCs), two-level atoms (TLAs), and Jaynes-Cummings emitters (JCEs) in waveguide-QED systems. Taking 10-photon states as an example, we reveal some novel physical results that differ from those for few-photon cases. We verify that OCs do not change the statistics of the incident photon states, being independent of the photon number. However, for the TLAs and JCEs, the photon number strongly impacts the photon bunching and anti-bunching behaviors. As the photon number increases, there exists a maximum strength for the photon-photon correlation induced by the JCE. Especially, the scattered waves by the TLA (or JCE) exhibit extremely different statistics behaviors for the 10-photon cases from those for the bi-photon. These distinguishable conclusions for the tens-of-photon states and the matrix-product-state theory pave the way for the multi-photon manipulation.

Gabriele Mesquita Silva, Adriane Saraiva Nunes, Gisele Bezerra da Silva

Among the elements that impact Infant Mortality, Perinatal Mortality stands out, which involves deaths that occur during the period that begins at 22 completed weeks (or 154 days) of gestation (fetal period) and ends at 7 completed days after birth, that is, from 0 to 6 days of life (early neonatal period). The objective of this research is to describe the profile of perinatal deaths reported in municipalities of Piauí’s Coastal Plain from 2013 to 2017. This is a retrospective, descriptive study with a quantitative analysis approach, resulting from the Course Completion Work entitled ‘Perinatal mortality profile in municipalities of Piaui’s Coastal Plain’. The sample consisted of death certificates and infant death and fetal death investigation forms of children whose mothers lived in the Coastal Plain, PI, and who had their deaths confirmed in the perinatal period, between January 2013 and December 2017. During the study period, the Perinatal Mortality Rate (PMR) of the Coastal Plain, PI, was 22.97 deaths per 1,000 births, with little variation between 2013 and 2017. Fetal deaths were predominant, comprising 61.9% of the sample. Hospital deaths that occurred in Parnaíba were the most frequent, revealing this to be the reference municipality in the region. This shows the need for greater attention on the part of health professionals and managers to such conditions, in order to improve the quality of care for pregnant women, parturient women, and newborns.

Murat Doğan, Sevinç Şahbaz, Timuçin Uğurlu et al.

Abstract The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF). The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties. The viscosity of the formulations varied between 14.400 - 48.500 cPs, with the greatest viscosity values determined in K2 formulation. F2 formulation showed the highest water absorption capacity. According to the studies of the mechanical properties, H2 formulation (0.153±0.018 N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm2) formulation, the highest bio-adhesion values. Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line. According to the BrdU cell proliferation results, B1 (197.82±2.48%) formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%) formulation exhibited the highest HaCaT cell proliferation ability. In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.

Raquel Martínez

El Consejo General de Colegios de Farmacéuticos (CGCOF) apuesta decididamente por potenciar el valor asistencial de los farmacéuticos y poder prestar una cartera de Servicios Profesionales Farmacéuticos Asistenciales (SPFA) concertados desde las farmacias al Sistema Sanitario. Para ello, necesitamos actuar en red; tener la infraestructura que nos permita un trabajo colaborativo del conjunto de la red de 22.137 farmacias en España.…

Hirofumi Nagai, Tsutomu Shimada, Yoshimitsu Takahashi et al.

Abstract Background Gefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy. Methods Japanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis. Results A total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486–14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129–0.900, P = 0.030). Conclusions BMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.

Ji Su Hwang, Seok Gi Kim, Tae Hwan Shin et al.

Cancer is a group of diseases causing abnormal cell growth, altering the genome, and invading or spreading to other parts of the body. Among therapeutic peptide drugs, anticancer peptides (ACPs) have been considered to target and kill cancer cells because cancer cells have unique characteristics such as a high negative charge and abundance of microvilli in the cell membrane when compared to a normal cell. ACPs have several advantages, such as high specificity, cost-effectiveness, low immunogenicity, minimal toxicity, and high tolerance under normal physiological conditions. However, the development and identification of ACPs are time-consuming and expensive in traditional wet-lab-based approaches. Thus, the application of artificial intelligence on the approaches can save time and reduce the cost to identify candidate ACPs. Recently, machine learning (ML), deep learning (DL), and hybrid learning (ML combined DL) have emerged into the development of ACPs without experimental analysis, owing to advances in computer power and big data from the power system. Additionally, we suggest that combination therapy with classical approaches and ACPs might be one of the impactful approaches to increase the efficiency of cancer therapy.

Jeffrey Atkinson

This review looks at the factors that may influence practice in the future. Transformation could occur at 3 levels. Firstly, the traditional profession of the pharmacist as a dispenser of medicines is expanding. Secondly, the pharmacist’s activities are progressing into new healthcare fields. Thirdly, other changes are stimulated by global developments. This review may be helpful for pharmacy and healthcare leaders looking at the future configuration and aims of their pharmacy services.

Bohayra Mortazavi, Fazel Shojaei, and Masoud Shahrokhi

Recently, Bafekry et al. [Appl. Phys. Lett. 120, 189901 (2022)] reported their density functional theory (DFT) results on the elastic constants of C6N7 monolayer. They predicted non-zero elastic constants along the out-of-plane direction for a single-layered material, which contradicts with basic physics of the stiffness tensor for plane stress condition. Moreover, in their work Young's modulus is erroneously calculated. On the basis of DFT calculations, herein we predicted the C11, C12 and C66 of the C6N7 monolayer to be 286, 73 and 107 GPa, respectively, equivalent with an in-plane Youngs modulus of 267 GPa. Using DFT calculations and a machine learning interatomic potential, we also show that C6N7 monolayer shows isotropic elasticity.

Bohayra Mortazavi, Fazel Shojaei, and Masoud Shahrokhi

Recently, Bafekry et al. [Appl. Phys. Lett. 119, 142102 (2021)] reported their density functional theory (DFT) results on the elastic constants of a novel C6N7 monolayer. They predicted a very soft elastic modulus of 36.29 GPa for the C6N7 monolayer, which is remarkably low for carbon-nitride 2D lattices. Using DFT calculations, we predict a remarkably higher elastic modulus of 267 GPa for this monolayer. The maximum tensile strength is also predicted to be 20.5 GPa, revealing the outstanding mechanical properties of the C6N7 monolayer.

Amelia-Naomi Sabo, Sarah Jannier, Guillaume Becker et al.

Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC/MS² analysis, was used to develop a population pharmacokinetic model (Monolix^® software). A mono-compartmental model with first-order absorption and elimination best fit the data. The only covariate retained for the final model was “body surface area” (D1 and D8). The model also demonstrated that 1.5 mg/m² would be the recommended sirolimus dose for further studies and that steady-state TDM is necessary to adjust the dosing regimen in atypical profiles (36.4% of the population). No correlation was found between sirolimus trough concentrations and efficacy and/or observed toxicities. The study reveals the relevance of sirolimus TDM in pediatric oncology as it is needed in organ transplantation.