<abstract>This study investigates the effect of particle size on the compression characteristics of wet- (fluid-bed granulation - FBG) and dry-granulated (slugging - DGS) tableting mixtures. Particle-size distribution, flowability, compressibility, using the Heckel and Walker model, compactibility and elastic recovery as well as friability and disintegration were determined and compared between the two particle size fractions (180-400 μm, 400-710 μm) and initial unsieved mixtures. The results showed that the particle size of granules had no effect on the compressibility of the FBG and DGS mixtures, due to the high fragmenting nature of the formulation used in this study. On the other hand, compactibility was particle size dependent, as larger-sized fractions showed higher crushing strength, lower friability, and lower elastic recovery. This was attributed to increased fragmentation of larger particles, allowing stronger bonding between uncontaminated surface areas. As a result of better rearrangement of particles, both initial tableting mixtures showed lower compressibility and lower compactibility compared to their sieved fractions.</abstract>

Faculty of Pharmacy, 1000 Ljubljana Slovenia

A compressibility and compactibility study of real tableting mixtures: the effect of granule particle size

<abstract><title style='display:none'>Abstract</title>(1,4,5-Triphenylimidazol-2-yl-thio)butyric acid hydrazide (3) was obtained via alkylation of 1,4,5-triphenylimidazol-2- thiol (1) with ethylbromobutyrate, followed by addition of hydrazine hydrate. Treatment of acid hydrazide 3 with carbon disulfide in an ethanolic potassium hydroxide solution gave the intermediate potassium dithiocarbazinate salt, which was cyclized to 4-amino-5-[(1,4,5-triphenylimidazol- -2-yl)thiopropyl]-2H-1,2,4-triazole-3-thione (4) in the presence of hydrazine hydrate. Condensation of compound 3 with alkyl/arylisothiocyanate afforded the corresponding 1-[4-(1,4,5-triphenylimidazol-2-ylthio)butanoyl]-4-alkyl/arylthiosemicarbazides (5-7), which upon refluxing with sodium hydroxide, yielded the corresponding 1,2,4-triazole - -3-thiols 8-10. Under acidic conditions, compounds 4-6 were converted to aminothiadiazoles 11-13. Moreover, the series of Schiff bases 14-18 were synthesized from the condensation of compound 3 with different aromatic aldehydes. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral analyses. They were also preliminarily screened for their antimicrobial activity.</abstract>

Department of Chemistry Faculty of Sciences, Taibah University Al-Madinah Al-Munawarah P.O. Box 30002, Saudi Arabia

Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf Laboratoire de Chimie and Electrochimie des Complexes Métalliques (LCECM) USTO-MB, P.O. Box 1505 Oran El M`nouar, Algeria

Department of Chemistry Faculty of Sciences, Taibah University Al-Madinah Al-Munawarah P.O. Box 30002, Saudi Arabia 2 Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf Laboratoire de Chimie and Electrochimie des Complexes Métalliques (LCECM) USTO-MB, P.O. Box 1505 Oran El M`nouar, Algeria

King Abdullah University of Science and Technology (KAUST) Saudi Arabia

Synthesis and characterization of some novel 1,2,4-triazoles, 1,3,4-thiadiazoles and Schiff bases incorporating imidazole moiety as potential antimicrobial agents

<abstract>
<title style='display:none'>Abstract</title>
A good therapeutic alliance is relevant for healthcare providers exposed to patients’ suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (<italic>n</italic> = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40–70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm <italic>vs</italic>. low scores 80 ± 75 mm, <italic>p</italic> &lt; 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they “gained new insight”, “felt better”, or “felt content with their doctor’s treatment”. What´s more, patients who affirmed “I benefit from the treatment” experienced increased pain relief (benefit 40 ± 30 <italic>vs</italic>. non-benefit 19 ± 26 mm, <italic>p</italic> = 0.010) and improved quality of life (benefit 33 ± 25 <italic>vs</italic>. non-benefit 18 ± 16 mm, <italic>p</italic> = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.
</abstract>

Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational study

<abstract xml:lang="en"><title style='display:none'>Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of ibuprofen derivatives</title>In order to reduce the ulcerogenic effect of ibuprofen, its carboxylic group has been converted into 5-membered heterocyclic rings. Various 1,3,4-oxadiazoles (3-8, 16-21), 1,2,4-triazoles (22-27), 1,3,4-thiadiazoles (28-30), and 1,2,4-triazine (9) derivatives of ibuprofen were prepared by cyclization of 2-(4-<italic>i</italic>-butylphenyl) propionic acid hydrazide (2) and <italic>N1</italic>-[2-(4-<italic>i</italic>-butylphenyl) propionyl]-<italic>N4</italic>-alkyl/arylthiosemicarbazides (10-15) under various reaction conditions. The cyclized derivatives were screened for their anti-inflammatory activity by the carrageenan induced rat paw edema method and showed 50 to 86% inhibition, whereas the standard drug ibuprofen showed 92% inhibition at the same oral dose. Five compounds, 7, 16, 18, 22 and 30 that showed more than 80% anti-inflammatory activity were selected to study their analgesic, ulcerogenic and lipid peroxidation activities. All the tested compounds showed a significant reduction in ulcerogenic activity compared to ibuprofen through the severity index 0.5 to 0.8, <italic>vs.</italic> ibuprofen 1.8. The compounds, that showed less ulcerogenic effect also produced less malondialdehyde content in gastric mucosa, which is one of the end products of lipid peroxidation. The results of biological studies showed that oxadiazole derivative 16 as the lead molecule with maximum anti-inflammatory, analgesic and minimum ulcerogenic and lipid peroxidation activities.</abstract>

Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of ibuprofen derivatives

<abstract>Influence of some commercially available types of microcrystalline cellulose (MCC) on the stability of certain active pharmaceutical ingredients (APIs), when in contact, has been investigated. Two structurally similar APIs, perindopril erbumine (PER) and enalapril maleate (EM), both well-known angiotensin-converting enzyme inhibitors were used. The main properties of an MCC that could determine the stability for each API were measured and correlated to the stability of these two APIs in binary mixtures. The stability of these APIs differed when in contact with different types of MCC. The dominant properties of MCC from one manufacturer were surface features that influenced the stability of PER and acidity that influenced the stability of EM. In the case of MCC from other manufacturers, unbound water was stability determining for both substances.</abstract>

Krka d.d. Novo mesto, Stability Testing Department, 8501 Novo mesto, Slovenia

University of Ljubljana, Faculty of Pharmacy, 1000 Ljubljana, Slovenia

Influence of different types of commercially available microcrystalline cellulose on degradation of perindopril erbumine and enalapril maleate in binary mixtures / Vpliv različnih tipov komercialno dostopne mikrokristalne celuloze na razpad erbuminijevega perindoprilata in enalaprilijevega maleata v binarnih zmeseh

<abstract xml:lang="en"><title style='display:none'>Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib</title>The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The <italic>in vitro</italic> skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (<italic>J</italic>ss), permeability coefficient (<italic>K</italic>p) and enhancement ratio (<italic>E</italic>r) was observed in nanoemulsion formulations T1 and T2 (<italic>p</italic> &lt; 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% (<italic>m/m</italic>) of CXB, 10% (<italic>m/m</italic>) of oil phase (Sefsol 218 and Triacetin), 50% (<italic>m/m</italic>) of surfactant mixture (Tween-80 and Transcutol-P) and 40% (<italic>m/m</italic>) water. The anti-inflammatory effects of formulation T2 showed a significant increase (<italic>p</italic> &lt; 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB.</abstract>

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

<abstract>
<title style='display:none'>Abstract</title>
Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.
</abstract>

The potential of three-dimensional printing for pediatric oral solid dosage forms

<abstract>
<title style='display:none'>Abstract</title>
This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with <italic>deprescribing intervention trials</italic> (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with <italic>medication cessation trials</italic> (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with <italic>deprescribing intervention trials</italic>. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of <italic>medication cessation trials,</italic> a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.
</abstract>

Deprescribing: An umbrella review

<abstract>
<title style='display:none'>Abstract</title>
The principal function of skin is to form an effective barrier between the human body and its environment. Impaired barrier function represents a precondition for the development of skin diseases such as atopic dermatitis (AD), which is the most common inflammatory skin disease characterized by skin barrier dysfunction. AD significantly affects patients’ quality of life, thus, there is a growing interest in the development of novel delivery systems that would improve therapeutic outcomes. Herein, eight novel lyotropic liquid crystals (LCCs) were investigated for the first time in a double-blind, interventional, before-after, single-group trial with healthy adult subjects and a twice-daily application regimen. LCCs consisted of constituents with skin regenerative properties and exhibited lamellar micro-structure, especially suitable for dermal application. The short- and long-term effects of LCCs on TEWL, SC hydration, erythema index, melanin index, and tolerability were determined and compared with baseline. LCCs with the highest oil content and lecithin/Tween 80 mixture stood out by providing a remarkable 2-fold reduction in TEWL values and showing the most distinctive decrease in skin erythema levels in both the short- and long-term exposure. Therefore, they exhibit great potential for clinical use as novel delivery systems for AD treatment, capable of repairing skin barrier function.
</abstract>

Clinical application of hempseed or flaxseed oil-based lyotropic liquid crystals: Evaluation of their impact on skin barrier function

<abstract>
<title style='display:none'>Abstract</title>
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an <italic>in vitro</italic> glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
</abstract>

Forecasting the effect of water gastric emptying patterns on model drug release in an <italic>in vitro</italic> glass-bead flow-through system

<abstract>
<title style='display:none'>Abstract</title>
In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.
</abstract>

Population pharmacokinetics of ramipril in patients with chronic heart failure: A real-world longitudinal study

<abstract>
<title style='display:none'>Abstract</title>
Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used “off-label” as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3–5 ng mL–1. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL–1. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL–1 in neonatal, and maternal samples, respectively.
</abstract>

Determination of remifentanil in neonatal dried blood spots by liquid chromatography-tandem mass spectrometry

<abstract><title style='display:none'>Abstract</title> Nanosponges are a novel class of hyper-crosslinked polymer based colloidal structures consisting of solid nanoparticles with colloidal sizes and nanosized cavities. These nano-sized colloidal carriers have been recently developed and proposed for drug delivery, since their use can solubilize poorly water-soluble drugs and provide prolonged release as well as improve a drug’s bioavailability by modifying the pharmacokinetic parameters of actives. Development of nanosponges as drug delivery systems, with special reference to cyclodextrin based nanosponges, is presented in this article. In the current review, attempts have been made to illustrate the features of cyclodextrin based nanosponges and their applications in pharmaceutical formulations. Special emphasis has been placed on discussing the methods of preparation, characterization techniques and applications of these novel drug delivery carriers for therapeutic purposes. Nanosponges can be referred to as solid porous particles having a capacity to load drugs and other actives into their nanocavity; they can be formulated as oral, parenteral, topical or inhalation dosage forms. Nanosponges offer high drug loading compared to other nanocarriers and are thus suitable for solving issues related to stability, solubility and delayed release of actives. Controlled release of the loaded actives and solubility enhancement of poorly water-soluble drugs are major advantages of nanosponge drug delivery systems.</abstract>

C. U. Shah College of Pharmacy S.N.D.T. Women’s University, Santacruz Mumbai-400049, India

SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, VileParle Mumbai-400056, India

Cyclodextrin based nanosponges for pharmaceutical use: A review

<abstract>In the era of nanoparticulate controlled and site specific drug delivery systems, use of solid lipids to produce first generation lipid nanoparticles, solid lipid nanoparticles (SLN), became a revolutionary approach in the early nineties. The present review is designed to provide an insight into how SLN are finding a niche as promising nanovectors and forms a sound basis to troubleshoot the existing problems associated with traditional systems. Herein, authors had tried to highlight the frontline aspects prominent to SLN. An updated list of lipids, advanced forms of SLN, methods of preparation, characterization parameters, and various routes of administration of SLN are explored in-depth. Stability, toxicity, stealthing, targeting efficiency and other prospectives of SLN are also discussed in detail. The present discussion embodies the potential of SLN, now being looked up by various research groups around the world for their utility in the core areas of pharmaceutical sciences, thereby urging pharmaceutical industries to foster their scale-up.</abstract>

R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur-425405, India

Rajarshi Shahu College of Pharmacy and Research, Pune-411033, India

H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur-425405, India

Formulation Research and Development Department, Marksans Pharma., Ltd., Verna Industrial Estate, Verna-403722 India

Baxil Pharma, Pvt. Ltd., Nainital Highway, Shyampur, Haridwar-249408 India

Solid lipid based nanocarriers: An overview / Nanonosači na bazi čvrstih lipida: Pregled

<abstract><title style='display:none'>Abstract</title> Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self- -nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemulsion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions.</abstract>

Krka, d.d., Novo mesto, 8501 Novo mesto, Slovenia

Fakulteta za farmacijo, 1000 Ljubljana,Slovenia

Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs

<abstract xml:lang="en"><title style='display:none'>Metal ions, Alzheimer's disease and chelation therapy</title>In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.</abstract>

Metal ions, Alzheimer's disease and chelation therapy

<abstract xml:lang="en"><title style='display:none'>A study of rivastigmine liposomes for delivery into the brain through intranasal route</title>The present study is mainly aimed at delivering a drug into the brain <italic>via</italic> the intranasal route using a liposomal formulation. For this purpose, rivastigmine, which is used in the management of Alzheimer's disease, was selected as a model drug. Conventional liposomes were formulated by the lipid layer hydration method using cholesterol and soya lecithin as lipid components. The concentration of rivastigmine in brain and plasma after intranasal liposomes, free drug and per oral administration was studied in rat models. A significantly higher level of drug was found in the brain with intranasal liposomes of rivastigmine compared to the intranasal free drug and the oral route. Intranasal liposomes had a longer half-life in the brain than intranasally or orally administered free drug. Delivering rivastigmine liposomes through the intranasal route for the treatment of Alzheimer's disease might be a new approach to the management of this condition.</abstract>

A study of rivastigmine liposomes for delivery into the brain through intranasal route

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Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

 Acta Pharmaceutica (AP) is an international, scientific, multidisciplinary journal, devoted to the pharmaceutical and allied sciences, which contains articles predominantly on core biomedical and...

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 Acta Pharmaceutica (AP) is an international, scientific, multidisciplinary journal, devoted to the pharmaceutical and allied sciences, which contains...

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The Journal of Croatian Pharmaceutical Society

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