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When Rankine or Coulomb theories are used to design a retaining wall, it is accepted that the retaining wall will experience a lateral displacement. By allowing the wall to move laterally, the earth pressure decreases on the active side of the wall and wall and earth pressure increases on the passive side, and therefore, more economical walls can be obtained when the lateral displacement is allowed. This lateral displacement is usually not calculated when designing a retaining wall. An experimental investigation is carried out to study the lateral displacement of a retaining wall subjected to dynamic loads with different load amplitude vibration, absolute frequencies, backfill sand relative densities, and different distances between the retaining wall and the loading source. The objectives of this study are to trace the lateral displacement of retaining wall under dynamic loads other than earthquakes such as the traffic load caused by trucks or railroads by direct measurement of displacements. The model footing used in this study is square. On a cohesionless soil, the tests were carried out using a dynamic load. The studied variables were as follows: three load amplitudes (0.25, 0.5, and 1 ton), three vibration frequencies (0.5, 1, and 2 Hz), two relative densities of sandy soil (30% loose sand and 70% dense sand), and three different distances between the foundation and the retaining wall. Observations show that the lateral displacement increased by increasing the load amplitude and decreased by increasing the distance between the foundation and the retaining wall. There is insignificant consequence of frequency on the cumulative lateral displacement. The lateral displacement decreased by increasing the density of sandy soil.

In order to satisfy the requirements of environmentally friendly construction projects and minimize greenhouse gas emissions, it was necessary to focus on utilizing nanomaterials instead of conventional materials to enhance clay soils; nano Magnesium Oxide was suggested for this study. The compression and unconfined compressive strength tests were achieved to assess the compressibility behavior and strength of silty clay treated using nano magnesium oxide. Additionally, an investigation into the alteration of the clay microstructure was conducted using field emission scanning electron microscopy (FE-SEM) tests. The silty clay utilized in this research is characterized by a compression index 0.23 and an undrained shear strength of 53 kPa. The soil was treated by adding different percentages of nano-MgO (0.4%, 0.5%, 0.6%, and 0.8%), and the curing period was seven days. The treated soil samples were prepared based on the optimal water content and maximal dry density of the natural soil. The results indicate that utilization of nano Magnesium Oxide leads to a reduction in both values of the index of compression (Cc) and recompression index (Cr), in addition to a decrease in the value of the coefficient of compressibility (av). Also, the test finding for unconfined compressive strength demonstrates a noticeable increase in strength as the percentage of nano-MgO increases, accompanied by a reduction in failure strain. Adding 0.6% (the optimum percentage) of nano Magnesium oxide enhances the strength by about 114% and decreases the value of the compression index by about 36% compared with natural soil.

Radical prostatectomy is a commonly performed procedure for the treatment of localized prostate cancer. One of the long-term complications is erectile dysfunction. There is little consensus on the optimal management; however, it is agreed that treatment must be prompt to prevent fibrosis and increase oxygenation of penile tissue. It is vital that patient expectations are discussed, a realistic time frame of treatment provided, and treatment started as close to the prostatectomy as possible. Current treatment regimens rely on phosphodiesterase 5 inhibitors as a first-line therapy, with vacuum erection devices and intraurethral suppositories of alprostadil as possible treatment combination options. With nonresponders to these therapies, intracavernosal injections are resorted to. As a final measure, patients undergo the highly invasive penile prosthesis implantation. There is no uniform, objective treatment program for erectile dysfunction post-radical prostatectomy. Management plans are based on poorly conducted and often underpowered studies in combination with physician and patient preferences. They involve the aforementioned drugs and treatment methods in different sequences and doses. Prospective treatments include dietary supplements and gene therapy, which have shown promise with there proposed mechanisms of improving erectile function but are yet to be applied successfully in human patients. [ABSTRACT FROM AUTHOR]

The objective of the study was to produce a single strength juice from local orange and to study the changes in vitamin C content after addition of sodium sorbate (0.03, 0.06 and 0.12%) or different quantities of phosphoric acid (to reach the required pH) or both compounds. Therefore, packaging juice and storing at 25°C for 16 weeks and at 35°C for 8 weeks. The major purpose was to produce and store orange juice without heat treatment. Also to conducting heating treatment (Pasteurized juice, sweetened pasteurized juice or microwave pasteurized juice) and packaging and storing at room temperature for 16 weeks. In general the results showed no significant differences in vitamin C content either at zero period of storage or at 7 and 25°C of all the treatments, while the treatment with 0.03% sorbate was significantly different comparing with the other treatments. During the storage period vitamin C content was gradually and significantly decreased in all treatments compared to the control treatment, in which vitamin C content was increased during the first 8 weeks of storage, then decreased till the end of storage period at 7, 25 and 35°C. The effect of interaction (% of sorbate, storage temperature and storage period) showed no significant differences in vitamin C content between all the treatments compared to the control treatment during the storage period at 7 and 25°C, while there was a significant difference between the treatment in case of interaction of (quantity of phosphoric acid, storage temperature and storage temperature and storage period) and (materials added, storage temperature and storage period) of some treatment during storage at 7 and 25°C. A significant and gradual decrease in vitamin C content was noticed for different heating temperatures. [ABSTRACT FROM AUTHOR]

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.

Antimicrobial resistance has emerged as a significant danger to global health, and the need for more effective antimicrobial resistance (AMR) control has been highlighted. Cinnamic acid is abundant in plant products and is a potential starting material for further modification, focusing on the development of new antimicrobial compounds. In the following review, we describe the classification of critical antibacterial-guided reactions applied to the main skeleton structure of cinnamic acid derivatives over the last decade. Of all of the main parts of cinnamic acids, the phenyl ring and the carboxylic group significantly affect antibacterial activity. The results presented in the following review can provide valuable insights into considerable features in the organic modification of cinnamic acids related to antibacterial medication development and the food industry.

This research aims to develop the formulation of Dissolving Microneedle Piperine (DMNs PIP) and evaluate the effect of polymer concentration on characterisation and permeation testing results in ex vivo. DMNs PIP were prepared from varying concentrations of piperine (PIP) (10, 15, and 20% w/w) and polymers of polyvinyl alcohol (PVA): Polyvinyl pyrrolidone (30:60 and 60:25), respectively. Then the morphological evaluation of the formula was carried out, followed by mechanical strength testing. Furthermore, the density, LOD, and weight percentage of piperine in the dried microneedle were calculated and the determination of volume, needle weight and piperine weight and analysed. Ex vivo testing, X-Ray Diffraction, FTIR and hemolysis tests were carried out. PIP with PVA and PVP (F1) polymers produced DMN with mechanical strength (8.35 ± 0.11%) and good penetration ability. In vitro tests showed that the F1 polymer mixture gave good penetration (95.02 ± 1.42 μg/cm2), significantly higher than the F2, F3, F4, and F5 polymer mixtures. The DMNs PIP characterisation results through XRD analysis showed a distinctive peak in the 20-30 region, indicating the presence of crystals. The FTIR study showed that the characteristics of piperine found in DMNs PIP indicated that piperine did not undergo interactions with polymers. The results of the ex vivo study through DMNs PIP hemolytic testing showed no hemolysis occurred, with the hemolysis index below the 5% threshold reported in the literature. These findings indicate that DMNs PIP is non-toxic and safe to use as alternative for treating inflammation.

Sildenafil citrate (SIL) as a first-line treatment for erectile dysfunction is currently reported to have poor solubility and bioavailability. Moreover, SIL undergoes first-pass metabolism when taken orally and its injection can lead to discomfort. In this study, we introduce a novel transdermal delivery system that integrates hydrogel-forming microneedles with the inclusion complex tablet reservoir. The hydrogel-forming microneedle was prepared from a mixture of polymers and crosslinkers through a crosslinking process. Importantly, the formulations showed high swelling capacity (>400 %) and exhibited adequate mechanical and penetration properties (needle height reduction < 10 %), penetrating up to five layers of Parafilm® M (assessed to reach the dermis layer). Furthermore, to improve the solubility of SIL in the reservoir, the SIL was pre-complexed with β-cyclodextrin. Molecular docking analysis showed that SIL was successfully encapsulated into the β-cyclodextrin cavity and was the most suitable conformation compared to other CD derivatives. Moreover, to maximize SIL delivery, sodium starch glycolate was also added to the reservoir formulation. As a proof of concept, in vivo studies demonstrated the effectiveness of this concept, resulting in a significant increase in AUC (area under the curve) compared to that obtained after administration of pure SIL oral suspension, inclusion complex, and Viagra® with relative bioavailability > 100 %. Therefore, the approach developed in this study could potentially increase the efficacy of SIL in treating erectile dysfunction by being non-invasive, safe, avoiding first-pass metabolism, and increasing drug bioavailability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Telmisartan (TEL) is a promising antihypertensive agent among other angiotensin receptor blockers. However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogel-forming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with β-cyclodextrin (βCD). Phase solubility analysis showed an A p -type diagram, indicating a higher-order complex between TEL and βCD, with respect to βCD. A ratio of TEL:βCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

Background Emergency contraception (EC) plays a pivotal role in the prevention of unintended pregnancies following unprotected sexual intercourse. Men's awareness regarding emergency contraception is pivotal for informed decision-making and for enhancing reproductive health in this context. This study investigated Syrian men's awareness and perspectives on emergency contraception to inform diverse reproductive health initiatives. Methods We conducted a cross-sectional study in Syria, from June 2022 and April 2023. Our study included male participants aged 18 years or older who held Syrian nationality and volunteered to participate. The data collection involved administering a questionnaire comprising three sections (knowledge, attitude, and barrier assessment), encompassing a total of 30 questions. Data analysis was performed using the Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY). Results Most participants were aged 18-25 (65.7%) and single (75.4%) and held a university degree (79.3%). The knowledge of emergency contraception was low (36.1%), with the Internet and social media (77.5%) being the primary sources of information. While 89% held positive attitudes toward emergency contraception, only 37.3% supported nonprescription availability. Age, income, and desire for children were associated with knowledge, attitudes, and the use of emergency contraception. Men aged 26-35 exhibited the highest positive attitude (8.11±1.83). Those desiring no children showed higher attitude scores (7.42±2.04). Income was positively associated with knowledge (adjusted odds ratio {AOR}=1.75 and confidence interval {CI}=1.02-2.99) and emergency contraception use (AOR=2.87 and CI=1.27-6.48). Conclusion This study underscores the knowledge gap regarding emergency contraception in Syrian men. Despite positive attitudes, awareness remains limited, particularly among those of childbearing age. Targeted education and improved accessibility to emergency contraception can enhance its use among men, particularly in those with low socioeconomic status and younger age groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alibrahim et al.)

Background: Since March 2011, more than 1 million people, mostly men, have been arrested, detained, and tortured by the Assad regime. Published literature does not reflect the evolution of symptoms after male sexual and physical violence in detention. This cohort study examines the constellation and evolution of self-reported symptoms after male conflict-related sexual violence (CRSV) in Syrian state detention., Methods: Sexual, psychological, and physical symptoms and conditions experienced by a cohort of 106 male detainees after CRSV in Syrian regime detention were evaluated over a ten-year period (2012-2022). Men sought forensic medical expert evaluations (FMEs) to document torture and later consented to semi-structured interviews (SSIs), a median of 8.8 years after their detention. A standard data collection tool was used to assess symptoms and conditions during FMEs (Time 3), and at the time of the SSI (Time 4), during which men also reported symptoms experienced during detention (Time 1) and after detention release (Time 2)., Findings: 30.2% of men spent more than 1 year in detention and 9.4% were detained >5 years. 90% reported being slapped, punched, kicked, hit with objects, 60.4% of men reported torture with multiple devices, and 48.1% reported being burned or electrocuted. Multiple sexual violence types were reported during detention: 97.2% forced nudity, 45.3% violence to genitals or anus, 30.2% collective sexual humiliation, and 9.4% rape. Men recalled nearly universal presence of acute pain, bleeding wounds, skin infections, sleep disturbances, fear, sadness, anxiety, and despair during detention. By Time 4, acute physical and psychological conditions were fading or absent, while scars, avoidance, intrusive memories, lack of trust, self-isolation, chronic pain, anger, and low self-esteem were reported by ≥50%. The most persistently reported symptoms following detention through the SSI included scars, pain, intrusive memories, and avoidance in ≥50% of men. At the SSI, 26.4% of men reported erectile dysfunction and 23.6% challenges with sexual relations., Interpretation: Men reported persistent symptoms and conditions years after CRSV, torture and detention. The unique constellation of findings and their evolution in male CRSV survivors, particularly increasing rates of anger, distrust, and self-isolation, must urgently inform design and delivery of support services and health care., Funding: This study was funded by the United Kingdom Foreign Commonwealth and Development Office and the Arts and Humanities Research Council through the project 'Understanding and Addressing the Impact of Invisibility on Conflict-Related Male Sexual Violence in Syria'., Competing Interests: Authors Kivlahan and Elliott serve as medical and legal expert consultants to Synergy for Justice and as researchers for Synergy for Justice and the funding entity UK Foreign Commonwealth and Development Office and the Arts and Humanities Research Council. Elliott also serves as a Deployable Civilian Expert for UK Foreign Commonwealth and Development Office, working with LDHR from 2012 to 2015 as a UK expert. Author Garcia-Pereira served as a paid consultant to LDHR for data analyses. Authors AlSharif, Halak, Yonso, AlHafez, and Odaimi consultants to LDHR. Author Aswad serves as executive director (a paid employee of LDHR), and in that capacity, manages other LDHR grants not directly relevant to the submitted work and accepts only travel expenses for his attendance at human rights meetings. There are no other conflicts to disclose., (© 2023 The Authors.)

Rheumatoid diseases, including rheumatoid arthritis, osteoarthritis, and fibromyalgia, are characterized by progressive inflammation in the musculoskeletal system, predominantly affecting the joints and leading to cartilage and bone damage. The resulting pain and ongoing degradation of the musculoskeletal system contribute to reduced physical activity, ultimately impacting quality of life and imposing a substantial socioeconomic burden. Unfortunately, current therapeutics have limited efficacy in slowing disease progression and managing pain. Thus, the development of novel and alternative therapies is imperative. Cannabinoids possess beneficial properties as potential treatments for rheumatoid diseases due to their anti-inflammatory and analgesic properties. Preclinical studies have demonstrated promising results in halting disease progression and relieving pain. However, there is a scarcity of patient clinical studies, and the available data show mixed results. Consequently, there are currently no established clinical recommendations regarding the utilization of cannabis for treating rheumatoid diseases. In this review, we aim to explore the concept of cannabis use for rheumatoid diseases, including potential adverse effects. We will provide an overview of the data obtained from preclinical and clinical trials and from retrospective studies on the efficacy and safety of cannabis in the treatment of rheumatoid diseases.

Chronic inflammation is a significant concern due to its association with various pathological conditions. As a result, extensive research has been conducted to identify new natural products that can effectively treat acute inflammation, which has the potential to inhibit the chronic inflammation. In our study, we aimed to identify Indonesian medicinal plants with the ability to inhibit proinflammatory agents, specifically targeting NF-κB, a crucial regulator of gene transcription involved in the production of proinflammatory proteins/cytokines. Through a series of identification processes, we found that Piper retrofractum (Javanese chili) extract demonstrated promising inhibitory effects on NF-κB and proinflammatory molecules. Further investigation was conducted using a variety of assays, including reporter assay, viability test, ELISA, and Western blotting. The results revealed that the extract significantly reduced LPS, NO, COX-2, IL-6, IL-1, and NF-κB through the TLR4 axis. Notably, Piper retrofractum extract was found to enhance the survival of human keratinocytes by protecting them from cell death induced by TRAIL, a member of the TNF superfamily. Moreover, immunohistochemistry analysis in an Imiquimod-induced skin inflammation mice model showed downregulation of COX-2 and IL-1β expression upon treatment with the extract. In conclusion, our findings suggest that Piper retrofractum extract possesses anti-inflammatory properties by reducing proinflammatory cytokine production through inhibition of NF-κB signaling pathway. These promising results highlight the potential of Piper retrofractum extract as a candidate for future drug development in the clinical treatment of inflammation-related conditions, offering hope for the advancement of therapeutic interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Cytokine storm refers to the dysregulated production of inflammatory mediators leading to hyperinflammation. They are often detrimental, and worsen the severity of COVID-19 and other infectious or inflammatory diseases. Cannabinoids are known to have anti-inflammatory effects but their possible therapeutic value on cytokine storms has not been fully elucidated. In vivo and ex vivo studies were carried out to investigate the effects of high-THC and high-CBD extracts on cytokine production in immune cells. Significant differences between the extracts were observed. Subsequent experiments focusing on a specific high CBD extract (CBD-X) showed significant reductions in pro-inflammatory cytokines in human-derived PBMCs, neutrophils and T cells. In vivo mouse studies, using a systemically inflamed mouse model, showed reductions in pro-inflammatory cytokines TNFα and IL-1β and a concurrent increase in the anti-inflammatory cytokine IL-10 in response to CBD-X extract treatment. Lung inflammation, as in severe COVID-19 disease, is characterized by increased T-cell homing to the lungs. Our investigation revealed that CBD-X extract impaired T-cell migration induced by the chemoattractant SDF1. In addition, the phosphorylation levels of T cell receptor (TCR) signaling proteins Lck and Zap70 were significantly reduced, demonstrating an inhibitory effect on the early events downstream to TCR activation. In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1β, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract. The results presented in this work offer that certain high-CBD extract has a high potential in the management of pathological conditions, in which the secretion of cytokines is dysregulated, as it is in severe COVID-19 disease or other infectious or inflammatory diseases., Competing Interests: This study received funding from Raphael Pharmaceutical Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or decision to submit it for publication. All authors declare no other competing interests., (Copyright © 2022 Aswad, Hamza, Pechkovsky, Zikrach, Popov, Zohar, Shahar and Louria-Hayon.)

As human beings, we are bound by time. It is essential for daily functioning, and yet our ability to keep track of time is influenced by a myriad of factors (Block & Zakay, 1997, Psychonomic Bulletin & Review, 4[2], 184-197). First and foremost, time estimation has been found to depend on whether participants estimate the time prospectively or retrospectively (Hicks et al., 1976, The American Journal of Psychology, 89[4], 719-730). However, there is a paucity of research investigating differences between these two conditions in tasks over two minutes (Tobin et al., 2010, PLOS ONE, 5[2], Article e9271). Moreover, estimates have also been shown to be influenced by cognitive load. We thus investigated participants' ability to keep track of time during a visual and memory search task and manipulated its difficulty and duration. Two hundred and ninety-two participants performed the task for 8 or 58 minutes. Participants in the prospective time judgment condition were forewarned of an impending time estimate, whereas participants in the retrospective condition were not. Cognitive load was manipulated and assessed by altering the task's difficulty. The results revealed a higher overestimation of time in the prospective condition compared with the retrospective condition. However, this was found in the 8-minute task only. Overall, participants significantly overestimated the duration of the 8-minute task and underestimated the 58-minute task. Finally, cognitive load had no effect on participants' time estimates. Thus, the well-known cross-over interaction between cognitive load and estimation paradigm (Block et al., 2010, Acta Psychologica, 134[3], 330-343) did not extend to a longer duration in this experiment., (© 2021. The Psychonomic Society, Inc.)

Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Paland, Pechkovsky, Aswad, Hamza, Popov, Shahar and Louria-Hayon.)

Background: Microparticles (MPs) are small (0.1-1 &#956;m) cell-derived vesicles released during activation or apoptosis, with a surface-exposed phosphatidylserine along with antigens indicating the cellular origin. The level of MPs is known to be elevated in thromboembolic diseases and malignancies; it is believed that MPs are not only amplifying but can also initiate the thrombogenesis processes. BCR/ABL negative myeloproliferative neoplasms (MPNs) are clonal haematopoietic diseases, which include polycythemia vera, essential thrombocythemia and primary myelofibrosis. One of the main problems of MPN patients is high risk and incidence of thrombosis which affect the survival, quality of life and life expectancy., Patients and Methods: The clinical significance of circulating MPs was assessed in a group of 179 patients with BCR/ABL-negative MPNs. Analysis of MPs was done using flow cytometry on 417 samples, and MPs procoagulation activity was performed using a functional assay called Zymuphen MP-activity (Hyphen Biomed, Neuville-sur-oise, France) on 274 samples., Results: Significantly higher absolute and relative count of platelet MPs was found in MPN patients when compared with healthy group, respectively (p = 0.001, p = 0.043). Erythrocyte MPs were also significantly higher in MPN patients than in the healthy group (p &lt; 0.001). Procoagulation activity of MPs was as well significantly higher in patients compared to the control group (p &lt; 0.001). Patients with primary myelofibrosis had decreased absolute and relative count of platelet MPs compared to polycythemia vera and essential thrombocythemia patients, respectively (p = 0.008, p = 0.014). Presence of JAK2V617F mutation was associated with higher absolute and relative count of platelet MPs, respectively (p = 0.045, p = 0.029)., Conclusion: Although some literature data support the hypothesis of a direct relation between MPs and thrombotic events in MPN patients, further studies are needed to evaluate the clinical implication of MPs in the hypercoagulation state of MPN patients.

Objectives: The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs., Materials: A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes., Method: The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules., Results: By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab., Conclusion: The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

The engulfment of apoptotic polymorphonuclear cells (PMN) during the resolution of inflammation leads to macrophage reprogramming culminating in reduced proinflammatory and increased anti-inflammatory mediator secretion. The atypical chemokine receptor D6/ACKR2 is expressed on apoptotic PMN and plays an important role in regulating macrophage properties during and after engulfment. In this study, we found that the inflammatory chemokine CCL5 is mostly retained (75%) during the resolution of zymosan A peritonitis in mice. Moreover, this chemokine is secreted by resolution-phase macrophages (2.5 ng/ml) and promotes their reprogramming in vivo in D6 +/+ mice (2-fold increase in IL-10/IL-12 ratio) but not their D6 -/- counterparts. In addition, CCL5 enhanced macrophage reprogramming ex vivo exclusively when bound to D6 +/+ apoptotic PMN. Signaling through p38MAPK and JNK in reprogrammed macrophages was enhanced by CCL5-bound apoptotic PMN (3.6-4 fold) in a D6-dependent manner, and was essential for reprogramming. Thus, CCL5 exerts a novel proresolving role on macrophages when acting in concert with apoptotic PMN-expressed D6., (Copyright © 2017 by The American Association of Immunologists, Inc.)

The oxidative demethylation procedure for a new epoxy lignan isolated from Piper nigrum was applied to the synthesis of 3'-methoxy-3",4"-(methylenedioxy)-2,5-epoxylignan-4'-ol-6'-one. This compound inhibited the mRNA expression of the protein patched homolog (Ptch) in human pancreatic cancer cells (PANC1) and therefore might be valuable as a probe for tumor-related disease. The pharmacokinetic profile of 3'-methoxy-3",4"-(methylenedioxy)-2,5-epoxylignan-4'-ol-6'-one was rapidly determined using ultra-fast liquid chromatography. The compound was rapidly absorbed in blood., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Colorectal cancers are significant causes of morbidity and mortality and existing therapies often perform poorly for individuals afflicted with advanced disease. Oncolytic virotherapy is an emerging therapeutic modality with great promise for addressing this medical need. Herein we describe the in vivo testing of recombinant variants of the tanapoxvirus (TPV). Recombinant viruses were made ablated for either the 66R gene (encoding a thymidine kinase), the 2L gene (encoding a TNF-binding protein), or both. Some of the recombinants were armed to express mouse chemotactic protein 1 (mCCL2/mMCP-1), mouse granulocyte-monocyte colony stimulating factor (mGM-CSF), or bacterial flagellin (FliC). Tumors were induced in athymic nude mice by implantation of HCT 116 cells and subsequently treated by a single intratumoral injection of one of the recombinant TPVs. Histological examination showed a common neoplastic cell type and a range of immune cell infiltration, necrosis, and tumor cell organization. Significant regression was seen in tumors treated with virus TPV/Δ2L/Δ66R/fliC, and to a lesser extent the recombinants TPV/Δ2L and TPV/Δ66R. Our results suggest that oncolytic recombinants of the TPV armed with activators of the innate immune response may be effective virotherapeutic agents for colorectal cancers in humans and should be explored further to fully realize their potential.

The aim of this paper is to report a clinical case with bilateral missing mandibular second premolars that were restored by metal-ceramic inlay-retained fixed dental prostheses. The first prosthesis was of a traditional design and the second was of a modified design. The suggested design is created by modifying the retainer wings of the traditional resin-bonded inlay-retained fixed dental prosthesis and covering the wings with composite resin. The modified design is relatively conservative, esthetic and provides an extra element for the retention of posterior metal-ceramic inlay-retained fixed dental prostheses.

Objectives: The objectives of this study are to study how tooth loss affects the utility of the dentition from both patient and professional perspectives and to compare patient and professional utility values., Methods: One hundred six patients and 118 dentists were asked to read 19 different written scenarios accompanied by visual images and models, describing mouths with missing teeth, and to indicate on a visual analog scale the value of that oral health state., Results: Both groups of participants attached the greatest utility to missing incisor teeth and disutility of tooth loss decreased as the tooth in question became nearer the back of the mouth. When dentist and patient utility values for the loss of different tooth types were compared, using independent t-tests, differences were statistically significant for only one tooth loss scenario - the loss of upper canines., Conclusions: The patient and professional groups valued tooth loss scenarios in a similar way. This finding is contrary to the majority of previous studies comparing patient and professional utilities., (© 2013 American Association of Public Health Dentistry.)