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Nowadays, conventional anticancer therapy suffers many pitfalls, including drastic side effects and limited therapeutic efficacy resulting from diminished oral bioavailability. So, in an attempt to enhance their poor solubility and oral bioavailability along with the cytotoxic activity, the developed lead compounds (C1 and C2) were loaded in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified vesicles adopting thin film hydration technique. The formulations of the aforementioned candidates (F1 and F2, respectively) were elected as the optimum formula with desirability values of 0.701 and 0.618, respectively. Furthermore, an outstanding enhancement in the drug's cytotoxic activity against different cancer cell lines (MCF-7, HepG-2, MDA-MB-321, A375, and MGC-803) after being included in the nano-TPGS-modified optimum formula was noticed relative to the unformulated compounds. The formula F1 showed the best cytotoxic activities against HepG-2 with an IC 50  = 3 µM. Furthermore, regarding MCF-7, F1 was shown to be the most potent and protective among all the tested formulations with an IC 50  = 6 µM. Besides, F1 exerted the best caspase 3/7 activity stimulation (around a 5-folds increase) compared to control in the MCF-7 cell line. Notably, it was disclosedthat both C1 and C2 induced cell cycle arrest at the resting S growth phase. Moreover, C1 and C2 decreased tubulin concentrations by approximately 2-folds and 6-folds, respectively. Meanwhile, the conducted molecular docking studies ensure the eligible binding affinities of the assessed compounds. Besides, MD simulations were performed for 1000 ns to confirm the docking results and study the exact behavior of the target candidates (C1 and C2) toward the CBS., 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 © 2023 Elsevier B.V. All rights reserved.)

Influenza viruses belong to the Orthomyxoviridae family and cause acute respiratory distress in humans. The developed drug resistance toward existing drugs and the emergence of viral mutants that can escape vaccines mandate the search for novel antiviral drugs. Herein, the synthesis of epimeric 4'-methyl-4'-phosphonomethoxy [4'-C-Me-4'-C-(O-CH 2 P═O)] pyrimidine ribonucleosides, their phosphonothioate [4'-C-Me-4'-C-(O-CH 2 P═S)] derivatives, and their evaluation against an RNA viral panel are described. Selective formation of the α- l-lyxo epimer, [4'-C-(α)-Me-4'-C-(β)-(O-CH 2 -P(═O)(OEt) 2 )] over the β- d-ribo epimer [4'-C-(β)-Me-4'-C-(α)-(O-CH 2 -P(═O)(OEt) 2 )] was explained by DFT equilibrium geometry optimizations studies. Pyrimidine nucleosides having the [4'-C-(α)-Me-4'-C-(β)-(O-CH 2 -P(═O)(OEt) 2 )] framework showed specific activity against influenza A virus. Significant anti-influenza virus A (H1N1 California/07/2009 isolate) was observed with the 4'-C-(α)-Me-4'-C-(β)-O-CH 2 -P(═O)(OEt) 2 -uridine derivative 1 (EC 50  = 4.56 mM, SI 50  > 56), 4-ethoxy-2-oxo-1(2H)-pyrimidin-1-yl derivative 3 (EC 50  = 5.44 mM, SI 50  > 43) and the cytidine derivative 2 (EC 50  = 0.81 mM, SI 50  > 13), respectively. The corresponding thiophosphonates 4'-C-(α)-Me-4'-C-(β)-(O-CH 2 -P( S)(OEt) 2 ) and thionopyrimidine nucleosides were devoid of any antiviral activity. This study shows that the 4'-C-(α)-Me-4'-(β)-O-CH 2 -P(═O)(OEt) 2 ribonucleoside can be further optimized to provide potent antiviral agents., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives ( 5 - 14 ) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. The investigated compounds displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacin as a reference control. Obviously, compounds 6b and 10 unveiled IC 50 values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC 50 value of 3.80 μM. Furthermore, a significant docking binding score was encountered by compound 6b (-7.73 kcal/mol), surpassing ciprofloxacin (-7.29 kcal/mol). Additionally, both compounds 6b and 10 revealed high GIT absorption without passing the blood brain barrier. Finally, the conducted structure-activity relationship study assured the usefulness of the hydrazine moiety as a molecular hybrid for activity either in cyclic or opened form., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A new series of Schiff-benzimidazole hybrids 3a - o has been designed and synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analysis tools. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI single- and five-dose protocols. Consequently, four compounds were further examined against the most sensitive lung cancer A549 and NCI-H460 cell lines. Compounds 3e and 3g were the most active, achieving 3.58 ± 0.53, 1.71 ± 0.17 and 1.88 ± 0.35, 0.85 ± 0.24 against A549 and NCI-H460 cell lines, respectively. Moreover, they showed remarkable inhibitory activity on the VEGFR-2 TK with 86.23 and 89.89%, respectively, as compared with Sorafenib (88.17%). Moreover, cell cycle analysis of NCI-H460 cells treated with 3e and 3g showed cellular cycle arrest at both G1 and S phases (supported by caspases-9 study) with significant pro-apoptotic activity, as indicated by annexin V-FITC staining. The binding interactions of these compounds were confirmed through molecular docking studies; the most active compounds displayed complete overlay with, and a similar binding mode and pose to, Sorafenib, a reference VEGFR-2 inhibitor.

Background: A common contributory factor to falls is the use of medicines, especially those commonly known as “fall-risk increasing drugs” (FRIDs). The use of FRIDs is common among older people (OP). However, OP and their family caregivers (FCGs) are largely unaware of FRIDs and their risks in increasing the risk of falls (ROF). Methods: A booklet which aims to provide information on topics related to FRIDs was developed. The booklet was reviewed by a panel of 14 reviewers, and the content validity index (CVI) for each subsection of the booklet was computed. Pilot testing of the booklet utilized a pre-post intervention study design and included 50 OP and 50 FCGs as study participants. Perceived knowledge of the participants was assessed prior to and after completing the booklet. Participants’ opinions on the usefulness and usability of the booklet were also obtained. Results: The booklet contained eight sections and each subsection of the booklet had a CVI ranging from 0.93 to 1.00. Completing the booklet resulted in improved perceived knowledge scores for each perceived knowledge item among both the OP and FCG groups (all items: p-value < 0.001). The participants perceived the booklet as useful and usable, as evidenced by almost all the perceived usefulness and usability items having a score of over 4.0. Conclusions: The FRIDs booklet developed in this study had good content validity and was widely accepted by the OP and FCGs. The positive effect on the participants’ knowledge of topics related to FRIDs means that the booklet could be useful as a patient education tool to enhance FRIDs knowledge and awareness among OP and FCGs.

Background: Rheumatoid arthritis (RA) is a known debilitating autoimmune disease. Immune-suppressants that are used for disease treatment have serious side effects, therefore, trivalent chromium (Cr (III)); which has shown evidence of its influences on some inflammatory pathways and cytokines; was used in this study for the first time to be assessed for its therapeutic effect in RA rat model and was compared to prednisolone in a trial to find a treatment with lesser side effects., Methods: Adult male albino rats were randomly divided into four groups: normal, untreated RA, prednisolone treated RA (1.25 mg/kg/day) and Cr (III) treated RA groups (80 μg/kg/day), induction of RA was done by subcutaneous complete Freund adjuvant injection. Study duration was 4 weeks throughout which arthritis scoring and weight measurement were pursued. Histopathological examination and immunohistochemical FOXP3 assessment were done for joint biopsies. Serum inflammatory markers (interleukin 17, interleukin 10, CRP) and synovial erosive arthritis marker (Cathepsin G) were measured. HDL and non-HDL cholesterol were estimated as well., Results: Cr (III) treatment showed marked clinical and histopathological improvement, also astonishing anti-inflammatory effects (increase in FOXP3 expression and interleukin 10, with decrease in interleukin 17, CRP and synovial Cathepsin G) to the extent that Cr (III) effects on inflammation abolishment were comparable to that of prednisolone and even better at some aspects. Moreover, Cr (III) was protective from side effects, i.e., weight gain and dyslipidemia that were seen with prednisolone treatment., Conclusions: Cr (III) is promising in treating RA and it lacks some side effects of accustomed immune-modulatory agents including prednisolone. Further experimental studies and clinical trials should be held to see the efficacy of Cr (III) in different doses and to assess its long term side effects when used for rheumatoid arthritis and other autoimmune diseases treatment., (© 2022. The Author(s).)

A new series of vinyl amide-, imidazolone-, and triazinone-linked combretastatin A-4 analogues have been designed and synthesised. These compounds have been evaluated for their cytotoxic activity against MDA-MB-231 breast cancer cells. The triazinone-linked combretastatin analogues (6 and 12) exhibited the most potent cytotoxic activity, in sub-micromolar concentration compared with combretastatin A-4 as a reference standard. The results of β-tubulin polymerisation inhibition assay appear to correlate well with the ability to inhibit β-tubulin polymerisation. Additionally, these compounds were subjected to biological assays relating to cell cycle aspects and apoptosis induction. In addition, the most potent compound 6 was loaded on PEG-PCL modified diamond nanoparticles (PEG-PCL-NDs) and F4 was picked as the optimum formula. F4 exhibited enhanced solubility and release over the drug suspension. In the comparative cytotoxic activity, PEG-PCL modified F4 was capable of diminishing the IC50 by around 2.89 times for nude F4, while by 3.48 times relative to non-formulated compound 6 .

Resveratrol (RSV) is a phytoceutical polyphenolic compound exhibiting a well evidenced wide range of therapeutic activities. Unfortunately, its diminished aqueous solubility and extensive metabolism in gastro intestinal tract (GIT) and liver prohibit its biological activity and systemic availability. Herein the conducted study PEG stabilized emulsomes (PEMLs) were customized to enclose RSV aiming to boost its biological availability and antiviral activity. PEGylating the vesicles not only grant the promoted steric stability of the system but also being beneficial in exaggerating the intestinal permeability and extending the period of circulation of the drug, hence its targeted clinical use. The Investigation of the influence of predetermined variables on the physical characterization of formulae (entrapment efficiency EE%, particle size PS and zeta potential ZP) was implemented utilizing Design Expert® software. (F4) with desirability value (0.772), picked to be the optimal formula, which is fabricated utilizing 35 mg compritol as the lipidic core and 60 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-Mpeg-2000). The dominance of the F4 relative to RSV dispersion was affirmed by the data acquired from ex-vivo and pharmacokinetic studies. In addition, F4 exhibited significant lower EC 50 value (0.0127 µg/mL) relative to that of RSV dispersion(0.338 µg/mL) by around 26 times denoting the capability of the formulation to boost the antiviral activity. To a great extent, F4 was able to significantly suppress the inflammatory response and oxidative stress resulted from MERS-CoV infection on comparison with RSV dispersion. Finally, the potentiality of PEMLs as nano-panel with boosted both antiviral and oral bioavailability for RSV could be deduced based on the outcomes mentioned herein.

A new series of nicotinonitrile derivatives 2 - 7 was designed and synthesized from the starting material ( E )-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one ( 1 ) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2 - 7 were characterized based on FTIR, 1 H-NMR, and 13 C-APT NMR spectra as well as elemental microanalyses. The target compounds 2 - 7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2 , 4a , and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a , b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a , b could be adequate molluscicidal molecules against M. cartusiana land snails.

Background: Thrombotic conditions triggered by SARS-CoV-2 virus can result in high mortality, especially in pregnant women as they are already in a hypercoagulability state. This thereby leads to excessive inflammation that will increase the risk of thromboembolic (TE) complications. Objective: The aim of this study is to review the prevalence of thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and intervillous thrombosis, and their preventive strategies among pregnant women infected with COVID-19. Method: The articles were retrieved from online databases PubMed and ScienceDirect published from February 2020 to April 2022. Findings: A total of 5249 participants including 5128 pregnant women and 121 placentas from 19 studies were identified for having TE complications after being infected with COVID-19. The types of TE complications that developed within pregnant women were disseminated intravascular coagulation (DIC) ( n = 44, 0.86%), unmentioned thromboembolic complications (TE) ( n = 14, 0.27%), intervillous thrombosis (IVT) ( n = 9, 0.18%), pulmonary embolism (PE) ( n = 6, 0.12%), COVID-19 associated coagulopathy (CAC) ( n = 5, 0.10%), and deep venous thrombosis (DVT) ( n = 2, 0.04%). Whereas the prevalence of TE complications reported from studies focusing on placenta were IVT ( n = 27, 22.3%), subchorionic thrombus (SCT) ( n = 9, 7.44%), and placental thrombosis ( n = 5, 4.13%). Thromboprophylaxis agent used among pregnant women include low molecular weight heparin (LMWH) at prophylactic dose ( n = 9). Conclusions: The prevalence of thromboembolic complications among pregnant women infected by COVID-19 is low with DIC being the most common form and placental thrombosis being the least common form of TE complications that occurred within pregnant women infected with COVID-19. Anticoagulation, in particular LMWH (variable dose), is frequently used to prevent TE complications., Competing Interests: The authors declare no conflict of interest.

A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9 , 10 and 11 exhibited good cytotoxic potency with IC 50 values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9 , 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.

A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC 50 values 0.65 and 0.92 μM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of c aspase 3/7. C aspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of c aspase 3/7 may occur via mitochondrial apoptotic pathway.

A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.

Background: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome., Methods: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality., Results: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality., Conclusions: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis., Competing Interests: Conflict of interest: James Melhorn has nothing to disclose. Conflict of interest: Andrew Achaiah has nothing to disclose. Conflict of interest: Francesca M. Conway has nothing to disclose. Conflict of interest: Elizabeth M. F. Thompson has nothing to disclose. Conflict of interest: Erik W. Skyllberg has nothing to disclose. Conflict of interest: Joseph Durrant has nothing to disclose. Conflict of interest: Neda A. Hasan has nothing to disclose. Conflict of interest: Yasser Madani has nothing to disclose. Conflict of interest: Prasheena Naran has nothing to disclose. Conflict of interest: Bavithra Vijayakumar has nothing to disclose. Conflict of interest: Matthew J. Tate has nothing to disclose. Conflict of interest: Gareth E. Trevelyan has nothing to disclose. Conflict of interest: Irfan Zaki has nothing to disclose. Conflict of interest: Catherine A. Doig has nothing to disclose. Conflict of interest: Geraldine Lynch has nothing to disclose. Conflict of interest: Gill Warwick has nothing to disclose. Conflict of interest: Avinash Aujayeb has nothing to disclose. Conflict of interest: Karl A. Jackson has nothing to disclose. Conflict of interest: Hina Iftikhar has nothing to disclose. Conflict of interest: Jonathan H. Noble has nothing to disclose. Conflict of interest: Anthony Y. K. C. Ng has nothing to disclose. Conflict of interest: Mark Nugent has nothing to disclose. Conflict of interest: Philip J. Evans has nothing to disclose. Conflict of interest: A. Hastings has nothing to disclose. Conflict of interest: Harry R. Bellenberg has nothing to disclose. Conflict of interest: Hannah Lawrence has nothing to disclose. Conflict of interest: Rachel L. Saville has nothing to disclose. Conflict of interest: Nikolas T. Johl has nothing to disclose. Conflict of interest: Adam N. Grey has nothing to disclose. Conflict of interest: Huw C. Ellis has nothing to disclose. Conflict of interest: Cheng Chen has nothing to disclose. Conflict of interest: Thomas L. Jones has nothing to disclose. Conflict of interest: Nadeem Maddekar has nothing to disclose. Conflict of interest: Shahul Leyakathali Khan has nothing to disclose. Conflict of interest: Ambreen Iqbal Muhammad has nothing to disclose. Conflict of interest: Hakim Ghani has nothing to disclose. Conflict of interest: Yadee Maung Maung Myint has nothing to disclose. Conflict of interest: Cecillia Rafique has nothing to disclose. Conflict of interest: Benjamin J. Pippard has nothing to disclose. Conflict of interest: Benjamin R. H. Irving has nothing to disclose. Conflict of interest: Fawad Ali has nothing to disclose. Conflict of interest: Viola H. Asimba has nothing to disclose. Conflict of interest: Aqeem Azam has nothing to disclose. Conflict of interest: Eleanor C. Barton has nothing to disclose. Conflict of interest: Malvika Bhatnagar has nothing to disclose. Conflict of interest: Matthew P. Blackburn has nothing to disclose. Conflict of interest: Kate J. Millington has nothing to disclose. Conflict of interest: Nicholas J. Budhram has nothing to disclose. Conflict of interest: Katherine L. Bunclark has nothing to disclose. Conflict of interest: Toshit P. Sapkal has nothing to disclose. Conflict of interest: Giles Dixon has nothing to disclose. Conflict of interest: Andrew J. E. Harries has nothing to disclose. Conflict of interest: Mohammad Ijaz has nothing to disclose. Conflict of interest: Vijayalakshmi Karunanithi has nothing to disclose. Conflict of interest: Samir Naik has nothing to disclose. Conflict of interest: Malik Aamaz Khan has nothing to disclose. Conflict of interest: Karishma Savlani has nothing to disclose. Conflict of interest: Vimal Kumar has nothing to disclose. Conflict of interest: Beatriz Lara Gallego has nothing to disclose. Conflict of interest: Noor A. Mahdi has nothing to disclose. Conflict of interest: Caitlin Morgan has nothing to disclose. Conflict of interest: Neena Patel has nothing to disclose. Conflict of interest: Elen W. Rowlands has nothing to disclose. Conflict of interest: Matthew S. Steward has nothing to disclose. Conflict of interest: Richard S. Thorley has nothing to disclose. Conflict of interest: Rebecca L. Wollerton has nothing to disclose. Conflict of interest: Sana Ullah has nothing to disclose. Conflict of interest: David M. Smith has nothing to disclose. Conflict of interest: Wojciech Lason has nothing to disclose. Conflict of interest: Anthony J Rostron has nothing to disclose. Conflict of interest: Najib M Rahman has nothing to disclose. Conflict of interest: Rob J Hallifax has nothing to disclose., (Copyright ©The authors 2022.)

New furan-based derivatives have been, designed, synthesized, and evaluated for their cytotoxic and tubulin polymerization inhibitory activities. DNA flow cytometric study of pyridine carbohydrazide 4 and N -phenyl triazinone 7 demonstrated G 2 /M phase cell cycle disruptions. Accumulation of cells in the pre-G1 phase and positive annexin V/PI staining, which may be caused by degeneration or fragmentation of the genetic components, suggested that cell death occurs via an apoptotic cascade. Furthermore, compounds 4 and 7 had a strong pro-apoptotic impact through inducing the intrinsic mitochondrial mechanism of apoptosis. This mechanistic route was verified by an ELISA experiment that indicated a considerable rise in the levels of p53 and Bax and a drop in the level of Bcl-2 when compared with the control.

Competing Interests: Competing interests: None declared.

Background: Due to the emergence of resistance to available anticancer agents, the demand for new cytotoxic agents has grown., Objective: This study aims at synthesis and cytotoxic evaluation of new acrylic acid derivatives bearing quinolinone and halogenated quinolinone derivatives against three cancer cell lines., Methods: New acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties were synthesized and screened for their cytotoxic activity against breast MCF-7, liver HepG2, and colon HCT-116 cancer cell lines., Results: Molecules 3 and 8 showed the most potent cytotoxic activity against HCT-116. DNA flow cytometry assay showed cell cycle arrest at the G1 phase and cellular apoptosis. Moreover, molecules 3 and 8 showed cyclin-dependent kinase 2 (CDK2) inhibitory activity compared to the untreated control sample., Conclusion: Acrylic acid derivatives bearing quinolinone and halogenated quinolinone moieties represent an important core and could be used as a lead for further development of drug compounds in order to achieve promising therapeutic results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (T c ), spin polarization, half magnetic ferromagnetism and transport properties of ZnX 2 Se 4 (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of T c is perceived for ZnCr 2 Se 4 . The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) μ B of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔE crystal , exchange energies Δ x ( d ), Δ x ( pd ) and exchange constants (N o α and N o β). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0-400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 10 11 W/mK 2 ) among studied compounds.

The objective of this paper is to confine piperine, a poor oral bioavailable herbal drug into bile salt based nano vesicles for improving its aqueous solubility, hence, its therapeutic activity. Piperine-loaded bilosomes were fabricated adopting thin film hydration technique according to 3 2 .2 1 full factorial design to investigate the impact of different formulation variables on the characters of bilosomes: entrapment efficiency (EE%), particle size, and % of drug released post 8 h (Q8hr). The selected optimum formula was F2 (enclosing 1% bile salt, brij72 as a surfactant, and ratio of surfactant:cholesterol was 9:1) with desirability value 0.801, exhibiting high EE% (97.2 ± 0.8%) nanosized spherical vesicles (220.2 ± 20.5 nm) and Q8hr (88.2%±5.6). The superiority of the optimized formula (F2) over the drug suspension was revealed via ex vivo permeation study, also pharmacokinetic study denoted to the boosted oral bioavailability of piperine-loaded bilosome compared to piperine suspension. Moreover, antiviral activity and safety margin of F2 was significantly higher than that of the drug suspension. The ability of piperine to interact with the key amino acids in the receptor binding domain 4L3N as indicated by its docking configuration, rationalized its observed activity. Furthermore, F2 significantly reduce oxidant markers, inflammatory cytokines in MERS-CoV-infected mice. Hence, bilosomes can be considered as a carrier of choice for piperine with potential antiviral and anti-inflammatory activities.

Vitamin K antagonist such as warfarin reduces the risk of stroke in atrial fibrillation (AF) patients. Since warfarin has a narrow therapeutic index, its administration needs to be regularly monitored to avoid any adverse clinical outcomes such as stroke and bleeding. The quality of anticoagulation control with warfarin therapy can be measured by using time in therapeutic range (TTR). This review focuses on the prevalence of AF, quality of anticoagulation control (TTR) and adverse clinical outcome in AF patients within different ethnic groups receiving warfarin therapy for stroke prevention. A literature search was conducted in Embase and PubMed using keywords of "prevalence," "atrial fibrillation," "stroke prevention," "oral anticoagulants," "warfarin," "ethnicities," "race" "time in therapeutic range," "adverse clinical outcome," "stroke, bleeding." Articles published by 1st February 2020 were included. Forty-one studies were included in the final review consisting of AF prevalence ( n = 14 studies), time in therapeutic range ( n = 18 studies), adverse clinical outcome ( n = 9 studies) within different ethnic groups. Findings indicate that higher prevalence of AF but better anticoagulation control among the Whites as compared to other ethnicities. Of note, non-whites had higher risk of strokes and bleeding outcomes while on warfarin therapy. Addressing disparities in prevention and healthcare resource allocation could potentially improve AF-related outcomes in minorities., 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 Zawawi, Abdul Halim Zaki, Ming, Goh and Zulkifly.)

Introduction: Sufficient data pertaining to the impact of the Coronavirus disease 2019 (COVID-19) on pediatric cancer patients is still lacking. The aim of this prospective study was to describe clinical management and outcomes of COVID-19 in pediatric oncology patients., Patients and Methods: Conducted between May 1, 2020 and November 30, 2020, this study included 76 pediatric oncology patients with confirmed COVID-19. Remdesivir (RDV) was the antiviral therapy used., Results: The median age of patients was 9 years. Sixty patients were on first line treatment. Hematological malignancies constituted 86.8% of patients. Severe to critical infections were 35.4% of patients. The commonest symptom was fever (93.4%). Chemotherapy was delayed in 59.2% of patients and doses were modified in 30.2%. The 60-day overall survival (OS) stood at 86.8%, with mortalities occurring only among critical patients. Of sixteen acute leukemia patients in the first induction therapy, 13 survived and 10 achieved complete remission. A negative RT-PCR within 2 weeks and improvement of radiological findings were statistically related to disease severity (P = .008 and .002, respectively). Better OS was associated with regression of radiological findings after 30 days from infection (P = .002). Forty-five patients received RDV, 42.1% had severe and critical forms of infection compared to 25.7% in the No-RDV group and yet OS was comparable in both groups., Conclusion: Most pediatric cancer patients with COVID-19 should have good clinical outcomes except for patients with critical infections. Cancer patients can tolerate chemotherapy including induction phase, alongside COVID-19 treatment. In severe and critical COVID-19, RDV might have a potential benefit., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4-(furan-2-ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4 H )-one (1), and they are evaluated for their inhibitory activity against β-tubulin polymerization. The target molecules 2-5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent β-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. 2 3 full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE-mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = -22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound's cytotoxic activity (IC 50 = 0.75 ± 0.03 µM) instead of (IC 50 = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.

A new series of 2,4-disubstituted benzo[ g ]quinoxaline molecules have been synthesized, using naphthalene-2,3-diamine and 1,4-dibromonaphthalene-2,3-diamine as the key starting materials. The structures of the new compounds were confirmed by spectral data along with elemental microanalyses. The cytotoxic activity of all synthesized benzo[ g ]quinoxaline derivatives was assessed in vitro against the breast MCF-7 cancer cell line. The tested molecules revealed good cytotoxicity toward the breast MCF-7 cancer cell line, especially compound 3 . The results of topoisomerase IIβ inhibition assay revealed that compound 3 exhibits potent inhibitory activity in submicromolar concentration. Additionally, compound 3 was found to cause pre-G1 apoptosis, and slightly increase the cell population at G1 and S phases of the cell cycle profile in MCF-7 cells. Finally, compound 3 induces apoptosis via Bax activation and downregulation of Bcl2, as revealed by ELISA assay.

The efficacy of LaNaTaO 3 perovskites decoration RuO 2 at diverse contents for the photocatalytic H 2 generation has been explored in this study. The photocatalytic performance of RuO 2 co-catalyst onto mesoporous LaNaTaO 3 was evaluated for H 2 under UV illumination. 3%RuO 2 /LaNaTaO 3 perovskite photocatalyst revealed the highest photocatalytic H 2 generation performance, indicating that RuO 2 nanoparticles could promote the photocatalytic efficiency of LaNaTaO 3 perovskite significantly. The H 2 evolution rate of 3%RuO 2 /LaNaTaO 3 perovskite is 11.6 and 1.3 times greater than that of bare LaNaTaO 3 perovskite employing either 10% CH 3 OH or pure H 2 O, respectively. Interestingly, the photonic efficiency of 3%RuO 2 /LaNaTaO 3 perovskite was enhanced 10 times than LaNaTaO 3 perovskite in the presence of aqueous CH 3 OH solutions as a hole sacrificial agent. The high separation of charge carriers is interpreted by the efficient hole capture using CH 3 OH, hence leading to greater H 2 generation over RuO 2 /LaNaTaO 3 perovskites. This is attributed to an adjustment position between recombination electron-hole pairs and also the reduction of potential conduction alignment as a result of RuO 2 incorporation. The suggested mechanisms of RuO 2 /LaNaTaO 3 perovskites for H 2 generation employing either CH 3 OH or pure H 2 O were discussed. The photocatalytic performances of the perovskite photocatalyst were elucidated according to the PL intensity and the photocurrent response investigations., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A novel series of N-1 arylidene amino imidazole-2-thiones were synthesized, identified using IR, 1 H-NMR, and 13 C-NMR spectral data. Cytotoxic effect of the prepared compounds was carried out utilizing three cancer cell lines; MCF-7 breast cancer, HepG2 liver cancer, and HCT-116 colon cancer cell lines. Imidazole derivative 5 was the most potent of all against three cell lines. DNA flow cytometric analysis showed that, imidazoles 4d and 5 exhibit pre-G1 apoptosis and cell cycle arrest at G2/M phase. The results of the VEGFR-2 and B-Raf kinase inhibition assay revealed that compounds 4d and 5 displayed good inhibitory activity compared with reference drug erlotinib.

Background: The histological response to neoadjuvant chemotherapy (NAC) in pediatric patients with Ewing sarcoma family of tumors (ESFT) can predict the disease-free survival. Therefore, a noninvasive method for response assessment is needed. Using the currently established imaging modalities, mass reduction does not always correlate with the percentage of necrosis., Objective: To determine the potential role of 18 fluorine-labeled fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET) metabolic parameters in the prediction of poor histological response to NAC in pediatric patients with ESFT., Methods: Thirty-six patients who were treated with NAC and surgery at the Children's Cancer Hospital, Egypt, were prospectively included in this study. All patients underwent two studies; a PET/CT study before NAC and another one after NAC completion. Metabolic PET parameters were measured in each study. The ability of each of these parameters, their pretreatment and pre-local control values, as well as the percentage reduction between their pretreatment and pre-local control values, were evaluated to differentiate between good and poor responders using the histological response as a standard reference., Results: Neither the pretreatment value nor the percentage reduction of any of the measured PET parameters predicted poor histological response. After NACcompletion, metabolic tumor volume (MTV) at the threshold of an SUV of 2.5 isocontour (MTV(2.5) post ), MTV at the threshold of hepatic reference SUVmean (MTV(HR) post ), and total lesion glycolysis at the threshold of hepatic reference SUVmean (TLG(HR) post ) predicted poor histological response (P  = 0.006, 0.018, and 0.003, respectively). The cutoff values of 90% reduction of TLG(HR) and maximum standardized uptake value (SUVmax) post ≤2.5 could differentiate between good and poor responders., Conclusion: FDG PET parameters can predict poor histological response to NAC in ESFT patients. MTV and TLG at the thresholds of an SUV of 2.5 isocontour and hepatic reference SUVmean are the two most promising thresholds in predicting the response of patients. The cutoff value of SUVmax post ≤2.5 predicts poor histological response., (© 2020 Wiley Periodicals LLC.)

A series of imidazolin-2-thione derivatives was synthesized and structurally confirmed through the use of different spectroscopic techniques such as infrared, nuclear magnetic resonance, and mass spectrometry along with elemental analyses. The breast cancer cell line MCF-7 was utilized in the evaluation of the cytotoxic activity of the prepared molecules. The tested molecules 3 and 7 exhibited the best results on MCF-7 cells, with mean IC 50 values of 3.26 and 4.31 µM, respectively. The results of the VEGFR-2 assay indicated that compounds 3 and 7 displayed a good inhibition of the VEGFR-2 kinase enzyme. Additionally, DNA flow cytometry of compounds 3 and 7 showed cell cycle arrest at the G0/G1 phase, cell apoptosis, and marked DNA fragmentation in MCF-7 cells. Finally, compounds 3 and 7 were proved to upregulate the activation of effector caspase-3/7, as presented by the caspase-3/7 green flow cytometry assay., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

Vanadium carbide is known, for its hardness and other unique properties, as a refractory material. The synthesis of vanadium carbide is always associated with the utilization of expensive active metals, such as aluminum, calcium and magnesium, as a reducing agent to extract the vanadium metal from its corresponding oxide, followed by carbidization. The carbidization of reduced vanadium requires a complicated process and elevated temperature. Mechanical activation to synthesize vanadium carbide from its corresponding oxide and carbon source represents a promising, straightforward and less energy-intensive route. In the present study, vanadium carbide is synthesized by the carbothermic reduction of a mechanically activated mixture of V 2 O 5 and carbon black as reducing agents without any additives. The reduction process is monitored by means of thermogravimetric analysis. The reduction products are characterized by X-ray diffraction and field emission scanning electron microscope. It is found that V 8 C 7 with an average crystallite size of 88 nm can be synthesized from a V 2 O 5 -C mixture after milling for 15 h and further heating at 1050 °C for 1 h in an inert atmosphere.

Novel azole derivatives 3-30 were designed, synthesized, and screened for their antitumor activity on HepG2 cell line. The cytotoxicity screening demonstrated that imidazolone 8 and triazoles 25 and 29 exhibited more potent cytotoxic activities by 1.21-, 4.75-, and 1.8-fold compared to Sorafenib (SOR). Furthermore, vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme inhibition assay declared that compounds 25 and 29 had inhibitory activity at the nanomolar concentration. Moreover, the tested compounds exhibited good β-tubulin (TUB) polymerization inhibition percentages. In addition, DNA flow cytometry analysis over HepG2 cells indicated that triazoles 25 and 29 demonstrated arrest at G 1 and G 2 /M phase of the cell cycle and induced apoptotic activity by increasing sub-G 1 phase. Finally, mechanistic studies of the proapoptotic activities of compounds 8, 10, 11, 25, and 29 indicated that they induced upregulation of P53, Fas/Fas-ligand, and BAX/BCL-2 ratio expression that resulted in increasing the active caspase 3/7 percentages and trigger apoptosis., 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 © 2020 Elsevier Inc. All rights reserved.)

Background: Searching for new cytotoxic agents with apoptosis induction may represent a viable strategy for cancer treatment to overcome the increased resistance to available anticancer agents., Objective: The purpose of the current study was aimed at preparation and anticancer evaluation of two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives against two cancer cell lines., Methods: Two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives were prepared and screened for their cytotoxicity against breast MCF-7 and liver HepG-2 cancer cell lines as well as normal breast MCF-10a., Results: The tested molecules revealed good cytotoxicity and selectivity toward cancer cell lines relative to normal cells. These compounds were analyzed by DNA flow cytometry on MCF-7 cells. They were found to cause G2/M phase arrest and induced apoptosis at the pre-G1 phase. In addition, increased caspase 3/7 activity and decreased osteopontin expression verified the apoptotic activity., Conclusion: The potent compounds discovered in this study can be a hit for the discovery of new cytotoxic agents and are worthy of further investigation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Complete metastasectomy is the best predictor of survival in patients with osteosarcoma pulmonary metastases. There has been some controversy in the literature regarding the prognostic significance of the timing of occurrence of lung metastasis., Methods: We reviewed the clinical course of all osteosarcoma patients with pulmonary metastases treated by metastasectomy in our hospital from January 2008 through December 2016. Each patient who underwent metastasectomy was placed into one of three groups based on whether lung metastases were present at initial presentation (Group 1), developed during chemotherapy (Group 2), or appeared after completion of chemotherapy (Group 3). Data were obtained retrospectively and follow-up was obtained until the end of June 2017., Results: We identified 170 patients with pulmonary nodules of whom 99 (58.2%) underwent at least one metastasectomy (149 thoracotomies). Eleven patients had benign pulmonary nodules and were excluded. The other 88 patients were classified as Group 1 (37), Group 2 (18) or Group 3 (33). The median follow-up was 35 months (range 8 to 99). Postmetastasis 5-year overall survival (OS) was 38.1 ± 6.4%; event-free survival (EFS) was 25 ± 5.3%. By group, postmetastasis 5-year OS and EFS were 34.3 ± 13% and 18 ± 9.3% in Group 1, 8 ± 6.5% and 6.5 ± 5% in Group 2, and 52 ± 11.4% and 25 ± 9% in Group 3 (P < 0.001). In univariate analysis, the only significant factors associated with survival were timing of occurrence of lung metastasis and the number of lung nodules found., Conclusion: The timing of occurrence of lung metastasis is an important prognostic factor among osteosarcoma patients eligible for metastasectomy. Patients whose metastases occurred during chemotherapy had the worst survival., Level of Evidence: Level II., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [ 3 H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G 2 /M phase. Compounds 4c, 5e and 7c exhibit low to moderate β-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent β-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo. In addition, compounds 4c, 5e and 7c show strong topoisomerase (topo) II inhibitory activity in nano-molar concentration, compared to known topo inhibitor as etoposide. Finally, apoptotic inducing activity over MCF-7 of compounds 4c, 5e, 6c and 7c is due to up-regulation of p53, increased Bax/Bcl-2 ratio and caspase3/7 levels 2-fold higher than podo., (Published by Elsevier Masson SAS.)

Background: Critically ill patients are hypermetabolic and have increased energy requirements, making nutritional support a vital intervention. In the Intensive Care Units, enteral nutrition is based on opinions rather than evidence-based practices. Therefore, there is a need to identify the barriers to evidence based practice protocols for enteral feeding of patients in Jordanian ICUs., Aims: To explore Jordanian ICU nurses' perceived barriers for enteral nutrition that hinders them from utilizing the recommended EN guidelines., Methods: A descriptive cross-sectional design was utilized using self-administered questionnaire. A total of 131 nurses participated from different hospitals representing different healthcare sectors in Jordan., Results: The five barriers subscales' means were almost equal ranging from 4.04 (Delivery of EN to the Patient) to 4.33 (ICU Resources) (out of 7). The most important barrier was "Not enough nursing staff to deliver adequate nutrition" (M=4.80, SD=1.81, 60%), followed by "Fear of adverse events due to aggressively feeding patients" (M= 4.59, SD=1.50, 56%). Although no significant differences in the mean barrier score were revealed, minimal significant differences were revealed that were distributed among different barrier subscales., Conclusion: Participants moderately perceived barriers with more focus on insufficient resources in ICU and among healthcare providers. Such barriers are modifiable and manageable, making their identification and management crucial for optimal patient care. This study confirms that enteral nutrition is a multidisciplinary responsibility.

Background: Actinic keratosis (AK), the most common premalignant skin condition, can represent a management challenge. Treatment should not only be effective, but also well tolerated and allow for good cosmesis on typical sun-exposed highly visible body sites., Objectives: The primary objective was to compare the lesion response and subject preference for topical methyl aminolaevulinate (MAL)-photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK., Methods: In this 24-week, multicentre, randomized, intraindividual (right-left) study, subjects received both one treatment session of MAL-PDT and a double freeze-thaw cryotherapy; the treatments were randomly allocated to either side of the face/scalp. Lesions with a noncomplete response were retreated after 12 weeks. The primary assessments were the subject's overall preference and lesion response at week 24. Secondary assessments included lesion response at week 12, cosmetic outcome, subject and investigator cosmetic outcome preference at week 24, and investigator overall preference at week 24. Skin discomfort and adverse events were also evaluated., Results: In total, 119 subjects with 1,501 lesions were included in the study. At week 12, treatment with MAL-PDT resulted in a significantly larger rate of cured lesions relative to cryotherapy (percentage lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1% for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for subject and investigator preferences as well as cosmetic outcome favoured MAL-PDT. Both treatment regimens were safe and well tolerated., Conclusions: The present study shows that, when treated with both MAL-PDT and cryotherapy, subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze-thaw cryotherapy.

Colloid degeneration is a rare but well-recognized entity, usually occurring on chronically sun-exposed skin. We report a case occurring on penile skin with no history of such exposure.

Treatment of trigeminal trophic syndrome is challenging and often unsatisfactory, particularly in patients with cognitive impairment. We report the novel use of a thermoplastic dressing in two patients with trigeminal trophic syndrome. Use of the dressing resulted in successful healing of ulceration in both patients, which has been maintained in the short term, representing a simple and economical therapeutic option in the management of this difficult condition.

The V-beam pulsed-dye laser (PDL) (595 nm) has gained popularity in the treatment of port wine stains (PWS). It uses longer pulse durations than the standard flashlamp-pumped pulsed-dye laser (FPDL) (585 nm) and has an in-built cooling system to protect the epidermis. This should, theoretically, reduce the treatment-associated side effects, including discomfort. The aim of this questionnaire-based study was to confirm the clinical impression that V-beam PDL is well tolerated. The results were compared with a historical group of 62 PWS patients treated with FPDL. Fifty-one patients took part in the current study. Only 35.7% (vs. 81% in the historical comparison group) required topical anaesthetic prior to laser treatment. A shortening in the duration of bruising (8 vs. 10 days) and of symptoms such as burning and tightness (3 vs. 10 days) was recorded. Lifestyle change after treatment was recorded by fewer patients (39 vs. 57%). We conclude that V-beam PDL is better tolerated than FPDL when used at therapeutic levels in patients with PWS.

Background: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD., Objective: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD., Methods: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales., Results: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects., Conclusion: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.

Background: Patients with severely damaged skin are more likely to develop skin malignancies. However, suturing following excision of tumors is difficult due to their fragile skin., Objective: To evaluate the effectiveness of a technique using butyl-2-cyanoacrylate tissue adhesive in split skin grafts in patients with severely damaged skin., Method: The technique was used in 19 patients with 24 skin tumors. Two patients also had multiple skin biopsies to assess the biodegradability of the adhesive., Results: Split skin grafts were applied successfully in all patients. The adhesive was completely absorbed without a foreign body reaction within 6 months., Conclusion: We recommend the use of butyl-2-cyanoacrylate in split skin grafting patients with severely damaged skin.

Following publication of treatment guidelines for patients with psoriasis, a six-centre audit was undertaken to assess current therapeutic practice for two second-line treatments, PUVA and methotrexate. The audit consisted of random sampling of casenotes by external auditors from a paired dermatology department, and assessment by questionnaire. One hundred and eight PUVA and 118 methotrexate casenotes were audited. The commonest indications for treatment were: (a) failure of tropical therapy--PUVA (mean 81% of casenotes), methotrexate (84%); (b) repeated hospital admissions--PUVA (16%), methotrexate (25%). For both PUVA and methotrexate, some aspects of treatment were well documented: PUVA--psoralen dosage (91%), response to PUVA (89%), cumulative lifetime UVA dosage (81%); methotrexate--pretreatment assessment of full blood count (91%), urea and electrolytes (85%), liver function tests (84%). For other aspects documentation was less complete: PUVA--no documentation of presence/absence of skin cancer history (66%), note of photoactive drugs (32%); methotrexate--concurrent medication (69%), history of presence/absence of liver disease (36%). Another aspect which was poorly documented in both PUVA and methotrexate notes was whether advice on contraception/fertility had been given. There was no indication in 29 of 32 casenotes of females of child-bearing age receiving PUVA, and 52 of 63 case notes of relevant patients on methotrexate. This project has demonstrated that formal, multicentre audit based on published guidelines is a practical proposition.

The activities of leucocyte alkaline phosphatase were determined in 511 patients with normal and pathological pregnancy. Mean values were compared and the enzyme followed up, and the conclusion was drawn that leucocyte alkaline phosphatase was no safe indicator of foetal condition. No direct relationship were found to exist between leucocyte alkaline phosphatase, total oestrogens, HSAP, HLAP, HPL, and oxytocinase.