Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago.

BACKGROUND: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. METHODS: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. RESULTS: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. CONCLUSIONS: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception.

2-Alkyl-Substituted-4-Amino-Thieno[2,3-d]Pyrimidines: Anti-Proliferative Properties to In Vitro Breast Cancer Models.

Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-d]pyrimidines 2-5 were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine 3 with IC50 13.42 µg/mL (IC50 0.045 µM), followed by compound 4 (IC50 28.89 µg/mL or IC50 0.11 µM). The thienopyrimidine 4 revealed higher selectivity to MCF-7 and lower activity (IC50 367 µg/mL i.e., 1.4 µM) than compound 3 with MCF-10A cells. With respect to MDA-MB-231 cells, ester 2 manifested the highest effect with IC50 52.56 µg/mL (IC50 0.16 µM), and 2-ethyl derivative 4 revealed IC50 62.86 µg/mL (IC50 0.24 µM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.

Novel Approach in Rectovaginal Fistula Treatment: Combination of Modified Martius Flap and Autologous Micro-Fragmented Adipose Tissue.

In this paper, we introduce an innovative therapeutic approach for managing rectovaginal fistulas (RVF), by combining the modified Martius flap and micro-fragmented adipose tissue (MFAT) enriched with mesenchymal stem cells (MSC). This novel approach aims to deal with the difficulties associated with RVF, a medically complex condition with a lack of effective treatment options. We present the case of a 45-year-old female patient with a 15-year history of Crohn's disease (CD). During the preceding eight years, she had encountered substantial difficulties resulting from a rectovaginal fistula (RVF) that was active and considerable in size (measuring 3.5 cm in length and 1 cm in width). Her condition was accompanied by tissue alterations at both the vaginal and rectal openings. Following her admission to our hospital, the patient's case was discussed during both surgical and multidisciplinary hospital team (IRB) meetings. The team decided to combine a modified Martius flap with autologous MFAT containing MSCs. The results were remarkable, leading to comprehensive anatomical and clinical resolution of the RVF. Equally significant was the improvement in the patient's overall quality of life and sexual satisfaction during the one-year follow-up period. The integration of the modified Martius flap with MFAT emerges as a highly promising approach for addressing CD-related RVFs that had historically been, and still are, difficult to treat, given their often refractory nature and low healing success rates.

Laser texturing of additively manufactured implants: A tool to programme biological response.

The advent of additive manufacturing (AM) is rapidly shaping healthcare technologies pushing forward personalisation and enhanced implant functionalisation to improve clinical outcomes. AM techniques such as powder bed fusion (PBF) have been adopted despite the need to modify the as-built surface post manufacture. Medical device manufacturers have focused their efforts on refining various physical and chemical surface finishing approaches, however there is little consensus and some methods risk geometry alteration or contamination. This has led to a growing interest in laser texturing technologies to engineer the device surface. Herein, several bioinspired micro and nano textures were applied to laser PBF Ti-6Al-V4 substrates to alter physicochemical properties and in-turn we sought to understand what influences these alterations had on a human osteosarcoma cell line (MG63). Significant variations in roughness and time dependent contact angles were revealed between different patterns provide a tool to elicit desired biological responses. All surface treatments effectively enhanced early cell behaviour and in particular coverage was increased for the micro-textures. Influence of the patterns on cell differentiation was less consistent with alkaline phosphatase content increased only for the channel, grid and dual textures. While long term (21 days) mineralisation was found to be significantly enhanced in grids, dual, triangles and shark skin textures. Further regression analysis of all physicochemical and biological variables indicated that several properties should be used to strongly correlate cell behaviour, resulting in 82 % of the 21 day mineralisation dataset explained through a combination of roughness kurtosis and glycerol contact angle. Overall, this manuscript demonstrates the ability of laser texturing to offer tailored cell-surface interactions, which can be tuned to offer a tool to drive functional customisation of anatomically customised medical devices.

Laser-Enabled Surface Treatment of Disposable Endoscope Lens with Superior Antifouling and Optical Properties.

Endoscopes are ubiquitous in minimally invasive or keyhole surgeries globally. However, frequent removal of endoscopes from the patient's body due to the lens contaminations results in undesirable consequences. Therefore, a cost-effective process chain to fabricate thermoplastic-based endoscope lenses with superior antifouling and optical properties is proposed in this research. Such multifunctional surface response was achieved by lubricant impregnation of nanostructures. Two types of topographies were produced by femtosecond laser processing of metallic molds, especially to produce single-tier laser-induced periodic surface structures (LIPSS) and two-tier multiscale structures (MS). Then, these two LIPSS and MS masters were used to replicate them onto two thermoplastic substrates, namely polycarbonate and cyclic olefin copolymer, by using hot embossing. Finally, the LIPSS and MS surfaces of the replicas were infiltrated by silicone oils to prepare lubricant-impregnated surfaces (LIS). Droplet sliding tests revealed that the durability of the as-prepared LIS improved with the increase of the lubricant viscosity. Moreover, the single-tier LIPSS replicas exhibited longer-lasting lubricant conservation properties than the MS ones. Also, LIPSS-LIS replicas demonstrated an excellent optical transparency, better than the MS-LIS ones, and almost match the performance of the reference polished ones. Furthermore, the LIPSS-LIS treatment led to superior antifouling characteristics, i.e., regarding fogging, blood adhesion, protein adsorption, and microalgae attachment, and thus demonstrated its high suitability for treating endoscopic lenses. Finally, a proof-of-concept LIPSS-LIS treatment of endoscope lenses was conducted that confirmed their superior multifunctional response.

New C2- and N3-Modified Thieno[2,3-d]Pyrimidine Conjugates with Cytotoxicity in the Nanomolar Range.

AIMS: The aim of the current study was to develop and explore a series of new cytotoxic agents based on the conjugation between the thieno[2,3-d]pyrimidine moiety and a second pharmacophore at the C2 or N3 position. BACKGROUND: As the thieno[2,3-d]pyrimidine core is a bioisostere of the 4-anilinoquinazoline, various new thienopyrimidine derivatives were synthesized by modifying the structure of the clinically used anticancer quinazoline EGFR inhibitors of the first generation - gefitinib, and second-generation - dacomitinib and canertinib. It was reported that some thieno[2,3-d]pyrimidine derivatives showed improved EGFR inhibitory activity. On the other hand, the benzimidazole heterocycle is present as a pharmacophore unit in the structure of many clinically used chemotherapeutic agents. Some 2-aminobenzimidazole derivatives, possessing anticancer activity, demonstrated EGFR inhibition and the benzimidazole derivative EGF816 is currently in the second phase of clinical trials. OBJECTIVE: The objectives of the study were the design of a novel series thieno[2,3-d]pyrimidines, synthesis of the compounds and investigation of their effects towards human cancer HT-29, MDA-MB-231, HeLa, HepG2 and to normal human Lep3 cell lines. (American Type Culture Collection, ATCC, Rockville, MD, USA). METHODS: The synthetic protocol implemented cyclocondensation of 2-amino-thiophenes and nitriles in an inert medium, aza- Michael addition to benzimidazole derivatives and nucleophylic substitution at the N3 place. MTS test was used in order to establish the cytotoxicity of the tested compounds. SAR analysis and in silico assessment of the inhibitory potential towards human oncogenic V599EB-Raf were performed using Molinspiration tool and Molecular Operating environment software. RESULTS: The MTS test data showed that almost all studied thieno[2,3-d]pyirimidines (9-13, 21-22 and 25) manifest high inhibitory effect on cell proliferation at nanomolar concentrations, whereas compounds 9 (IC50 = 130 nM) and 10 (IC50 = 261 nM) containing amino acid moiety, and 21 (IC50 = 108 nM) possessing two thienopyrimidine moieties attached to a 1,3-disubstituted benzimidazole linker, revealed many times lower toxicity against Lep3 cells compared to the cancer cells. Thienopyrimidines 11-13 possessed high selectivity against HeLa cells. Compound 13 showed high inhibitory activity against MDA-MB-231 and HepG2, with IC50 1.44 nM and 1.11 nM respectively. To outline the possible biological target of the studied coumpounds, their potential to interact with human oncogenic V599EB-Raf was explored by a docking study. As a result, it was suggested that the benzimidazolyl and glycyl fragments could enhance the binding ability of the new compounds by increasing the number of hydrogen bond acceptors and by stabilizing the inactive form of the enzyme. CONCLUSION: The thienopyrimidines tested in vitro for human cancer HT-29, MDA-MB-231, HeLa, HepG2 and normal human Lep3 cell lines demonstrated cytotoxicity in the nanomolar range. It was established that compounds 9, 10 and 21 showed many times lower toxicity against normal Lep3 cells that can provide a high selectivity towards all four cancer cell lines at small concentrations. Based on the analysis of the structure-activity relationship, the observed trends in the cytotoxicity could be related to the lipophilicity and the topological polar surface area of the tested compounds. The docking study on the potential of the new thieno[2,3-d]pyrimidine-4-ones to interact with mutant V599EB-Raf showed that the compounds might be able to stabilize the enzyme in its inactive form.

Lab-on-a-Contact Lens Platforms Fabricated by Multi-Axis Femtosecond Laser Ablation.

Contact lens sensing platforms have drawn interest in the last decade for the possibility of providing a sterile, fully integrated ocular screening technology. However, designing scalable and rapid contact lens processing methods while keeping a high resolution is still an unsolved challenge. In this article, femtosecond laser writing is employed as a rapid and precise procedure to engrave microfluidic networks into commercial contact lenses. Functional microfluidic components such as flow valves, resistors, multi-inlet geometries, and splitters are produced using a bespoke seven-axis femtosecond laser system, yielding a resolution of 80 µm. The ablation process and the tear flow within microfluidic structures is evaluated both experimentally and computationally using finite element modeling. Flow velocity drops of the 8.3%, 20.8%, and 29% were observed in valves with enlargements of the 100%, 200%, and 300%, respectively. Resistors yielded flow rate drops of 20.8%, 33%, and 50% in the small, medium, and large configurations, respectively. Two applications were introduced, namely a tear volume sensor and a tear uric acid sensor (sensitivity 16 mg L-1 ), which are both painless alternatives to current methods and provide reduced contamination risks of tear samples.

Thieno[2,3-d]pyrimidin-4(3H)-one Derivatives of Benzimidazole as Potential Anti- Breast Cancer (MDA-MB-231, MCF-7) Agents.

AIMS: The purpose of this study was the synthesis of some new thienopyrimidine derivatives of 1,3-disubstituted benzimidazoles and the evaluation of their cytotoxicity against MDA-MB-231, MCF-7, and 3T3 cells lines. BACKGROUND: An overexpression or mutational activation of TK receptors EGFR and HER2/neu is characteristic of tumors. It has been found that some thieno[2,3-d]pyrimidines exhibited better inhibitory activity against Epidermal Growth Factor Receptor (EGFR/ErbB-2) tyrosine kinase in comparison to aminoquinazolines. Breast cancer activity towards MDA-MB-231 and MCF-7 cell lines by inhibiting EGFR was revealed by a novel 2-arylbenzimidazole. This motivated the synthesis of new thienopyrimidines possessing benzimidazole fragments in order to evaluate their cytotoxicity to the above-mentioned cell lines. OBJECTIVE: The objectives of the study were to design and synthesize a novel series of thieno[2,3-d]pyrimidines bearing biologically active moieties, such as 1,3-disubstituted-benzimidazole heterocycle, structurally similar to diaryl ureas in order to evaluate their cytotoxicity against MDA-MB-231, and MCF-7 breast cancer cell lines. METHODS: N,N-disubstituted benzimidazole-2-one carbonitriles were synthesized by Aza-Michael addition and used as precursors to generate some of the new thieno[2,3-d]pyrimidines in acidic medium The interaction of chloroethyl-2-thienopyrimidines, 2-amino-benzimidazole and benzimidazol-2-one nitriles under solid-liquid transfer catalysis conditions led to new thienopyrimidines. MTT assay for cell survival was performed in order to evaluate the cytotoxicity of the tested compounds. A fluorescence study was conducted to elucidate some aspects of the mechanism of action. RESULTS: The effects of nine synthesized compounds were investigated towards MDA-MB-231, MCF-7 and 3T3 cell lines. Thieno[2,3-d]pyirimidine-4-one 16 (IC50 - 0.058µM) and 21 (IC50 - 0.029µM) possess high cytotoxicity against MDA-MB-231 cells after 24h. The most cytotoxic compounds against breast cancer MCF-7 cells was compound 21 (IC50 - 0.074µM), revealing lower cytotoxicity against mouse fibroblast 3T3 cells with IC50 - 0.20µM. SAR analysis was performed. Fluorescence study of the treatment of MDA-MB cells with compound 21 was carried out in order to clarify some aspects of the mechanism of action. CONCLUSION: The relationship between cytotoxicity of compounds 14 and 20 against MCF-7 and 3T3 cells can suggest a similar mechanism of action. The antitumor potential of the tested compounds proves the necessity for further investigation to estimate the exact inhibition pathway in the cellular processes. The fluorescence study of the treatment of MDA-MB cells with compound 21 showed a rapid process of apoptosis.

Functionalization of Plastic Parts by Replication of Variable Pitch Laser-Induced Periodic Surface Structures.

Surface functionalization of plastic parts has been studied and developed for several applications. However, demand for the development of reliable and profitable manufacturing strategies is still high. Here we develop and characterize a new process chain for the versatile and cost-effective production of sub-micron textured plastic parts using laser ablation. The study includes the generation of different sub-micron structures on the surface of a mold using femtosecond laser ablation and vario-thermal micro-injection molding. The manufactured parts and their surfaces are characterized in consideration of polymer replication and wetting behavior. The results of the static contact angle measurements show that replicated Laser-Induced Periodic Surface Structures (LIPSSs) always increase the hydrophobicity of plastic parts. A maximum contact angle increase of 20% was found by optimizing the manufacturing thermal boundary conditions. The wetting behavior is linked to the transition from a Wenzel to Cassie-Baxter state, and is crucial in optimizing the injection molding cycle time.

Anti-Biofouling Properties of Femtosecond Laser-Induced Submicron Topographies on Elastomeric Surfaces.

Antibacterial coatings are often employed to elastomer surfaces to inhibit bacterial attachment. However, such approaches could lead to increased antibiotic resistance. Surface micro-/nanotexturing is gaining significant attention recently, as it is a passive approach to reduce bacterial adhesion to surfaces. To this end, this work aims to assess the anti-biofouling functionality of femtosecond laser-induced submicron topographies on biomedical elastomer surfaces. Femtosecond laser processing was employed to produce two types of topographies on stainless-steel substrates. The first one was highly regular and single scale submicron laser-induced periodic surface structures (LIPSS) while the second one was multiscale structures (MSs) containing both submicron- and micron-scale features. Subsequently, these topographies were replicated on polydimethylsiloxane (PDMS) and polyurethane (PU) elastomers to evaluate their bacterial retention characteristics. The submicron textured PDMS and PU surfaces exhibited long-term hydrophobic durability up to 100 h under immersed conditions. Both LIPSS and MS topographies on PDMS and PU elastomeric surfaces were shown to substantially reduce (>89%) the adhesion of Gram-negative Escherichia coli bacteria. At the same time, the anti-biofouling performance of LIPSS and MS topographies was found to be comparable with that of lubricant-impregnated surfaces. The influence of physical defects on textured surfaces on the adhesion behavior of bacteria was also elucidated. The results presented here are significant because the polymeric biomedical components that can be produced by replication cost effectively, while their biocompatibility can be improved through femtosecond surface modification of the respective replication masters.

Laser Micromachining of Lithium Niobate-Based Resonant Sensors towards Medical Devices Applications.

This paper presents a micromachining process for lithium niobate (LiNbO3) material for the rapid prototyping of a resonant sensor design for medical devices applications. Laser micromachining was used to fabricate samples of lithium niobate material. A qualitative visual check of the surface was performed using scanning electron microscopy. The surface roughness was quantitatively investigated using an optical surface profiler. A surface roughness of 0.526 µm was achieved by laser micromachining. The performance of the laser-micromachined sensor has been examined in different working environments and different modes of operation. The sensor exhibits a Quality-factor (Q-factor) of 646 in a vacuum; and a Q-factor of 222 in air. The good match between the modelling and experimental results shows that the laser-micromachined sensor has a high potential to be used as a resonance biosensor.

Effects of Top-hat Laser Beam Processing and Scanning Strategies in Laser Micro-Structuring.

The uniform energy distribution of top-hat laser beams is a very attractive property that can offer some advantages compared to Gaussian beams. Especially, the desired intensity distribution can be achieved at the laser spot through energy redistribution across the beam spatial profile and, thus, to minimize and even eliminate some inherent shortcomings in laser micro-processing. This paper reports an empirical study that investigates the effects of top-hat beam processing in micro-structuring and compares the results with those obtainable with a conventional Gaussian beam. In particular, a refractive field mapping beam shaper was used to obtain a top-hat profile and the effects of different scanning strategies, pulse energy settings, and accumulated fluence, i.e., hatch and pulse distances, were investigated. In general, the top-hat laser processing led to improvements in surface and structuring quality. Especially, the taper angle was reduced while the surface roughness and edge definition were also improved compared to structures produced with Gaussian beams. A further decrease of the taper angle was achieved by combining hatching with some outlining beam passes. The scanning strategies with only outlining beam passes led to very high ablation rates but in expense of structuring quality. Improvements in surface roughness were obtained with a wide range of pulse energies and pulse and hatch distances when top-hat laser processing was used.

Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4.

A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14) as the most effective inhibitor (IC50 = 34.17 ± 5.11 µM). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 µM. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme-inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.

Response of Saos-2 osteoblast-like cells to laser surface texturing, sandblasting and hydroxyapatite coating on CoCrMo alloy surfaces.

Cobalt chrome alloys are commonly used in orthopaedic implants where high stiffness and wear resistance are required. This study proposes Laser Surface Texturing (LST) as a cost-effective mean for producing bioinspired surface textures in order to improve the performance of CoCrMo orthopaedic implants. Cobalt-chrome alloy disks were modified using three different LST strategies: i) micro-scale texturing using a nanosecond laser source; (ii) micro-scale texturing with an ultrashort laser source and (iii) bioinspired sub-micron scale texturing with an ultrashort laser source. The modified disks were characterized and compared to blasted, hydroxyapatite coated and polished surface finishes. Saos-2 osteoblast-like cells were seeded on the different surfaces and their proliferation and morphology was assessed. The laser modification increases the surface energy of the CoCrMo alloy disks when compared to their untreated counterparts. The bioinspired sub-micron textured surfaces exhibited the highest cell metabolic activity on day 7 of the MTT assay.

Synthesis and DNase I inhibitory properties of some 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines.

A series of six novel and six known thieno[2,3-d]pyrimidin-4-amines 2-13 were synthesized, and further were used as a starting material for preparation of a small series of eight novel thieno[2,3-d]pyrimidin-4-phthalimides 14-21. Eight compounds, five amine and three phthalimide derivatives, inhibited bovine pancreatic DNase I with an IC50 below 200 µM, being more effective than referent inhibitor crystal violet. Phthalimide derivatives 16, 18 and 19 exhibited higher DNase I inhibitory activity compared to their amine precursors 7, 10 and 11. Compound 19, as the most potent (IC50 = 106 ±â€¯16 µM), offers a good starting point for a design of new DNase I inhibitors. The Pharma RQSAR model showed a significant enhancement of thieno[2,3-d]pyrimidines activity using aryl substituents at R1 position. The E-State RQSAR model clarified the most important structural fragments relevant for DNase I inhibition. Molecular docking and Site Finder module defined the thieno[2,3-d]pyrimidines interactions with the most important catalytic residues of DNase I, including Glu 39, His 134, Asp 168 and His 252. We also found that steric effects and increase of molecular volume play a vital role in DNase I inhibition.

Femtosecond laser ablation of dentin and enamel for fast and more precise dental cavity preparation.

PURPOSE: The purpose of the present work was to achieve fast and more precise ablation in dentin and enamel by using a commercial femtosecond laser system with high repetition rate, whilst avoiding any collateral irreversible damages in the hard tissue and pulp area. METHODS: We used fluence of the incident laser pulses which was marginally higher than the ablation threshold for dentin and enamel. The study was based on the hypothesis that femtosecond laser operating with a repetition rate in the range of 100-500 kHz can controllably ablate dental tissue obtaining sufficiently high removal rate whilst avoiding any collateral irreversible damages in the hard tissue and pulp area. RESULTS: The ablation yielded the formation of 1 mm3 craters with well-defined precise vertical cavity sides and edges. Advantageous high porosity and numerous interconnected pores were introduced in the ablated zones. Thermal load and hence collateral thermo-mechanical damages were avoided and the crystalline structure of the tooth constituent hydroxyapatite was preserved. CONCLUSION: The ultrafast femtosecond laser used in our work hold the promise of a significant drilling ability without collateral thermomechanical effects. It achieves high processing efficiency, overcomes disadvantages of other laser systems reported and can be used to develop an instrument for cavity preparation based on fast and precise ablation. Our further aim is to exceed the speed of traditional drilling instruments and thus to reduce the treatment time which in turn will bring comfort to the patient.

Correction: Femtosecond laser ablation of transparent microphotonic devices and computer-generated holograms.

Correction for 'Femtosecond laser ablation of transparent microphotonic devices and computer-generated holograms' by Tawfiq Alqurashi, et al., Nanoscale, 2017, 9, 13808-13819.

Femtosecond laser ablation of transparent microphotonic devices and computer-generated holograms.

Femtosecond laser ablation allows direct patterning of engineering materials in industrial settings without requiring multistage processes such as photolithography or electron beam lithography. However, femtosecond lasers have not been widely used to construct volumetric microphotonic devices and holograms with high reliability and cost efficiency. Here, a direct femtosecond laser writing process is developed to rapidly produce transmission 1D/2D gratings, Fresnel Zone Plate lenses, and computer-generated holograms. The optical properties including light transmission, angle-dependent resolution, and light polarization effects for the microphotonic devices have been characterized. Varying the depth of the microgratings from 400 nm to 1.5 µm allowed the control over their transmission intensity profile. The optical properties of the 1D/2D gratings were validated through a geometrical theory of diffraction model involving 2D phase modulation. The produced Fresnel lenses had transmission efficiency of ∼60% at normal incidence and they preserved the polarization of incident light. The computer-generated holograms had an average transmission efficiency of 35% over the visible spectrum. These microphotonic devices had wettability resistance of contact angle ranging from 44° to 125°. These devices can be used in a variety of applications including wavelength-selective filters, dynamic displays, fiber optics, and biomedical devices.

Femtosecond laser directed fabrication of optical diffusers.

Optical diffusers are widely used in filament lamps, imaging systems, display technologies, lasers, and Light Emitting Diodes (LEDs). Here, a method for the fabrication of optical diffusers through femtosecond laser machining is demonstrated. Float glass surfaces were ablated with femtosecond laser light to form nanoscale ripples with dimensions comparable to the wavelength of visible light. These structures produce highly efficient and wide field of view diffusers. The machined patterns altered the average surface roughness, with the majority of particles in the range of a few hundred nanometers. The optical diffusion characteristic and a maximum diffusion angle of near 172° was achieved with optimum machining parameters. The transmission performance of the diffusers was measured to be ∼30% across the visible spectrum. The demonstrated technique has potential for producing low-cost large area optical devices. The process benefits from the flexibility of the laser writing method and enables the production of custom optical diffusers.

Synthesis, anticancer activity and photostability of novel 3-ethyl-2-mercapto-thieno[2,3-d]pyrimidin-4(3H)-ones.

Some derivatives of 3-ethyl-2-mercapto-thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized using ethyl 2-aminothiophene-3-carboxylates as precursors in order to estimate their cytotoxicity, respectively proliferative activity. Thienopyrimidinones containing thiosemicarbazide as well as 1,3,4-thiadiazole moieties were evaluated for their cytotoxical effect on four cancer cell lines: HT-29, breast cancer cells MDA-MB-231, HeLa, HepG2 as well as human diploid cell line Lep-3. Compounds 5b, 6a and 6b revealed cytotoxicity to the four studied cancer cell lines. The highst cytotoxicity against MDA-MB-31 exhibited the thiosemicarbazide 5b with IC50 2.31.10(-4) µM, but most active towards HT-29 cell lines was thienopyrimidine 6c with IC50 0.001 µM. Compound 6a showed the highest inhibitory activity with IC50 - 0.99 µM to human liver carcinoma HepG2 cells and low cytotoxicity towards Lep3 (IC50 = 191 µM). The thienopyrimidine derivative linked to thiadiazole 6b was toxic to the four studied cancer cell lines, especially to HeLa (IC50-0.83 µM), and besides that the compound demonstrated toxicity to Lep 3 cells at very high concentration 89 × 10(3) µM. The solid-state photostability of the derivatives 5a-c and 6a-c was tested by irradiation with UV light. All of the studied compounds show solid-state photostability in 240 min of irradiation. Using MOE software molecular docking of the three ligands 5b, 6b and 7 was accomplished into an internal pocket formed by the activation segment and the P-loop of (V599E)B-Raf. It was established that the binding of the ligands to (V599E)B-Raf promotes an inactive conformation of the enzyme.