Integrated Approach of Life Cycle Assessment and Experimental Design in the Study of a Model Organic Reaction: New Perspectives in Renewable Vanillin-Derived Chemicals.

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization.

Very Large Pore Mesoporous Bioactive Silicate Glasses: Comparison of Behavior toward Classical Mesoporous Bioactive Glasses in Terms of Drug Loading/Release and Bioactivity.

Considering the increase in patients who suffer from osteoporosis and the bone defects that occur in these patients, bone tissue regeneration is a promising option to solve this problem. To achieve a synergistic effect between the synthesis of a proper structure and bioactive/pharmaceutical activity, ions with a physiological effect can be added to silica structures, such as Ca2+, thanks to its bioactive behavior, and Ga3+ for its antibacterial and anticancer action. In this work, the synthesis of large pore mesoporous silica (LPMS), potential bioactive glasses containing Ca2+ and Ga3+, has been studied. Corresponding structures, in terms of composition, have been synthesized following the Sol-Gel EISA (Evaporation Induced Self-Assembly) process (obtaining Classical Mesoporous Silica, MS). Pore structure characterization of LPMSs and MSs has been performed using N2 adsorption/desorption and Hg-porosimetry, showing the presence of pores for LPMSs in the range of 20-60 and 200-600 nm. Nisin, a polycyclic antibacterial peptide, has been used for load tests. The load and release tests performed highlight a higher loading and releasing, doubled for LPMSs if compared to MSs. To confirm the maintenance of the structure of LPMSs and their mechanical strength and resistance, scanning electron microscopy images were acquired before and after release tests. Ca and Ga release in SBF has been studied through inductively coupled plasma-optical emission spectroscopy (ICP-OES), showing a particularly high release of these ions performed with LPMSs. The bioactive behavior of Ca-containing structures has been confirmed using FT-IR (Fourier-transform infrared spectroscopy), SEM-EDS (Scanning Electron Microscope-Energy Dispersive Spectroscopy), and X-ray powder diffraction (XRDP). In conclusion, LPMSs showed better loading and releasing properties compared with classical MS and better release in terms of active ions. In addition, it has also been demonstrated that LPMSs have bioactive behavior (a well-known characteristic of MSs).

Cholangiocarcinoma-on-a-chip: A human 3D platform for personalised medicine.

Background & Aims: Cholangiocarcinoma (CCA) is a primary liver tumour characterised by a poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the tumour niche. We aimed to develop an innovative patient-specific CCA-on-chip platform. Methods: A CCA tumour microenvironment was recapitulated on a microfluidic three-channel chip using primary CCA cells, cancer-associated fibroblasts (CAFs), endothelial cells, and T cells isolated from CCA specimens (n = 6). CAF and CCA cells were co-cultured in the central channel, flanked by endothelial cells in one lateral channel, recreating a tubular structure. An extensive characterisation of this platform was carried out to investigate its diffusion ability, hydrogel properties, and changes in matrix composition. Cell phenotype and functional properties were assessed. Results: Primary cells seeded on the microfluidic device were shown to reproduce the architectural structure and maintain the original phenotype and functional properties. The tumour niche underwent a deep remodelling in the 3D device, with an increase in hydrogel stiffness and extracellular matrix deposition, mimicking in vivo CCA characteristics. T cells were incorporated into the device to assess its reliability for immune cell interaction studies. Higher T cell migration was observed using cells from patients with highly infiltrated tumours. Finally, the drug trial showed the ability of the device to recapitulate different drug responses based on patient characteristics. Conclusions: We presented a 3D CCA platform that integrates the major non-immune components of the tumour microenvironment and the T cell infiltrate, reflecting the CCA niche. This CCA-on-chip represents a reliable patient-specific 3D platform that will be of help to further elucidate the biological mechanisms involved in CCA and provide an efficient tool for personalised drug testing. Impact and implications: An innovative patient-specific cholangiocarcinoma (CCA)-on-chip platform was successfully developed, integrating the major components of the tumour microenvironment (tumour cells, cancer-associated fibroblasts, endothelial cells, and immune infiltrate) and faithfully mimicking the CCA niche. This CCA-on-chip represents a powerful tool for unravelling disease-associated cellular mechanisms in CCA and provides an efficient tool for personalised drug testing.

Cigarette Smoking and Intracranial Aneurysms: A Pilot Analysis of SNPs in the CYP2A6 Gene in the Italian Population.

BACKGROUND: Cigarette smoking is a modifiable risk factor associated with formation and rupture of intracranial aneurysms (IAs). Cytochrome P450 2A6 (CYP2A6) is the main enzyme implied in catabolism of nicotine and xenobiotics, giving rise to oxidative stress products. Our study investigated the associations between specific single-nucleotide polymorphisms (SNPs) in the CYP2A6 gene and the presence of sporadic IAs in a cluster of Italian patients, as well as their rupture regarding cigarette smoking habit. METHODS: Three hundred and thirty-one Italian patients with sporadic IAs were recruited in a single institution. We recorded data on clinical onset with subarachnoid hemorrhage (SAH) and smoking habit. Genetic analysis was performed with a standard procedure on peripheral blood samples: CYP2A6 ∗1B2, CYP2A6 ∗2, and CYP2A6 ∗14 SNPs were analyzed in the study group along with 150 healthy control subjects. Statistical analysis was conducted according to genetic association study guidelines. RESULTS: In the patient cohort, the frequency of aSAH was significantly higher in current smokers (P < 0.001; OR=17.45), regardless of the pattern of CYP2A6 SNPs. There was a correlation between IA rupture and cigarette smoking in patients with the heterozygous CYP2A6 ∗1B2 allele (P < 0.001; OR=15.47). All patients carrying the heterozygous CYP2A6 ∗14 allele had an aSAH event (100%), regardless of smoking habit, although this correlation was not statistically significant (P = 1). CONCLUSIONS: According to our findings, a cigarette smoker carrying a fully active CYP2A6 enzyme (heterozygous ∗1B2 allele) may have an increased risk of IA rupture compared to those with functionally less active variants: further investigation on a larger sample is needed to verify this result. The role of the heterozygous CYP2A6 ∗14 allele in aSAH is yet to be clarified.

Development of Stable Amino-Pyrimidine-Curcumin Analogs: Synthesis, Equilibria in Solution, and Potential Anti-Proliferative Activity.

With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin's low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine-curcumin derivatives is reported. The compounds were fully characterized (1H/13C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells.

Phosphorus Acquisition Efficiency and Transcriptomic Changes in Maize Plants Treated with Two Lignohumates.

Lignohumates are increasing in popularity in agriculture, but their chemistry and effects on plants vary based on the source and processing. The present study evaluated the ability of two humates (H1 and H2) to boost maize plant performance under different phosphorus (P) availability (25 and 250 µM) conditions in hydroponics, while understanding the underlying mechanisms. Humates differed in chemical composition, as revealed via elemental analysis, phenol and phytohormone content, and thermal and spectroscopic analyses. H1 outperformed H2 in triggering plant responses to low phosphorus by enhancing phosphatase and phytase enzymes, P acquisition efficiency, and biomass production. It contained higher levels of endogenous auxins, cytokinins, and abscisic acid, likely acting together to stimulate plant growth. H1 also improved the plant antioxidant capacity, thus potentially increasing plant resilience to external stresses. Both humates increased the nitrogen (N) content and acted as biostimulants for P and N acquisition. Consistent with the physiological and biochemical data, H1 upregulated genes involved in growth, hormone signaling and defense in all plants, and in P recycling particularly under low-P conditions. In conclusion, H1 showed promising potential for effective plant growth and nutrient utilization, especially in low-P plants, involving hormonal modulation, antioxidant enhancement, the stimulation of P uptake and P-recycling mechanisms.

Very Large Pores Mesoporous Silica as New Candidate for Delivery of Big Therapeutics Molecules, Such as Pharmaceutical Peptides.

The synthesis of a scaffold that can accommodate big molecules with a pharmaceutical role is important to shield them and maintain their biological activity. In this field, silica particles with large pores (LPMS) are innovative supports. Large pores allow for the loading of bioactive molecules inside the structure and contemporarily their stabilization and protection. These purposes cannot be achieved using classical mesoporous silica (MS, pore size 2-5 nm), because their pores are not big enough and pore blocking occurs. LPMSs with different porous structures are synthesized starting from an acidic water solution of tetraethyl orthosilicate reacting with pore agents (Pluronic® F127 and mesitylene), performing hydrothermal and microwave-assisted reactions. Time and surfactant optimization were performed. Loading tests were conducted using Nisin as a reference molecule (polycyclic antibacterial peptide, with dimensions of 4-6 nm); UV-Vis analyses on loading solutions were performed. For LPMSs, a significantly higher loading efficiency (LE%) was registered. Other analyses (Elemental Analysis, Thermogravimetric Analysis and UV-Vis) confirmed the presence of Nisin in all the structures and its stability when loaded on them. LPMSs showed a lower decrease in specific surface area if compared to MS; in terms of the difference in LE% between samples, it is explained considering the filling of pores for LPMSs, a phenomenon that is not allowed for MSs. Release studies in simulated body fluid highlight, only for LPMSs, a controlled release, considering the longer time scale of release. Scanning Electron Microscopy images acquired before and after release tests shows the LPMSs' maintenance of the structure, demonstrating strength and mechanical resistance of structures. In conclusion, LPMSs were synthesized, performing time and surfactant optimization. LPMSs showed better loading and releasing properties with respect to classical MS. All collected data confirm a pore blocking for MS and an in-pore loading for LPMS.

Radiolabeled Chalcone Derivatives as Potential Radiotracers for ß-Amyloid Plaques Imaging.

Natural products often provide a pool of pharmacologically relevant precursors for the development of various drug-related molecules. In this review, the research performed on some radiolabeled chalcone derivatives characterized by the presence of the α-ß unsaturated carbonyl functional group as potential radiotracers for the imaging of ß-amyloids plaques will be summarized. Chalcones' structural modifications and chemical approaches which allow their radiolabeling with the most common SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) radionuclides will be described, as well as the state of the art regarding their in vitro binding affinity and in vivo biodistribution and pharmacokinetics in preclinical studies. Moreover, an explanation of the rationale behind their potential utilization as probes for Alzheimer's disease in nuclear medicine applications will be provided.

Alginate Beads Containing Cerium-Doped Mesoporous Glass and Curcumin: Delivery and Stabilization of Therapeutics.

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica. In this work, various systems have been synthesized: starting from mesoporous silica glasses (MGs), cerium-containing MGs have been produced; then, these systems have been loaded with 4 to 6% of curcumin. Finally, various MGs at different compositions have been included in alginate beads. In vitro studies showed that these hybrid materials enable the stabilization and effective delivery of curcumin and that a synergic effect can be achieved if Ce3+/Ce4+ and curcumin are both part of the beads. From swelling tests, it is possible to confirm a controlled curcumin release compartmentalized into the gastrointestinal tract. For all beads obtained, a curcumin release sufficient to achieve the antioxidant threshold has been reached, and a synergic effect of cerium and curcumin is observed. Moreover, from catalase mimetic activity tests, we confirm the well-known catalytic activity of the couple Ce3+/Ce4+. In addition, an extremely good radical scavenging effect of curcumin has been demonstrated. In conclusion, these systems, able to promote an enzymatic-like activity, can be used as drug delivery systems for curcumin-targeted dosing.

Taxonomical and functional composition of strawberry microbiome is genotype-dependent.

INTRODUCTION: Specific microbial communities are associated to host plants, influencing their phenotype and fitness.Despite the rising interest in plant microbiome, the role of microbial communities associated with perennial fruit plants remains overlooked. OBJECTIVES: This work provides the first comprehensive descriptionof the taxonomical and functional bacterial and fungal microbiota of below- and above-ground organsof three commercially important strawberry genotypes under cultural conditions. METHODS: Strawberry-associatedfungal and bacterial microbiomes were characterised by Next-Generation Sequencing and the potential functions expressed by the bacterial microbiome were analysed by both in silico and in vitro characterisation of plant growth-promoting abilities of native bacteria. Additionally, the association between the strawberry microbiome, plant disease tolerance, plant mineral nutrient content, and fruit quality was investigated. RESULTS: Results showed that thestrawberry core microbiome included 24 bacteria and 15 fungal operational taxonomicunits (OTUs).However, plant organ and genotype had a significant role in determining the taxonomical and functional composition of microbial communities. Interestingly, the cultivar with the highesttolerance against powdery mildew and leaf spot and the highest fruit productivity was the only one able to ubiquitously recruit the beneficial bacterium, Pseudomonasfluorescens, and to establish a mutualistic symbiosis with the arbuscular mycorrhizaRhizophagus irregularis. CONCLUSION: This work sheds light on the interaction of cultivated strawberry genotypes with a variety of microbes and highlights the importance of their applications to increase the sustainability of fruit crop production.

Curcumin-Based ß-Diketo Ligands for Ga3+: Thermodynamic Investigation of Potential Metal-Based Drugs.

Curcumin is known for its therapeutic properties; among these, antioxidant, anti-inflammatory and anti-cancer ones stand out. Besides, curcumin metal complexes have shown widespread application in medicine and can be exploited as lead structures for developing metal-based drugs. Unfortunately, curcumin is poorly bioavailable, mainly due to its instability in physiological conditions; this weakness is tightly connected to the presence of the ß-diketo moiety undergoing tautomeric equilibrium. Stability and metal-chelating ability can be tuned by modulating the electronic effects and steric hindrance close to the ß-diketo moiety; in addition, formation of a metal complex shifts the tautomeric equilibrium towards the ß-keto-enol form and increases stability in biological media. Among the metals used in clinical therapy, gallium nitrate has shown to have significant antitumor activity against non-Hodgkin lymphoma and bladder cancer, thus indicating that gallium-based drugs have potential for further development as antineoplastic agents with improved therapeutic activity. Curcuminoids have demonstrated high affinity for gallium(III), allowing the formation of stable positively charged M:L 1:2 ß-diketonate complexes that benefit from the therapeutic activity of both the metal and the ligand. Seven new curcumin derivatives were synthesized and completely characterized. The new derivatives retain the solvent-dependent keto-enol tautomerism, with the prevalence of the diketo form in aqueous solution. Enhanced stability in simulated physiological conditions was observed in comparison to the lead compound curcumin. The presence of Ga3+ anticipates the dissociation of the enolic proton, allowing chelate complex formation, and simultaneously it shifts the tautomeric equilibrium towards the keto-enol form. A complete 1H/13C NMR and UV-Vis study was performed to define the metal-to-ligand stoichiometry ratio and the overall stability constants. In addition, we demonstrated that some of the derivatives have increased antiproliferative activity on colon cancer cells compared to curcumin and antioxidant properties. On the whole, the synthesized curcumin-based molecules may act as new gallium(III) chelators with improved stability with respect to curcumin and could open interesting perspectives for the development of novel therapeutic agents for cancer.

Photo and Soft Lithography for Organ-on-Chip Applications.

Organs-on-Chip devices are generally fabricated by means of photo- and soft lithographic techniques. Photolithography is a process that involves the transfer of a pattern onto a substrate by a selective exposure to light. In particular, in this chapter two different photolithography methods will be described: liquid and dry photolithography. In liquid photolithography, a silicon wafer is spin-coated with liquid photoresist and exposed to UV light in order to be patterned. In dry photolithography, the silicon wafer is laminated with resist dry film before being patterned through UV light. In both cases, the UV light can be collimated on top of the wafer either through photomasks or by direct laser exposure. The obtained patterned wafer is then used as a mold for the soft lithographic process (i.e., replica molding) to produce polymer-based microdevices.

Hybrid Robotics for Endoscopic Transnasal Skull Base Surgery: Single-Centre Case Series.

BACKGROUND: Only preclinical studies and case reports have described robotic surgery for endoscopic transnasal skull base surgery. OBJECTIVE: To evaluate the role of a novel robotic endoscope holder, developed for transsphenoidal surgery. METHODS: Patients were prospectively enrolled for 3 mo at the Neurosurgery Unit of Brescia. Endoscope Robot® was used to assist during the sphenoidal phase of the approach, tumor removal, and skull base reconstruction. A Likert scale questionnaire was given to all surgeons after each procedure. Patients who underwent robotic-assisted surgery were matched with nonrobotic ones for pathology and type of procedure. All surgical videos were evaluated during bimanual phases. RESULTS: Twenty-one patients underwent robot-assisted, endoscopic transsphenoidal surgery for different pathologies (16 pituitary adenomas, 3 chordomas, 1 craniopharyngioma, 1 pituitary exploration for Cushing disease) for a total of 23 procedures (1 patient underwent 2 endoscopic revisions of a skull base reconstruction). Subjective advantages reported by surgeons included smoothness of movement, image steadiness, and improvement of maneuvers in narrow spaces and with angled endoscopes; as the main limitation, Endoscope Robot® appeared to be relatively heavy during the initial endoscope positioning. A comparative analysis with a historical matched cohort documented similar clinical outcomes, while endoscope lens cleaning and position readjustments were significantly less frequent in robotic procedures. CONCLUSION: Although confirmation in larger studies is needed, Endoscope Robot® was a safe and effective tool, especially advantageous in lengthy interventions through deep and narrow corridors.

Clinical considerations on a right operculo-insular cavernous angioma: an illustrative case.

The insular cortex is considered one of the most complex regions of the brain, defined as the "hub" of somatosensory areas. Here, we examine the case of a surgically treated haemorrhagic cavernoma involving the middle and posterior insular cortex, presenting both sensory, gustative and speech symptoms. By reviewing the recent findings in humans' and primates' basic research, we illustrated clinical and radiological correlations of the reported case, confirming insular role in sensitive and gustatory functions.

Liver-Heart on chip models for drug safety.

Current pre-clinical models to evaluate drug safety during the drug development process (DDP) mainly rely on traditional two-dimensional cell cultures, considered too simplistic and often ineffective, or animal experimentations, which are costly, time-consuming, and not truly representative of human responses. Their clinical translation thus remains limited, eventually causing attrition and leading to high rates of failure during clinical trials. These drawbacks can be overcome by the recently developed Organs-on-Chip (OoC) technology. OoC are sophisticated in vitro systems capable of recapitulating pivotal architecture and functionalities of human organs. OoC are receiving increasing attention from the stakeholders of the DDP, particularly concerning drug screening and safety applications. When a drug is administered in the human body, it is metabolized by the liver and the resulting compound may cause unpredicted toxicity on off-target organs such as the heart. In this sense, several liver and heart models have been widely adopted to assess the toxicity of new or recalled drugs. Recent advances in OoC technology are making available platforms encompassing multiple organs fluidically connected to efficiently assess and predict the systemic effects of compounds. Such Multi-Organs-on-Chip (MOoC) platforms represent a disruptive solution to study drug-related effects, which results particularly useful to predict liver metabolism on off-target organs to ultimately improve drug safety testing in the pre-clinical phases of the DDP. In this review, we focus on recently developed liver and heart on chip systems for drug toxicity testing. In addition, MOoC platforms encompassing connected liver and heart tissues have been further reviewed and discussed.

Applications of Radiolabelled Curcumin and Its Derivatives in Medicinal Chemistry.

Curcumin is a natural occurring molecule that has aroused much interest among researchers over the years due to its pleiotropic set of biological properties. In the nuclear medicine field, radiolabelled curcumin and curcumin derivatives have been studied as potential radiotracers for the early diagnosis of Alzheimer's disease and cancer. In the present review, the synthetic pathways, labelling methods and the preclinical investigations involving these radioactive compounds are treated. The studies entailed chemical modifications for enhancing curcumin stability, as well as its functionalisation for the labelling with several radiohalogens or metal radionuclides (fluorine-18, technetium-99m, gallium-68, etc.). Although some drawbacks have yet to be addressed, and none of the radiolabelled curcuminoids have so far achieved clinical application, the studies performed hitherto provide useful insights and lay the foundation for further developments.

Experimental liver models: From cell culture techniques to microfluidic organs-on-chip.

The liver is one of the most studied organs of the human body owing to its central role in xenobiotic and drug metabolism. In recent decades, extensive research has aimed at developing in vitro liver models able to mimic liver functions to study pathophysiological clues in high-throughput and reproducible environments. Two-dimensional (2D) models have been widely used in screening potential toxic compounds but have failed to accurately reproduce the three-dimensionality (3D) of the liver milieu. To overcome these limitations, improved 3D culture techniques have been developed to recapitulate the hepatic native microenvironment. These models focus on reproducing the liver architecture, representing both parenchymal and nonparenchymal cells, as well as cell interactions. More recently, Liver-on-Chip (LoC) models have been developed with the aim of providing physiological fluid flow and thus achieving essential hepatic functions. Given their unprecedented ability to recapitulate critical features of the liver cellular environments, LoC have been extensively adopted in pathophysiological modelling and currently represent a promising tool for tissue engineering and drug screening applications. In this review, we discuss the evolution of experimental liver models, from the ancient 2D hepatocyte models, widely used for liver toxicity screening, to 3D and LoC culture strategies adopted for mirroring a more physiological microenvironment for the study of liver diseases.

25th Anniversary of Molecules-Recent Advances in Inorganic Chemistry.

Celebrating the "25th Anniversary of Molecules" with a Special Issue dedicated to "Recent Advances in Inorganic Chemistry" strengthens the renewed role that inorganic chemistry, one of the oldest chemistry divisions, has lately earned thanks to cutting-edge perspectives and interdisciplinary applications, eventually receiving the veneration and respect which its age might require [...].

Plasma-enhanced protein patterning in a microfluidic compartmentalized platform for multi-organs-on-chip: a liver-tumor model.

A microfluidic technique is presented for micropatterning protein domains and cell cultures within permanently bonded organs-on-chip devices. This method is based on the use of polydimethylsiloxane layers coupled with the plasma ablation technique for selective protein removal. We show how this technique can be employed to generate a multi-organin vitromodel directly within a microscale platform suitable for pharmacokinetic-based drug screening. We miniaturized a liver model based on micropatterned co-cultures in dual-compartment microfluidic devices. The cytotoxic effect of liver-metabolized Tegafur on colon cancer cell line was assessed using two microfluidic devices where microgrooves and valves systems are used to model drug diffusion between culture compartments. The platforms can reproduce the metabolism of Tegafur in the liver, thus killing colon cancer cells. The proposed plasma-enhanced microfluidic protein patterning method thus successfully combines the ability to generate precise cell micropatterning with the intrinsic advantages of microfluidics in cell biology.

Chiari malformation type 1: are we doing less with more? Illustrative case.

BACKGROUND: Classic treatment of Chiari malformation type 1 consists of foramen magnum decompression. Selected patients may require occipitocervical fixation, transoral odontoidectomy, tonsillectomy, and so forth. Treatment standardization does not yet exist, and some patients risk being overtreated. OBSERVATIONS: A 20-year-old man with headache and Chiari malformation type 1 underwent extradural bone decompression. One year later, he was managed with the extradural section of his filum terminale. Eighteen months later, the patient underwent monitoring of intracranial pressure, occipitocervical stabilization, transoral odontoidectomy, minimally invasive subpial tonsillectomy, and occipital cranioplasty. His headache never changed, and he progressively developed hemiparesis and swallowing and respiratory disturbances. Two years later, a new magnetic resonance imaging scan showed extended syringomyelia with scarce peritonsillar subarachnoid space. The umpteenth operation consisted of the removal of a constricting epidural scar, arachnoid dissection, total tonsillectomy, creation of a wide subarachnoid space, and dural sac augmentation. The patient's initial postoperative course was smooth, and his headache improved. However, 8 days after surgery, the patient acutely presented with vegetative disturbances and died because of malignant brainstem edema of unknown origin. LESSONS: The story of this patient is not so uncommon. He underwent all the possible surgical treatments rather than a timely adequate osteodural decompression. Probably, he received less with more.