bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Topical Diltiazem (2%) with Topical Glyceryl Trinitrate (0.2%) as a Conservative Treatment for Anal Fissure
Authors: Ansari Nisar Ahmad , Bhore Almol , Musa Osman
Published: December 2020

Introduction: An anal fissure is defined as a split in the mucosa extending from the anal verge towards the dentate line and most common proctologic symptom. The management of anal fissures is diverse and range from non-operative techniques like dietary changes, topical ointments (2% diltiazem, 0.2% glyceryl trinitrate), botulinum toxin injections and sitz baths to surgical intervention. Aim: To evaluate and compare the efficiency of Topical Glycerine Nitrate (0.2%) with Topical Diltiazem (2%) in patients with anal fissures. Materials and Methods: Out of 100 patients of anal fissure, 50 were selected for treatment with topical application of 2% Diltiazem and were classified as Group I while rest 50 selected for topical application of 0.2% Glyceryl trinitrate and were classified as Group II. Patients were followed for a period of six weeks (weekly follow-up) to evaluate the healing effect of above two topical ointments. Results: On follow-up at week six, patients relieved of all the complaints were assessed as fully cured and patients still having any of the complaints were assessed as partially cured. Full cure was observed in significantly higher proportion of cases of Group I as compared to Group II (88.0% vs. 68.0%), rest of the patients of both the groups had partial cure. Majority of the patients of both the groups did not observe any side effects (Group I-94.0% and Group II-84.0%), remaining patients of Group I reported side effects of Itching (6.0%) while remaining patients of Group II reported headache as side effect (16.0%). Difference in side effects of patients of above two groups was found statistically significant. Conclusion: Findings of the present study indicated that topical diltiazem (2%) was more effective as compared to glyceryl trinitrate (0.2%) for conservative treatment of anal fissure. Diltiazem was capable to provide full relief of complaints within six weeks to majority of the cases (88.0%).
Retrospective Study of Three-port versus Standard Four-port Laparoscopic Cholecystectomy: A Single Surgical Unit Experience of 1456 Patients
Authors: Srivastava Vivek , Ansari Mumtaz Ahmad , Shukla Vijay Kumar , Basu Somprakas
Published: December 2020

Introduction: Although laparoscopic surgeries have proven beyond doubt their benefit in terms of early recovery, better patient care and cost-effectiveness, the quest for reduction in either the size or number of ports still continues. Aim: To compare the safety, outcome, and advantages between three-port versus four-port Laparoscopic Cholecystectomy (LC) in acute and chronic cholecystitis. Materials and Methods: Medical records of 1456 patients that underwent LC (three- or four-port) for acute and chronic cholecystitis from January 2015 to December 2019 (60 months) were retrospectively analysed. All patients were given the same anaesthetic drugs for induction and maintenance, with standard anaesthetic protocol. The results were compared for both the techniques in terms of operating time, conversion rate, intraoperative complications, immediate postoperative complications, pain score, analgesic requirement and hospital stay. Results: Total 1456 patients underwent LC; 1282 were female and 174 were male. The mean age of the patients was 39.2 years (range 18-70 years). The three-port LC technique was performed on 816 (56.04%) patients, while the traditional four-port LC technique was performed on 640 (43.96%) patients. Visual Analog Score (VAS) in the postoperative period at six hour was 2.11±0.82 in three-port group versus 3.17±1.12 in four-port group, this suggests that there was a significant difference in pain in these two groups in the early postoperative period (p<0.001). In three-port group, the requirement of analgesic drug was significantly less as compared to four-port group (2.86±0.98 versus 3.22±0.87; p<0.001). There was no statistically significant difference in the mean operating time, duration of hospital stay, intra and postoperative complications, days to return to normal activity, satisfaction score and conversion rate (p=0.087, p=0.061, p=0.578, p=0.555, p=0.572 and p=0.145, respectively). Conclusion: Three-port LC is a feasible, effective and safe technique that further enhances the surgical outcome in terms of postoperative pain, fewer needs for analgesic medication.
Interaction between tissue transglutaminase and phospholipid vesicles
Authors: Fésüs László , Horváth Andrea , Hársfalvi Jolán
Published: July 2002

A specific interaction between purified liver transglutaminase and small unilamellar phospholipid vesicles at the lipid phase transition have been revealed. The enzyme‐induced perturbation of the bilayer is sufficient for phase transition release of encapsulated carboxyfluorescein from the vesicles. The size of the enzyme—phospholipid recombinants depends upon the protein—phospholipid ratio as shown on Sepharose 4B elution profile. The activity of transglutaminase inserted into the bilayer is greatly reduced. The interaction does not occur when the phospholipid vesicle are in the solid or liquid phase and it requires the structural integrity of the enzyme.
The triplet state of the primary donor of the green photosynthetic bacterium Chloroflexus aurantiacus
Authors: den Blanken H.J. , Vasmel H. , Jongenelis A.P.J.M. , Hoff A.J. , Amesz J.
Published: July 2002

The technique of absorbance‐detected electron spin resonance in zero magnetic field (ADMR) was applied to investigate the structure of the reaction center of the facultatively aerobic green bacterium Chloroflexus aurantiacus. The triplet‐minus‐singlet absorbance difference spectrum thus obtained at 1.2K shows a clear resemblance to those earlier reported for Rhodopseudomonas viridis and Rps. sphaeroides R‐26. The most prominent features are the bleaching of the Qy band of the primary electron donor at 887 nm and the appearance of a narrow band at 807 nm upon triplet formation. We conclude that the primary electron donor P‐865 of Chloroflexus aurantiacus is a BChl a dimer with Qy and Qx absorbance bands at 887 and 606 nm, respectively, at 1.2 K; apparently the triplet state is localized on an optical time scale on one of the constituent pigments of the dimer. The zero field splitting parameters |D| and, |E| of P‐865 are 197.7 (± 0.7) × 10−4 cm−1 and 47.3 (± 0.7) × 10−4 cm−1, respectively. Decay rates of 12 660 (± 750) s−1, 14 290 (± 800) s−1 and 1690 (± 50) s−1 were observed for the x, y and z triplet sublevels, respectively.
Human apolipoprotein A‐II: complete nucleic acid sequence of preproapoA‐II
Authors: Lackner Karl J. , Law Simon W. , Brewer H.Bryan
Published: July 2002

The complete cDNA nucleic acid sequence of preproapolipoprotein (apo) A‐II, a major protein constituent of high density lipoproteins, has been determined on clones from a human liver ds‐cDNA library. Clones containing ds‐cDNA for apoA‐II were identified in the human liver ds‐cDNA library using synthetic oligonucleotides as probes. Of 3200 clones screened, 4 reacted with the oligonucleotide probes. The DNA sequence coding for amino acids −17 to +17 of apoA‐II were determined by Maxam‐Gilbert sequence analysis of restriction fragments isolated from one of these clones, pMDB2049. The remainder of the cDNA sequence was established by sequence analysis of a primer extension product synthesized utilizing a restriction fragment near the 5'‐end of clone pMDB2049 as primer with total liver mRNA. The apoA‐II mRNA encodes for a 100 amino acid protein, preproapoA‐II that has an 18 amino acid prepeptide and a 5 amino acid propeptide terminating with a basic dipeptide (Arg‐Arg) at the cleavage site to mature apoA‐II.
Deoxynojirimycin inhibits the formation of Glc3Man9GlcNAc2‐PP‐dolichol in intestinal epithelial cells in culture
Authors: Romero Pedro A. , Friedlander Paula , Herscovics Annette
Published: July 2002

1‐Deoxynojirimycin N‐Methyl‐1‐deoxynojirimycin
Glucosidase inhibitor
Dolichol‐linked oligosaccharide
Processing
Four identical subunits in jack fruit seed agglutinin offer only two saccharide binding sites
Authors: Appukuttan P.S. , Basu Debkumar
Published: July 2002

Gel filtration of jack fruit seed agglutinin in 6 M guanidine hydrochloride confirmed our earlier report that the native 39.5‐kDa protein was a tetramer of identical noncovalently associated 10‐kDa subunits. Binding studies by the fluorescence quenching method using 4‐methylumbelliferyl α‐D‐galactoside as well as equilibrium dialysis using p‐nitrophenyl α‐D‐galactoside indicated only two binding sites per tetramer. This behaviour resembles the half‐of‐the‐sites reactivity in certain enzymes and is discussed in view of the small subunit size.
Murine interleukin‐2 receptor subunits differentially detected with anti‐interleukin‐2 monoclonal antibodies
Authors: Takemoto Hiroshi
Published: July 2002

Cross‐linking of radioiodinated interleukin‐2 to murine CTLL‐2 cells enabled detection of 70 kDa, 85 kDa and 105 kDa complexes of IL‐2 and its binding proteins under the high‐affinity binding condition. A series of anti‐interleukin‐2 monoclonal antibodies (L15, L20, L23, L34, and L61) were tested for their activity to immunoprecipitate these cross‐linked complexes. L61, which had strong neutralizing activity, precipitated only the 70 kDa complex. L15, L20, and L34, which also had neutralizing activity, precipitated not only the 70 kDa complex but also the 85 kDa complex. L23, which had practically no neutralizing activity, precipitated the 105 kDa complex as well as the 85 kDa complex. These results suggest that there are at least three distinct receptor binding sites for each receptor subunit on the interleukin‐2 molecule, which are discernible by these monoclonal antibodies and that the 105 kDa complex may play a significant role in the formation of the high‐affinity receptor complex and the signal transduction.
Use of synthetic peptides to study the substrate specificity of a thylakoid protein kinase
Authors: Michel Hanspeter , Bennett John
Published: July 2002

Seven synthetic peptide analogs of the phosphorylation site of the light‐harvesting chlorophyll a/b complex II (LHC II) were used to examine the substrate specificity of thylakoid‐bound LHC II kinase in higher plants. The peptides were phosphorylated by spinach and pea thylakoid membranes in which LHC II kinase had been activated by illumination. Phosphorylation was under redox control, as shown by the inhibitory ability of 20μM diuron. Apparent K
m(peptide) values ranged from 26 μM for a highly basic peptide with multiple sites for phosphorylation to 1.2 mM for a peptide lacking basic residues on the N‐terminal side of the phosphorylation site. Both serine and threonine residues were phosphorylated but the relative rates depended on peptide sequence. A comparison of our data with published LHC II sequences indicates that almost all known LHC II molecules have phosphorylatable sequences.
Modified reaction centers from Rhodobacter sphaeroides R26
Authors: Struck A. , Cmiel E. , Katheder I. , Scheer H.
Published: July 2002

Monomeric bacteriochlorophylls BA and BB in photosynthetic reaction centers from Rhodobacter sphaeroides R26 were exchanged with (132‐hydroxy‐) bacteriochlorophylls containing a 3‐vinyl‐ or 3‐(α‐hydroxyethyl)‐substituent instead of the 3‐acetyl group. The corresponding binding sites must be tolerant to the introduction of the polar residue at C‐132
and modifications of the 3‐acetyl group. According to HPLC analysis, the exchange with both pigments amounts to ≦ 50% of the total BChl contained in the complex, corresponding to ≦ 100% of the monomeric BChl aBA,B. The absorption spectra show significant changes in the Qx and Qy‐region of the monomeric bacteriochlorophylls. By contrast, the absorption of the primary donor (P870) and reversible photobleaching is retained. The circular dichroism is also unchanged in the 870 nm region. The positive cd band located at around 800 nm in native reaction centers, shifts with the (blue‐shifted) Qy absorption(s) of BA and/or BB, whereas the position of the negative one remains nearly unaffected. The data indicate that the latter is the upper excitonic band of the primary donor, and that there is little interaction of the monomeric BA/BB with the primary donor.
Isolation and characterization of active N‐terminal truncated apo‐ and holoenzyme of mammalian liver tyrosine aminotransferase
Authors: Lorber Bernard , Dietrich Jean-Bernard , Kern Daniel
Published: July 2002

Limited proteolysis was used to probe the structure of the apo‐ and holoenzyme of rat liver tyrosine aminotransferase. Both were subjected to trypsinolysis and the major fragments were isolated and characterized. Trypsin cleaves the apoenzyme after residues Arg57, Lys64, and Lys71 and the holoenzyme after Arg37 and Lys38. The difference in the accessibility of the enzyme deprived or associated with pyridoxal 5′‐phosphate reflects two distinct conformations. The activity, the affinity for the ligands and the thermostability of the purified truncated enzyme forms are similar to those of the native apo‐ and holoenzyme. A model for the domain structure of mammalian tyrosine aminotransferase and a mechanism for its rapid turnover are proposed.
Altered substrate selectivity of PKC‐η pseudosubstrate site mutants
Authors: Dekker Lodewijk V. , McIntyre Peter , Parker Peter J.
Published: July 2002

Three protein kinase C (PKC)‐η mutants were constructed in which the whole or part of the pseudosubstrate site was replaced with corresponding parts of the PKC‐α pseudosubstrate site. The resulting chimaeric kinases were compared with wild‐type PKC‐η in their ability to phosphorylate a PKC‐η peptide substrate or histone. Changes in the pseudosubstrate site of pkc‐η are accompanied by changes in substrate selectivity, indicating that the substrate selectivity observed for PKC‐η is at least in part due to its pseudosubstrate site.
Cloning and sequence of the cDNA coding for rat type II Fcγ receptor of mast cells
Authors: Boček Petr , Pecht Israel
Published: July 2002

A clone encoding the rat type II Fcγ receptor was isolated from a cDNA library of the rat mucosal mast cell line RBL‐2H3 and its sequence determined. The predicted amino acid sequence is highly homologous with the mouse type II as well as rat type III Fcγ receptors. The site of alternative splicing which generates the mouse FcγRb2 isoform is completely conserved. Hence we consider the new sequence to encode a rat FcγRII b2 isoform. In further analogy to the mouse receptor, no consensus motif known to be involved in accessory chain association was observed in the transmembranal domain. The importance of the identification of this receptor for investigation of the immunological stimulation of mast cells is discussed.
Does the HIV Nef protein mimic the MHC?
Authors: Hobohm Uwe , Sander Chris
Published: July 2002

The sequence of the HIV Nef protein has no significant homology to other proteins in the SwissProt database, and experimental data concerning its function are sparse and contradictory. Using a novel protein sequence comparison method, we find similarities between different Nef sequences and the α chain of human MHC class I proteins. The possible biological implications of this finding are discussed.
Interleukin 2 mediates p72syk activation in peripheral blood lymphocytes
Authors: Qin Suofu , Inazu Tetsuya , Yang Cheng , Sada Kiyonao , Taniguchi Takanobu , Yamamura Hirohei
Published: July 2002

The ability of interleukin 2 (IL‐2) to stimulate p72
syk
activity in intact porcine peripheral blood lymphocytes was examined. We demonstrated that IL‐2 activated p72
syk
in a time‐ and dose‐dependent number, for which its peak time and maximum responsive dose were 5 min and 100 U/ml, respectively. This activation was observed only in cytosolic fractions and not in membrane ones. However, IL‐2 failed to induced calcium mobilization. Moreover, IL‐2‐inducible p72
syk
activation was not affected when extra and intracellular calcium was depleted. These data suggest that the IL‐2 signaling pathways through p72
syk
in peripheral blood lymphocytes is different, at least in part, from other agonist, such as concanavalin A in polymorphonuclear neutrophils which can trigger both the activation of p72
syk
and intracellular calcium mobilization.
Inulin synthesis by a combination of purified fructosyltransferases from tubers of Helianthus tuberosus
Authors: Lüscher Marcel , Erdin Christian , Sprenger Norbert , Hochstrasser Urs , Boller Thomas , Wiemken Andres
Published: July 2002

Sucrose‐sucrose 1‐fructosyltransferase (1‐SST) was purified 100‐fold from tubers of Helianthus tuberosus L. The purified enzyme was essentially devoid of invertase activity and could be separated by isoelectric focusing into five isoforms which all were composed of two subunits (59 and 26 kDa). Fructan‐fructan 1‐fructosyltransferase (1‐FFT) was purified from the same source [M. Lüscher et al. (1993) New Phytologist 123, 437–442). When incubated individually with sucrose, 1‐FFT was inactive while 1‐SST formed isokestose (trimer) and, upon prolonged incubation, some nystose (tetramer). When a combination of the two enzymes was incubated with sucrose, a series of oligofructosides with a degree of polymerization of up to 20 was formed. Amino acid sequences of tryptic peptide fragments from both 1‐SST and 1‐FFT indicate that these enzymes are highly homologous with plant invertases.
Use of midazolam for ECT anesthesia: effects on antidepressive efficacy and seizure duration. Preliminary findings
Authors: Auriacombe M , Grabot D , Lincheneau PM , Zeiter D , Tignol J
Published: July 2002

Midazolam is a short acting benzodiazepine that has been used for electroconvulsive therapy (ECT) anesthesia. The purpose of this study was to determine whether midazolam used for this purpose would impair the antidepressive efficacy of ECT. In a double-blind random-assignment study midazolam was compared to methohexital on the antidepressive efficacy of bilateral ECT as measured by the reduction in the Montgomery Asberg Depression Rating Scale (MADRS) scores and seizure duration. Sixteen DSM-III-R major depressive disorder patients with melancholia were included. Midazolam and methohexital did not differ in their effects on the MADRS score or seizure duration; no correlation was found between seizure duration and outcome of depression for either group. Our preliminary findings do not support the claim that benzodiazepines should not be used during bilateral ECT.
Structural basis for the catalytic mechanism and substrate specificity of the ribonuclease α‐sarcin
Authors: Campos-Olivas Ramón , Bruix Marta , Santoro Jorge , Martínez del Pozo Alvaro , Lacadena Javier , Gavilanes JoséG. , Rico Manuel
Published: July 2002

α‐Sarcin is a ribosome‐inactivating protein which selectively cleaves a single phosphodiester bond in a universally conserved sequence of the major rRNA. The solution structure of α‐sarcin has been determined on the basis of 1898 distance and angular experimental constraints from NMR spectroscopy. It reveals a catalytic mechanism analogous to that of the T1 family of ribonucleases while its exquisite specificity resides in the contacts provided by its distinctive loops.
Intracellular degradation of secretion defect‐type mutants of antithrombin is inhibited by proteasomal inhibitors
Authors: Tokunaga Fuminori , Shirotani Hiroko , Hara Kazuya , Kozuki Daisuke , Omura Satoshi , Koide Takehiko
Published: July 2002

To examine the cellular basis for secretion defect‐type antithrombin deficiency, we expressed two mutants, P→stop (Pro429 to stop codon) and ΔGlu (deletion of Glu313). Pulse‐chase experiments using stably transfected BHK cells showed that little (<5%) of P→stop mutant as well as ΔGlu mutant was secreted and the total amount of radioactivity was significantly reduced, suggesting an intracellular degradation. The degradation was not inhibited by brefeldin A, indicating it occurring in a preGolgi apparatus. However, the degradation was strongly inhibited by proteasomal inhibitors, such as carbobenzoxy‐l‐leucyl‐l‐leucyl‐l‐leucinal (LLL), carbobenzoxy‐l‐leucyl‐l‐leucyl‐l‐norvalinal (LLnV) and lactacystin. By endoglycosidase H digestion and immunofluorescence staining, these mutants were shown to localize in the endoplasmic reticulum (ER). These results suggest that the secretion defect‐type mutants of antithrombin are degraded by proteasome through the ER‐associated quality control mechanism in the cells.
Formulation of objective indices to quantify machine failure risk analysis for interruptions in radiotherapy
Authors: Kawahara Daisuke , Nakano Hisashi , Saito Akito , Ochi Yusuke , Nagata Yasushi
Published: December 2020

Objectives

To evaluate the effect of interruption in radiotherapy due to machine failure in patients and medical institutions using machine failure risk analysis (MFRA).

Material and methods

The risk of machine failure during treatment is assigned to three scores (biological effect, B; occurrence, O; and cost of labor and repair parts, C) for each type of machine failure. The biological patient risk (BPR) and the economic institution risk (EIR) are calculated as the product of and () and and (), respectively. The MFRA is performed in two linear accelerators (linacs).

Result

The multileaf collimator (MLC) fault has the highest BPR and second highest EIR. In particular, TrueBeam has a higher BPR and EIR for MLC failures. The total EIR in TrueBeam was significantly higher than that in Clinac iX. The minor interlock had the second highest BPR, whereas a smaller EIR. Meanwhile, the EIR for the LaserGuard fault was the highest, and that for the monitor chamber fault was the second highest. These machine failures occurred in TrueBeam. The BPR and EIR should be evaluated for each linac. Further, the sensitivity of the BPR, it decreased with higher and α/β values. No relative difference is observed in the BPR for each machine failure when and α/β were varied.

Conclusion

The risk faced by patients and institutions in machine failure may be reduced using MFRA.

Advances in knowledge

For clinical radiotherapy, interruption can occur from unscheduled downtime with machine failures. Interruption causes sublethal damage repair. The current study evaluated the effect of interruption in radiotherapy owing to machine failure on patients and medical institutions using a new method, that is, machine failure risk analysis.
Tailored and Highly Stretchable Sensor Prepared by Crosslinking an Enhanced 3D Printed UV‐Curable Sacrificial Mold
Authors: Peng Shuqiang , Wang Zian , Lin Jinbin , Miao Jia‐Tao , Zheng Longhui , Yang Zhi , Weng Zixiang , Wu Lixin
Published: December 2020

Taking advantage of unlimited geometry design, 3D printed sacrificial mold cast with highly conductive polymer composites is used to prepare a sensor with designed structures. However, the disposal of the mold in a mild condition while the refined structures can be maintained is still a challenge. Herein, a bifunctional monomer hydrolyzable hindered urea acrylate is synthesized to create a cross‐linked polymer network, preventing the dissolution of printed parts in the uncured resin. 3D printed scaffolds can be hydrolyzed in hot water, which provides an attractive option for sacrificial molds. Also, a porous flexible strain sensor (PFSS) is fabricated by casting polyurethane/carbon nanotubes composites into the sacrificial molds, which demonstrates a high stretchability (≈510%) and an excellent recoverability. Meantime, the pressure sensitivity (0.111 kPa−1) and a long‐term electrical resistance of PFSS is characterized. The resistance response signal remains nearly unchanged after 100 compressive loading cycles at a large strain of 60%. Benefiting from the design freedom of 3D printing, a practical application of the PFSS with a complex and customized structure to monitor human motion is demonstrated. These results prove that the sacrificial molding process has great potential for user‐specific stretchable wearable devices.
Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model
Authors: Adhikari Aniruddha , Mondal Susmita , Das Monojit , Biswas Pritam , Pal Uttam , Darbar Soumendra , Bhattacharya Siddhartha Sankar , Pal Debasish , Saha‐Dasgupta Tanusri , Das Anjan Kumar , Mallick Asim Kumar , Pal Samir Kumar
Published: December 2020

The potentiality of nano‐enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, it is shown that citrate functionalized manganese‐based biocompatible nanoscale material (C‐Mn3O4 NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C‐Mn3O4 nanozyme is further established in a preclinical animal model of Huntington's disease (HD), a prevalent progressive neurodegenerative disorder, which has no effective medication to date. Management of HD in preclinical animal trial using a biocompatible (non‐toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.
Gold‐Mushroom Microelectrode Arrays and the Quest for Intracellular‐Like Recordings: Perspectives and Outlooks
Authors: Teixeira Henrique , Dias Catarina , Aguiar Paulo , Ventura João
Published: December 2020

The ongoing search to decode the brain communication system has propelled major advancements in bioelectronics research. From these, planar microelectrode arrays (MEAs) offer the possibility to record neuronal signals for extremely long periods of time and to probe fundamental principles of learning and adaptation. Unfortunately, MEAs have low neuronal coupling and are thus insensitive to sub‐threshold neuronal signals such as post‐synaptic responses. To surpass this major limitation, a novel category based on 3D high aspect ratio microstructures has emerged. In particular, gold‐mushroom microelectrode arrays (GMμEAs) have appeared as a solution. Their unique morphology, promoting cell engulfment without penetrating the neuron, prevents the occurrence of cell repairing mechanisms common in other microelectrodes. This new class of recording and/or stimulating devices have opened the door to the vast communication system of neuronal cells by enhancing the cell–microelectrode interface. This review compiles the fundamentals of these promising devices including their fabrication, work principles and focusing on how the different morphological parameters affect the recording performance. Although limitations exist, there is a growing interest to explore the new solutions that GMμEAs still offer, both as an electrophysiological tool (e.g., cell guidance) or in applications such as plasmonics.
Biointegrated Fluidic Milling
Authors: Widerker Daniel , Paratore Federico , Bercovici Moran , Kaigala Govind
Published: December 2020

This paper presents a device (“fluidic biomill”) and method for integrated mechanical structuring and biofunctionalization of microfluidic channels, enabling rapid prototyping of biochips. The fluidic biomill leverages hydrodynamic flow confinements (HFCs) to localize the interaction between a fluid and a substrate to a microscale region. By confining organic solvents, and scanning with the biomill over the substrate surface, microchannels as deep as 90 µm are fluidically milled. Subsequently, by switching the confined fluid from a milling solution to a patterning solution, biomolecules are immobilized on the surface of the microchannel. An in‐depth analysis of fluidic milling rates and milled microchannel properties is presented, along with a discussion on the dominant factors in controlling the dimensions of the fluidically milled channel. To demonstrate the utility of this method, a biotin functionalized biochip is fabricated in less than 5 min out of a polystyrene slide and its functionalities are validated by implementing on‐chip electrokinetic sample focusing, pressure driven flow, and a surface‐based reaction.
The effect of curvature on chondrocytes migration and bone mesenchymal stem cells differentiation
Authors: Cao Xing , Liu Xiangli , Liu Yan , Ma Rui , Sun Shichang
Published: December 2020

Numerous cells grow in columnar tissues and organs with different curvatures and curvature gradients. Therefore, it is necessary to study the effect of curvature on cell behavior to control and promote cell development. Herein, we prepared polydimethylsiloxane (PDMS) with different micro‐nano patterns using ultraviolet soft lithography. Hydrophilic polydopamine (PDA) was modified on the PDMS surface to prepare PDMS/PDA to improve its biocompatibility. The PDMS/PDA was characterized by contact angle tester and scanning electron microscopy (SEM). The effect of curvature on bone cell migration and differentiation was studied through SEM, inverted phase contrast microscope and fluorescence microscopy. We found that different curvatures had different effects on the bone cell migration and differentiation. Chondrocytes migrated rapidly in grooves with a curvature range of 1/575–1/875 μm−1. Bone mesenchymal stem cells (BMSCs) had high efficiency of differentiation into chondrocytes in the grooves with a curvature range of 1/775–1/1375 μm−1. Furthermore, BMSCs showed high efficiency of differentiation into chondrocytes at the edges of micro‐nano patterns with different perimeter curvatures, and the differentiation efficiency was the highest at 120° convex curvature. This work shows that curvature is a principle to be considered in bone tissue regeneration engineering and provides inspiration for future biomaterials design.
Synthesis of New Tyrosol‐Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability
Authors: Romanucci Valeria , Giordano Maddalena , De Tommaso Gaetano , Iuliano Mauro , Bernini Roberta , Clemente Mariangela , Garcia‐Viñuales Sara , Milardi Danilo , Zarrelli Armando , Di Fabio Giovanni
Published: December 2020

Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modulation might have a positive and synergic effect in contrasting AD‐related impairments. Herein, a new and efficient fragment‐based approach towards tyrosol phosphodiester derivatives (TPDs) has been developed starting from suitable tyrosol building blocks and exploiting the well‐established phosphoramidite chemistry. The antioxidant activity of new TPDs has been tested as well as their ability to inhibit Aβ protein aggregation. In addition, their metal chelating ability has been evaluated as a possible strategy to develop new natural‐based entities for the prevention or therapy of AD. Interestingly, TPDs containing a catechol moiety have demonstrated highly promising activity in inhibiting the aggregation of Aβ40 and a strong ability to chelate biometals such as CuII and ZnII.
Widespread myofascial dysfunction and sensitisation in women with endometriosis‐associated chronic pelvic pain: A cross‐sectional study
Authors: Phan Vy T. , Stratton Pamela , Tandon Hannah K. , Sinaii Ninet , Aredo Jacqueline V. , Karp Barbara I. , Merideth Melissa A. , Shah Jay P.
Published: December 2020

Background

Chronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.

Objective

Characterize the presence and distribution of pain, myofascial dysfunction and sensitisation beyond the pelvis in women with endometriosis‐associated chronic pelvic pain.

Methods

Cross‐sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain‐focused abdominopelvic gynaecologic examination with the identification of pelvic floor muscle spasm. Neuro‐musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger points in 13 paired muscles. Pressure‐pain thresholds were measured over interspinous ligaments and trigger points. Women completed the body territories element of the Body Pain Index.

Results

All women had a pelvic floor muscle spasm that they self‐identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure‐pain thresholds and trigger points in over two‐thirds of 26 assessed regions. Widespread spinal segmental sensitisation was present in 17/30, thoracic in 21/30 and lumbosacral/pelvic in 18/30. Cervical sensitisation manifested as low pressure‐pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p = .024) and lumbosacral/pelvic (p = .036) sensitisation and report over 10 painful body areas (p = .009).

Conclusions

Women with endometriosis‐associated chronic pelvic pain often have myofascial dysfunction and sensitisation beyond the pelvic region that may be initiated or maintained by on‐going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population.

Clinicaltrials.gov identifier: NCT01553201.

Significance

Women with endometriosis often have pelvic pain persisting after surgery despite hormonal therapies and these women have regional pelvic sensitisation and myofascial dysfunction. Pelvic floor muscle spasm is a major pain focus in this population. Sensitisation and myofascial dysfunction are widespread, beyond the pelvic region. On‐going pelvic floor spasm may initiate or maintain sensitisation. Myofascial/sensitisation manifestations warrant consideration when managing pain in this population.
Dependence‐like behaviour in patients treated for medication overuse headache: A prospective open‐label randomized controlled trial
Authors: Rouw Carolien , Munksgaard Signe B. , Engelstoft Ida M.S. , Nielsen Mia , Westergaard Maria L. , Jensen Rigmor H. , Bendtsen Lars , Carlsen Louise N.
Published: December 2020

Background

Dependence‐like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence‐like behaviour is unknown.

Objectives

To compare patient‐reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to 6 months.

Methods

Patients with MOH were randomized to (1) withdrawal combined with preventive medication from start (W+P), (2) preventive medication without withdrawal (P), or (3) withdrawal with optional preventive medication 2 months after withdrawal (W). At baseline, 2, and 6 months, patients filled out SDS (used for measurements of dependence‐like behaviour and treatment feasibility), Headache Under‐Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires.

Results

Out of 120 patients with MOH, 100 completed the 6‐month follow‐up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After 6 months, the SDS score was reduced by 3.69 (95% CI 3.23–4.49) in the W+P arm, by 3.19 (95% CI 2.43–3.96) in the W arm, and by 1.65 (95% CI 0.96–2.33) in the P arm (p = 0.04). At baseline and after 2 months, the P arm was considered the most feasible treatment, but at 6‐month follow‐up, there was no difference in feasibility score, change in HURT score, or quality of life.

Conclusions

Dependence‐like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH.

Significance

Withdrawal combined with preventive medication from start is the treatment strategy that reduces dependence‐like behaviour the most in MOH patients. Patients initially considered preventive treatment without withdrawal as the most feasible treatment. However, no difference in feasibility between the three arms was found at 6‐month follow‐up. Withdrawal combined with preventive medication is recommended for treatment of MOH.
Formation Mechanism Analysis of Shear‐Induced Microgel Filaments during Microfluidic Gelation
Authors: Fukushima Shuhei , Takayama Yuriko , Nasuno Eri , Yanagida Yasuko , Kato Norihiro
Published: December 2020

Dynamic microfluidic gelation enables the fabrication of bundle‐structured multiple parallel microgel filaments from an aqueous two‐phase system. The formation mechanism of shear‐induced filaments from an alginate (Alg)/polyvinyl alcohol (PVA) blend is studied using red‐colored PVA and a titanium alkoxide PVA crosslinker. Bundle‐structured Alg microgel filaments are formed through contact with a Ca2+ crosslinker. In this process, the PVA acts as a sacrificial polymer to maintain the Alg gel filaments because approximately 90% of the red‐colored PVA is released from the Ca2+‐crosslinked Alg gel filaments into the wash water. In addition, the fabrication of PVA gel filaments shows that the sacrificial PVA is also transformed into fibrillar domains under shear. However, the filament structure cannot be formed from a single‐phase PVA/Alg solution. These results clearly show that the bundle‐structured gel filaments are maintained by preventing the fusion of filaments during gelation based on the tendency of the non‐crosslinked filaments to cause splitting of the gelled filaments.
Adaptive Lipid Immiscibility and Membrane Remodeling Are Active Functional Determinants of Primary Ciliogenesis
Authors: Bernabé‐Rubio Miguel , Bosch‐Fortea Minerva , García Esther , Bernardino de la Serna Jorge , Alonso Miguel A.
Published: December 2020

Lipid liquid–liquid immiscibility and its consequent lateral heterogeneity have been observed under thermodynamic equilibrium in model and native membranes. However, cholesterol‐rich membrane domains, sometimes referred to as lipid rafts, are difficult to observe spatiotemporally in live cells. Despite their importance in many biological processes, robust evidence for their existence remains elusive. This is mainly due to the difficulty in simultaneously determining their chemical composition and physicochemical nature, whilst spatiotemporally resolving their nanodomain lifetime and molecular dynamics. In this study, a bespoke method based on super‐resolution stimulated emission depletion (STED) microscopy and raster imaging correlation spectroscopy (RICS) is used to overcome this issue. This methodology, laser interleaved confocal RICS and STED‐RICS (LICSR), enables simultaneous tracking of lipid lateral packing and dynamics at the nanoscale. Previous work indicated that, in polarized epithelial cells, the midbody remnant licenses primary cilium formation through an unidentified mechanism. LICSR shows that lipid immiscibility and its adaptive collective nanoscale self‐assembly are crucial for the midbody remnant to supply condensed membranes to the centrosome for the biogenesis of the ciliary membrane. Hence, this work poses a breakthrough in the field of lipid biology by providing compelling evidence of a functional role for liquid ordered‐like membranes in primary ciliogenesis.
What patients want to know, and what we actually tell them: The ABIDE project
Authors: Fruijtier Agnetha D. , Visser Leonie N.C. , Bouwman Femke H. , Lutz Rogier , Schoonenboom Niki , Kalisvaart Kees , Hempenius Liesbeth , Roks Gerwin , Boelaarts Leo , Claus Jules J. , Kleijer Mariska , de Beer Marlijn , van der Flier Wiesje M. , Smets Ellen M.A.
Published: December 2020

Background

We studied to what degree and at whose initiative 25 informational topics, formerly identified as important, are discussed in diagnostic consultations.

Methods

Audio recordings of clinician–patient consultations of 71 patients and 32 clinicians, collected in eight Dutch memory clinics, were independently content‐coded by two coders. The coding scheme encompassed 25 informational topics.

Results

Approximately half (Mdn = 12) of the 25 topics were discussed per patient during the diagnostic process, with a higher frequency among individuals receiving a dementia diagnosis (Mdn = 14) compared to others (Mdn = 11). Individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of patients. Patients and/or care partners rarely initiated topic discussion (10%). When they did, they often enquired about one of the least frequently addressed topics.

Conclusion

Most patients received information on approximately half of the important informational topics. Providing the topic list to patients and care partners beforehand could allow consultation preparation and stimulate participation.
Safety and tolerability of GRF6019 in mild‐to‐moderate Alzheimer's disease dementia
Authors: Hannestad Jonas , Koborsi Katie , Klutzaritz Vicki , Chao Whitney , Ray Rebecca , Páez Antonio , Jackson Sam , Lohr Scott , Cummings Jeffrey L. , Kay Gary , Nikolich Karoly , Braithwaite Steven
Published: December 2020

Introduction

This phase 2 trial evaluated the safety, tolerability, and feasibility of repeated infusions of the plasma fraction GRF6019 in mild‐to‐moderate Alzheimer's disease.

Methods

In this randomized, double‐blind, dose‐comparison trial, 47 patients were randomized 1:1 to receive daily infusions of 100 mL (n = 24) or 250 mL (n = 23) of GRF6019 for 5 consecutive days over two dosing periods separated by a treatment‐free interval of 3 months.

Results

The mean (standard deviation [SD]) age of the enrolled patients was 74.3 (6.9), and 62% were women. Most adverse events (55%) were mild, with no clinically significant differences in safety or tolerability between the two dose levels. The mean (SD) baseline Mini‐Mental State Examination score was 20.6 (3.7) in the 100 mL group and 19.6 (3.7) in the 250 mL group; at 24 weeks, the within‐patient mean change from baseline was –1.0 points (95% confidence interval [CI], –3.1 to 1.1) in the 100 mL group and +1.5 points (95% CI, –0.4 to 3.3) in the 250 mL group. The within‐patient mean change from baseline on the Alzheimer's Disease Assessment Scale‐Cognitive subscale was –0.4 points (95% CI, –2.9 to 2.2) in the 100 mL group, while in the 250 mL group it was –0.9 points (95% CI, –3.0 to 1.2). The within‐patient mean change from baseline on the Alzheimer's Disease Cooperative Study‐Activities of Daily Living was –0.7 points in the 100 mL group (95% CI, –4.3 to 3.0) and –1.3 points (95% CI, –3.4 to 0.7) in the 250 mL group. The mean change from baseline on the Category Fluency Test, Clinical Dementia Rating Scale–Sum of Boxes, Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change, and Neuropsychiatric Inventory Questionnaire was similar for both treatment groups and did not show any worsening.

Discussion

GRF6019 was safe and well tolerated, and patients experienced no cognitive decline and minimal functional decline. These results support further development of GRF6019.
Digital pen technology for conducting cognitive assessments: a cross-over study with older adults
Authors: Heimann-Steinert A. , Latendorf A. , Prange A. , Sonntag D. , Müller-Werdan U.
Published: December 2020

Many digitalized cognitive assessments exist to increase reliability, standardization, and objectivity. Particularly in older adults, the performance of digitized cognitive assessments can lead to poorer test results if they are unfamiliar with the computer, mouse, keyboard, or touch screen. In a cross-over design study, 40 older adults (age M = 74.4 ± 4.1 years) conducted the Trail Making Test A and B with a digital pen (digital pen tests, DPT) and a regular pencil (pencil tests, PT) to identify differences in performance. Furthermore, the tests conducted with a digital pen were analyzed manually (manual results, MR) and electronically (electronic results, ER) by an automized system algorithm to determine the possibilities of digital pen evaluation. ICC(2,k) showed a good level of agreement for TMT A (ICC(2,k) = 0.668) and TMT B (ICC(2,k) = 0.734) between PT and DPT. When comparing MR and ER, ICC(2,k) showed an excellent level of agreement in TMT A (ICC(2,k) = 0.999) and TMT B (ICC(2,k) = 0.994). The frequency of pen lifting correlates significantly with the execution time in TMT A (r = 0.372, p = 0.030) and TMT B (r = 0.567, p < 0.001). A digital pen can be used to perform the Trail Making Test, as it has been shown that there is no difference in the results due to the type of pen used. With a digital pen, the advantages of digitized testing can be used without having to accept the disadvantages.
Determination of low environmental free cyanide concentrations in freshwaters
Authors: Knopf Burkhard , Rüdel Heinz , Hansknecht Dirk , Klawonn Thorsten , Kreuzer Knut
Published: December 2020

Cyanide compounds are naturally emitted into the environment in low levels by degradation processes or emitted from anthropogenic sources. In surface water, complex cyanide compounds as well as “free cyanide” are present. The latter term covers hydrogen cyanide and cyanide compounds which easily liberate hydrogen cyanide under slightly acidic conditions. Especially free cyanide may cause adverse effects in the environment. To exclude negative impacts on freshwater systems, in the context of the European Water Framework Directive (WFD), preventive regulatory activities for free cyanide are currently under discussion. However, established analytical methods for quantification of free cyanide only obtain limits of quantification (LOQs) in the range of 1 μg L−1. Thus, these methods are not sufficiently sensitive for a potential environmental quality standard (EQS) compliance monitoring at water concentrations below the current predicted no effect concentration (PNEC) level of free cyanide. In the present study, a standardized continuous flow analysis (CFA) method for quantification of low free cyanide concentrations was adapted by applying a special system which allows an ultra-sensitive photometric detection of a colored cyanide derivative. By this means, LOQs in a range of one magnitude below the PNEC are achievable. The method was validated according to ISO/IEC 17025 requirements. Free cyanide concentrations in tested surface water samples from a small river and a barrier lake with low anthropogenic influences were very low and clearly below the PNEC. The results prove that the adapted CFA method is suitable for the analysis of low concentration free cyanide in freshwaters and appropriate for a possible EQS compliance monitoring.