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Cellulose mixed esters (CMEs) substituted with two different types of acyl groups are promising polymeric materials with various tunable properties but are arduous to produce. This is because of the insolubility of cellulose in common solvents, and thus, the industrial production of CMEs with desired degrees of substitution (DSs) requires a costly multistep process. To accomplish their facile production, homogeneous reactions have been performed using ionic liquids (ILs) as solvents for cellulose. However, the high viscosity of the cellulose-IL solutions causes insufficient mixing in batch reactors; thereby, favoring low cellulose concentrations with long reaction times (typically hours). Herein, we demonstrate a rapid and scalable production of CMEs by exploiting the excellent shear mixing of a twin-screw extruder as a flow reactor. A co-solvent system comprising an IL, 1-ethyl-3-methylimidazolium acetate, and dimethyl sulfoxide was applied to dissolve cellulose at a high concentration (15 wt.%) via twin-screw extrusion. During continuous extrusion at 80 °C, cellulose reacted with two acyl reagents, isopropenyl acetate (IPAc) and vinyl propionate (VPr) (2.5:0.5, mol/mol), to yield cellulose acetate propionate (CAP) within minutes. The CAP was stably produced during the operation time of 50 min with an average isolated yield of 71%. The DSs of the acetyl and propionyl groups of CAP were 1.77 and 0.50, respectively, corresponding to sufficiently high conversion rates of 70% for IPAc and 100% for VPr.

Summary: Background: To evaluate the safety and effectiveness of preparing instent femoropopliteal lesion with photoablative laser atherectomy or plain balloon angioplasty (POBA) prior to drug-coated balloon (DCB) angioplasty. Patients and methods: The prospective, multicenter, randomized study enrolled patients with Rutherford-Becker-class (RBC) 1 to 5 and instent lesions located in superficial femoral artery and/or popliteal artery above the knee joint. Primary endpoint was target lesion percent stenosis at 1 year as determined by the angiographic core-laboratory. Secondary endpoints included procedural success, major adverse event rate, clinical improvement and improvement in ankle-brachial index (ABI), clinically-driven target lesion revascularization (CD-TLR), and primary patency rate at until 2-year follow-up. Results: The study was terminated prior to the enrollment goal due to slow enrollment. Thirty patients were included in the laser plus DCB cohort and 31 patients in the control cohort. Primary endpoint was not significantly different (p=0.331). Procedural success was 83.3% and 87.1% for the laser plus DCB and the control cohort, respectively. Serious adverse events at 30 days and 1-year were not statistically different between the two cohorts. For the ABI, significant improvements were present at discharge as well as at the follow-up visits. This was also evident for the RBC at the follow-up visits. One- and two-year freedom from CD-TLR was 86.7% vs. 87.1%, and 63.6% vs. 72%, respectively. Duplex derived primary patency was 90% at 6-months, 65.5% at one year and 56.5% at two year for the laser cohort and 90.3%, 75.9% and 53.8% for the control cohort. Conclusions: Safety of instent photoablative laser atherectomy followed by DCB angioplasty is confirmed by this study. Due to the small sample size, no benefit over POBA as vessel preparation could be shown.

This study investigated causes of attenuation of cerebrospinal fluid (CSF) signal on heavily T2-weighted (T2W) images in dogs with thoracolumbar disc extrusion. Medical records and magnetic resonance images were retrospectively reviewed. Dogs were classified into the following grades; grade 1, non-ambulatory paraparesis; grade 2, paraplegia with deep pain perception and grade 3, paraplegia without deep pain perception. The length of intramedullary T2W hyperintensity of the spinal cord, cranial/ caudal expansion of extradural compressive materials (ECM), and the CSF signal attenuation were measured. Ratios to the second lumbar vertebra (L2) were calculated for the length of intramedullary T2W hyperintensity (T2W:L2), cranial/caudal expansion of ECM (ECML:L2), and CSF signal attenuation (CSF:L2). The dogs were classified into focal or extended T2W hyperintensity groups according to the length [focal, shorter than length of L2; extended, longer than L2]. The area of EMC and the spinal canal were measured on transverse images at the lesion deriving occupancy ratio. The correlation between CSF:L2 and other data were analysed, and CSF:L2 was compared between the grades. In dogs with intramedullary T2W hyperintensity, the locations of CSF attenuation and the hyperintensity were compared if those locations were matched. Fifty-five dogs were included, 36 of which showed intramedullary T2W hyperintensity. Twenty-two of 36 dogs were considered as match of the location of the CSF attenuation and hyperintensity. CSF:L2 was significantly correlated with T2W:L2 in dogs with extended T2W hyperintensity (

Organoids, which are multicellular clusters with similar physiological functions to living organs, have gained increasing attention in bioengineering. As organoids become more advanced, methods to form complex structures continue to develop. There is evidence that the extracellular microenvironment can regulate organoid quality. The extracellular microenvironment consists of soluble bioactive molecules, extracellular matrix, and biofluid flow. However, few efforts have been made to discuss the microenvironment optimal to engineer specific organoids. Therefore, this review article examines the extent to which engineered extracellular microenvironments regulate organoid quality. First, we summarize the natural tissue and organ's unique chemical and mechanical properties, guiding researchers to design an extracellular microenvironment used for organoid engineering. Then, we summarize how the microenvironments contribute to the formation and growth of the brain, lung, intestine, liver, retinal, and kidney organoids. The approaches to forming and evaluating the resulting organoids are also discussed in detail. Impact statement Organoids, which are multicellular clusters with similar physiological function to living organs, have been gaining increasing attention in bioengineering. As organoids become more advanced, methods to form complex structures continue to develop. This review article focuses on recent efforts to engineer the extracellular microenvironment in organoid research. We summarized the natural organ's microenvironment, which informs researchers of key factors that can influence organoid formation. Then, we summarize how these microenvironmental controls significantly contribute to the formation and growth of the corresponding brain, lung, intestine, liver, retinal, and kidney organoids. The approaches to forming and evaluating the resulting organoids are discussed in detail, including extracellular matrix choice and properties, culture methods, and the evaluation of the morphology and functionality through imaging and biochemical analysis.

Silmitasertib (CX-4945) is currently being investigated in clinical trials against various types of cancer. The U.S. Food and Drug Administration (FDA) has already granted orphan drug designation to the compound for the treatment of advanced cholangiocarcinoma, medulloblastoma, and biliary tract cancer. Silmitasertib inhibits the serine/threonine protein kinase CK2, which exerts a proliferation-promoting and anti-apoptotic effect on cancer cells. In view of current and future applications, the measurement of silmitasertib levels in plasma is expected to play an important role in the evaluation of therapeutic and toxic concentrations in cancer patients. In the present work, we therefore present an LC–MS/MS method for the quantification of silmitasertib in human plasma. Using a simple liquid–liquid extraction with ethyl acetate and a mixture of n-hexane and ethyl acetate, this method can be performed in any laboratory with mass spectrometry. The validation was carried out according to the FDA guideline.

Summary: Background: The RECcording COurses of vasculaR Diseases (RECCORD) registry established by the German Society of Angiology – Society for Vascular Medicine aimed to address the lack in contemporary real-world data regarding current practice of medical and interventional care in vascular patients. We herein report the demographic and procedural characteristics of the first 1000 patients undergoing endovascular revascularization (EVR) for symptomatic peripheral artery disease (PAD). Patients and methods: RECCORD is an observational, prospective, multicenter, all-comers registry. Only patients undergoing EVR for symptomatic PAD are included and followed up for at least 1 year. Demographic characteristics, comorbidities, previous peripheral vascular interventions, medication, clinical stage of lower extremity artery disease (Rutherford category), hemodynamic parameters, and procedural data including complications are recorded via an entirely web-based platform. Results: Of the first 1000 patients (mean age 70 ± 10 years, 35% female) with 1096 EVR at 1477 vascular segments of the lower extremities, 25.0% were at the stage of chronic limb threatening ischemia (CLTI) and 75.0% at non-CLTI. The femoropopliteal segment was the dominant target lesion site (61.0%), followed by iliac (26.4%) and below-the-knee EVR (10.3%). Only angioplasty was performed in 130 EVR (11.9%), adjunctive drug coated balloons (DCB) in 498 (45.4%), additional stenting in 633 (57.8%). Debulking devices were used in 106 (9.7%) EVR. Clinical (Rutherford categories) and hemodynamic parameters (ankle-brachial-index) as well as secondary preventive medication were significantly improved post EVR. Periprocedural complications occurred in 63 (5.7%) EVR with pseudoaneurysm as the leading complication type in 26 (2.4%) EVR. Conclusions: The baseline data of the first 1000 patients from the RECCORD registry representing the real-world setting illustrate that the majority of EVR are performed in patients with claudication. Adjunctive use of DCB and stenting are the dominant types of EVR, while periprocedural complications are at an acceptable low rate.

This study investigated causes of attenuation of cerebrospinal fluid (CSF) signal on heavily T2-weighted (T2W) images in dogs with thoracolumbar disc extrusion. Medical records and magnetic resonance images were retrospectively reviewed. Dogs were classified into the following grades; grade 1, non-ambulatory paraparesis; grade 2, paraplegia with deep pain perception and grade 3, paraplegia without deep pain perception. The length of intramedullary T2W hyperintensity of the spinal cord, cranial/ caudal expansion of extradural compressive materials (ECM), and the CSF signal attenuation were measured. Ratios to the second lumbar vertebra (L2) were calculated for the length of intramedullary T2W hyperintensity (T2W:L2), cranial/caudal expansion of ECM (ECML:L2), and CSF signal attenuation (CSF:L2). The dogs were classified into focal or extended T2W hyperintensity groups according to the length [focal, shorter than length of L2; extended, longer than L2]. The area of EMC and the spinal canal were measured on transverse images at the lesion deriving occupancy ratio. The correlation between CSF:L2 and other data were analysed, and CSF:L2 was compared between the grades. In dogs with intramedullary T2W hyperintensity, the locations of CSF attenuation and the hyperintensity were compared if those locations were matched. Fifty-five dogs were included, 36 of which showed intramedullary T2W hyperintensity. Twenty-two of 36 dogs were considered as match of the location of the CSF attenuation and hyperintensity. CSF:L2 was significantly correlated with T2W:L2 in dogs with extended T2W hyperintensity (p = 0.0002), while CSF:L2 was significantly correlated with ECML:L2 in dogs with focal or no T2W hyperintensity (p = 0.0103 and p = 0.0364, respectively). CSF:L2 in grade 3 was significantly greater than those in patients who were grade 1 or 2 (both p < 0.001). In conclusion, higher CSF:L2, which was frequently seen in grade 3, would be most consistent with a higher T2W:L2 which might indicate spinal cord swelling.

In geological disposal for high-level radioactive waste, bentonites are planned to be used as the buffer material surrounding radioactive waste in Japan. Bentonite-based buffer material requires low water permeation for delaying contact between groundwater and the waste. Because of the extremely long half-lives of radionuclides of the waste, several barriers including the buffer material are designed to maintain workability of the geological disposal facility for tens of thousands of years. However, in the disposal circumstances with high water pressure, high temperature and various groundwater chemistries, occurrence of cementation and consequently property changes of the bentonite in the buffer are concerned. Few studies are available to understand the effect of cementation on bentonite properties because of the difficulties of simulating long-term alteration process experimentally. From the viewpoint of natural analogues, cementation process of the buffer may be regarded as part of formation process of bentonite ore. Thus, in this study, permeability tests were conducted on three kinds of Na-type bentonite ores with different geological ages from respectively, Japan, USA, and China to see the influence of cementation on permeability of bentonites. For comparison, undisturbed and reconstituted specimens were prepared. The results show that difference of hydraulic conductivities of the undisturbed and reconstituted specimens for each ore is less than one order, and this difference seems not to correlate with the geological age of the ores. From these results, the influence of cementation on the hydraulic properties of bentonite buffer seems small. It may also be a counteracted result by cementation effects in terms of restriction of the swelling of montmorillonite and blockage of water flow paths.

Paclitaxel beschichtete Ballons (DCB) und Stents (DES) fuhren in der Behandlung femoropoplitealer Lasionen zu hoheren Offenheitsraten und weniger Reinterventionen. Dem Verdacht einer erhohten Mortalitat in Metaanalysen steht eine reduzierte Mortalitat in Analysen groser Krankenkassendaten entgegen. DCB und DES sind daher in selektionierten Patienten nach entsprechender Aufklarung immer noch indiziert.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is indispensable for reproduction in mammals. Kisspeptin neurons in the hypothalamic arcuate nucleus (ARC), referred to as KNDy neurons because of the coexpression of neurokinin B and dynorphin A, are considered as components of the GnRH pulse generator that produces rhythmic GnRH secretion. The present study aimed to investigate if peripheral administration of PF-4455242, a κ-opioid receptor (KOR, a dynorphin A receptor) antagonist, facilitates pulsatile luteinizing hormone (LH) secretion and GnRH pulse generator activity in estrogen-treated ovariectomized Shiba goats to determine the possibility of using KOR antagonists to artificially control ovarian activities. PF-4455242 was intravenously infused for 4 h (1 or 10 μmol/kg body weight/4 h) or as a single subcutaneous injection (1 or 10 μmol/kg body weight). In a separate experiment, the same KOR antagonist (10 μmol/kg body weight/4 h) was intravenously infused during the recording of multiple unit activity (MUA) in the ARC that reflects the activity of the GnRH pulse generator to test the effects of KOR antagonist administration on GnRH pulse generator activity. Intravenous infusion and single subcutaneous injection of the KOR antagonist significantly increased the frequency of LH pulses compared with controls. Intravenous infusion of KOR antagonist also significantly increased the frequency of episodic bursts in the MUA. The present study demonstrates that peripherally administered KOR antagonist stimulates pulsatile LH secretion by acting on the GnRH pulse generator, and peripheral administration of PF-4455242 can be used to facilitate pulsatile LH secretion, which in turn facilitates ovarian activities in farm animals.

The purpose of this study is to develop a new pallet structure using the inexpensive hinoki wood, which is produced in the Ehime Prefecture, having the same strength as the conventional Oregon pine wood. A new pallet structure was proposed for achieving high-strength by improving the flexural stiffness and compressive stiffness and achieving high-cost performance by using the inexpensive hinoki wood. The results obtained in this study are summarized as follows: deflection of the new type is reduced compared to the standard type, due to the increased bending rigidity of the edge board and deck board; compressive displacement of the new model decreases, as the compressive stiffness of the pallet legs increases; new mold pattern 6 made is higher in strength and rigidity than the standard mold; cost of the new type #6 is 72% of that of the standard type pallet, and cost can be reduced by 28%.

Introduction Solriamfetol (Sunosi) is a dopamine/norepinephrine reuptake inhibitor approved (EU/US) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnoea (OSA) (37.5–150 mg/day). This study characterised real-world dosing and titration with solriamfetol in patients with narcolepsy. Methods A retrospective patient chart review was conducted among US-based physicians prescribing solriamfetol. Initiation strategies were de novo (no prior EDS medication), transition (switched/switching from existing EDS medications to solriamfetol), or add-on (adding solriamfetol to current EDS medication). Results Twenty-three physicians entered data from 70 patients with narcolepsy (type 1, 24/70; type 2, 46/70; mean+/-SD age, 40+/-11 years; 57% female; 6 also had OSA). EDS was mainly moderate (59%) or severe (36%). Nineteen patients (27%) initiated de novo, 31 (44%) transitioned, and 20 (29%) were add-on. Most patients started solriamfetol at 75 mg (86%) and were stable at 150 mg (76%). Most (67%) had 1 dose adjustment; median (range) time to a stable dose was 14 (1–60) days. EDS severity (44% of patients) was frequently considered when titrating. Fourteen of 22 (64%) transitioning from wake-promoting agents (WPAs) stopped them abruptly; 5/9 (56%) using stimulants tapered off. Discussion In a real-world study, most physicians prescribing solriamfetol to patients with narcolepsy started at 75 mg, tapered stimulants, abruptly discontinued WPAs, and made 1 dose adjustment. Support Jazz Pharmaceuticals

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Endocrine disrupting chemicals (EDC) include synthetic compounds that mimic the structure or function of natural hormones. While most studies utilize live embryos or primary cells from adult fish, these cells rapidly lose functionality when cultured on plastic or glass substrates coated with extracellular matrix proteins. This study hypothesizes that the softness of a matrix with adhered fish cells can regulate the intercellular organization and physiological function of engineered hepatoids during EDC exposure. We scrutinized this hypothesis by culturing zebrafish hepatocytes (ZF-L) on collagen-based hydrogels with controlled elastic moduli by examining morphology, urea production, and intracellular oxidative stress of hepatoids exposed to 17β-estradiol. Interestingly, the softer gel drove cells to form a cell sheet with a canaliculi-like structure compared to its stiffer gel counterpart. The hepatoids cultured on the softer gel exhibited more active urea production upon exposure to 17β-estradiol and displayed faster recovery of intracellular reactive oxygen species level confirmed by gradient light interference microscopy (GLIM), a live-cell imaging technique. These results are broadly useful to improve screening and understanding of potential EDC impacts on aquatic organisms and human health.

For the purpose of future visualization of the flow field in superfluid helium-4, clusters of the triplet state excimer

Jabuticaba is a fruit native to Brazil, appreciated for its flavor and is also very nutritious, but it is a seasonal fruit and highly perishable. Therefore, drying is a good alternative for its conservation. The purpose of this work was to use drum drying to obtain jabuticaba flakes using corn starch as the main carrier agent. The sorption isotherm of the flakes at 25 °C was also studied, as well as the determination of the critical storage condition and the estimation of product shelf life through the permeability of different packages to the water vapor using mathematical models. The drum drying conditions were: temperature of 144 °C; residence time of 18 seconds; addition of 20% (dry basis) of corn starch and 0.5% (d.b.) of glyceryl monostearate. The final product was analyzed with respect to its physicochemical and technological properties. The sorption isotherm of the flakes was determined at 25 °C, using the gravimetric method with saturated solutions (0.11 ≤ aw ≤ 0.84). After the process, the flakes presented good retention of anthocyanins and total phenolic compounds, besides a high antioxidant activity. The water solubility of the product was around 70% and the hygroscopicity was approximately 24%. The equilibrium experimental points of the isotherm were better adjusted by the GAB model, with a monolayer moisture value of 12.74% (w.b) and a critical aw of 0.432.

Introduction Solriamfetol (Sunosi) is a dopamine/norepinephrine reuptake inhibitor approved (EU/US) to treat excessive daytime sleepiness (EDS) in adults with OSA (37.5–150 mg/day) or narcolepsy (75–150 mg/day). This study examined characteristics of patients with OSA initiating solriamfetol and prescribers’ rationales. Methods This descriptive study included a retrospective patient chart review among US-based physicians prescribing solriamfetol for patients with OSA/narcolepsy. Solriamfetol initiation strategies were classified as de novo (no prior EDS medication), transition (switched/switching from existing EDS medications), or add-on (adding to current EDS medication). Results Physicians (n=24) entered data from 50 patients with OSA (mean+/-SD age, 52+/-9.1 years; 62% male). EDS was primarily moderate (56%) or severe (36%). Mean+/-SD Apnea-Hypopnoea Index at OSA diagnosis was 33.1+/-19.7 (n=37). The most common nonpharmacologic treatment was positive airway pressure (n=39, 78%); 36/39 (92%) were considered adherent. Common comorbidities included obesity (BMI>/=30) (n=25, 50%), cardiovascular disorders (n=16, 32%), and type 2 diabetes (n=14, 28%). Twenty-two (44%) patients were de novo, 26 (52%) transitioned (primarily from wake-promoting agents [18/26, 69%]), and 2 (4%) added solriamfetol (to stimulants). The efficacy of solriamfetol prompted most discussions to prescribe de novo (18/22, 82%); a desire for improved efficacy and/or augmentation of other medications prompted most transitioning (15/26, 58%) and add-on (2/2, 100%) therapy. At data collection, 48 (96%) patients were stable on solriamfetol; one each discontinued due to lack of efficacy and side effects. Discussion Efficacy was a key consideration for physicians prescribing solriamfetol for EDS in a real-world sample of patients with OSA. Support Jazz Pharmaceuticals

Was ist neu? Medikamenten-beschichtete Ballons bei femoro-poplitealen Läsionen Medikamenten-beschichtete Ballons (DCB) führen in der Behandlung von femoro-poplitealen Läsionen zu besseren Offenheitsraten als die einfache Ballondilatation und zu ähnlichen bis besseren Offenheitsraten als die Stentimplantation. Vorteil ist die Vermeidung von permanentem Fremdmaterial in Regionen, die einer ständigen mechanischen Beanspruchung unterworfen sind und die Möglichkeit, die Prozedur an derselben Stelle wiederholen zu können bzw. chirurgische Zugangswege offenzuhalten. Bei Auftreten von Dissektionen oder einem Recoil bietet sich die fokale Implantation möglichst kurzer Stents in den betroffenen Segmenten an. Die primäre Implantation Medikamenten-beschichteter Stents zeigt darüber hinaus keinen weiteren Vorteil und ist auf längere Sicht mit den Nachteilen der Implantation von Fremdmaterial in Bewegungssegmenten behaftet. Nicht medikamentöse und medikamentöse Begleittherapie Die Kombination aus interventioneller Behandlung und supervidiertem Gehtraining zeigt die besten Erfolgsaussichten einer dauerhaften Verbesserung der Gehstrecke bei Patienten mit femoro-poplitealen Läsionen und ist einer alleinigen interventionellen Behandlung oder einem alleinigen Gehtraining überlegen. Darüber hinaus werden aktuell große randomisierte, kontrollierte Studien durchgeführt, die den Einfluss niedrig dosierter direkter Antikoagulanzien auf die kardiovaskuläre Komplikationsrate nach Intervention untersuchen. Die Ergebnisse dieser Studien werden Aufschluss geben über die optimale antithrombotische Therapie nach Intervention im femoro-poplitealen Stromgebiet.

Consumption of biofortified foods such as sweet potatoes with high content of β-carotene may reduce deficiency of this micronutrient. The development of biofortified sweet potato chips expands the distribution and offers an alternative to the consumption of this product. The aim of this study was to evaluate the thermal blanching methods (steam and in boiling water) in β-carotene retention in the production of dehydrated biofortified sweet potato chips with air circulation at 65°C. The raw material, the chips blanched in steam and in boiling water had a content of β-carotene of 501.86 ± 53.65, 490.23 ± 30.00 and 473.91 ± 11.43 µg g-1 (d.b.) respectively. The retention of β-carotene for steam and boiling water blanching was 97.7 and 94.4% respectively. The blanching conditions followed by drying used in the processing to obtain sweet potato chips were adequate as they resulted in β-carotene high retention.

We developed a new real-time radiation sensor using an organic semiconductor and measured its β-particle detection sensitivity. This sensor is fabricated by simply combining a p-type semiconductor, polyaniline (Pani), with an n-type semiconductor, TiO2, and processing the compound. Since Pani and TiO2 are both inexpensive materials, the sensor can be fabricated at a lower cost than inorganic semiconductor sensors. The signal of each fabricated sensor was measured by a charge sensitive ADC for the irradiation of β-particles. The response signal data of the ADC for each irradiation was measured to calculate the detection efficiency of the detector. The maximum detection efficiency measured as β-particle sensitivity of the sensor was 1%. This β-particle sensitivity is higher than that reported of Pani sensors in the past.

This volume explores the world of northern Italian wine porters, brentatori, and their saint, Alberto, from the medieval period to the late eighteenth century. Little illuminates a heretofore under...

As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.

The development of β-carotene rich sweet potato products, such as chips, provides a healthy consumption option with a long shelf life. The objective of this study was to evaluate the influence of the packaging systems on the stability of the chips. The chips were processed and packaged with nitrogen in PET(polyester)/Al(aluminum foil)/LDPE(low density polyethylene), metallized PET/LDPE, BOPP(biaxially oriented polypropylene)/metallized BOPP and BOPP/metallized BOPP with an oxygen scavenger; and also without nitrogen in BOPP/metallized BOPP, and stored at 25 °C and 75% RH. The shelf life of the chips packed in BOPP/metBOPP without nitrogen was 153 days, losing 61% of the β-carotene, and leading to sensory alterations in the flavor, odor and color. The shelf life of the chips packaged with nitrogen in PETmet/LDPE was defined as 184 days due to sensory alterations involving the loss of crispness. The chips packaged with nitrogen in PET/Al/LDPE, BOPP/metBOPP and BOPP/metBOPP with an oxygen scavenger retained 90%, 83% and 80% respectively of the β-carotene, and showed no significant sensory alterations during 207 days of storage.

Arteriogenesis is an inflammatory process associated with rapid cellular changes involving vascular resident endothelial progenitor cells (VR-EPCs). Extracellular cell surface bound 20S proteasome has been implicated to play an important role in inflammatory processes. In our search for antigens initially regulated during collateral growth mAb CTA 157-2 was generated against membrane fractions of growing collateral vessels. CTA 157-2 stained endothelium of growing collateral vessels and the cell surface of VR-EPCs. CTA 157-2 bound a protein complex (760 kDa) that was identified as 26 kDaα7 and 21 kDaβ3 subunit of 20S proteasome in mass spectrometry. Furthermore we demonstrated specific staining of 20S proteasome after immunoprecipitation of VR-EPC membrane extract with CTA 157-2 sepharose beads. Functionally, CTA 157-2 enhanced concentration dependently AMC (7-amino-4-methylcoumarin) cleavage from LLVY (N-Succinyl-Leu-Leu-Val-Tyr) by recombinant 20S proteasome as well as proteasomal activity in VR-EPC extracts. Proliferation of VR-EPCs (BrdU incorporation) was reduced by CTA 157-2. Infusion of the antibody into the collateral circulation reduced number of collateral arteries, collateral proliferation, and collateral conductancein vivo.In conclusion our results indicate that extracellular cell surface bound 20S proteasome influences VR-EPC functionin vitroand collateral growthin vivo.

Abstract. Background: The prevalence of peripheral artery disease (PAD) is increasing worldwide. Revascularization procedures constitute a cornerstone of the therapy in PAD, not only in critical limb ischaemia but increasingly also in patients with intermittent claudication. The German Society of Angiology – Society for Vascular Medicine is establishing a nationwide, prospective, multicentre registry to address the lack of contemporary real life data regarding current practice of medical and interventional care in vascular patients and its subsequent long-term outcome. Patients and methods: The RECording COurses of vasculaR Diseases registry (RECCORD registry) is an observational, prospective, multicentre, all-comers registry platform. In the initial phase, patients referred for endovascular revascularization of PAD of the lower limbs will be prospectively included and followed up for at least one year. At baseline, data on patients’ demographic characteristics, comorbidities, previous peripheral interventions, medication, and clinical stage of PAD (Rutherford category), haemodynamic parameters, and procedural data including complications will be assessed. Major adverse cardiac and limb events will be recorded at planned (at six and 12 months) and at any unplanned visits. The therapeutic management will be exclusively left to the discretion of the vascular specialists. Results and conclusions: The RECCORD registry will provide a comprehensive dataset depicting the current real life practice and outcome of vascular care. The seven predefined quality indicators will be used for benchmarking the participating centres. Moreover, identifying factors promoting a favourable outcome might pave the way for an evidence-based therapeutic strategy and a dedicated therapeutic pathway for patients with PAD including patient-oriented best interventional approaches. In the future, the RECCORD registry may provide a general platform to study the courses of various defined vascular diseases in order to get detailed insights into the real life current practice of health care provided to vascular patients.

For developing an accelerator-driven system (ADS), many studies, such as those on accelerator development, subcritical system neutronics, materials irradiation effects, and thermal hydraulics, are required. In the Research Reactor Institute at Kyoto University (KURRI), ADS is planned as a future neutron source. Recent activities of relevant ADS studies at KURRI are introduced herein.

Synthesis and cooperative functions of hybrid materials composed of enzyme and semiconducting layers are described in this chapter. The hybrids were produced via a simple physical interaction between the components, that is, electrostatic interaction in an aqueous solution. To form interstratifying enzymes in the galleries, solution pH, which is a key parameter to decide surface potential, should be adjusted appropriately. In other words, enzymes should have an opposite charge when compared to that of the layers at an identical pH. Even though the intercalation slightly reduced enzymatic activity as compared to those of the free enzymes, stability under cruel conditions was drastically improved due to screening effect of semiconducting layers from extrinsic stimuli. In addition, photochemical control of redox enzymes sandwiched between semiconducting layers was accomplished. Light irradiation of the hybrids induced band gap excitation of the layers, and holes produced in the valence band activated the enzymes. It was revealed that the semiconducting layers with magnetic elements might be useful to magnetic application (separation) of enzymes as similar to conventional magnetic beads.

Synthesis and cooperative functions of hybrid materials composed of enzyme and semiconducting layers are described in this chapter. The hybrids were produced via a simple physical interaction between the components, that is, electrostatic interaction in an aqueous solution. To form interstratifying enzymes in the galleries, solution pH, which is a key parameter to decide surface potential, should be adjusted appropriately. In other words, enzymes should have an opposite charge when compared to that of the layers at an identical pH. Even though the intercalation slightly reduced enzymatic activity as compared to those of the free enzymes, stability under cruel conditions was drastically improved due to screening effect of semiconducting layers from extrinsic stimuli. In addition, photochemical control of redox enzymes sandwiched between semiconducting layers was accomplished. Light irradiation of the hybrids induced band gap excitation of the layers, and holes produced in the valence band activated the enzymes. It was revealed that the semiconducting layers with magnetic elements might be useful to magnetic application (separation) of enzymes as similar to conventional magnetic beads.

A farinha de batata-doce, quando elaborada a partir de raízes com alto teor de β-caroteno, é fonte de pró-vitamina A, que apresenta efeitos benéficos na saúde humana. Visando contribuir com o suprimento de vitamina A na alimentação de populações carentes, a EMBRAPA tem selecionado e melhorado culturas via biofortificação, como da batata-doce, e pesquisado o desenvolvimento de produtos com esta matéria-prima biofortificada. Complementando esses desenvolvimentos, o objetivo deste estudo foi comparar o efeito do tipo de embalagem e do sistema de acondicionamento do produto na preservação de carotenoides de farinha de batata-doce biofortificada. A farinha foi acondicionada com e sem vácuo, em embalagens com diferentes barreiras ao oxigênio, vapor d'água e luz (PET/Al/PEBD, PETmet/PEBD, PEBD/PA/PEBD e PEBD) e estocada a 25 °C/75%UR com e sem exposição à luz por um ano. Perdas de 50% de carotenoides totais e β-caroteno ocorreram na farinha em PETmet/PEBD e PEBD sem vácuo, aos 50 dias de estocagem, em razão do teor de oxigênio residual presente no espaço livre e também da alta permeação de oxigênio pelo material no caso do PEBD, no qual a composição do ar foi mantida durante todo o estudo. Perdas de 50% de carotenoides ocorreram aos 90 dias com ou sem exposição à luz no produto em PEBD/PA/PEBD com vácuo, indicando que a reação de oxidação de carotenoides sob luz se restringe apenas à farinha em contato com a superfície da embalagem. Sob vácuo e em PETmet/PEBD, os teores de carotenoides na farinha diminuíram ligeiramente e foram mantidos no PET/Al/PEBD, até 360 dias de estocagem. Os resultados indicaram que a redução do teor de oxigênio no espaço livre da embalagem por meio da aplicação de vácuo aliada ao uso de materiais de embalagem com barreira ao oxigênio da ordem de grandeza de PET com metalização barreira são os fatores mais importantes na preservação de carotenoides em farinha de batata-doce biofortificada. Sweet potato flour, when made from roots with high β-carotene contents, is a source of pro-vitamin A, presenting beneficial effects for human health. Thus aiming at contributing to the supply of vitamin A in the diet of more needy populations, EMBRAPA has selected and improved some crops via biofortification, such as the sweet potato, and developed products with the biofortified raw material. Complementing these developments, the purpose of this study was to correlate the effect of the type of package and packaging system on the product, in the preservation of the carotenoids in the biofortified sweet potato flour. The flour was packed with and without vacuum in packs with different oxygen, water vapour and light barriers (PET/Al/LDPE, PETmet/LDPE, LDPE/PA/LDPE and LDPE) and stored at 25 °C/75%RH with and without exposure to light. Losses of 50% of the total carotenoids and β-carotene occurred in the flour packed in PETmet/LDPE and LDPE without vacuum after 50 days of storage, due to the residual oxygen in the headspace and the high oxygen transmission rate in the case of LDPE, where the internal atmosphere showed the composition of air throughout the study. Losses of 50% carotenoids occurred after 90 days with and without exposure to light in the flour packed in LDPE/PA/LDPE with vacuum, indicating that in the presence of light, the carotenoid oxidation reaction is restricted to flour in contact with the surface of the package. Under vacuum and packed in PETmet/LDPE, the carotenoid contents of the flour reduced slightly, but were preserved for up to 360 days of storage when packed in PET/Al/LDPE. The results indicate that the key factors to preserve carotenoids in biofortified sweet potato flour are the reduction of the oxygen level in the headspace of the package by the application of vacuum, together with the use of packaging materials with an oxygen barrier as good as that of PET with a metalized barrier.

A micro wire-mesh sensor ( μ WMS) based on an electrical conductivity measurement between electrodes installed on the walls has been developed for gas–liquid two-phase flow measurements in a narrow rectangular channel. This measuring method applies a principle of conventional wire-mesh tomography, which can measure the instantaneous void fraction distributions in the cross-section of the relatively large flow channel. In two-phase flow measurement using μ WMS the void fraction distributions in the narrow channel were obtained by the measured conductivities between electrodes arranged on each wall. Therefore, the gas phase structures and the bubble behaviors can be investigated in the flow channel with narrow gap. In the present paper, a μ WMS for the air–water flow between parallel flat plates with a gap of 3 mm was developed and simultaneous measurements with a high speed video camera were conducted to compare the measured results in bubbly flow.