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Appropriately modified thermoresponsive hydrogels, such as poly(N-isopropylacrylamide) hydrogels, bring an opportunity for a variety of biomedical applications. Incorporating compounds with different properties into poly(N-isopropylacrylamide) hydrogels offers opportunities to enhance their mechanical, self-healing ability, adhesiveness, thermal responsiveness, and drug release capabilities. In this study, we investigated the influence of Au–sulfur interactions on the properties of the poly(N-isopropylacrylamide) hydrogels after introducing N,N′-bis(acryloyl)cystine (a newly synthesized cross-linker), modified gold nanoparticles, and a p(NIPAm-BISS) nanogel into the hydrogel matrix. Our findings demonstrated that poly(N-isopropylacrylamide) hydrogels with these compounds exhibited higher mechanical strength (65% tensile stress and 25% elongation), faster thermal responsiveness, controllable self-healing [85% recovery after 2 min, using a NIR laser (800 nm, 0.75 W)], skin adhesiveness, and enhanced drug release (0.08 mg·mL–1, a 93% improvement). These results may contribute to advancements in the design of temperature-responsive hydrogels tailored for specific biomedical needs, such as targeted drug delivery with the use of a NIR laser and tissue engineering.

In the course of our research into enzyme-triggered CO-releasing molecules (ET-CORMs), we were interested in using 2-acetoxy-5-azido-1,3-cyclohexadiene–Fe(CO)3(rac-2) as a building block for further structural modification by means of Cu-catalyzed azide–alkyne cycloaddition (CuAAC click chemistry). Treatment of [2-acetoxy-cyclohexadienyl–Fe(CO)3]+[PF6]−with Zn(N3)2, TMS-N3, or NaN3surprisingly afforded 2-acetoxy-1-azido-2,4-cyclohexadiene–Fe(CO)3(rac-9) as the main product. We could show that rac-2is primarily formed under kinetic control but undergoes a rapid isomerization to rac-9(as the thermodynamic product) in a formal vinylogous Winstein rearrangement under concomitant migration of the Fe(CO)3moiety. This unprecedented reaction displays a 1st order kinetics and appears to proceed via an ionic (rather than a concerted intramolecular) mechanism as supported by crossover experiments using deuterated compounds. The CuAAC reaction of rac-9with propargylic alcohol afforded triazole rac-13, which was demonstrated (by headspace-gas chromatography (GC)) to act as an ET-CORM in the presence of porcine liver esterase.

In the course of an attempt to synthesize 2-acyloxycyclohexa-1,3-diene-Fe(CO)3complexes in nonracemic form, we reinvestigated the “fully diastereoselective” Fe(CO)3complexation of (S,S)-2-ketopinoyloxy-1,3-cyclohexadiene, which had been described by Yeh and co-workers (Organometallics2001, 20, 289−295). However, after cleaving off the chiral auxiliary unit, we only obtained racemic complexes, also for a related substrate. For this reason, we performed control experiments to exclude possible racemization mechanisms and confirmed the configurational integrity of the dienol-Fe(CO)3intermediates using stereochemically defined dihydrocarvone-derived complexes. We finally could show that the complexation described by Yeh actually proceeds without any detectable diastereoselectivity. At the end, the virtually inseparable diastereomers of the chiral complexation products could be distinguished by careful NMR and chiral HPLC analyses.

Supplemental digital content is available in the text.INTRODUCTION:Posthemorrhagic hydrocephalus (PHH) is a common disease process encountered in neonates. Management often includes cerebrospinal fluid (CSF) aspiration through ventricular access devices (VADs). However, a common concern surrounding serial access of implanted subcutaneous reservoirs includes introduction of infection. In addition, there is great variability in aseptic technique. Therefore, the authors sought to evaluate the incidence of VAD access-associated infections in the literature and compare them with the rate of infection found at our institution. We also highlight the use of a preassembled VAD access kit and standardized access protocol, as well as the role of provider education, in maintaining safety and sterility during serial VAD access. METHODS:A single-institution retrospective review was performed for PHH patients younger than 1 year old undergoing serial CSF aspirations via implanted VADs (2009–2019). Patients were excluded if they had a ventriculoperitoneal shunt placed as primary intervention. MEDLINE search for reports of serial VAD access in PHH was also performed. Reports were excluded if they did not include full-text articles in the English literature. RESULTS:At our institution, subcutaneous reservoirs were placed in 37 neonates with PHH for serial CSF aspiration. No infections occurred after a total of 630 taps (average, 17 taps per reservoir; range, 0–83) and 10 420 collective reservoir days (average, 282 per patient; range, 6–3700). Only 2 reservoirs required revision for malfunction. Serial VAD taps for PHH were described in 14 articles in the medical literature, with 7.9% (n = 47/592) of patients reported with tap-related infectious complications. CONCLUSION:A standardized VAD access kit, along with stringent adherence to access protocol, can significantly minimize risk of infection associated with serial VAD access. These principles can be generalized to percutaneous aspiration of CSF from subcutaneous reservoirs placed for other indications to promote safety and sterility of this common procedure.

The gray wolf Canis lupusrange in central Europe is dynamically expanding, reconnecting previously isolated populations. Thus, a recent paper has proposed to merge the current Baltic and Central European (CE) wolf management units, which are no longer isolated by distance. However, recent genetic findings indicate that these two populations are not genetically homogenous. Here we review the most recent data on wolf genetic structure in central Europe and show that even though the CE and Baltic wolves represent the same phylogeographic lineage, their demographic history has resulted in significant genetic structure between these two populations. While the groups are interconnected by moderate gene flow, it is not high enough to reduce the strong founder signal observed in the CE population, suggesting that population dynamics within the CE wolf range are largely independent from those of its source (Baltic) population. Consequently, a management unit combining the CE and Baltic wolves would not form a demographically coherent entity. Thus, we recommend that conservation management units maintain their separate status.

To describe the patient and cycle characteristics of women who undergo intrauterine insemination (IUI) immediately after an unsuccessful oocyte retrieval.

The mistreatment of trainees is known to lead to burnout, loss of empathy, and career changes. Medical students in particular are vulnerable to mistreatment due to their lack of seniority and frequent transitions to new teams. Traditionally, initiatives to eliminate medical student mistreatment have focused on preventing their victimization surrounding verbal, physical, and sexual misconduct. While initiatives to eliminate these types of behaviors are exceedingly important, the most common form of mistreatment that is reported by medical students is not these active forms of abuse. Instead, students on their clinical rotations more frequently report the covert “obstruction of learning” or “exclusion from the medical team” as the most common form of mistreatment experienced. Though the passive neglect of a medical student is not seemingly as serious an offense as active abuse, it can certainly have an impactful, lasting negative effect on student development, morale, and career choice. In this perspective, we recognize the importance of observational learning as a component of medical education, but state that the neglect or exclusion of a medical student should not be considered acceptable and should be labeled what it is—a form of mistreatment. We additionally provide examples for how to prevent medical student neglect by establishing a supportive and inclusive teaching environment.

Limited studies on the benefits of blastocyst transfer in advanced maternal age (AMA) (≥40 years) have been reported. Our objective was to find whether blastocyst-stage embryo transfer improves pregnancy and live birth rates in women ≥40 years who have 3 or more good-quality cleavage-stage embryos.

Background and Objectives: Treosulfan (dihydroxybusulfan), licensed for the treatment of ovarian carcinoma, is investigated in clinical trials as a myeloablative agent for conditioning prior to hematopoietic stem cell transplantation. Clinical experience shows that treosulfan exhibits lower organ toxicity than busulfan, including hepatotoxicity. Elimination of busulfan primarily via enzymatic conjugation with glutathione (GSH) in the liver is considered to be the main cause of the drug’s hepatotoxicity and interpatient clearance variability. It is believed that treosulfan undergoes no hepatic metabolism but empirical evidence is lacking. The aim of this kinetic study was to verify if treosulfan is capable of conjugating with GSH. Methods: Treosulfan (200 µM) was incubated at pH 7.2 and 37 °C with 5 mM GSH in the presence or absence of human liver cytosol, the main store of glutathione S-transferase in the body. Concentrations of treosulfan were determined using liquid chromatography–tandem mass spectrometry and then subjected to kinetic analysis. Results: The decay of treosulfan in the solution followed a one-exponential model in the presence of either GSH or liver cytosol and GSH. The first-order reaction rate constants (0.25 h-1) did not differ statistically from those found for treosulfan conversion in pH 7.2 buffer only. Conclusion: Treosulfan does not undergo either spontaneous or enzymatic conjugation with GSH at a noticeable rate. The result indicates that the clearance of treosulfan is independent of glutathione S-transferase activity, GSH stores, and co-administration of drugs utilizing the GSH metabolic pathway.

The paper deals with comprehensive quality and physical parameters of commercial cokes. It aims to present comparative analysis of acquired values with standards found in other literature sources. There were analysed 15 samples of coke from current industrial operation. There were carried out chemical analysis, CSR and CRI characterization. Density, porosity, compressive strength, friction coefficient, volume of particles were determined. There was performed one-way analysis of variance (ANOVA) by Statistica v.12.0 (StatSoft, Inc., Tulsa, USA) to determine significant correlation between the measured parameters. The highest correlation coefficents were noted between the pycnometer density of cokes and CSR index (r = 0.925) and CRI index (r = -0.828). The comparative analysis of quality and physical parameters with values mentioned in literature revealed the significant differences in the values of apparent density, bulk density and true density of pulverized samples.

A hydrogel based on poly(N-isopropylacrylamide) (NIPA) crosslinked with the diacryloyl derivative of cystine (BISS) was synthesized using the free radical polymerization. The NIPA-BISS hydrogel rich in cystine appeared to be a competitive sorbent and has been applied to efficiently remove heavy metal pollutants, mainly cadmium and lead ions, from water. Sorption capacity, kinetics of sorption, swelling behavior and effect of pH on sorption were investigated. Scanning electron microscopy and FTIR analysis were employed to monitor the changes that took place in the NIPA-BISS hydrogels after the adsorption of Cd(II) and Pb(II).

In multimillennial global warming simulations with the GISS‐E2‐R climate model, we observe multicentennial shutdowns with restoration and fast overshooting in North Atlantic Deep Water production despite the absence of exogenous freshwater input. AMOC (Atlantic Meridional Overturning Circulation) cessation is associated with a sea surface salinity reduction, initiated by increases in precipitation over evaporation as the climate warms. These multicentury shutdowns are the direct result of cooling in the North Atlantic associated with an aerosol indirect effect on cloud cover. The local cooling reduces evaporation within the North Atlantic, while warming elsewhere provides moisture to maintain nearly unperturbed precipitation in this region. As global warming continues, warm temperature (low density) anomalies spread northward at depth in the North Atlantic eventually destabilizing the water column, even though precipitation input at the surface is initially unchanged. Internal ocean freshwater transports do not play an important role in initiating this behavior, as assumed by some standard metrics of AMOC stability. The importance of the aerosol indirect effect in these runs is due to its role in strengthening the sea surface temperature‐evaporation feedback; this suggests a renewed focus on surface flux observations to help assess overturning stability. The length of the AMOC reduction, and its rapid recovery, may be relevant to the onset and end of the Younger Dryas, which occurred within a warming climate during the last deglaciation. In the Goddard Institute for Space Studies (GISS) climate model, when global warming due to higher CO2levels was sufficiently advanced, and the effect of aerosols on cloud cover included, the North Atlantic overturning ocean circulation shuts down. It stayed off for about 1,000 years and then suddenly resumed. Such a situation seemingly arose during the deglaciation from the last ice age. In both cases, it involved a warming planet and a relatively cooler North Atlantic ocean to begin the process and continued warming at depth in the ocean to end it. Were this to happen in the real world, it would be an additional complication for the climate system. Global warming simulations with aerosol contributions produce NADW oscillation analogous to events during deglacial warmingThe North Atlantic circulation ceases and after a millennium is abruptly restored due to warming at depthLength of perturbations and rapid recovery with overshooting resemble the Younger Dryas event

The article offers information on different tools for mechanics, along with suggestions for using the tools. Topics include the 1617EVS router from Bosch; suggestions for using the router like using it seat a drawer bottom in drawer sides, front and back; the Roper Whitney hand punch, tips for using the tool; and the Super Sawzall from Milwaukee Electric Tool.

A key challenge in the synthesis of non-ionic surfactants is the opposite polarity of the substrates and the connected challenge of using homogeneous catalysis. We present the telomerisation of β-myrcene with N-methylglucamine to C20-N-alkylated polyols, which show surface activity. The use of aqueous solvent systems along with amphiphilic ligands bridges the polarity gap and generates high reactivities.

The article offers step-by-step instructions for making a firewood rack.

In this study, we present a thermoresponsive thin hydrogel layer based on poly(N-isopropylacrylamide), functionalized with β-cyclodextrin groups (p(NIPA-βCD)), as a novel electrochemically controlled release system. This thin hydrogel layer was synthesized and simultaneously attached to the surface of a Au quartz crystal microbalance (QCM) electrode using electrochemically induced free radical polymerization. The process was induced and monitored using cyclic voltammetry and a quartz crystal microbalance with dissipation monitoring (QCM-D), respectively. The properties of the thin layer were investigated by using QCM-D and scanning electron microscopy (SEM). The incorporation of β-cyclodextrin moieties within the polymer network allowed rhodamine B dye modified with ferrocene (RdFc), serving as a model metallodrug, to accumulate in the p(NIPA-βCD) layer through host–guest inclusion complex formation. The redox properties of the electroactive p(NIPA-βCD/RdFc) layer and the dissociation of the host–guest complex triggered by changes in the oxidation state of the ferrocene groups were investigated. It was found that oxidation of the ferrocene moieties led to the release of RdFc. It was crucial to achieve precise control over the release of RdFc by applying the appropriate electrochemical signal, specifically, by applying the appropriate potential to the electrode. Importantly, the electrochemically controlled RdFc release process was performed at a temperature similar to that of the human body and monitored using a spectrofluorimetric technique. The presented system appears to be particularly suitable for transdermal delivery and delivery from intrabody implants.

A novel microgel, the volume of which can be reversibly changed by using an electrochemical trigger, was successfully synthesized. To this end, a monomer based on N-(3-aminopropyl)methacrylamide modified with ferrocenecarboxylic acid was obtained and co-polymerized with acrylic acid and N,N′–methylenebisacrylamide. Using the distillation precipitation polymerization method, spherical, smooth-surfaced microgel particles ca.500 nm in diameter were obtained. The presence of ferrocene groups in the microgel was shown with nuclear magnetic resonance spectroscopy, energy dispersive X-ray spectroscopy, and cyclic voltammetry methods. Dynamic light scattering experiments showed that the microgel size strongly depends on the oxidation state of the ferrocene groups. Next, cyclic voltammetry and chronoamperometry combined with quartz crystal microbalance measurements, obtained with an Au electrochemical quartz crystal microbalance electrode modified with the microgel, proved that the microgel size could be controlled by an electrochemical trigger. More interestingly, the electro-response was found to strongly depend on pH. In acidic pH, where almost all carboxylic groups are protonated, the oxidation of ferrocene groups led to a decrease in the registered frequency shift, related to the microgel swelling process. In alkaline pH, where many carboxylic groups are ionized, the oxidation of ferrocene led to an increase in frequency, related to the microgel shrinking process. These processes were found to be reversible and relatively fast.

The article offers step-by-step instructions for making a workbench.

The article previews several products, including the 10-inch benchtop drill press from Harbor Freight Central Machinery, a 6-inch benchtop jointer from Shop Fox, and a 10-inch band saw from Craftsman.

The work presents the possibility of application of inexpensive iron-base powders in the production of sintered diamond tools. It has been shown that ball-milled Fe-Ni-Cu-Sn-C and Fe-Mn-Cu-Sn-C powders can be consolidated to a virtually pore-free condition by hot pressing at 900°C. The as-consolidated materials are characterised by a combination of high hardness, mechanical strength and resistance to abrasion. Their properties can be widely modified by changing the milling time.

IMPORTANCE Despite the documented prevalence and clinical ramifications of physician distress, few rigorous studies have tested interventions to address the problem. OBJECTIVE To test the hypothesis that an intervention involving a facilitated physician small-group curriculum would result in improvement in well-being. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 74 practicing physicians in the Department of Medicine at the Mayo Clinic in Rochester, Minnesota, conducted between September 2010 and June 2012. Additional data were collected on 350 nontrial participants responding to annual surveys timed to coincide with the trial surveys. INTERVENTIONS The intervention involved 19 biweekly facilitated physician discussion groups incorporating elements of mindfulness, reflection, shared experience, and small-group learning for 9 months. Protected time (1 hour of paid time every other week) for participants was provided by the institution. MAIN OUTCOMES AND MEASURES Meaning in work, empowerment and engagement in work, burnout, symptoms of depression, quality of life, and job satisfaction assessed using validated metrics. RESULTS Empowerment and engagement at work increased by 5.3 points in the intervention arm vs a 0.5-point decline in the control arm by 3 months after the study (P = .04), an improvement sustained at 12 months (+5.5 vs +1.3 points; P = .03). Rates of high depersonalization at 3 months had decreased by 15.5% in the intervention arm vs a 0.8% increase in the control arm (P = .004). This difference was also sustained at 12 months (9.6% vs 1.5% decrease; P = .02). No statistically significant differences in stress, symptoms of depression, overall quality of life, or job satisfaction were seen. In additional comparisons including the nontrial physician cohort, the proportion of participants strongly agreeing that their work was meaningful increased 6.3% in the study intervention arm but decreased 6.3% in the study control arm and 13.4% in the nonstudy cohort (P = .04). Rates of depersonalization, emotional exhaustion, and overall burnout decreased substantially in the trial intervention arm, decreased slightly in the trial control arm, and increased in the nontrial cohort (P = .03, .007, and .002 for each outcome, respectively). CONCLUSIONS AND RELEVANCE An intervention for physicians based on a facilitated small-group curriculum improved meaning and engagement in work and reduced depersonalization, with sustained results at 12 months after the study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01159977

Acute myeloid leukemia (AML) is a highly malignant disease that is not curable in the majority of patients. Numerous non-random genetic abnormalities are known, among which several translocations such as PLZF/RARα or AML1/ETO are known to aberrantly recruit histone deacetylases. Deacetylase inhibitors (DACi) are promising drugs leading to growth inhibition, cell cycle arrest, premature senescence and apoptosis in malignant cells. It is believed that DACi may have clinical efficacy by eradicating the most primitive population of leukemic stem and progenitor cells, possibly by interfering with self-renewal.The aim of the study was to investigate the effects of DACi on leukemic stem and progenitor cells using murine transduction-transplantation models of hematopoietic cells harboring the leukemia-associated fusion proteins (LAFP) PLZF/RARα or a truncated AML1/ETO protein (AML1/ETO exon 9). We show that the self-renewal and short-term repopulation capacity of AML1/ETO- or PLZF/RARα-expressing Sca1+/lin-stem and progenitor cells are profoundly inhibited by clinically applicable concentrations of the DACi dacinostat and vorinostat. To further investigate the mechanisms underlying these effects, we examined the impact of DACi on the transcription factor c-MYC and the Polycomb group protein BMI1, which are induced by LAFP and involved in leukemic transformation. In AML1/ETO or PLZF/RARα-positive 32D cells, DACi-mediated antiproliferative effects were associated with downregulation of BMI1 and c-MYC protein levels. Similar effects were demonstrated in primary samples of cytogenetically defined high-risk AML patients. In conclusion, DACi may be effective as maintenance therapy by negatively interfering with signaling pathways that control survival and proliferation of leukemic stem and progenitor cells.