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Context The coronavirus disease 2019 (COVID-19) pandemic created a rapid and unprecedented shift in our medical system. Medical providers, teams, and organizations have needed to shift their visits away from face-to-face visits and toward telehealth (both by phone and through video). Palliative care teams who practice in the community setting are faced with a difficult task: How do we actively triage the most urgent visits while keeping our vulnerable patients safe from the pandemic? Measures The following are recommendations created by the Palo Alto Medical Foundation Palliative Care and Support Services team to help triage and coordinate for timely, safe, and effective palliative care in the community and outpatient setting during the ongoing COVID-19 pandemic. Patients are initially triaged based on location followed by acuity. Interdisciplinary care is implemented using strict infection control guidelines in the setting of limited personal protective equipment resources. We implement thorough screening for COVID-19 symptoms at multiple levels before a patient is seen by a designated provider. Conclusions/Lessons Learned We recommend active triaging, communication, and frequent screening for COVID-19 symptoms for palliative care patients been evaluated in the community setting. An understanding of infection risk, mutual consent between designated providers, patients, and their families are crucial to maintaining safety while delivering community-based palliative care during the COVID-19 pandemic.

NIR irradiation accounts for 52% of the solar irradiance energy reaching the earth, most of which is transferred to thermal energy. This work was undertaken in order to investigate the possibility of applying NIR reflective coatings on cotton fabric with the purpose of surface temperature reduction when irradiated with solar light. Commercial titania was modified by means of calcination treatments. Phase transition from anatase to rutile and growth in particle size were induced, and both processes resulted in an increase of NIR reflectance of the calcined TiO 2 . Irregular-shaped TiO 2 particles with sizes of 293–618 nm were obtained. The highest solar reflectance occurred in the TiO 2 sample with an anatase:rutile ratio of 35:65 and a particle diameter of 563 nm. By applying the NIR reflective coating consisting of calcined TiO 2 on cotton fabric, a lower surface temperature was recorded with a maximum difference of 3.9 °C. It was found that a chitosan-TiO 2 coating could provide a better wash fastness than TiO 2 alone.

A sol–gel method to synthesize nanocrystalline anatase in aqueous medium at room temperature is presented. Unlike other sol–gel synthesis routes reported, no inorganic acids or heat treatment were used in this method. Comprehensive characterization of TiO2 nanoparticles including crystal structures and morphology was performed. The effect of precursor concentration and aging time on crystallinity and crystallite size was studied. It has been found that while crystallization occurred at room temperature, the longer the aging time, the greater the crystallinity. Precursor concentration has a slight effect on the crystallite size and affects the aging time and the viscosity of the sol.

SummaryThe explosion of sequence information in bacteria makes developing high-throughput, cost-effective approaches to matching genes with phenotypes imperative. Using E. coli as proof of principle, we show that combining large-scale chemical genomics with quantitative fitness measurements provides a high-quality data set rich in discovery. Probing growth profiles of a mutant library in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us to study gene essentiality, discover leads for gene function and drug action, and understand higher-order organization of the bacterial chromosome. We highlight new information derived from the study, including insights into a gene involved in multiple antibiotic resistance and the synergy between a broadly used combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set, publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource for both the microbiological and bioinformatic communities, as it provides high-confidence associations between hundreds of annotated and uncharacterized genes as well as inferences about the mode of action of several poorly understood drugs.

We describe herein a novel series of 3-amino-4-hydrazine-cyclobut-3-ene-1,2-diones as potent and selective inhibitors against the CXCR2 chemokine receptor and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Furthermore, these alkyl-hydrazine series inhibitors such as 5b demonstrated acceptable metabolic stability when incubated in human and rat microsomes.

The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5) is described. High-throughput screening of an extensive series of ECLiPStrade mark compound libraries led to the identification of compound 1 as a dual inhibitor of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5). Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the alpha(v)beta(3) and alpha(v)beta(5) integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile.

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

Rapid technological development in computer video conferencing and digital video photography over the last decade makes it easier than ever for teacher educators to use the technology in facilitating reflective practice. This paper reports recent developments in the use of multipoint desktop videoconferencing (MDVC) in preservice teaching practice in Singapore. In addition to regular video conferencing, preservice teachers now have opportunities to view their own teaching video clips and receive feedback from their peers and university supervisors. The experience helped enhance professional development of preservice teachers by allowing them to share ideas, experiences and teaching resources in real time with an audience wider than the schools where they taught.

The effects of pH of conventional lactate-based peritoneal dialysis solutions (LPDS) on the net ultrafiltration and solute removal in intermittent peritoneal dialysis (IPD) were studied. Conventional LPDS is rendered acidic to minimize the caramelization of glucose. Fifteen stable uremic patients were put on weekly IPD with a conventional 1.5% LPDS (hourly 2 L cycle for 60 L). pH of the LPDS was raised to around 7.4 by the addition of 1.4 mmol sodium hydroxide (1 M solution) to each litre of LPDS under an aseptic condition before the commencement of dialysis. A similar study was performed with the same 15 patients but the sodium hydroxide was replaced by a similar amount of sodium chloride. The net ultrafiltration, removal of urea, creatinine, sodium, and potassium were determined and compared. Serum levels of urea, creatinine, sodium, and potassium were also measured before and after the IPD. No peritonitis was encountered during the study. The net ultrafiltration volume in the euvolemic LPDS group was greater than the acidic LPDS group although this was not statistically significant [(mean ±SD) 2526 ±910 mL and 2186 ±750 mL, respectively, p = 0.21]. The clearances of urea, creatinine, sodium, and potassium showed no differences in both groups. We concluded that the ultrafiltration, clearances of urea, creatinine, sodium, and potassium in IPD were not affected by the pH of a LPDS from our results and a larger study is warranted to see the effect of dialysate pH on the peritoneal membrane.

The mouse leukotriene B4 receptor (m-BLTR) gene was cloned. Membrane fractions of human embryonic kidney 293 cells stably expressing m-BLTR demonstrated a high affinity and specific binding for leukotriene B4 (LTB4, Kd = 0.24 +/- 0.03 nM). In competition binding experiments, LTB4 was the most potent competitor (Ki = 0.23 +/- 0.05 nM) followed by 20-hydroxy-LTB4 (Ki = 1.1 +/- 0.2 nM) and by 6-trans-12-epi-LTB4 and LTD4 (Ki > 1 microM). In stably transfected Chinese hamster ovary cells, LTB4 inhibited forskolin-activated cAMP production and induced an increase of intracellular calcium, suggesting that this receptor is coupled to Gi- and Go-like proteins. In Xenopus laevis melanophores transiently expressing m-BLTR, LTB4 induced the aggregation of pigment granules, confirming the inhibition of cAMP production induced by LTB4. BLT receptors share significant sequence homology with chemokine receptors (CCR5 and CXCR4) that act as human immunodeficiency virus (HIV) coreceptors. However, among the 16 HIV/SIV strains tested, the human BLT receptor did not act as a coreceptor for virus entry into CD4-expressing cells based on infection and cell-cell fusion assays. In 5-lipoxygenase-deficient mice, the absence of leukotriene B4 biosynthesis did not detectably alter m-BLT receptor binding in membranes obtained from glycogen-elicited neutrophils. Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation.

A novel γ-turn mimetic 2 has been prepared based on retro amide peptide design. Incorporation of this mimetic into linear peptide fibrinogen receptor antagonist 7 (GPIIb/IIIa receptor) affords the opportunity to test models of antagonist pharmacophore.

Introduction Barrett’s oesophagus (BO) occurs as consequence of reflux and is a risk factor for oesophageal adenocarcinoma (OAC). The current “gold-standard” for diagnosing BO is endoscopy which remains prohibitively expensive and impractical as a population screening tool. Therefore, we aimed to investigate the epidemiological factors and symptoms associated with BO in order to develop a pre-screening tool to aid decision making for diagnostic referrals. Methods A prospective (training) cohort of 1603 patients attending for gastroscopy was used for identification of risk factors to develop a risk prediction model. Factors significantly associated with BO in the univariate analysis were selected to develop a prediction model that was validated in an independent, external cohort of 504 patients in primary care. We used two definitions of BO in the current study: 1) columnar lined epithelium of oesophagus (CLE) of any length reported in the endoscopy report with columnar epithelium on biopsy 2) an intestinal metaplasia confirmed on histopathological assessment with endoscopic length of BO ≥2 cm (IM ≥ 2 cm). Results An eight-factor panel, including age, sex, smoking status, heartburn, acid reflux, chest pain, abdominal pain, anti-reflux medication, was identified from the training cohort with an area under the ROC curve (AUC) of 0.74 (95%CI: 0.70–0.77) for CLE, and 0.80 (95% CI: 0.75–0.84) for IM ≥ 2cm. This panel was significantly associated with BO in the external cohort, and the odds ratios for each factor increase were 1.43 (95%CI: 1.02–2.01) and 1.30 (95%CI: 1.04–1.62) for CLE and IM ≥ 2cm, respectively. The AUCs of the 8-factor panel for CLE and IM ≥ 2cm in the external cohorts were 0.85 (95%CI: 0.77–0.92) and 0.78 (95%CI: 0.71–0.84), respectively. After controlling for over-fitting, the AUCs dropped to 0.65 (95% CI: 0.54–0.77) and 0.67 (95%CI: 0.60–0.74), respectively. Conclusion An eight-factor panel can help predict the presence of BO and has the potential to be applied in the general population with GORD symptoms as a pre-screening tool to help select patients for further investigation. Disclosure of Interest None Declared.

Cyclic voltammetry and UV/VIS spectrometry studies show that 4'-(9-acridinylamino)-methanesulfon- m -anisidide (mAMSA) can be oxidized electrochemically to N 1 -methylsulfonyl- N 4 -(9-acridinyl)-3-methoxy-2, 5-cyclohexadiene-1,4-diimine (mAQDI) in Tris buffer, pH 7.5. The formal potential of this 2-electron process, as determined by spectroelectrochemical techniques, was 0.141 V versus saturated calomel electrode. Voltammetric data also indicate that an electron transfer reaction between mAMSA and Cu(II) was thermodynamically favored. Two lines of evidence suggest that mAQDI and Cu(I) are the active species in DNA breakage: (1) mAQDI, in the presence of Cu(I), induced both single- and double-strand DNA breakage of the superhelical pDPT275 form I DNA. mAQDI or Cu(I), when used alone, was less effective. (2) The DNA-breaking activity of an mAMSA-Cu(II) mixture was kinetically correlated with the production of both Cu(I) and mAQDI. Thin-layer Chromatographie studies showed that mAMSA was oxidized to mAQDI which, in turn, was hydrolyzed. The end product was identified as 9-aminoacridine. When DNA breakage activity was measured as a function of reaction time, a biphasic response was observed. Maximal DNA-breaking activity was obtained upon mixing mAMSA and Cu(II) for 2–4 hr, depending on the concentrations of mAMSA and Cu(II), and was followed by a subsequent decrease in breakage. The decrease appears to be due to the decrease in Cu(I) production and the hydrolysis of mAQDI. These results substantiate the proposed mechanism that DNA breakage induced by mAMSA-Cu(II) involves a rate-limiting electron transfer step to form mAQDI and Cu(I), which are the active species for DNA breakages.

During the past several years, substantial progress in understanding the receptors and signal transduction processes for peptidyl leukotrienes has been reported. Receptors have been identified and characterized, the major steps in the signal transduction pathway have been described, and the genetic and epigenetic regulatory processes have been characterized. Very recent studies have defined the mechanisms by which LTE4 acts as a partial agonist at the LTD4 receptor. The cloning of the genes for the proteins involved in the major steps of the signalling process has also been initiated. Stanley Crooke and co-authors summarize this recent progress and present their current notions about the LTD4 receptor signalling process.

4′-(9-Acridinylamino)methanesulfon- m -anisidide (mAMSA) interacts with red cell membranes, resulting in the formation of fluorescent protein adducts. The mAMSA-membrane protein adducts exhibited an emission fluorescence maximum at 445 nm, with two shoulders at approximately 425 and 470 nm. The major labeled proteins were identified as spectrins 1 and 2 and bands 3, 4.1, 4.2 and 5. The fluorescence intensity increased with increasing mAMSA concentrations (0.03 to 1.5 mM), time (15–120 min), and temperature of the reaction. Results from sodium dodecyl sulfate gel electrophoresis show that mAMSA caused no detectable change in the molecular weight of membrane proteins. This indicates that mAMSA is a monofunctional, noncrosslinking agent. Other acridine analogs, 9-aminoacridine and acridine, did not fluorescently label membrane proteins, suggesting that the presence of the acridine nucleus is not sufficient for labeling. Addition of 2-mercaptoethanol to the mAMSA-membrane reaction mixtures reversed the fluorescence labeling. Furthermore, pretreatment of membrane proteins with N -ethylmaleimide or iodoacetamide prevented the formation of fluorescent mAMSA-membrane protein adducts. These data suggest that mAMSA interacts with sulfhydryl groups of the membrane proteins. When the membrane sulfhydryl groups were assayed by labeling with N -[ ethyl -2- 3 H ]ethylmaleimide, it was shown that the accessible membrane sulfhydryl groups were reduced after the mAMSA treatment. The above results suggest that mAMSA covalently binds to the sulfhydryl groups in the red cell membrane, with the production of fluorescent mAMSA-protein adducts.