A Suzuki Coupling Based Route to 2,2'-Bis(2-indenyl)biphenyl Derivatives

Because of the promising performance in olefin polymerization of 2,2'-bis(2-indenyldiyl)biphenyl zirconium dichloride, we developed a new and broadly applicable route to 2,2'-bis(2-indenyl)biphenyl derivatives. Reaction of the known 2,2'-diiodobiphenyl with the new 2-indenyl boronic acid did not result in the desired 2,2'-bis(2-indenyl)biphenyl (10); instead an isomer thereof, (spiro-1,1-(2,2'-biphenyl)-2-(2-indenyl)indane), was obtained. It was found that compound 10 could be made via a palladium-catalyzed reaction of 2,2-biphenyldiboronic acid with 2-bromoindene under standard Suzuki reaction conditions. However, the yield of this reaction was low at low palladium catalyst loadings, due to a competitive hydrolysis reaction of 2,2-biphenyldiboronic acid. HTE techniques were used to find an economically viable protocol. Thus, use of the commercially available 1.0 molar solution of (n-Bu)4NOH in methanol with cosolvent toluene led to precipitation of the pure product in a fast and clean reaction, using only 0.7 mol % (0.35 mol % per C-C) of the expensive palladium catalyst.

Water-associated nosocomial infections.

yesIt is estimated that 5-10% of hospitalised patients in developed countries contract hospital acquired infections (HAI). Increasing levels of antimicrobial resistance manifested by many HAI-causing pathogens such as Acinetobacter spp in the intensive care unit (ICU) setting present a significant challenge to those managing these infections. Consequently, much attention has been focused on the prevention of HAIs. Particular emphasis has been placed on interventions intended to interrupt patient-to-patient transmission of pathogens, such as enhanced hand hygiene and identification of patients colonised with methicillin-resistant Staphylococcus aureus (MRSA) using rapid DNA-based screening techniques. However, comparatively little attention has been given to the hospital environment, including water supplies, as a source of nosocomial pathogens of importance for patients on the critical care unit. This article reviews the role of hospital water sources in the epidemiology of HAI and new technologies which can be employed in the prevention and control of such infections

Guidelines for e-reference library services for distance learners and other remote users.

Until recently the provision of distance education was undertaken mainly by various professional associations and commercial agencies offering vocational training. Library provision to meet the needs of registered students was limited. Over the past 30 years, however, the delivery of higher and further education to students studying at a distance has become a core part of the activity of many academic institutions: a few specialist higher education institutions such as the Open Universities established in Britain and India, and some conventional universities that established teaching centres away from their main campuses

Patient initiated follow-up in cancer patients: A systematic review

Background: Patient-initiated follow-up (PIFU) is increasingly being implemented for oncology patients, particularly during the COVID-19 pandemic, given the necessary reduction in face-to-face hospital outpatient appointments. We do not know if PIFU has a positive (or negative) impact on overall, or progression free, survival. Objectives: To investigate the impact of PIFU on overall survival, progression free survival, patient satisfaction, psychological morbidity, specifically quality of life (QoL) and economic costs compared to hospital follow up (HFU), for any type of cancer. Methods: We carried out a systematic review using five electronic databases: MEDLINE, CINAHL, EMBASE, PsycInfo and Cochrane Central Register of Controlled Trials. Studies were eligible if they were controlled clinical trials comparing PIFU with another form of active follow-up. Effectiveness was assessed using the primary outcome of overall survival and secondary outcomes of progression free survival, patient satisfaction, psychological morbidity, QoL and cost effectiveness. Results: Eight studies met the inclusion criteria and were included. Only one study included survival as a primary outcome and indicated no significant differences between hospital-based follow-up and PIFU, although not adequately powered to detect a difference in survival. For secondary outcomes, few differences were found between PIFU and other forms of active follow-up. One study reported significant differences in fear of cancer recurrence between PIFU and HFU although did not reach the limit of clinical significance; in the short term, fear decreased significantly more in hospital based follow-up. Conclusion: We do not have evidence to support the impact of PIFU on survival or progression free survival. Fully powered randomized controlled trials are required to determine the full impact of PIFU in the longer term

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

Reproductive hormones affect all stages of life from gamete production, fertilization, fetal development and parturition, neonatal development and puberty through to adulthood and senescence. The reproductive hormone cascade has, therefore, been the target for the development of numerous drugs that modulate its activity at many levels. As the central regulator of the cascade, gonadotropin-releasing hormone (GnRH) agonists and antagonists have found extensive applications in treating a wide range of hormone-dependent diseases, such as precocious puberty, prostate cancer, benign prostatic hyperplasia, endometriosis and uterine fibroids, as well as being an essential component of in vitro fertilization protocols. The neuroendocrine peptides that regulate GnRH neurons, kisspeptin and neurokinin B, have also been identified as therapeutic targets, and novel agonists and antagonists are being developed as modulators of the cascade upstream of GnRH. Here, we review the development and applications of analogues of the major neuroendocrine peptide regulators of the reproductive hormone cascade: GnRH, kisspeptin and neurokinin B.The Medical Research Council (South Africa), the National Research Foundation, the University of Pretoria and the University of Cape Town. CLN is a Claude Leon Foundation Postdoctoral Research Fellow.http://www.nature.com/nrendohb2016Mammal Research InstituteZoology and Entomolog

Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B

Human rhinovirus (HRV) infections up-regulate proinflammatory mediators and growth factors that are associated with exacerbations of inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase (MMP)-9 was shown to be increased in the airways of patients with asthma and COPD. We sought to determine whether HRV infection modulated the expression of MMP-9 and its highest-affinity inhibitor, the tissue inhibitor of metalloproteinase (TIMP)-1, and we explored the mechanism by which this modulation occurs. In vitro studies, using RT-PCR, ELISA, zymography, and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein, and activity were increased upon infection with HRV, whereas TIMP-1 mRNA and protein remained unchanged. These results were verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. Human rhinovirus infections were shown to up-regulate NF-kappaB, and NF-kappaB has also been reported to play a role in the expression of MMP-9. We therefore investigated the role of NF-kappaB in HRV-induced MMP-9 expression. Using two inhibitors of IkappaBalpha kinase beta, we observed a concentration-dependent decrease in HRV-induced MMP-9 expression. The role of NF-kappaB in HRV-induced MMP-9 expression was further confirmed using MMP-9 promoter luciferase constructs, which demonstrated that an NF-kappaB site at -620/-607 base pairs was necessary for HRV-induced MMP-9 expression. Electrophoretic mobility shift assays and supershift assays confirmed the nuclear translocation and binding of p50/p65 NF-kappaB subunits to an MMP-9-specific NF-kappaB oligonucleotide. This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling

Variability in water column respiration in Salish Sea waters and implications for coastal and ocean acidification

Water column respiration is a key driver of carbon cycling, ocean acidification, and oxygen dynamics in marine ecosystems. However, empirical estimates of the range and variability of respiration and its relative contribution to ocean acidification are seldom measured. In 2014, we began measuring respiration rates at multiple sites in the central Salish Sea (San Juan Islands, Bellingham Bay) and then initiated routine monitoring of water column respiration at multiple sites in Padilla Bay National Estuarine Research Reserve (NERR). Measurements in Padilla Bay were integrated into the well-established NERR System Wide Monitoring Program (SWMP). Our investigation revealed that 1) rates of respiration vary seasonally and appear to be associated with changes in organic matter supply and, to a lesser extent, temperature, and 2) incoming deeper waters of marine origin are characterized by relatively low rates of respiration (i.e. ~5ugO2/L/h). To further explore underlying mechanisms, we conducted a series of manipulative experiments to investigate the direct effect of increasing ocean temperature and organic matter supply on rates of respiration. These experiments revealed that respiration can more than triple in response to increases in organic carbon supply and that this response may be influenced by seasonal changes in the export of organic matter and detritus from the extensive eelgrass meadows of Padilla Bay. Our field sampling and manipulative experiments have produced empirical estimates of respiration that can be included in models and projections of water quality and ocean acidification for the Puget Sound, and provide insight into the response of inland marine waters of the Pacific Northwest to a warmer, more acidified ocean