Bioconjugation of Green Fluorescent Protein via an Unexpectedly Stable Cyclic Sulfonium Intermediate

Bioconjugation of superfolder GFP involving the formation of an unusually stable, and unprecedented, cyclic sulfonium species is described. This sulfonium can undergo smooth reaction with a range of nucleophiles to give sulfur-, selenium- and azide-modified GFP derivatives in high conversions

Current indications for open Kuntscher nailing of femoral shaft fractures

We retrospectively reviewed 32 patients with fractures of the femoral shaft treated with open Kuntscher nailing. All fractures were simple transverse, short oblique or Winquist-Hensen type I and 11 comminuted diaphyseal fractures. Average operating time was 45 minutes (35 to 55 minutes). Patients were discharged from the hospital within 7 days of surgery. All fractures healed within 12-14 weeks and the union rate was 100%. One patient developed superficial wound infection. Two nails were too long proximally and two nails protruded into the knee joints. There were no rotational deformities nor shortening. One patient had limited knee flexion (less than 60o) and one fracture united in 8o varus. We concluded that open Kuntscher nailing is still indicated in the following situations: in hospitals with no traction table and image intensifier, in obese patients, in Grade I and II compound fractures, in polytrauma patients, in irreducible fractures and in patients with vascular injuries.Keywords: Kuntscher nail, intramedullary nail, femoral fractur

Multiparticulate Drug Delivery Systems for Controlled Release

Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled or delayed release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. The release of drug from microparticles depends on a variety of factors including the carrier used to form the multiparticles and the amount of drug contained in them. Consequently, multiparticulate drug delivery systems provide tremendous opportunities for designing new controlled and delayed release oral formulations, thus extending the frontier of future pharmaceutical development. Keywords: Dose dumping, Microparticles, Multiparticulate delivery system, Delayed release Tropical Journal of Pharmaceutical Research Vol. 7 (3) 2008: pp. 1067-107

Southern hemisphere plants show more delays than advances in flowering phenology

Shifts in flowering phenology have been studied in detail in the northern hemisphere and are a key plant response to climate change. However, there are relatively fewer data on species' phenological shifts in the southern hemisphere. We combined historic field data, data from herbarium specimens dating back to 1842 and modern field data for 37 Australian species to determine whether species were flowering earlier in the year than they had in the past. We also combined our results with data compiled in the southern and northern hemispheres, respectively, to determine whether southern hemisphere species are showing fewer advances in flowering phenology through time. Across our study species, we found that 12 species had undergone significant shifts in flowering time, with four species advancing their flowering and eight species delaying their flowering. The remaining 25 species showed no significant shifts in their flowering phenology. These findings are important because delays or lack of shifts in flowering phenology can lead to mismatches in trophic interactions between plants and pollinators or seed dispersers, which can have substantial impacts on ecosystem functioning and primary productivity. Combining our field results with data compiled from the literature showed that only 58.5% of southern hemisphere species were advancing their flowering time, compared with 81.6% of species that were advancing their flowering time in the northern hemisphere. Our study provides further evidence that it is not adequate for ecologists to assume that southern hemisphere ecosystems will respond to future climate change in the same way as ecosystems north of the Equator. Synthesis. Field data and data from the literature indicate that southern hemisphere species are showing fewer advances in their flowering phenology through time, especially in comparison to northern hemisphere species

A novel approach to the site-selective dual labelling of a protein via chemoselective cysteine modification

Local protein microenvironment is used to control the outcome of reaction between cysteine residues and 2,5-dibromohexanediamide. The differential reactivity is exploited to introduce two orthogonal reactive handles onto the surface of a double cysteine mutant of superfolder green fluorescent protein in a regioselective manner. Subsequent elaboration with commonly used thiol and alkyne containing reagents affects site-selective protein dual labelling

The role of the future physician: building on shifting sands

The role of the future physician in the NHS is of interest to current doctors, patients, policymakers and the wider public. Amid the COVID-19 pandemic, it has never been more clear that the healthcare needs of the population, and the technical and scientific advances with which to solve them, are rapidly evolving and the medical workforce must adapt to these changes to deliver personalised healthcare. This article considers the current challenges that need to be addressed to deliver a future physician-led healthcare service that works for its patients. Key themes are expanded upon, including the changing healthcare workforce, digital and technological innovation, service delivery, complex conditions and changing patient demographics. The impact and challenges of the ongoing COVID-19 pandemic on these factors are highlighted. Avenues for development are suggested, both in postgraduate medical training and the health service as a whole. These changes will be required to deliver the physicians of the future, imbued with the skills and attributes they will need to provide a high standard of care in the mid-21st century

Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis

Disulfide bridging offers a convenient approach to generate site-selective antibody conjugates from native antibodies. To optimise the reagents available to achieve this strategy, we describe here the use of dibromomaleimides designed to undergo accelerated post-conjugation hydrolysis. Conjugation and hydrolysis, which serve to 'lock' the conjugates as robustly stable maleamic acids, is achieved in just over 1 h. This dramatic acceleration is also shown to infer significant improvements in homogeneity, as demonstrated by mass spectrometry analysis

Management of pregnancy in women with rheumatoid arthritis

Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal–fetal medicine specialist for risk assessment and advice

alpha,alpha '-Dihydroxyketone formation using aromatic and heteroaromatic aldehydes with evolved transketolase enzymes

Transketolase mutants have been identified that accept aromatic acceptors with good stereoselectivities, in particular benzaldehyde for which the wild type enzyme showed no activity

Individual participant data (IPD) meta-analysis of psychological relapse prevention interventions versus control for patients in remission from depression: A protocol

This is the final version. Available from the publisher via the DOI in this record.Psychological interventions and antidepressant medication can be effective interventions to prevent depressive relapse for patients currently in remission of depression. Less is known about overall factors that predict or moderate treatment response for patients receiving a psychological intervention for recurrent depression. This is a protocol for an individual participant data (IPD) meta-analysis which aims to assess predictors and moderators of relapse or recurrence for patients currently in remission from depression. Methods and analysis Searches of PubMed, PsycINFO, Embase and Cochrane Central Register of Controlled Trials were completed on 13 October 2019. Study extractions and risk of bias assessments have been completed. Study authors will be asked to contribute IPD. Standard aggregate meta-analysis and IPD analysis will be conducted, and the outcomes will be compared with assess whether results differ between studies supplying data and those that did not. IPD files of individual data will be merged and variables homogenised where possible for consistency. IPD will be analysed via Cox regression and one and two-stage analyses will be conducted. Ethics and dissemination The results will be published in peer review journals and shared in a policy briefing as well as accessible formats and shared with a range of stakeholders. The results will inform patients and clinicians and researchers about our current understanding of more personalised ways to prevent a depressive relapse. No local ethics approval was necessary following consultation with the legal department. Guidance on patient data storage and management will be adhered to. PROSPERO registration number CRD42019127844.Amsterdam Public Health Institute Collaborativ