Systematic evaluation of benzoylation for liquid chromatography-mass spectrometry analysis of different analyte classes.

LC-MS is an indispensable tool for small molecule analysis in many fields; however, many small molecules require chemical derivatization to improve retention on commonly used reversed-phase columns and increase ionization. Benzoyl chloride (BzCl) derivatization is commonly used for derivatization of primary and secondary amines and phenolic alcohols, though evidence exists that with proper reaction conditions (i.e., specific bases), other hydroxyl groups may be derivatized too. Previous studies have examined BzCl concentration, reaction times, and reaction temperatures for derivatization of amines and phenols for LC-MS analysis; however, use of different bases, base concentration, and extending to conditions to hydroxyl groups for LC-MS analysis has not been well-studied. To address this understudied area and identify reaction conditions for both amino and hydroxyl groups, we performed a systematic study of reaction conditions on multiple classes of potential targets. For selected derivatization methods, detection limits and performance in a variety of biological matrices were assessed. Results highlight the importance of tailoring derivatization methods for a given application as they varied by molecule and/or molecule class. Compared to the standard BzCl method commonly used, alternative methods were identified to better derivatize challenging analytes (glucosamine, choline, cortisol, uridine, cytidine) with detection limits reaching 1100, 9, 38, 170, and 67 nM compared to undetectable, 170, 86, 1000, and 86 nM respectively. Sub-nanomolar detection limits were achieved for norepinephrine with alternative derivatization approaches. Improved derivatization methods for several classes and molecules including nucleosides, steroids, and molecules containing hydroxyl groups were also identified.

Capillary electrophoresis Western blot using inkjet transfer to membrane.

Traditional Western blots are commonly used to separate and assay proteins; however, they have limitations including a long, cumbersome process and large sample requirements. Here, we describe a system for Western blotting where capillary gel electrophoresis is used to separate sodium dodecyl sulfate-protein complexes. The capillary outlet is threaded into a piezoelectric inkjetting head that deposits the separated proteins in a quasi-continuous stream of <100 pL droplets onto a moving membrane. Through separations at 400 V/cm and protein capture on a membrane moving at 2 mm/min, we are able to detect actin with a limit of detection at 8 pM, or an estimated 5 fg injected. Separation and membrane capture of sample containing 10 proteins ranging in molecular weights from 11 - 250 kDa was achieved in 15 min. The system was demonstrated with Western blots for actin, ß-tubulin, ERK1/2, and STAT3 in human A431 epidermoid carcinoma cell lysate.

The Impact on Ambulance Mobilisations of an Increasing Age Profile of Telecare Service Users Receiving Advanced Proactive, Personalised Telecare in Spain-a Longitudinal Study 2014-2018.

Advanced proactive personalised telecare services in Spain have helped service users to live independently in their own homes for longer. Concern was however noted regarding potential impacts on ambulance mobilisations as time in the service, and mean age at cessation, increased. The purpose of this study was to investigate these impacts. A longitudinal study of a telecare service user population in Spain (n = 202.1 k to 247.9 k) was undertaken using anonymised operational data collected in the delivery of proactive and personalised telecare services over the period 2014-2018. For the studied population, ambulance mobilisation on a per-person/per-annum (pp/pa) basis reduced despite the increasing age profile at cessation and with the characteristics of the population at registration remaining otherwise similar over the period. The study identified the positive correlation coefficient between ambulance mobilisations and service user's dependency levels, and marginal negative correlation in older age bands. In conclusion, the increasing age at cessation has not correlated with an increased proportion of higher dependency service users. Indeed, the share of those over 85 years in the high dependency level decreased. This indicates that the changes in the telecare service which appear to have contributed to increased time living independently may also have helped ensure those continuing to live independently remain in lower risk bands.

The use of bacterial polysaccharides in bioprinting.

Additive manufacturing or 3D printing has spearheaded a revolution in the biomedical sector allowing the rapid prototyping of medical devices. The recent advancements in bioprinting technology are enabling the development of potential new therapeutic options with respect to tissue engineering and regenerative medicines. Bacterial polysaccharides have been shown to be a central component of the inks used in a variety of bioprinting processes influencing their key features such as the mechanical and thermal properties, printability, biocompatibility, and biodegradability. However, the implantation of any foreign structure in the body comes with an increased risk of bacterial infection and immunogenicity. In recent years, this risk is being potentiated by the rise in nosocomial multidrug-resistant bacterial infections. Inks used in bioprinting are being augmented with antimicrobials to mitigate this risk. The applications of bacterial polysaccharide-based bioinks have the potential to act as a key battlefront in the war against antibiotic resistance. This paper reviews the range of bacterial polysaccharides used in bioprinting and discusses the potential of various bioactive polysaccharides to be integrated into these inks.

Incomplete removal of basal cell carcinoma: what is the value of further surgery?

INTRODUCTION: Surgical management of skin cancer is an important part of modern maxillofacial surgery. The common tumours treated are squamous cell carcinoma, malignant melanoma and some benign lesions, but the largest group of tumours are the basal cell carcinomas. Although only locally aggressive, if they are not completely removed, recurrence may occur and be troublesome, especially in the head and neck. Even in this region, incomplete excision is uncommon, less than 20 %, but management of positive margins remains controversial. This review evaluates the effectiveness of a further surgical intervention after a positive margin. MATERIALS AND METHODS: A retrospective audit was undertaken to determine the rate of positive margins within the unit and subsequently the percentage of residual tumour found in any secondary excisions. RESULTS: The results show that in a sample of 247 patients, 11 % had positive peripheral margins. A second excision only showed that 36 % had any evidence of residual tumour. DISCUSSION: The study raises the question of the value of further surgery. Finally, the authors suggest a more focused approach to the finding of a positive margin before the patient is offered more treatment.

Europe's forgotten cancer, what is OMF surgery's role?

We outline the principles of management of skin cancers, and highlight the role of oral and maxillofacial surgery.

The ecological complexity of the Thai-Laos Mekong River: I. Geology, seasonal variation and human impact assessment on river quality.

The objective of this study is to assess the variation of pollution in the Thai-Laos Mekong associated with seasonal dynamics concomitant with the natural geological features and human activities that impact on the adverse quality of the river. The complex ecology of the 1500 km stretch of the Thai-Laos Mekong River has been studied in this paper to understand the relationship with the geomorphology, with the sub-tropical monsoonal climate and the impact of human activity. Sub-surface geology controls the nature and extent of the drainage basin and of the river channel. The volume flow of the river varies naturally and dynamically in phase with the rainfall; traditional models based on steady state hydraulics are inappropriate. Continuous erosion of the river banks and bed generates a sediment load of impure silt, mica, quartz and clay minerals that inhibits light penetration and limits the primary productivity of the river. The river separates two countries at different stages of development; it flows through or close to eight non-industrial conurbations (Populations 350,000-2,000,000) but is otherwise sparsely populated. The river is used for subsistence agriculture, village transport, fishing including aquaculture and as a source of domestic water. Hydroelectricity is generated from the Laos tributaries. The river is a depository for partially treated urban waste and untreated village waste, hence populations of E.coli bacteria sometimes render the water unsuitable for drinking unless treated with the highest value of 240/100 ml found at station 7 during the summer season of 2003. Furthermore the river is polluted by trace metals, notably cadmium and mercury, and by Polycyclic Aromatic Hydrocarbons (PAHs), which are particularly concentrated in the sediments. Previous work has shown that cadmium and mercury exceed the Probable Effect Level (PEL) values of Canadian Environmental Quality Guidelines and that the PAH concentrations were also greater than the Interim Sediment Quality Guidelines (ISQG). Consequently the fish stock, a vital source of protein for the local human population maybe seriously affected. As conflict between the demands of human activities will be exacerbated by the continuing development of the basin; monitoring must be continued and a better model of the river's ecology is needed to predict the impact of development.

The effects of telephone prompting on attendance for starting treatment and retention in treatment at a specialist alcohol clinic.

OBJECTIVE: To examine the effects of telephone prompting on attendance for the start of treatment and retention in treatment in a specialist alcohol clinic. METHOD: The study setting was a specialist alcohol treatment clinic. Participants were 172 clients attending as out-patients. An ABABAB design was used with planned alternating conditions, respectively, with or without a telephone prompt the day before the client was due to attend, over a succession of six consecutive 4-week periods. RESULTS: Clients who were prompted were more likely to start treatment and attend further treatment sessions than clients who were not prompted. CONCLUSIONS: Telephone prompting is a simple and effective way to improve attendance for the start of treatment and retention in alcohol treatment.

Retrospective review of donor site complications after harvest of cancellous bone from the anteriomedial tibia.

Donor site morbidity is important in deciding the site for harvest of cancellous bone for alveolar bone grafts. Many studies have supported the view that tibia is safe with few complications in the short term. We know of no studies on the long-term complications to the donor site after tibial bone grafting in children with alveolar clefts. The casenotes of 40 children who had had tibial bone grafts for alveolar clefts were studied retrospectively, and parents or patients were contacted by telephone and a standardised questionnaire was used to assess any long term complications at the donor site. We found none. We found no evidence of long-term complications at the donor site in children who had had proximal tibial bone grafting for secondary repair of alveolar clefts. We conclude that the proximal tibia is a safe site from which to obtain cancellous bone graft for alveolar clefts in children. This study is preliminary, and highlights the need for a randomised trial.

Carcinoma of the midline dorsum of the tongue.

We present a case of an 80 year old female who had previously been diagnosed with lichen planus of the tongue dorsum some 10 years previously. Due to a change in the appearance of the lesion a biopsy revealed squamous cell carcinoma of the tongue. We discuss this rare diagnosis in conjunction with the possibility of an association of squamous cell carcinoma and lichen planus.

Minimal intervention as a preparation for the treatment of alcohol dependency.

OBJECTIVE: To investigate the use of a minimal intervention as a preparation for treatment of alcohol dependency. METHOD: A randomized-controlled trial with 361 treatment seekers in an alcohol treatment unit in Northwest England. Study variables included recent alcohol intake, participants' views of their drinking problem, and several self-report scale scores. Experimental group participants received an advance leaflet containing advice on reducing alcohol intake. RESULTS: At follow-up participants in the leaflet group were more likely to view their drinking problem as a learnt behaviour. There was a non-significant tendency for more of the leaflet group to attend for assessment by comparison with controls. Significant improvements occurred over time in readiness to change (recognition subscale), self efficacy and dependency, independent of group allocation. CONCLUSIONS: The tendency toward increased attendance rates should be confirmed in a larger sample. Findings have potential implications for the usage of treatment preparatory material.

Treatment outcome following day care for alcohol dependency: the effects of reducing programme length.

Because of the need to maximise treatment adherence and minimise costs, the duration of treatment for alcohol problems should not be longer than is necessary to achieve clinical benefit. The present authors have previously demonstrated the effectiveness of a 10-week outpatient treatment programme. In this paper, they evaluate the effects of reducing the length of the programme to 6 weeks by comparing the outcomes to those of the original programme. One hundred and twenty-four patients were followed up 11 months after choosing the revised 6-week programme. Eighty-eight patients (71%) were successfully contacted. Data collected included alcohol-related problems, use of other services, drinking patterns throughout the follow-up period and details of alcohol intake for the week prior to interview. Reducing the programme length significantly increased the number of patients completing the programme at no cost to clinical effectiveness.

Treatment setting and treatment outcome in alcohol dependency: residential and day-care options compared.

When empowered to select either a residential or a day care treatment programme for problem drinking, more patients favour the latter option. Those completing the full programme, which was similar in content in both settings, were followed up at approximately 9 months after initial engagement in treatment. Attrition was a major problem, particularly in the day-patient sample. Of the 103 patients who began each programme, 91 completed the residential option but only 23 completed all sessions in the day-patient course. Day-care completers tended to have less severe alcohol-related problems than in-patient completers. They were also older, had experienced fewer episodes of alcohol-related admissions in the past and were less likely to show biochemical evidence of alcohol-related physical damage. Both groups showed positive changes in drinking intake, drink-related problems, the use of adjunct services and the self-ratings of improvement throughout the follow-up period. Outcome in the day programme completers group was, however, generally better than that shown by the in-patients. The results should be interpreted with caution owing to the significant inter-group differences at the start of treatment and the considerably higher non-attendance and attrition rates for the day-care programme. A cognitive-behavioural in-patient programme for alcohol dependent patients can be provided in a day-care setting. For some patients, this option is both attractive and effective.