Maxillofacial trauma and cerebrospinal fluid leak: a retrospective clinical study.

Objectives: To determine the prevalence of maxillofacial fractures associated with persistent CSF leak, and to assess its bearing on clinical outcomes of consecutive patients managed at our centre. Methods: This was a retrospective cross-sectional study. The medical records of patients over 11-year period were analysed for age, gender, etiology of injuries, duration between injury and presentation to the hospital, types of facial fracture and their treatments, treatment done to control CSF leak, and complication(s). Descriptive and bivariate statistics were computed. Results: Overall, 1473 patients were evaluated, 66 (4.5%) presented with craniofacial injuries associated with persistent CSF leak after 5 days of non-surgical treatment. Males (92.5%, P= 0.0000) and those in the 21 to 30 years age group (59.1 %, P=0.01) were predominant. The most common (68.2%) type of fracture combination was Le Fort I, II and III, NOE, zygomatic complex and mandible. The commonest clinical presentation of CSF leak was rhinorrhea only, in 66.7% of patients (P= 0.001). Conclusions: This study shows that the prevalence of maxillofacial fractures associated with persistent CSF leak was low, which was 4.5% of patients that presented with persistent CSF leak and 84.9% of the cases resolved after treatment of the various maxillofacial fractures.

Ameloblastoma of the jaws in children: an evaluation of cases seen in a tertiary hospital in South-Eastern Nigeria.

BACKGROUND: Ameloblastoma is one of the most common benign odontogenic tumours in Nigeria. It is considered uncommon in children. MATERIALS AND METHODS: This is a retrospective study of pediatric patients with histopathological diagnosis of ameloblastoma seen over seven years at the Oral and Maxillofacial Surgery Department of the University of Nigeria Teaching Hospital, Enugu, Nigeria. Relevant information was retrieved from patients' records and data obtained were analysed using SPSS version 23, the chi-square test was used to compare qualitative variables, a p-value of <0.05 was considered as significant. RESULTS: One hundred and thirty-six cases of ameloblastoma in all age groups were seen within the period. Thirty of the cases met the requirement. The mean age of the patients was 14.4 STD 2.03 (range from 10-17) years. Fourteen (46.7%) patients were male while 16 (53.3%) were female giving a ratio of 1:1.1. The duration of the lesion ranged from 3 months to 72 months (mean 15.07 months). Histologically, the follicular type (n=20, 66.7%) constitute the majority, while the clinical types were solid-multicystic (n=18, 60%) and unicystic (n=12, 40%). Enucleation was the treatment of choice in most (n=18, (60%)) of the patients. CONCLUSION: Ameloblastoma is relatively uncommon in children, especially those less than ten years of age. The solid-multicystic variety was the predominant type in the children studied. Most patients presented long after the onset of the tumour and enucleation with mechanical curettage produced satisfactory results in these patients. FUNDING: None declared.

A qualitative account of young people's experiences of alcohol screening and brief interventions in schools: SIPS Jr-HIGH trial findings.

BACKGROUND: The United Kingdom (UK) has seen a decrease in the number of young people drinking alcohol. However, the UK prevalence of underage drinking still ranks amongst the highest in Western Europe. Whilst there is a wealth of evidence reporting on the effectiveness of both primary, and secondary interventions, there are few reports of the experiences of young people who receive them. METHODS: The present study reports findings from interviews with 33 young people who were involved in an alcohol screening and brief intervention randomized controlled trial in schools in England. All interviews were analysed using inductive applied thematic analysis. RESULTS: Three major themes were identified following the analysis process: 1) drinking identities and awareness of risk; 2) access to support and advice in relation to alcohol use; and 3) appraisal of the intervention and potential impact on alcohol use. CONCLUSIONS: There appeared to be a reluctance from participants to describe themselves as someone who drinks alcohol. Furthermore, those who did drink alcohol often did so with parental permission. There was variation amongst participants as to how comfortable they felt talking about alcohol issues with school staff. Overall participants felt the intervention was useful, but would be better suited to 'heavier' drinkers.

EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.

Membrane-active peptides have been extensively studied to probe protein-membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein-membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.

Is prophylactic removal of impacted mandibular third molar justified in all patients? A prospective clinical study of patients 50 years and above.

BACKGROUND: The prophylactic extraction of asymptomatic impacted mandibular third molar is a contentious issue in dental practice. OBJECTIVE: To evaluate symptomatic impacted mandibular third molars in patients 50 years and above, and determine the burden of the impaction on the adjacent second molar. METHODS: This was a prospective clinical study over a three-year period. The diagnosis of impacted mandibular third molar and their associated pathology was made by clinical and radiological examination. The data obtained were age, sex, type of impaction, reason for surgical extraction, and the clinical condition of the adjacent second molar. RESULTS: Patients 50 years and above were 33.4%, and those with impaction 22.8%, while the symptomatic cases were in 18.4% patients. The age of the patients ranged from 52 to 84 years with male: female ratio, 2.3:1. In all the asymptomatic impactions, the adjacent second molars were disease-free, whereas 73.6% of the adjacent second molar related to symptomatic cases were asymptomatic (P=0.001). CONCLUSION: This study showed that 15.9% of impactions in 18.4% of patients were symptomatic and required surgical extraction, whereas the burden of impaction on the adjacent second molar was 26.4%, and these required only preventive and restorative treatments.

A qualitative exploration of school-based staff's experiences of delivering an alcohol screening and brief intervention in the high school setting: findings from the SIPS JR-HIGH trial.

BACKGROUND: Whilst underage drinking in the UK has been declining in recent years, prevalence is still higher than in most other Western European countries. Therefore, it is important to deliver effective interventions to reduce risk of harm. METHODS: Semi-structured interviews with staff delivering an alcohol screening and brief intervention in the high-school setting. The analysis was informed by normalization process theory (NPT), interviews were open coded and then a framework applied based on the four components of NPT. RESULTS: Five major themes emerged from the analysis. The majority of participants felt that the intervention could be useful, and that learning mentors were ideally suited to deliver it. However, there was a feeling that the intervention should have been targeted at young people who drink the most. CONCLUSIONS: The intervention was generally well received in schools and seen as an effective tool for engaging young people in a discussion around alcohol. However, in the future schools need to consider the level of staffing in place to deliver the intervention. Furthermore, the intervention could focus more on the long-term risks of initiating alcohol consumption at a young age.

A systematic review of qualitative evidence of cancer patients' attitudes to mindfulness.

Mindfulness has been described as a non-elaborative, non-judgmental, present-centred awareness in which each thought, feeling or sensation is acknowledged and accepted. The aim of the present study was to systematically search and synthesise qualitative evidence of cancer patients' attitudes to mindfulness. A systematic review of qualitative evidence was conducted following the SPICE framework. All cancers were included. Medline, Cinahl, Science Direct, O-Alster and New Bank were searched from the first available year to August 2016 using the search terms; wellbeing, mindfulness, qualitative. Two reviewers independently screened titles and abstracts; potentially relevant articles were retrieved and assessed independently by two reviewers. Data were extracted and quality assessed using Critical Appraisal Skills Programme (CASP) qualitative research checklist. In total, 233 studies conducted between 2005 and 2015 were identified with six included in the final analysis. Four themes were identified: Coping strategies developed through mindfulness course; Positive outcomes of mindful practice; Challenges with engaging in mindful practice; and Group identification and shared experience. The current evidence supports the view that mindfulness is an effective intervention to help people adjust to living with and beyond cancer however, more qualitative work is needed in this area.

Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C.

INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. METHOD: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION: Although the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.

Detecting beta-amyloid aggregation from time-resolved emission spectra.

The aggregation of beta-amyloids is one of the key processes responsible for the development of Alzheimer's disease. Early molecular-level detection of beta-amyloid oligomers may help in early diagnosis and in the development of new intervention therapies. Our previous studies on the changes in beta-amyloid's single tyrosine intrinsic fluorescence response during aggregation demonstrated a four-exponential fluorescence intensity decay, and the ratio of the pre-exponential factors indicated the extent of the aggregation in the early stages of the process before the beta-sheets were formed. Here we present a complementary approach based on the time-resolved emission spectra (TRES) of amyloid's tyrosine excited at 279 nm and fluorescence in the window 240-450 nm. TRES have been used to demonstrate sturctural changes occuring on the nanosecond time scale after excitation which has significant advantages over using steady-state spectra. We demonstrate this by resolving the fluorescent species and revealing that beta-amyloid's monomers show very fast dielectric relaxation, and its oligomers display a substantial spectral shift due to dielectric relaxation, which gradually decreases when the oligomers become larger.

The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) framework: protocol to determine a core outcome set for efficacy and effectiveness trials of alcohol screening and brief intervention.

BACKGROUND: The evidence base to assess the efficacy and effectiveness of alcohol brief interventions (ABI) is weakened by variation in the outcomes measured and by inconsistent reporting. The 'Outcome Reporting in Brief Intervention Trials: Alcohol' (ORBITAL) project aims to develop a core outcome set (COS) and reporting guidance for its use in future trials of ABI in a range of settings. METHODS/DESIGN: An international Special Interest Group was convened through INEBRIA (International Network on Brief Interventions for Alcohol and Other Drugs) to inform the development of a COS for trials of ABI. ORBITAL will incorporate a systematic review to map outcomes used in efficacy and effectiveness trials of ABI and their measurement properties, using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. This will support a multi-round Delphi study to prioritise outcomes. Delphi panellists will be drawn from a range of settings and stakeholder groups, and the Delphi study will also be used to determine if a single COS is relevant for all settings. A consensus meeting with key stakeholder representation will determine the final COS and associated guidance for its use in trials of ABI. DISCUSSION: ORBITAL will develop a COS for alcohol screening and brief intervention trials, with outcomes stratified into domains and guidance on outcome measurement instruments. The standardisation of ABI outcomes and their measurement will support the ongoing development of ABI studies and a systematic synthesis of emerging research findings. We will track the extent to which the COS delivers on this promise through an exploration of the use of the guidance in the decade following COS publication.

Assessing the delivery of alcohol screening and brief intervention in sexual health clinics in the north east of England.

BACKGROUND: Risky drinking is associated with risky sexual experiences, however the relationship between alcohol and sex is complex. The aim of the study was to assess the feasibility of delivering alcohol screening and brief interventions in genitourinary medicine (GUM) clinics. The objectives were to; understand the levels of alcohol use amongst patients; report on the number of alcohol interventions delivered; and to analyse the relationship between alcohol use with demographic data as well as diagnosed sexually transmitted infections (STIs) to see if there were any associations. METHODS: All new patients attending GUM between April 2012 and March 2013 self-completed the Alcohol Use Disorder Identification Test (AUDIT) prior to their clinical consultation. Where appropriate (scoring 8+ on AUDIT) the clinician would deliver up to 2-3 min of alcohol brief intervention. Descriptive statistics, t-tests, ANOVA and logistic regression were carried out as appropriate. RESULTS: AUDIT scores were available for 90% of all new patients (3058/3390) with an average mean score of 7.75. Of those who drank alcohol, 44% were categorised as being AUDIT positive, including 2% who had a score indicative of probable alcohol dependence (20+). 55 % (n = 638) of patients who screened positive on the AUDIT received a brief intervention whilst 24% (n = 674) of drinkers were diagnosed with a STI. Logistic regression modelling revealed that males, younger age groups and those of 'white' ethnicity were more likely to score positive on AUDIT. Patients classified as non-students, living in deprivation quintiles one to four and categorised as probable alcohol dependence on the AUDIT were more likely to be diagnosed with an STI. CONCLUSION: It is possible to embed alcohol screening into routine practice within sexual health services however further work is required to embed brief interventions particularly amongst increasing risk drinkers. If resources are limited, services may consider more targeted rather than universal alcohol screening to specific population groups. The study was undertaken in one GUM service in the North East of England and therefore findings may not be generalizable. The study did not assess efficacy of alcohol brief intervention in this setting.

Sheep from low-methane-yield selection lines created on alfalfa pellets also have lower methane yield under pastoral farming conditions.

Selection lines of sheep with low and high CH yield (g/kg DMI; CH/DMI) are being developed on the basis of feeding pelleted alfalfa hay at 2.0 times maintenance ME requirements in respiration chambers, but their divergence under predominant grazing conditions, as in New Zealand, is not known. The objectives of this study were to determine CH emissions and rumen fermentation characteristics in sheep from low and high CH/DMI selection lines while grazing pasture. Two grazing experiments were conducted with 42 selection line ewes in March 2013 (Exp. 1) and 98 selection line progeny ewe hoggets in October/November 2014 (Exp. 2), with CH emissions estimated by the SF tracer technique and DMI estimated by titanium oxide in combination with natural long-chain -alkanes. Total daily CH production (g/d) was similar between high and low CH/DMI selection line sheep in Exp. 1 and lower for low CH/DMI progeny compared with high CH/DMI progeny in Exp. 2 ( < 0.05). The CH/DMI tended to be 20% lower for low CH/DMI line sheep compared with high CH/DMI selection line sheep in Exp. 1 ( < 0.10) and was 15% lower for the low CH/DMI line in Exp. 2 ( < 0.01). Total VFA concentration and concentrations (m) of acetate, butyrate, and isobutyrate plus isovalerate were lower ( < 0.05) for low CH/DMI line sheep compared with high CH/DMI selection line sheep in both experiments. The current study indicates that differences in CH/DMI and VFA concentrations in selection line sheep, previously established on alfalfa pellets, are also present to a similar magnitude when grazing pasture.

High prevalence of alcohol use disorders in patients with inflammatory skin diseases.

BACKGROUND: There is a known association between psoriasis and heavy alcohol consumption. The association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined. OBJECTIVES: To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease. METHODS: We conducted an observational cross-sectional study in a single hospital outpatient department. We recruited 609 patients with either psoriasis, eczema, cutaneous lupus or other inflammatory disorders, and a reference population with skin lesions. Primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD). RESULTS: The observed prevalence of AUD was 30·6% in patients with psoriasis, 33·3% in those with eczema, 12·3% in those with cutaneous lupus, 21·8% in those with other inflammatory disease and 14·3% in those with non-inflammatory disease. Odds ratios (OR) for AUD in patients in the inflammatory groups compared with those in the noninflammatory groups, adjusted for age and sex, were as follows: psoriasis 1·65 [95% confidence interval (CI) 0·86-3·17], eczema 2·00 (95% CI 1·03-3·85), lupus 1·03 (95% CI 0·39-2·71), other inflammatory disease 1·32 (95% CI 0·68-2·56). ORs were reduced if also adjusted for Dermatology Life Quality Index (DLQI). The prevalence of DLQI ≥ 11 was 31·1% for psoriasis, 43·7% for eczema, 17·5% for cutaneous lupus, 17·2% for other inflammatory disease and 2·8% for noninflammatory disease. CONCLUSIONS: Patients with eczema attending a hospital clinic have been shown to have high levels of AUD of a similar level to patients with psoriasis and higher than patients with noninflammatory skin diseases.

A systematic review of the effectiveness of alcohol brief interventions for the UK military personnel moving back to civilian life.

BACKGROUND: Higher levels of alcohol consumption have been observed in the UK armed forces compared with the general population. For some, this may increase the risk of using alcohol as a coping strategy when adjusting to multiple life events occurring when moving back into civilian life. METHOD: A systematic review was conducted to determine the effectiveness of alcohol brief interventions for military personnel during transition. Electronic databases including Medline, Central, Healthcare Management Information Consortium (HMIC) and Embase, and grey literature, were searched. Two reviewers independently assessed potential studies for inclusion, extracted data and assessed quality of selected articles using an established instrument. RESULTS: Ten studies met criteria for inclusion. Studies were synthesised narratively. Interventions were heterogeneous, and bias within studies may have acted to increase or decrease their reported effectiveness. The findings suggest some evidence for effectiveness of self-administered web-based interventions, involving personalised feedback over a number of sessions, and system-level electronic clinical reminders. All studies were from the USA. Delivery of interventions by a clinician during motivational interviews was most effective for those with post-traumatic stress disorder symptoms. CONCLUSIONS: A UK trial of web-based interventions with personalised feedback is recommended.

Exploring men's perceptions of a community-based men's shed programme in England.

Background: Sheds have been used in Australia for decades as an intervention to try and promote 'health by stealth' among men by providing a social space for those who may be particularly vulnerable to poor mental health. Little is known about the impact of men's sheds in England. Methods: Members of 19 sheds from one local authority area were invited to participate in focus groups to explore their perceptions of their shed. In total, 32 men participated in five focus groups which were analysed using applied thematic analysis. Results: While some sheds run activities, the main driving factor of sheds was the social aspect, with many coming along for nothing more than a chat and a cup of tea, allowing men to recapture lost social networks from their working days. However, it was felt that there could be more formal links forged between individual groups, which may result in a better range of activities on offer. Conclusions: This study indicates that the shed can be an effective way of reducing social isolation in older men. However, further work is needed to understand what impact the shed has on physical and mental well-being.

Complications of the use of trans-osseous wire osteosynthesis in the managementof compound, unfavorable and non-comminuted mandibular angle fractures.

OBJECTIVE: To analyze cases of compound, unfavorable and non-comminuted mandibular angle fractures treated by trans-osseous wiring, presenting postoperative complications, in a low resource center. MATERIALS AND METHODS: This was a 13-year retrospective study of 1,324 fractures in 1,317 subjects. The predictor variables were age, gender, aetiology, time lag between injury and treatment, and concomitant mandibular and mid-facial fractures. The outcome variable was the development of complication(s) after treatment. Descriptive and bivariate statistics were computed with EPI INFO 7 version software, and the P value was set at 0.05. RESULTS: The sample size was composed of 63/1317 (4.8%) of patients with complications. There were 48 males and 15 females with male: female ratio of 3.2:1. The age of the patients ranged from 21 to 62 years (mean 37.4± 5.6 years). The test of significance showed statistically significant association between complications of mandibular angle fractures and increasing age (P<0.002), male gender (P<0.001), road traffic accident (P<0.001), longer time lag between injury and treatment of fractures (P<0.000), and concomitant mandibular fractures (P<0.000). Deranged occlusion (n=19, 28.8%) and limited mouth opening <35mm (n=16, 24.2%) were the common complications. The complications were successfully treated during follow-up. CONCLUSION: The use of trans-osseous wire osteosynthesis gave good results, and can still be useful in centres that are less well equipped and where access to rigid internal fixation with mini plates is either limited or unavailable. FUNDING: Self-funded.

Probing the Sudlow binding site with warfarin: how does gold nanocluster growth alter human serum albumin?

The search for new fluorescent molecules is vital to the advancement of molecular imaging and sensing for the benefit of medical and biological studies. One such class of new fluorescent molecule is fluorescent gold nanoclusters encapsulated in Human Serum Albumin (HSA-AuNC). In order to use this new fluorescent molecule as a sensor or fluorescent marker in biological imaging both in vitro and in vivo it is important to understand whether/how the proteins function is changed by the synthesis and presence of the gold nanoclusters inside the protein. Natural HSA acts as the main drug carrier in the blood stream, carrying a multitude of molecules in two major binding sites (Sudlow I and II). To test the effects of gold on the ability of HSA to act as a drug carrier we employed warfarin, an anticoagulant drug, as a fluorescent probe to detect changes between natural HSA and HSA-AuNCs. AuNCs are found to inhibit the take up of warfarin by HSA. Evidence for this is found from fluorescence spectral and lifetime measurements. Interestingly, the presence of warfarin bound to HSA also inhibits the formation of gold nanoclusters within protein. This research provides valuable insight into how protein function can change upon synthesis of AuNCs and how that will affect their use as a fluorescent probe.

A Coproduction Community Based Approach to Reducing Smoking Prevalence in a Local Community Setting.

Research highlights that asset-based community development where local residents become equal partners in service development may help promote health and well-being. This paper outlines baseline results of a coproduction evaluation of an asset-based approach to improving health and well-being within a small community through promoting tobacco control. Local residents were recruited and trained as community researchers to deliver a smoking prevalence survey within their local community and became local health champions, promoting health and well-being. The results of the survey will be used to inform health promotion activities within the community. The local smoking prevalence was higher than the regional and national averages. Half of the households surveyed had at least one smoker, and 63.1% of children lived in a smoking household. Nonsmokers reported higher well-being than smokers; however, the differences were not significant. Whilst the community has a high smoking prevalence, more than half of the smokers surveyed would consider quitting. Providing smoking cessation advice in GP surgeries may help reduce smoking prevalence in this community. Work in the area could be done to reduce children's exposure to smoking in the home.

Can a theoretical framework help to embed alcohol screening and brief interventions in an endoscopy day-unit?

INTRODUCTION AND AIMS: The National Institute for Health Care and Excellence recommend that alcohol screening and brief intervention (ASBI) should be routinely implemented in secondary care. This study used theoretical frameworks to understand how health professionals can be supported to adapt their behaviour and clinical practice. DESIGN AND METHODS: Staff training and support was conducted using theoretical frameworks. A 12-week study, delivering ASBI was carried out as part of routine practice in an endoscopy day-unit. Anonymised patient data were collected using the Alcohol Use Disorders Identification Tool (AUDIT) and whether patients received a brief intervention. Staff completed the Shortened Alcohol and Alcohol Problems Perceptions Questionnaire at three time points and took part in a focus group both pre and post study. RESULTS: For staff, levels or role adequacy, role legitimacy, motivation to discuss alcohol, security in their role, job satisfaction and commitment to working with patients who drink increased during the time of the study. 1598 individual patients were seen in the department in the timeframe. Of these, 1180 patients were approached (74%); 18% (n=207) of patients were AUDIT positive. DISCUSSION: This study has shown that it is possible to reach a high number of patients in a busy hospital out-patient department and deliver ASBI by working with staff using theoretical frameworks for training. Embedding evidence-based public health interventions into routine clinical environments is complex. The social system in which professionals operate requires consideration alongside individual professionals' real and perceived barriers and facilitators to change.

Locating the nucleation sites for protein encapsulated gold nanoclusters: a molecular dynamics and fluorescence study.

Fluorescent gold nanoclusters encapsulated by proteins have attracted considerable attention in recent years for their unique properties as new fluorescence probes for biological sensing and imaging. However, fundamental questions, such as the nucleation sites of gold nanoclusters within proteins and the fluorescence mechanism remain unsolved. Here we present a study of the location of gold nanoclusters within bovine serum albumin (BSA) combining both fully atomistic molecular dynamic (MD) simulations and fluorescence spectroscopic studies. The MD simulations show gold clusters growing close to a number of cysteine sites across all three domains of BSA, although just two major sites in domains IIB and IA were found to accommodate large clusters comprising more than 12 atoms. The dependence of the fluorescence on pH is found to be compatible with possible nucleation sites in domains IIB and IA. Furthermore, the energy transfer between tryptophan and gold nanoclusters reveals a separation of 29.7 Å, further indicating that gold nanoclusters were most likely located in the major nucleation site in domain IIB. The disclosure of the precise location of the gold nanoclusters and their surrounding amino acid residues should help better understanding of their fluorescence mechanism and aid their optimization as fluorescent nanoprobes.