Rapid screening of bacteriostatic and bactericidal antimicrobial agents against Escherichia coli by combining machine learning (artificial intelligence) and UV-VIS spectroscopy.

Antibiotics are compounds that have a particular mode of action upon the microorganism they are targeting. However, discovering and developing new antibiotics is a challenging and timely process. Antibiotic development process can take up to 10-15 years and over $1billion to develop a single new therapeutic product. Rapid screening tools to understand the mode of action of the new antimicrobial agent are considered one of the main bottle necks in the antimicrobial agent development process. Classical approaches require multifarious microbiological methods and they do not capture important biochemical and organism therapeutic-interaction mechanisms. This work aims to provide a rapid antibiotic-antimicrobial biochemical diagnostic tool to reduce the timeframes of therapeutic development, while also generating new biochemical insight into an antimicrobial-therapeutic screening assay in a complex matrix. The work evaluates the effect of antimicrobial action through "traditional" microbiological analysis techniques with a high-throughput rapid analysis method using UV-VIS spectroscopy and chemometrics. Bacteriostatic activity from tetracycline and bactericidal activity from amoxicillin were evaluated on a system using non-resistant Escherichia coli O157:H7 by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and UV-VIS spectroscopy (high-throughput analysis). The data were analysed using principal component analysis (PCA) and support vector machine (SVM) classification. The rapid diagnostic technique could easily identify differences between bacteriostatic and bactericidal mechanisms and was considerably quicker than the "traditional" methods tested.

The effect of quantity and quality of dietary fat intake on subcutaneous white adipose tissue inflammatory responses.

The global prevalence of obesity and obesity-associated cardiometabolic diseases is a significant public health burden. Chronic low-grade inflammation in metabolic tissues such as white adipose tissue (WAT) is linked to obesity and may play a role in disease progression. The overconsumption of dietary fat has been suggested to modulate the WAT inflammatory environment. It is also recognised that fats varying in degree of fatty acid saturation may elicit differential WAT inflammatory responses. This information has originated predominantly from animal or cell models and translation into human participants in vivo remains limited. This review will summarise human intervention studies investigating the effect of dietary fat quantity and quality on subcutaneous WAT inflammation, with a specific focus on the toll-like receptor 4 (TLR4)/NF-κB and nucleotide-binding and oligomerisation domain-like receptor, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome molecular signalling pathways. Overall, firm conclusions are hard to draw regarding the effect of dietary fat quantity and quality on WAT inflammatory responses due to the heterogeneity of study designs, diet composition and participant cohorts recruited. Previous studies have predominantly focused on measures of WAT gene expression. It is suggested that future work includes measures of WAT total content and phosphorylation of proteins involved in TLR4/NF-κB and NLRP3 signalling as this is more representative of alterations in WAT physiological function. Understanding pathways linking the intake of total fat and specific fatty acids with WAT metabolic-inflammatory responses may have important implications for public health by informing dietary guidelines aimed at cardiometabolic risk reduction.

Factors that influence quality and yield of circulating-free DNA: A systematic review of the methodology literature.

BACKGROUND: Circulating-free DNA (cfDNA) is under investigation as a liquid biopsy of cancer for early detection, monitoring disease progression and therapeutic response. This systematic review of the primary cfDNA literature aims to identify and evaluate factors that influence recovery of cfDNA, and to outline evidence-based recommendations for standardization of methods. METHODS: A search of the Ovid and Cochrane databases was undertaken in May 2018 to obtain relevant literature on cfDNA isolation and quantification. Retrieved titles and abstracts were reviewed by two authors. The factors evaluated include choice of specimen type (plasma or serum); time-to-processing of whole blood; blood specimen tube; centrifugation protocol (speed, time, temperature and number of spins); and methods of cfDNA isolation and quantification. FINDINGS: Of 4,172 articles identified through the database search, 52 proceeded to full-text review and 37 met the criteria for inclusion. A quantitative analysis was not possible, due to significant heterogeneity in methodological approaches between studies. Therefore, included data was tabulated and a textual qualitative synthesis approach was taken. INTERPRETATION: This is the first systematic review of methodological factors that influence recovery and quantification of cfDNA, enabling recommendations to be made that will support standardization of methodological approaches towards development of blood-based cancer tests.

Evolution of 2D tin oxides on the surface of molten tin.

The exfoliation of two dimensional (2D) oxides, established on the surface of specific liquid metals, has recently been introduced. One such liquid metal is molten tin, which forms a variety of surface 2D oxides. However, the development behaviour of these surface tin oxides is still unknown. Here the evolution of stoichiometry and thickness from single-layer SnO to highly oxidised multi-layer SnO2 in ambient oxygen is explored.

Patient satisfaction for carotid endarterectomy performed under local anaesthesia.

OBJECTIVES: To develop, validate and use a procedure specific questionnaire to evaluate patient experience and satisfaction following carotid endarterectomy (CEA) under either general (GA) or local anaesthesia (LA). METHODS: Twenty post-CEA patients were interviewed. Data were content analysed and recurrent themes used to generate the specific carotid endarterectomy experience questionnaire (CEA-EQ). The CEA-EQ consists of 15 pre-op and 13 postoperative questions. Validity was established by correlation with the FRS Patient Satisfaction with Surgical Services (SSSQ) and State form of the State Trait Anxiety Inventory (STAI-S) in 69 patients (35 LA, 34 GA). Subsequently 88 patients randomised to GA CEA and 88 to LA CEA received the CEA-EQ. A local anaesthetic intraoperative experience questionnaire (LA-EQ) was also developed and given to LA patients only. RESULTS: Validity was confirmed through significant correlations with the STAI-S (r=0.67, p<0.001) and the SSSQ (r=0.44, p<0.001). In the randomised prospective study response rates were greater than 90%. Overall experience and satisfaction with CEA was high. There was no statistically significant difference in anxiety, satisfaction or overall experience between anaesthetic techniques. LA CEA was associated with a significantly better perception of recovery. The majority of LA patients found the procedure acceptable. CONCLUSIONS: The CEA-EQ is a valid tool to assess qualitative aspects of CEA patient care. Overall satisfaction and experience with CEA is good and not related to anaesthetic technique. LA CEA is not associated with any increased anxiety, is tolerated by the majority of patients and is associated with a better perception of recovery.

Inbreeding depression and genetic load of sexually selected traits: how the guppy lost its spots.

To date, few studies have investigated the effects of inbreeding on sexually selected traits, although inbreeding depression on such traits can play an important role in the evolution and ecology of wild populations. Sexually selected traits such as ornamentation and courtship behaviour may not be primary fitness characters, but selection and dominance coefficients of their mutations will resemble those of traits under natural selection. Strong directional selection, for instance, through female mate-choice, purges all but the most recessive deleterious mutations, and the remaining dominance variation will result in inbreeding depression once populations undergo bottlenecks. We analysed the effects of inbreeding on sexually selected traits (colour pattern and courtship behaviour) in the male guppy, Poecilia reticulata, from Trinidad, and found a significant decline in the frequency of mating behaviour and colour spots. Such effects occurred although the genetic basis of these traits, many of which are Y-linked and hemizygous, would be expected to leave relatively little scope for inbreeding depression. Findings suggest that these sexually selected traits could reflect the genetic condition or health of males, and thus may be informative mate-cue characters for female choice as suggested by the 'good genes' model.

The Subjective Index of Physical and Social Outcome (SIPSO): a new measure for use with stroke patients.

OBJECTIVE: To develop a measure of social integration following stroke. DESIGN: Question and response scale generation from qualitative interview-based work followed by item and factor analytic methods of test construction. Analysis of the psychometric properties of final index. MEASURES: Frenchay Activities Index, Nottingham Health Profile, Wakefield Depression Inventory, Barthel Index. SETTING: Community setting, Bath, UK. SUBJECTS: Two hundred and sixty survivors of stroke, discharged at least six months previously from a general hospital. RESULTS: A 10-item Subjective Index of Physical and Social Outcome (SIPSO) was developed. Each question is scored on a scale of 0-4 with a low score indicating a poor level of integration. From the 157 completed questionnaires, total scores ranged from 0 to 40 with a median of 24 (interquartile range 15-32). Initial testing of the psychometric properties of the SIPSO suggest that it is able to provide assessment of two distinct areas of patient integration. From analysis of completed questionnaires it is suggested that questions 1-5 on the SIPSO measure a factor related to physical functioning/mobility whilst questions 6-10 measure a factor related to social/emotional functioning. Internal consistency, test-retest reliability and construct validity were established. CONCLUSIONS: The SIPSO provides a brief, valid and reliable assessment of an individual's ability to reintegrate to a 'normal' lifestyle. The SIPSO differs from other measures in that it provides assessment of both quantity and quality of activities and interaction, reflecting an individual's ability to reintegrate to his/her own satisfaction. As a 10-item self-report questionnaire the SIPSO can be administered quickly and cheaply to large numbers of patients.

Social reintegration after stroke: the first stages in the development of the Subjective Index of Physical and Social Outcome (SIPSO).

OBJECTIVE: To ensure at outset the content validity of a measure (to be developed) of social integration following stroke. DESIGN: Qualitative study, using in-depth interviews with patients at least six months following stroke. SETTING: Community setting, Bristol, UK. SUBJECTS: Thirty survivors of stroke, discharged at least six months previously from a neurological rehabilitation unit in a district general hospital. RESULTS: Patients reported a change, usually for the worse, in their levels of integration following stroke. More specifically they alluded to a decrease in both the quantity and quality of activities, especially with regard to leisure and those activities occurring outside the home. Social interaction was reduced in most patients, in terms of frequency and quality of contact. From the data, six dimensions of change in quality of interaction emerged. Finally, changes in patients' physical and financial environments were reported. Based on the findings, four diagrams were developed, providing a structure for questionnaire development. CONCLUSIONS: The results of this study confirm the findings of previously reported research. An individual's level of social integration can be affected by stroke in a wide variety of areas and along many different dimensions. Data from this study have highlighted the importance of the patient's subjective impression of the quality of both functional and social performance. This has provided the opportunity to develop a questionnaire based on the patient's perspective, rather than that of health professionals.

Ocular penetration of topical ciprofloxacin and norfloxacin drops and their effect upon eyelid flora.

A double blind, prospective study was undertaken to compare aqueous humour penetration of topical 0.3% norfloxacin and 0.3% ciprofloxacin and their effect upon normal eyelid flora in 39 patients undergoing cataract surgery. Lid swabs were taken before and after six 1 hourly applications of single drops of ciprofloxacin or norfloxacin given before surgery. Aqueous humour was aspirated at surgery and antibiotic concentration assayed using high performance liquid chromatography. The mean aqueous humour concentrations were: ciprofloxacin 220 ng ml-1, norfloxacin 140 ng ml-1. Although this difference was not statistically significant (p = 0.112) the trend demonstrated may be relevant clinically, especially considering the greater activity of ciprofloxacin. Both coagulase negative staphylococcal (p = 0.004) and total bacterial (p = 0.019) lid counts dropped sixfold after ciprofloxacin treatment but the smaller reductions noted after norfloxacin application did not achieve statistical significance (p > 0.1). The reduction of external eye flora experienced with ciprofloxacin suggests that this may be a useful presurgical prophylactic agent.