Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.

Characteristics of US military personnel with atrial fibrillation and associated deployment and retention rates.

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia impacting military occupational performances. Despite being a recognised disqualifying condition, there is no literature describing US military service members with AF. This study aims to describe members with AF diagnoses, the distribution of treatment strategies and associated deployment and retention rates. METHODS: Active duty service members identified with AF from 2004 to 2019 were investigated. Cardiovascular profiles, AF management strategies and military dispositions were assessed by electronic medical record review. RESULTS: 386 service members (mean age 35.0±9.4 years; 94% paroxysmal AF) with AF diagnoses were identified. 91 (24%) had hypertension followed by 75 (19%) with sleep apnoea. Mean CHA2DS2-VASc scores were low (0.39±0.65). Rhythm treatments were used in 173 (45%) followed by rate control strategies in 155 (40%). 161 (42%) underwent pulmonary vein isolation (PVI). In subgroup analysis of 365 personnel, 147 (40%) deployed and 248 (68%) remained active duty after AF diagnosis. Deployment and retention rates did not differ between those who received no medical therapy, rate control or rhythm strategies (p=0.9039 and p=0.6192, respectively). PVI did not significantly impact deployment or retention rates (p=0.3903 and p=0.0929, respectively). CONCLUSION: Service members with AF are young with few AF risk factors. Rate and rhythm medical therapies were used evenly. Over two-thirds met retention standards and 40% deployed after diagnosis. There were no differences in deployment or retention between groups who receive rate therapy, rhythm medical therapy or PVI. Prospective evaluation of the efficacy of specific AF therapies on AF burden and symptomatology in service members is needed.

Fibroblast growth factor-mediated crosstalk in cancer etiology and treatment.

It is becoming increasingly evident that multiple cell types within the tumor work together to drive tumour progression and impact on both the response to therapy and the dissemination of tumour cells throughout the body. Fibroblast growth factor signalling (FGF) is perturbed in a number of tumors, serving to drive tumor cell proliferation and migration, but also has a central role in orchestrating the plethora of cells that comprise the tumor microenvironment. This review focuses on how this family of signalling molecules can influence the interactions between tumor cells and their surrounding environment. Unraveling the complexities of FGF signalling between the distinct cell types of a tumor may identify additional opportunities for FGF-targeted compounds in therapy and could help combat drug resistance. Developmental Dynamics 246:493-501, 2017. © 2017 Wiley Periodicals, Inc.

Fourier-transform Raman spectroscopic study of a Neolithic waterlogged wood assemblage.

The use of Fourier-transform Raman spectroscopy for characterising lignocellulosics has increased significantly over the last twenty years. Here, an FT-Raman spectroscopic study of changes in the chemistry of waterlogged archaeological wood of Pinus sp. and Quercus sp. from a prehistoric assemblage recovered from northern Greece is presented. FT-Raman spectral features of biodeteriorated wood were associated with the depletion of lignin and/or carbohydrate polymers at various stages of deterioration. Spectra from the archaeological wood are presented alongside spectra of sound wood of the same taxa. A comparison of the relative changes in intensities of spectral bands associated with lignin and carbohydrates resulting from decay clearly indicated extensive deterioration of both the softwood and hardwood samples and the carbohydrates appear to be more deteriorated than the lignin. The biodeterioration of the archaeological timbers followed a pattern of initial preferential loss of carbohydrates causing significant loss of cellulose and hemicellulose, followed by the degradation of lignin.

Selective biodegradation in hair shafts derived from archaeological, forensic and experimental contexts.

BACKGROUND: Hair is degraded by the action of both dermatophytic and nondermatophytic microorganisms. The importance of understanding hair sample condition in archaeological and forensic investigation highlights the need for a detailed knowledge of the sequence of degradation in samples that have been either buried or left exposed at the ground surface. OBJECTIVES: To investigate the sequence of biodegradative change to human terminal scalp hair from archaeological and forensic contexts. METHODS: Cut modern scalp hair from three individuals with caucasoid-type hair was inoculated with soil microorganisms through soil burial in the field and under laboratory conditions to produce experimentally degraded samples. The degraded hair fibres were subjected to detailed histological examination using a combination of high-resolution light microscopy, transmission electron microscopy and scanning electron microscopy to investigate the nature and sequence of degradative change to hair structural components. RESULTS/DISCUSSION: Degradation was found to occur first within the least structurally robust components that afford the least resistance to microbial/chemical attack. The sequence of degradation (most to least-reflecting degree of vulnerability) in the hair cuticle was as follows: (1) intercellular delta-layer (cell membrane complex); (2) endocuticle; (3) cell membrane beta-layers; (4) exocuticle; (5) epicuticle; and (6) A-layer. In the hair cortex this was as follows: (I) intercellular delta-layer (cell membrane complex); (II) cell membrane beta-layers; (III) intermacrofibrillar matrix/nuclear remnants; (IV) microfibrils; (V) intermicrofibrillar matrix; and (VI) pigment granules (the hair fibre component that was the least vulnerable to degradation). CONCLUSIONS: The selective progress of degradation in the hair shaft has been charted and this provides a basis for further histological work in better understanding the condition of hair fibres derived from archaeological or forensic contexts as well as being relevant to investigation of diseased hair, in particular hair infected by dermatophytes and hair weakened by genetic hair shaft abnormalities.

Development of an interactive learning tool for teaching rheumatology--a simulated clinical case studies program.

OBJECTIVES: To promote independent self-study involving problem solving and decision analysis in the undergraduate medical curriculum, we have developed a series of interactive web-based clinical case studies. METHODS: An initial needs assessment was performed to determine students' attitudes to e-learning. From these results we designed a series of 30 interactive case studies for delivery from a web-server. RESULTS: A survey of 59 undergraduate students believed that online teaching resources were a useful supplement to existing teaching and they could see a positive use for e-learning. The interactive case studies program was well received by a broad range of respondents (n = 84) of different abilities and backgrounds who felt that the program was realistic and clearly presented in an intuitive manner. CONCLUSIONS: The recent increases in numbers of medical undergraduates, the trend towards student-centred learning and the emphasis on patient-related teaching means a great pressure on teachers and resources in medical schools. The case studies program we have developed was effective and well received by both biomedical and medical students. This approach may provide a way to increase the exposure of students to clinical cases involving interactive diagnostic and treatment procedures, that mimic real-world scenarios, but with fewer resource implications.

Histological correlates of post mortem mitochondrial DNA damage in degraded hair.

We have assessed the histological preservation of naturally degraded human hair shafts, and then assayed each for levels of amplifiable mitochondrial DNA and damage-associated DNA miscoding lesions. The results indicate that as sample histology is altered (i.e. as hairs degrade) levels of amplifiable mitochondrial DNA decrease, but no correlation is seen between histology and absolute levels of mitochondrial DNA miscoding lesions. Nevertheless, amplifiable mitochondrial DNA could be recovered across the complete range of the histological preservation spectrum. However, when template copy number is taken into consideration, a correlation of miscoding lesions with histology is again apparent. These relationships indicate that a potential route for the generation of misleading mitochondrial sequence data exists in samples of poor histology. Therefore, we argue that in the absence of molecular cloning, the histological screening of hair may be necessary in order to confirm the reliability of mitochondrial DNA sequences amplified from hair, and thus represents a useful tool in forensic mitochondrial DNA analyses.

Otago Diagnostic Laboratories' (ODL) Method for the detection of beta-lactamases in Enterobacteriaceae.

AIM: The rapid evolvement of beta-lactamases in Enterobacteriaceae is an important concern and the clinical microbiology laboratory is required to detect them, where possible, using a rapid, reliable, simple and low cost methodology. MATERIALS AND METHODS: A disc diffusion method using NCCLS breakpoints, Jarlier's principle and cefoxitin test for AmpC was carried out. It incorporated seven antimicrobial discs in one agar plate: cefotaxime, aztreonam, amoxicillin-clavulanate, ceftazidime, cefpodoxime, cefepime and cefoxitin. NCCLS disc confirmation test for extended-spectrum beta-lactamase (ESBL) was carried out simultaneously. RESULTS: AmpC, ESBL, CTX-M, and K1 were detected using these tests. The prevalence of ESBL was <1% in the hospital. CONCLUSION: The method is recommended for the phenotypic detection of beta-lactamases in Enterobacteriaceae or for confirmation after the results are obtained by conventional automated systems.

The influence of alcohol pre-treatment on the discriminative stimulus, subjective, and relative reinforcing effects of nicotine.

Alcohol intake may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining why alcohol increases tobacco smoking. In this study, cigarette smokers were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo. Three sessions then followed, in which the generalization of nicotine discrimination was tested across a range of doses (0--20 microg/kg) following pre-treatment with 0, 0.4, and 0.8 g/kg alcohol p.o. Intermittent 'topping' doses of alcohol maintained a steady breath alcohol level (BAL) throughout testing. Generalization testing involved both two- and three-choice ('novel' option) procedures. A visual discrimination task was also conducted to determine the specificity of effects of alcohol. Subjective and cardiovascular measures were obtained concurrent with discrimination responding. The relative reinforcing effects of nicotine were assessed after the end of generalization testing using a choice procedure. Alcohol pre-treatment had no significant effects on nicotine discrimination or self-administration behavior. Alcohol and nicotine each influenced selected subjective responses and heart rate, but virtually no interactions between the drugs were observed. Within the limitations of this study, these results do not support the notion that alcohol acutely alters nicotine's discriminative stimulus, subjective, or relative reinforcing effects at these low nicotine doses. Acute effects of alcohol on smoking behavior may be due to alterations in other effects of nicotine intake or in non-nicotine effects of tobacco smoking.

Development and assessment of a World Wide Web site for systemic lupus erythematosus patient information.

Patient education is an important component of the management of chronic diseases such as SLE. We have investigated the value of the World Wide Web as a medium for delivery of SLE patient information. Volunteers recruited from the clinic and from the website completed interviews and questionnaires aimed at defining their information needs. A new website was then established and its impact on users tested using knowledge questionnaires. The new website was used extensively (20-30 users each day) over the 24 month period of study until April 2001. A total of 510 participants completed an online questionnaire that showed that for some users it was their first use of the internet to gather lupus information, but the majority (58.9%) accessed it at least monthly for this purpose. We also found that, while most users (56.9%) found current disease information was at an appropriate level, 37.5% thought it was too basic. Knowledge questionnaires from 42 participants before and after using the site showed a significant rise in users' knowledge of the areas covered by the site. As far as we are aware this study is the first to show that a patient-oriented website can have a positive effect on disease knowledge. The relative ease with which good quality information can be disseminated via the web suggests that this medium is likely to be less costly and perhaps more educationally effective than printed information, and so is likely to become a primary vehicle for patient education. The website tested can be found at: www.rheumatology.bham.ac.uk/lupus/intro.html.

Computerized information-gathering in specialist rheumatology clinics: an initial evaluation of an electronic version of the Short Form 36.

OBJECTIVES: Longitudinal outcome data are important for research and are becoming part of routine clinical practice. We assessed an initial version of an electronic Short Form 36 (SF-36), a well-established health assessment questionnaire, in comparison with standard paper forms, in two specialist rheumatology clinics. METHODS: Out-patients (20 with systemic lupus erythematosus and 31 with vasculitis) were randomly selected to complete either paper (n=29) or electronic and paper SF-36 versions (n=51) before and after consultation (paper vs paper comparison). Data were evaluated as the response correlation, internal consistency, missing data, patient satisfaction and preference. RESULTS: There were very good correlations in SF-36 responses (P<0.001) between the paper and electronic forms and the paper and paper forms. Internal reliability coefficients (Cronbach's alpha) showed good internal consistency for all reported responses in either computer or paper forms. There were no missing data in the computerized version but 24% of patients failed to answer all of the paper form questions. Ease of use of the computer version was rated highly by 71% of all the respondents, and 69% would prefer to use the computer version in future. DISCUSSION: Computerized data collection is acceptable to patients and feasible in clinical settings. It provides responses that are at least comparable to those to the paper form, improves data capture and is available immediately.

Yesterday's hair--human hair in archaeology.

Hair removed from archaeological burials can tell us a lot about the diet and lifestyle of our ancestors--information that may survive because of the unique biology of hair formation. But hair is also biodegradable and the effects of time and burial conditions can result in conflicting evidence of past lives.

Provision of Internet-based rheumatology education (http://rheuma.bham.ac.uk).

OBJECTIVES: The Internet is becoming an important way of delivering medical information, and if used appropriately may assist in improving patients' self-management of their disease. We have established an arthritis education website ('Arthritis Help') and investigated its use over the last 2 yr. METHODS: Computer-generated log-file analysis and on-line questionnaires were used to create user profiles of our website. RESULTS: An average of 288 people visited our site each day, predominantly from America and the UK (49% of users). The typical questionnaire respondent (n = 770) was an American female with arthritis, aged 30+ yr, accessing the Internet from home. Typically, respondents had previously obtained information from medical staff or in written form, but were now more likely to use the Internet. One hundred and sixty-seven out of 585 respondents found our site to be useful, prompting them to seek more information (29%), change their behaviour or engage in more effective discussions with their physician (15%). CONCLUSIONS: These data indicate that it is possible to use the Internet to deliver medical information to its target audience, and that this process can have some impact on the way disease is self-managed. This information may aid more focused website design to maximize the use and potential benefits of such a resource.

Are ball pits the playground for potentially harmful bacteria?

Ball pits, enclosed play areas with padded floors and pits of small plastic balls, have become popular features for children at fast food restaurants. This pilot study sought to identify and confirm bacterial organisms that place children at a potential health risk in three play pits within fast food restaurants. Data for this descriptive study were randomly collected from restaurants offering play pits with multicolored, round, hollow, plastic balls within urban communities of the Tidewater region of Virginia. Specimens were collected from entrances into the ball pits as well as various areas of the bottom lining to incur a representative sample. Results indicated an increased level of normal flora as well as nonhuman flora, demonstrating that bacteria are present within the ball pits. The results question the safety of these play pits for both health care providers and parents. Nurses play a vital role in public awareness through health education. Disinfection protocol and proper handwashing are the keys to making ball pit play areas safe for children.

The effects of cardiopulmonary bypass on remifentanil kinetics in children undergoing atrial septal defect repair.

UNLABELLED: Cardiopulmonary bypass (CPB) can greatly influence the pharmacokinetics of opioids. This study investigated the pharmacokinetic profile of remifentanil in 12 pediatric patients undergoing CPB for repair of an atrial septal defect. All patients received remifentanil (5 microg/kg) over 1 min into a peripheral vein both before the onset of CPB and after the discontinuation of CPB. Arterial blood samples were obtained at defined time periods, and remifentanil concentration was determined using high-performance liquid chromatography ultraviolet detection. The pharmacokinetic profiles both before and after bypass were determined in all 12 patients. There was no change in the volume of distribution at steady state, the volume of the central compartment, or the alpha- and beta-elimination half-life. Although the clearance values increased 20% in the postbypass period (from 38.7 +/- 9.6 to 46.8 +/- 14 mL x kg(-1) x min(-1), there was no meaningful change in the coefficient of variation (from 25% to 30%). IMPLICATIONS: After cardiopulmonary bypass the clearance of remifentanil increases in children. However, the relative lack of change in the coefficient of variation suggests that remifentanil should be a predictable drug in the postcardiopulmonary bypass period.

Effects of central and peripheral nicotinic blockade on human nicotine discrimination.

Nicotine produces interoceptive stimulus effects in humans, which may be critical in understanding tobacco use. It has not yet clearly been demonstrated that discrimination of nicotine, or any drug, in humans is due to its central effects. We compared effects of mecamylamine (10 mg p.o.), a central and peripheral nicotine antagonist, on nicotine discrimination with those of trimethaphan (10-40 microg/kg per min i.v.), a peripheral nicotine antagonist only, and placebo. Smokers (n = 6) were first trained to reliably discriminate 0 versus 20 microg/kg nicotine by nasal spray and then tested on generalization of this discrimination across a range of nicotine doses (0, 3, 6, 12, 20 microg/kg) following antagonist/placebo pretreatment. Nicotine self-administration was also assessed after generalization testing by having participants intermittently choose between nicotine versus placebo spray. Compared with responding following placebo pre-treatment, discrimination of the highest dose of nicotine was significantly attenuated following mecamylamine but not trimethaphan. Similar results were observed for some subjective responses to nicotine. Mecamylamine also tended to increase nicotine self-administration. Consistent with previous animal studies, these results suggest that discriminative stimulus effects of nicotine in humans are mediated at least in part by its central effects.

Acute reinforcing effects of low-dose nicotine nasal spray in humans.

Tobacco smoking behavior is reinforced by nicotine intake, but there has been little human research examining self-administration of nicotine per se, isolated from tobacco. In this study, 10 smokers (5 men, 5 women) who wanted to quit smoking sampled 0 (placebo), 0.75, and 1.5 ug/kg/spray nicotine via nasal spray during separate lab sessions before engaging in a free choice session, involving ad lib access to all three spray doses. Subjects also ad lib smoked during another session. For the group as a whole, neither nicotine spray dose was self-administered significantly more than placebo during the free choice session, suggesting low abuse potential. However, 4 of 10 subjects self-administered 1.5 ug/kg/spray on more than 50% of all sprays (vs. 33% chance) and were designated nicotine "choosers," while the others were "nonchoosers." Choosers responded to initial nicotine spray exposure during sampling sessions with greater positive subjective effects (similar to their responses to tobacco smoking), smoked more during the ad lib smoking session (i.e., self-administered more nicotine via tobacco smoking), and tended to be more heavily dependent smokers. They did not report greater withdrawal relief or less aversive effects from nicotine, suggesting their greater nicotine choice reflected greater positive reinforcement rather than negative reinforcement. These results are consistent with the few existing studies demonstrating that acute nicotine intake per se, in the absence of tobacco, may be reinforcing in some smokers.

Fentanyl and alfentanil plasma protein binding in preterm and term neonates.

The effects of gestational age (GA) and plasma protein concentrations on the plasma protein binding of fentanyl and alfentanil were studied in preterm and term neonates. Binding experiments were performed using split-cell equilibrium dialysis. Fentanyl and alfentanil concentrations were measured using specific radioimmunoassay, and the proteins albumin and alpha-1-acid glycoprotein (AAG) were measured using radial immunodiffusion assays. In the preterm neonates, 77% of fentanyl and 65% of alfentanil was bound. In the term neonates, 70% of fentanyl and 79% of alfentanil was bound. The binding ratio of alfentanil showed a positive correlation with gestational age and AAG concentration. The binding ratio of fentanyl showed a weak, negative correlation with gestational age. These data indicate that fentanyl and alfentanil are not interchangeable at the GA studied because of age-related changes in protein binding.

Bioactivation and inactivation of aflatoxin B1 by human, mouse and rat liver preparations: effect on SCE in human mononuclear leucocytes.

The purpose of this study was to investigate the use of human and animal subcellular liver fractions in an in vitro evaluation of carcinogenic risk. The bioactivation and bioinactivation of the known genotoxic carcinogen aflatoxin B1 by human, mouse and rat liver preparations was investigated using the SCE assay in human lymphocytes as a genotoxic endpoint. There was a 10-fold variation in SCE response (1.1-11.6 SCE/Cell) in human mononuclear leucocytes (MNLs) after aflatoxin B1 was activated by human liver microsomes (n = 6). Activation correlated with the CYP1A2 phenotype of livers (r = 0.8; p < 0.05), but there was no correlation with either GST M1 genotype or epoxide hydrolase phenotype. Mouse liver microsomes activated aflatoxin B1 to a greater extent [(1 micro M) 12.8 +/- 2.51 SCE/Cell] than either rat [(10 micro M) 12.0 +/- 3.84 SCE/Cell or human (L25) [(10 micro M) 8.8 +/- 2.00 SCE/Cell liver microsomes. The addition of mouse liver cytosol and reduced glutathione (GSH) significantly (p < 0.001) reduced aflatoxin B1-dependent genotoxicity, whereas the addition of either human or rat cytosol (+GSH) was without effect. These data indicate that species variation in both bioactivation and bioinactivation can exist. Therefore there is a necessity for careful selection of activation systems from species whose biochemical profile reflects that of man.

Characterisation of the toxic metabolite(s) of naphthalene.

The toxicity of naphthalene and its metabolites has been investigated in vitro. Both naphthalene and its metabolite 1-naphthol were bioactivated by human hepatic microsomes to metabolite(s) which were toxic to mononuclear leucocytes (MNL). However 1-naphthol was more cytotoxic than naphthalene (49.8 +/- 13.9% vs. 19.0 +/- 10.0% cell death; P < 0.01), indicating that the toxicity of naphthalene is dependent on the bioactivation of 1-naphthol. CYP2E1-induced rat liver microsomes increased metabolism of naphthalene by 13% compared to control microsomes with a concomitant increase in both 1-naphthol and dihydrodiol formation. The cytotoxicity of naphthalene but not of 1-naphthol was increased by CYP2E1 induction, indicating that separate enzymes are involved in the bioactivation of 1-naphthol. The metabolites of 1-naphthol, 1,2-naphthoquinone (51.4 +/- 6.6% cell death) and 1,4-naphthoquinone (49.1 +/- 3.4% cell death) were directly toxic to MNL and depleted glutathione to 1.0% of the control levels. Both quinones were also genotoxic to human lymphocytes. In contrast, the primary metabolite of naphthalene, the 1,2-epoxide (0-100 microM) was neither cytotoxic nor genotoxic, and did not deplete glutathione. In conclusion, our data suggests that the cytotoxicity and genotoxicity of naphthalene is associated with the formation of quinones from 1-naphthol rather than naphthalene-1,2-epoxide.