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Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism. Proteobacteria and Firmicutes metabolized 5-fluorouracil to its inactive metabolite dihydrofluorouracil, mimicking the major host mechanism for drug clearance. The preTA operon was necessary and sufficient for 5-fluorouracil inactivation by E. coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice and was prevalent in the gut microbiomes of colorectal cancer patients. The conservation of both the targets and enzymes for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug efficacy and side-effect profiles.

To evaluate the effect of various rotational motions on the torque/force generation, surface wear, and shaping ability of the ProGlider glide path instrument (Dentsply Sirona).Mesiobuccal and mesiolingual canals of mandibular molars were selected based on the canal volume, length, angle of curvature (25°-40°), and radius of curvature (4-8 mm) after micro-computed tomographic scanning. The samples were randomly assigned to four groups (n = 13, each) according to movement kinematics [continuous rotation (CR; 300 rpm), optimum torque reverse motion (OTR; 180° forward and 90° reverse when torque0.4 N cm), time-dependent reciprocal motion (TmR; 180° forward and 90° reverse), and optimal glide path motion (OGP; a combination of 90° forward, 90° reverse, 90° forward, and 120° reverse)]. Instrumentation was performed with an automated root canal instrument and torque/force analysing device. Maximum torque/force values, canal volume changes, and canal-centring ratios at 1, 3, 5, and 7 mm were evaluated. Surface defects (pits, grooves, microcracks, blunt cutting edges, and disruption of cutting edges) and spiral distortion on the ProGlider instrument were scored at the tip and 5 mm short of the tip before and after five consecutive uses with scanning electron microscopy. The Kruskal-Wallis test followed by Dunn's post-test with Bonferroni correction and Wilcoxon signed-rank test were used to analyse the data (α = 0.05).Optimal glide path motion generated significantly less clockwise torque and greater upward force than other groups (p .05). OGP resulted in significantly fewer surface defects than CR (p .05). In OGP and CR, the tip exhibited more surface defects than 5 mm short of the tip (p .05). CR resulted in greater volume changes than OGP and TmR (p .05) and greater centring ratios (i.e., more deviation) than OGP at 1 mm and OTR at 3 mm (p .05).Under laboratory conditions using the ProGlider instrument, OGP generated significantly less clockwise torque and greater upward force than the other rotatory motions. OGP generated fewer superficial defects than CR, and the three modes of reciprocal rotation better maintained the apical curvature of root canals than CR with the ProGlider instrument.

AIM To evaluate how different rotational speeds affect the torque/force generation and shaping ability of rotary root canal instrumentation using JIZAI (MANI, Utsunomiya, Japan) nickel-titanium instruments in continuous rotation and optimum torque reverse (OTR) motion. METHODOLOGY Mesial root canals of extracted mandibular molars were instrumented up to size 25, 0.04 taper using JIZAI instruments, and anatomically matched canals were selected based on geometric features of the canal [canal volume (mm3 ), surface area (mm2 ), length, 15°-20° curvature and radius of curvature (4-8 mm)] after micro-computed tomographic scanning. An automated root canal instrumentation and torque/force analysing device was programmed to permit a simulated pecking motion (2 s downward and 1 s upward at 50 mm min-1 ). The selected canals were prepared with size 25, 0.06 taper JIZAI instruments using continuous rotation or OTR motion and further subdivided according to the rotational speed (300 or 500 rpm, n = 10 each). Real-time clockwise/counterclockwise torque and downward/upward force were recorded using a custom-made torque/force analysing device. Then, the registered pre- and post-operative micro-computed tomographic datasets were examined to evaluate the canal volume changes and centring ratios at 1, 3, 5 and 7 mm from the apical foramen. Data were analysed using two-way analysis of variance or the Kruskal-Wallis test and Mann-Whitney U test with Bonferroni correction (α = 5%). RESULTS Maximum upward force and clockwise torque were significantly smaller in 500 rpm groups than in 300 rpm groups (P .05). OTR motion developed higher maximum counterclockwise torque than continuous rotation (P .05). There was no file fracture in any of the groups. CONCLUSIONS Under laboratory conditions using JIZAI instruments, a rotational speed of 500 rpm generated significantly lower maximum screw-in forces and torque values than rotational speed of 300 rpm. Continuous rotation and OTR motion performed similarly in shaping the canals.

Background The deep ocean is characterized by low temperatures, high hydrostatic pressures, and low concentrations of organic matter. While these conditions likely select for distinct genomic characteristics within prokaryotes, the attributes facilitating adaptation to the deep ocean are relatively unexplored. In this study, we compared the genomes of seven strains within the genus Colwellia, including some of the most piezophilic microbes known, to identify genomic features that enable life in the deep sea. Results Significant differences were found to exist between piezophilic and non-piezophilic strains of Colwellia. Piezophilic Colwellia have a more basic and hydrophobic proteome. The piezophilic abyssal and hadal isolates have more genes involved in replication/recombination/repair, cell wall/membrane biogenesis, and cell motility. The characteristics of respiration, pilus generation, and membrane fluidity adjustment vary between the strains, with operons for a nuo dehydrogenase and a tad pilus only present in the piezophiles. In contrast, the piezosensitive members are unique in having the capacity for dissimilatory nitrite and TMAO reduction. A number of genes exist only within deep-sea adapted species, such as those encoding d-alanine-d-alanine ligase for peptidoglycan formation, alanine dehydrogenase for NADH/NAD+ homeostasis, and a SAM methyltransferase for tRNA modification. Many of these piezophile-specific genes are in variable regions of the genome near genomic islands, transposases, and toxin-antitoxin systems. Conclusions We identified a number of adaptations that may facilitate deep-sea radiation in members of the genus Colwellia, as well as in other piezophilic bacteria. An enrichment in more basic and hydrophobic amino acids could help piezophiles stabilize and limit water intrusion into proteins as a result of high pressure. Variations in genes associated with the membrane, including those involved in unsaturated fatty acid production and respiration, indicate that membrane-based adaptations are critical for coping with high pressure. The presence of many piezophile-specific genes near genomic islands highlights that adaptation to the deep ocean may be facilitated by horizontal gene transfer through transposases or other mobile elements. Some of these genes are amenable to further study in genetically tractable piezophilic and piezotolerant deep-sea microorganisms.

Background: Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. Method: We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. Results: Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8–100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3–100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7–94.8%. No consistent cross-reactivity was observed. Conclusion: Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

BackgroundSerological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data.MethodWe conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system.ResultsAmong specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed.ConclusionOur evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

Despite the remarkable microbial diversity found within humans, our ability to link genes to phenotypes is based upon a handful of model microorganisms. We report a comparative genomics platform for Eggerthella lenta and other Coriobacteriia, a neglected taxon broadly relevant to human health and disease. We uncover extensive genetic and metabolic diversity and validate a tool for mapping phenotypes to genes and sequence variants. We also present a tool for the quantification of strains from metagenomic sequencing data, enabling the identification of genes that predict bacterial fitness. Competitive growth is reproducible under laboratory conditions and attributable to intrinsic growth rates and resource utilization. Unique signatures of invivo competition ingnotobiotic mice include an adhesin enriched in poor colonizers. Together, these computational and experimental resources represent a strong foundation for the continued mechanistic dissection of the Coriobacteriia and a template that can be applied to study other genetically intractable taxa.

Pharmaceuticals are the top predictor of inter-individual variations in gut microbial community structure1, consistent with in vitro evidence that host-targeted drugs inhibit gut bacterial growth2 and are extensively metabolized by the gut microbiome3,4. In oncology, bacterial metabolism has been implicated in both drug efficacy5,6 and toxicity7,8; however, the degree to which bacterial drug sensitivity and metabolism can be driven by conserved pathways also found in mammalian cells remains poorly understood. Here, we show that anticancer fluoropyrimidine drugs inhibit the growth of diverse gut bacterial strains by disrupting pyrimidine metabolism, as in mammalian cells. Select bacteria metabolized 5-fluorouracil (5-FU) to its inactive metabolite dihydrofluorouracil (DHFU), mimicking the major host pathway for drug clearance. The preTA operon was necessary and sufficient for 5-FU inactivation in Escherichia coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice, and was prevalent in the gut microbiomes of colorectal cancer patients prior to and during treatment. The observed conservation of both the targets and pathways for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug disposition9, efficacy, and side effect profiles.

Article published in Annals of Tourism Research available at https://doi.org/10.1016/j.annals.2016.05.011

An obligately piezophilic strain was isolated from an amphipod crustacean obtained in the Challenger Deep region of the Mariana Trench during the DEEPSEA CHALLENGE expedition. The strain, MTCD1T, grew at extremely high hydrostatic pressures, with a growth range of 80–140 MPa (optimum, 120 MPa) at 6 °C. Phylogenetic analyses based on the 16S rRNA gene sequence indicate that it is closely affiliated with the genus Colwellia . Comparative 16S rRNA gene sequence analyses revealed 95.7, 95.5 and 95.2 % similarity to Colwellia maris ABE-1T, Colwellia piezophila Y233GT and Colwellia psychrerythraea ATCC 27364T, respectively. The major cellular fatty acids were C16 : 1, C16 : 0 and C22 : 6 (docosahexaenoic acid), and the sole isoprenoid quinone produced was ubiqinone-8. DNA G+C content was 48.6 mol%. The strain was positive for oxidase and catalase activities. Based on the results from this study, strain MTCD1T is a novel Gram-negative species of the genus Colwellia , and the name Colwellia marinimaniae sp. nov. (type strain MTCD1T=ATCC TSD-5T=JCM 30270T) is proposed. It is the most piezophilic organism yet described.

This paper revisits, empirically, the question of whether the choice of exchange rate regime (floating currency, fixed rate or intermediate arrangement) has a direct effect on the long-term growth of developing countries. We use fixed effects panel estimation on a relatively large sample of 70 developing countries for the period 1981 to 2004. In addition to controlling for the level of income of these economies, we draw from alternative exchange rate regime classification schemes and account for the presence of an explicit monetary anchor to characterize policy. Our results indicate the absence of any robust relation between the choice of exchange rate regime and economic growth. The policy implication of these findings is clear. The choice of exchange rate policy has no direct impact on the long-term growth of developing countries.

What is the impact of foreign direct investment (FDI) and portfolio investment flows on the economic growth of low-, lower middle- and upper middle-income countries? In this article we address this question using a dynamic panel model and a large data set of 126 developing countries for the period 1985 to 2002. Employing the system-generalized methods of moments (GMM) estimation approach, our findings suggest that only developing countries that have reached a minimum level of economic development and absorptive capacity are capturing the growth-enhancing effects of both forms of investment inflows.

PurposeThe aim of the study is to investigate the relative significance of the determinants of disaggregated capital flows (foreign direct investment and portfolio flows) to five developing countries, across different time horizons.Design/methodology/approachAn empirically tractable structural VAR model of the determinants of capital flows is developed, and variance decomposition and impulse response analyses are used to investigate the temporal dynamic effects of shocks to push and pull factors on foreign direct investment and portfolio flows.FindingsEstimation of the model using quarterly data for the period 1976‐2001 provides evidence supporting the hypothesis that shocks to real variables of economic activity such as foreign output and domestic productivity are the most important forces explaining the variations in capital flows to developing countries.Research limitations/implicationsThese findings highlight the concomitant need for policy makers in developing countries to design domestic policy that accounts for both external and internal shocks to real variables of economic activity.Originality/valuePrevious empirical studies on the determinants of capital flows to developing countries have mostly examined the capital flow variable in aggregate, and have largely overlooked the possibility that the relative significance of estimated coefficients of such determinants may vary across time horizons.

The present study was on 2nd MBBS (1/2011 batch) students at the University of Medicine-2, Yangon, Myanmar. Self-learning ability of students is gradually declining and students tend to neglect reading prescribed textbooks. Test marks have also declined considerably. Students find it difficult to identify salient points when answering questions. Thus, the present study aimed to study the effect of open-book exercise practice on closed-book tests results. Objectives were to identify the students’ scoring of a closed-book written tutorial and to compare the changes in closed-book written tutorial marks after regular open-book study.

Background: In clinical and field conditions, breath gas analysis has been widely used in evaluating carbohydrate digestion. A field study was performed to determine the prevalence of lactose malabsorption in Myanmar children and to evaluate the possibility of using breath methane excretion to indicate lactose malabsorption in a field situation. Methods: The study population consisted of 118 children aged 1 to 12 years. A hydrogen breath test after a lactose meal (2 g/kg, maximum 50 g) was used as a standard test. Results: Lactose malabsorption was detected in 16.7% of children aged 1 to 2.9 years, with the prevalence increasing with age from 40.5% of those aged 3 to 5.9 years to 88.5% of those aged 6 to 8.9 years and reaching 91.7% in those aged 9 to 11.9 years. Lactose malabsorption was more prevalent when children were weaned before 4 months of age (87.2 vs. 41.1%;p < 0.01). Compared with lactose-tolerant children, those with lactose malabsorption had significantly higher concentrations of breath hydrogen excretion 60 minutes after the lactose test meal. Breath methane excretion was also significantly higher in samples at 120 minutes in children with lactose malabsorption. Breath methane excretion of greater than or equal to 2 parts per million at 180 minutes as a diagnostic test for lactose malabsorption had a sensitivity of 61.5% and a specificity of 84.6%. Conclusion: The breath methane test for lactose malabsorption has a lower sensitivity and specificity than the breath hydrogen test and therefore does not replace the lactose breath hydrogen test.

It has been commonly believed that children in developing countries pass stools that are very different from those of developed countries. A community based study on defecation frequency, stool weight, and consistency was conducted in a cohort of 300 Myanmar (Burmese) children aged 1 to 4 years. Most (80.3%) children opened their bowels daily and none passed more than three stools a day. The mean (SD) defecation frequency was 6.98 (1.94) times a week and total stool weight was 596 (221) g a week. The majority (61%) of children passed soft stools. At all ages, there was no significant difference in the defecation frequency, stool weight, and consistency between boys and girls, those on adult style diet and those partially weaned, and between age groups.

Background: Little is known about the small intestinal mucosal pattern of Myanmar children. Methods: Duodenal, jejunal and ileal mucosal specimens obtained from children within 6 h of death were examined under a dissecting microscope with the objective of determining villus pattern in relation to site within the small intestine and then correlated with age. Results: Abnormalities in the small intestinal mucosa were detected at a very young age. In children under 1 year of age, the changes are more marked proximally and become less marked distally, perhaps reflecting exposure to the causative agent(s) in early life. Presumably these agents are ingested orally and inactivated progressively. The pattern in older children reflects more severe changes in the ileum. Conclusions: It is postulated that frequent intestinal infections or small bowel bacterial contamination could lead to damage of the intestinal mucosa.

We aimed to establish whether there was a variation in orocecal transit time (OCTT) in Myanmar children and whether shortened transit time correlated with malnutrition. OCTT was measured in 90 healthy Myanmar children aged 1-5 years, using the hydrogen breath test (10g in 10% aqueous solution). The relationships between OCTT, sex, age, and malnutrition status were assessed. OCTT for 1 to 5-year old children was 90.2 +/- 20min (mean +/- SD). There was no significant difference in mean OCTT between boys and girls, breast-fed and weaned children, malnourished and non-malnourished children. There was also no difference between age groups (1-2 years, 2-3 years, 3-4 years, and 4-5 years), and no correlation was found between age and orocecal transit time. The assessment of OCTT using the lactulose breath hydrogen test was found to be feasible and acceptable in the field setting. The OCTT of Myanmar children with rice as a staple food is similar to that of children from developed countries having a different diet, and no shortening of transit time was demonstrated in children with malnutrition.