Comparison of the salivary and dentinal microbiome of children with severe-early childhood caries to the salivary microbiome of caries-free children

peer-reviewedBackground The main objectives of this study were to describe and compare the microbiota of 1) deep dentinal lesions of deciduous teeth of children affected with severe early childhood caries (S-ECC) and 2) the unstimulated saliva of these children and 3) the unstimulated saliva of caries-free children, and to compare microbiota compositional differences and diversity of taxa in these sampled sites. Methods Children with S-ECC and without S-ECC were recruited. The saliva of all children with and without S-ECC was sampled along with the deep dentinal microbiota from children affected by S-ECC. The salivary microbiota of children affected by S-ECC (n = 68) was compared to that of caries-free children (n = 70), by Illumina MiSeq sequencing of 16S rRNA amplicons. Finally, the caries microbiota of deep dentinal lesions of those children with S-ECC was investigated. Results Using two beta diversity metrics (Bray Curtis dissimilarity and UniFrac distance), the caries microbiota was found to be distinct from that of either of the saliva groups (caries-free & caries-active) when bacterial abundance was taken into account. However, when the comparison was made by measuring only presence and absence of bacterial taxa, all three microbiota types separated. While the alpha diversity of the caries microbiota was lowest, the diversity difference between the caries samples and saliva samples was statistically significant (p < 0.001). The major phyla of the caries active dentinal microbiota were Firmicutes (median abundance value 33.5%) and Bacteroidetes (23.2%), with Neisseria (10.3%) being the most abundant genus, followed by Prevotella (10%). The caries-active salivary microbiota was dominated by Proteobacteria (median abundance value 38.2%) and Bacteroidetes (27.8%) with the most abundant genus being Neisseria (16.3%), followed by Porphyromonas (9.5%). Caries microbiota samples were characterized by high relative abundance of Streptococcus mutans, Prevotella spp., Bifidobacterium and Scardovia spp. Conclusions Distinct differences between the caries microbiota and saliva microbiota were identified, with separation of both salivary groups (caries-active and caries-free) whereby rare taxa were highlighted. While the caries microbiota was less diverse than the salivary microbiota, the presence of these rare taxa could be the difference between health and disease in these children

Assessing the clinical and cost-effectiveness of inpatient mental health rehabilitation services provided by the NHS and independent sector (ACER): protocol

Background: Mental health rehabilitation services provide specialist treatment to people with particularly severe and complex problems. In 2018, the Care Quality Commission reported that over half the 4,400 mental health inpatient rehabilitation beds in England were provided by the independent sector. They raised concerns that the length of stay and cost of independent sector care was double that of the NHS and that their services tended to be provided much further from people’s homes. However, there has been no research comparing the two sectors and we therefore do not know if these concerns are justified. The ACER Study (Assessing the Clinical and cost-Effectiveness of inpatient mental health Rehabilitation services provided by the NHS and independent sector) is a national programme of research in England, funded from 2021 to 2026, that aims to investigate differences in inpatient mental health rehabilitation provided by the NHS and independent sector in terms of: patient characteristics; service quality; patient, carer and staff experiences; clinical and cost effectiveness. Methods: ACER comprises a:1) detailed survey of NHS and independent sector inpatient mental health rehabilitation services across England; 2) qualitative investigation of patient, family, staff and commissioners’ experiences of the two sectors; 3) cohort study comparing clinical outcomes in the two sectors over 18 months; 4) comprehensive national comparison of inpatient service use in the two sectors, using instrumental variable analysis of routinely collected healthcare data over 18 months; 5) health economic evaluation of the relative cost-effectiveness of the two sectors. In Components 3 and 4, our primary outcome is ‘successful rehabilitation’ defined as a) being discharged from the inpatient rehabilitation unit without readmission and b) inpatient service use over the 18 months. Discussion: The ACER study will deliver the first empirical comparison of the clinical and cost-effectiveness of NHS and independent sector inpatient mental health rehabilitation services. Trial registration: ISRCTN17381762 retrospectively registered

The oral microbiota in colorectal cancer is distinctive and predictive

Background and aims: Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC. Methods: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103). Results: Several oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet. Conclusion: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states

Mutagenesis by microbe: The role of the microbiota in shaping the cancer genome

Cancers arise through the process of somatic evolution fueled by the inception of somatic mutations. We lack a complete understanding of the sources of these somatic mutations. Humans host a vast repertoire of microbes collectively known as the microbiota. The microbiota plays a role in altering the tumor microenvironment and proliferation. In addition, microbes have been shown to elicit DNA damage which provides the driver for somatic mutations. An understanding of microbiota-driven mutational mechanisms would contribute to a more complete understanding of the origins of the cancer genome. Here, we review the modes by which microbes stimulate DNA damage and the effect of these phenomena upon the cancer genomic architecture, specifically in the form of mutational spectra and mutational signatures

Short-Term Trends in Bastardy in Taiwan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68002/2/10.1177_036319908000500303.pd

Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites (BORTAS) experiment: design, execution and science overview

We describe the design and execution of the BORTAS (Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites) experiment, which has the overarching objective of understanding the chemical aging of air masses that contain the emission products from seasonal boreal wildfires and how these air masses subsequently impact downwind atmospheric composition. The central focus of the experiment was a two-week deployment of the UK BAe-146-301 Atmospheric Research Aircraft (ARA) over eastern Canada, based out of Halifax, Nova Scotia. Atmospheric ground-based and sonde measurements over Canada and the Azores associated with the planned July 2010 deployment of the ARA, which was postponed by 12 months due to UK-based flights related to the dispersal of material emitted by the Eyjafjallajökull volcano, went ahead and constituted phase A of the experiment. Phase B of BORTAS in July 2011 involved the same atmospheric measurements, but included the ARA, special satellite observations and a more comprehensive ground-based measurement suite. The high-frequency aircraft data provided a comprehensive chemical snapshot of pyrogenic plumes from wildfires, corresponding to photochemical (and physical) ages ranging from 45 sr 10 days, largely by virtue of widespread fires over Northwestern Ontario. Airborne measurements reported a large number of emitted gases including semi-volatile species, some of which have not been been previously reported in pyrogenic plumes, with the corresponding emission ratios agreeing with previous work for common gases. Analysis of the NOy data shows evidence of net ozone production in pyrogenic plumes, controlled by aerosol abundance, which increases as a function of photochemical age. The coordinated ground-based and sonde data provided detailed but spatially limited information that put the aircraft data into context of the longer burning season in the boundary layer. Ground-based measurements of particulate matter smaller than 2.5 μm (PM2.5) over Halifax show that forest fires can on an episodic basis represent a substantial contribution to total surface PM2.5

Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice

Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.9% lard) as control diet were fed to 160 male obese ob/ob mice after 2 azoxymethane injections. In comparison to control-fed mice, dysplasia, adenomas, or adenocarcinomas were detected in fewer mice on either bean fraction diet (percent reduction from control: whole beans 54%, P = 0.10; bean residue 81%, P = 0.003 ; bean extract 91%, P = 0.007) , and any type of colon lesions, including focal hyperplasia, were found in fewer mice on each of the 3 bean diets percent reduction from control: whole bean 56%, P= 0.04; bean residue 67%, P = 0.01; bean extract 87%, 373 374 G. BOBE ET AL. P = 0.0003. These results suggest that both the soluble and the insoluble fraction of the extract contribute to the cancer-protective effect of cooked navy beans. INTRODUCTION Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the fourth most common cause of cancer-related death worldwide (1). In the United States, CRC is the fourth leading cancer in incidence rates and the second leading cause of cancer-related mortality with a 5-yr survival rate of 64% (2). Despite the effectiveness of screening (3,4), there is limited impact for CRC prevention because of low screening rates (5). Nutrition remains critical for CRC prevention. It is estimated that nutrition could prevent 70-80% of all CRC cases (6). This is important, as the annual CRC treatment costs in the United States are estimated to be $6.5 billion (7). Two of the main risk factors for CRC, which are both diet related, are obesity and inflammation (8). Thus, ob/ob mice might provide a suitable animal model to study the link between diet and CRC because they have a mutation in the leptin gene, which results in hyperphagia, obesity, hyperinsulinemia, hyperglycemia, and increased inflammatory response to liposaccharides (9). Dry beans (Phaseolus vulgaris L.), which belong to the Leguminosae family, are a dietary staple in many Latin American, Eastern, and South African countries that potentially could prevent CRC (10,11). Ecological analysis indicates a decreased risk of death associated with colon cancer in countries with higher consumption of beans (12). In studies that have examined the association between colon cancer and individual intakes of legumes, the results indicate a protective effect in populations with higher legume consumption (13-18). In the only study that examined the effect of dry bean consumption separately, male participants, who consumed at least 31 g of cooked dry beans daily, had reduced risk of advanced adenomatous polyp recurrence in a 4-yr nutrition intervention study (Polyp Prevention Trial (19); unpublished data). In animal models, dry beans commonly consumed in the United States, such as pinto, black, and navy beans, reduced azoxymethane(AOM)-induced colon adenocarcinomas in F344 rat

Unilateral aplasia of both cruciate ligaments

Aplasia of both cruciate ligaments is a rare congenital disorder. A 28-year-old male presented with pain and the feeling of instability of his right knee after trauma. The provided MRI and previous arthroscopy reports did not indicate any abnormalities except cruciate ligament tears. He was referred to us for reconstruction of both cruciate ligaments. The patient again underwent arthroscopy which revealed a hypoplasia of the medial trochlea and an extremely narrow intercondylar notch. The tibia revealed a missing anterior cruciate ligament (ACL) footprint and a single bump with a complete coverage with articular cartilage. There was no room for an ACL graft. A posterior cruciate ligament could not be identified. The procedure was ended since a ligament reconstruction did not appear reasonable. A significant notch plasty if not a partial resection of the condyles would have been necessary to implant a ligament graft. It is most likely that this would not lead to good knee stability. If the surgeon would have retrieved the contralateral hamstrings at the beginning of the planned ligament reconstruction a significant damage would have occurred to the patient. Even in seemingly clear diagnostic findings the arthroscopic surgeon should take this rare abdnormality into consideration and be familiar with the respective radiological findings. We refer the abnormal finding of only one tibial spine to as the "dromedar-sign" as opposed to the two (medial and a lateral) tibial spines in a normal knee. This may be used as a hint for aplasia of the cruciate ligaments

Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model

Aims Many patients are unable to achieve guideline-recommended LDL cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP citrate lyase, significantly lowers LDL-C with or without background statin therapy in diverse populations. Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid. Methods And Results Bempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1-3 clinical studies. Dose-response models were developed for bempedoic acid monotherapy and bempedoic acid-statin combinations using previously published statin parameters. Simulations were performed using these models to predict change in LDL-C levels following treatment with bempedoic acid combined with clinically relevant doses of atorvastatin, rosuvastatin, simvastatin, and pravastatin. Dose-response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose" for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg. Conclusion These findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses