A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology

The numerous species that make up the oral microbiome are now understood to play a key role in establishment and maintenance of oral health. The ability to taxonomically identify community members at the species level is important to elucidating its diversity and association to health and disease. We report the overall ecological effects of using a toothpaste containing enzymes and proteins compared to a control toothpaste on the plaque microbiome. The results reported here demonstrate that a toothpaste containing enzymes and proteins can augment natural salivary defences to promote an overall community shift resulting in an increase in bacteria associated with gum health and a concomitant decrease in those associated with periodontal disease. Statistical analysis shows significant increases in 12 taxa associated with gum health including Neisseria spp. and a significant decrease in 10 taxa associated with periodontal disease including Treponema spp. The results demonstrate that a toothpaste containing enzymes and proteins can significantly shift the ecology of the oral microbiome (at species level) resulting in a community with a stronger association to health

Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits.

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with the structure and proteins of the pellicle layer, as well as microbes in the biofilm, remains unclear. The tooth enamel is a dense crystalline structure that is likely to act as a barrier to ENM penetration, but underlying dentinal tubules are not. Consequently, ENMs may be used to strengthen dentine or regenerate pulp tissue. ENMs have dental applications as antibacterials for infection control, as nanofillers to improve the mechanical and bioactive properties of restoration materials, and as novel coatings on dental implants. Dentifrices and some related personal care products are already available for oral health applications. Overall, the clinical benefits generally outweigh the hazards of using ENMs in the oral cavity, and the latter should not prevent the responsible innovation of nanotechnology in dentistry. However, the clinical safety regulations for dental materials have not been specifically updated for ENMs, and some guidance on occupational health for practitioners is also needed. Knowledge gaps for future research include the formation of protein corona in the oral cavity, ENM diffusion through clinically relevant biofilms, and mechanistic investigations on how ENMs strengthen the tooth structure

Interventions for preventing weight gain after smoking cessation

Background: Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting. Objectives: To systematically review the effects of: (1) interventions targeting post‐cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post‐cessation weight gain (referred to as 'Part 2'). Search methods: Part 1 ‐ We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020. Part 2 ‐ We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e‐cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists. Selection criteria Part 1 ‐ trials of interventions that targeted post‐cessation weight gain and had measured weight at any follow‐up point or smoking cessation, or both, six or more months after quit day. Part 2 ‐ trials included in the selected parent Cochrane reviews reporting weight change at any time point. Data collection and analysis: Screening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow‐up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta‐analysis using the inverse variance method for weight, and Mantel‐Haenszel method for smoking. Main results: Part 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk. An intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) −3.70 kg, 95% confidence interval (CI) −4.82 to −2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD −1.30 kg, 95% CI −3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study found that no‐one completed the VLCD intervention or achieved abstinence. Interventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I2 = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I2 = 26%). Some pharmacological interventions tested for limiting post‐cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low‐certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD −1.11 kg, 95% CI −1.93 to −0.29; 3 studies, 121 participants; I2 = 0%), but no evidence in the longer‐term 12 months (MD −0.44 kg, 95% CI −2.34 to 1.46; 4 studies, 530 participants; I2 = 41%). There was low to very low‐certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD −0.21 kg, 95% CI −2.28 to 1.86; 2 studies, 61 participants; I2 = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I2 = 0%). Part 2: We include 83 completed studies, 27 of which are new to this update. There was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD −0.25 kg, 95% CI −0.78 to 0.29; 4 studies, 404 participants; I2 = 0%). However, weight was reduced at 12 months (MD −2.07 kg, 95% CI −3.78 to −0.36; 3 studies, 182 participants; I2 = 0%). Both bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD −1.01 kg, 95% CI −1.35 to −0.67; 10 studies, 1098 participants; I2 = 3%); (fluoxetine MD −1.01 kg, 95% CI −1.49 to −0.53; 2 studies, 144 participants; I2 = 38%; low‐ and very low‐certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD −0.26 kg, 95% CI −1.31 to 0.78; 7 studies, 471 participants; I2 = 0%). No studies of fluoxetine provided data at 12 months. There was moderate‐certainty that NRT reduced weight at end of treatment (MD −0.52 kg, 95% CI −0.99 to −0.05; 21 studies, 2784 participants; I2 = 81%) and moderate‐certainty that the effect may be similar at 12 months (MD −0.37 kg, 95% CI −0.86 to 0.11; 17 studies, 1463 participants; I2 = 0%), although the estimates are too imprecise to assess long‐term benefit. There was mixed evidence of the effect of varenicline on weight, with high‐certainty evidence that weight change was very modestly lower at the end of treatment (MD −0.23 kg, 95% CI −0.53 to 0.06; 14 studies, 2566 participants; I2 = 32%); a low‐certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI −0.58 to 2.69; 3 studies, 237 participants; I2 = 0%). Authors' conclusions: Overall, there is no intervention for which there is moderate certainty of a clinically useful effect on long‐term weight gain. There is also no moderate‐ or high‐certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.</p

Interventions for preventing weight gain after smoking cessation

Background: Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting. Objectives: To systematically review the effects of: (1) interventions targeting post‐cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post‐cessation weight gain (referred to as 'Part 2'). Search methods: Part 1 ‐ We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020. Part 2 ‐ We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e‐cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists. Selection criteria Part 1 ‐ trials of interventions that targeted post‐cessation weight gain and had measured weight at any follow‐up point or smoking cessation, or both, six or more months after quit day. Part 2 ‐ trials included in the selected parent Cochrane reviews reporting weight change at any time point. Data collection and analysis: Screening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow‐up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta‐analysis using the inverse variance method for weight, and Mantel‐Haenszel method for smoking. Main results: Part 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk. An intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) −3.70 kg, 95% confidence interval (CI) −4.82 to −2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD −1.30 kg, 95% CI −3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study found that no‐one completed the VLCD intervention or achieved abstinence. Interventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I2 = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I2 = 26%). Some pharmacological interventions tested for limiting post‐cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low‐certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD −1.11 kg, 95% CI −1.93 to −0.29; 3 studies, 121 participants; I2 = 0%), but no evidence in the longer‐term 12 months (MD −0.44 kg, 95% CI −2.34 to 1.46; 4 studies, 530 participants; I2 = 41%). There was low to very low‐certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD −0.21 kg, 95% CI −2.28 to 1.86; 2 studies, 61 participants; I2 = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I2 = 0%). Part 2: We include 83 completed studies, 27 of which are new to this update. There was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD −0.25 kg, 95% CI −0.78 to 0.29; 4 studies, 404 participants; I2 = 0%). However, weight was reduced at 12 months (MD −2.07 kg, 95% CI −3.78 to −0.36; 3 studies, 182 participants; I2 = 0%). Both bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD −1.01 kg, 95% CI −1.35 to −0.67; 10 studies, 1098 participants; I2 = 3%); (fluoxetine MD −1.01 kg, 95% CI −1.49 to −0.53; 2 studies, 144 participants; I2 = 38%; low‐ and very low‐certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD −0.26 kg, 95% CI −1.31 to 0.78; 7 studies, 471 participants; I2 = 0%). No studies of fluoxetine provided data at 12 months. There was moderate‐certainty that NRT reduced weight at end of treatment (MD −0.52 kg, 95% CI −0.99 to −0.05; 21 studies, 2784 participants; I2 = 81%) and moderate‐certainty that the effect may be similar at 12 months (MD −0.37 kg, 95% CI −0.86 to 0.11; 17 studies, 1463 participants; I2 = 0%), although the estimates are too imprecise to assess long‐term benefit. There was mixed evidence of the effect of varenicline on weight, with high‐certainty evidence that weight change was very modestly lower at the end of treatment (MD −0.23 kg, 95% CI −0.53 to 0.06; 14 studies, 2566 participants; I2 = 32%); a low‐certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI −0.58 to 2.69; 3 studies, 237 participants; I2 = 0%). Authors' conclusions: Overall, there is no intervention for which there is moderate certainty of a clinically useful effect on long‐term weight gain. There is also no moderate‐ or high‐certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.</p

Heparan sulfate proteoglycan from human tubular basement membrane. Comparison with this component from the glomerular basement membrane

Heparan sulfate proteoglycan (HSPG) was extracted from human tubular basement membrane (TBM) with guanidine and purified by ion-exchange chromatography and gel filtration. The glycoconjugate was sensitive to heparitinase and resistant to chondroitinase ABC, had an apparent molecular mass of 200-400 kDa and consisted of 70% protein and 30% glycosaminoglycan. The amino acid composition was characterized by its high content of glycine, proline, alanine and glutamic acid. Hydrolysis with trifluoromethanesulfonic acid yielded core proteins of 160 and 110 kDa. The heparan sulfate (HS) chains obtained after alkaline NaBH4 treatment had a molecular mass of about 18 kDa. Results of heparitinase digestion and HNO2 treatment suggest a clustering of sulfate groups in the distal portion of the HS side chains. These chemical data are comparable to those obtained previously on glomerular basement membrane (GBM) HSPG (Van den Heuvel et al. (1989) Biochem. J. 264, 457-465). Peptide patterns obtained after trypsin, clostripain or V8 protease digestion of TBM and GBM HSPG preparations showed a large similarity. Polyclonal antisera and a panel of monoclonal antibodies raised against both HSPG preparations and directed against the core protein showed complete cross-reactivity in ELISA and on Western blots. They stained all basement membranes in an intense linear fashion in indirect immunofluorescence studies on human kidneys. Based on these biochemical and immunological data we conclude that HSPGs from human GBM and TBM are identical, or at least very closely related, proteins

Susceptibilities of Oral Bacteria and Yeast to Mammalian Cathelicidins

The effects of cathelicidins against oral bacteria and clinically important oral yeasts are not known. We tested the susceptibilities of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus sanguis, Candida krusei, Candida tropicalis and Candida albicans to the following cathelicidins: FALL39, SMAP29, and CAP18. SMAP29 and CAP18 were antimicrobial, whereas FALL39 did not exhibit antimicrobial activity. Future studies are needed to determine the potential use of these antimicrobial peptides in prevention and treatment of oral infections