Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

/pdf/biological-roles-of-glycans-zowb8sw07y.pdf

Biological Roles of Glycans

Placebo

BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

/pdf/interventions-for-treating-oral-mucositis-for-patients-with-wjcln0nmlw.pdf

Interventions for treating oral mucositis for patients with cancer receiving treatment.

Protection against ionizing radiation by antioxidant nutrients and phytochemicals

High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated. Implications for practice High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity.

Preventing and Managing Toxicities of High-Dose Methotrexate

Background
Xerostomia (the feeling of dry mouth) is a common symptom especially in older adults. Causes of dry mouth include medications, autoimmune disease (Sjogren's Syndrome), radiotherapy or chemotherapy for cancer, hormone disorders and infections.

Objectives
To determine which topical treatments for dry mouth are effective in reducing this symptom.

Search methods
We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (28 October 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4 2011), MEDLINE via OVID (1950 to 28 October 2011), EMBASE via OVID (1980 to 28 October 2011), CINAHL via EBSCO (1980 to 28 October 2011), AMED via OVID (1985 to 28 October 2011), CANCERLIT via PubMed (1950 to 28 October 2011).

Selection criteria
We included randomised controlled trials of topical interventions such as lozenges, sprays, mouthrinses, gels, oils, chewing gum or toothpastes for the treatment of dry mouth symptom. We classified interventions into two broad categories, saliva stimulants and saliva substitutes, and these were compared with either placebo or another intervention. We included both parallel group and crossover trials.

Data collection and analysis
Two or more review authors independently carried out data extraction and assessed risk of bias. Trial authors were contacted for additional information as required.

Main results
Thirty-six randomised controlled trials involving 1597 participants met the inclusion criteria. Two trials compared saliva stimulants to placebo, nine trials compared saliva substitutes to placebo, five trials compared saliva stimulants directly with saliva substitutes, 18 trials directly compared two or more saliva substitutes, and two trials directly compared two or more saliva stimulants. Only one trial was at low risk of bias and 17 were at high risk of bias. Due to the range of interventions, comparisons and outcome measures in the trials, meta-analysis was possible for only a few comparisons. Oxygenated glycerol triester (OGT) saliva substitute spray shows evidence of effectiveness compared to an electrolyte spray (standardised mean difference (SMD) 0.77, 95% confidence interval (CI) 0.38 to 1.15) which corresponds to approximately a mean difference of 2 points on a 10-point visual analogue scale (VAS) for mouth dryness. Both integrated mouthcare systems (toothpaste + gel + mouthwash) and oral reservoir devices show promising results but there is insufficient evidence at present to recommend their use. Although chewing gum is associated with increased saliva production in the majority of those with residual capacity, there is no evidence that gum is more or less effective than saliva substitutes.

Authors' conclusions
There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth. OGT spray is more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15) which is approximately equivalent to a mean difference of 2 points on a 10-point VAS scale for mouth dryness. Chewing gums appear to increase saliva production in those with residual secretory capacity and may be preferred by patients, but there is no evidence that gum is better or worse than saliva substitutes. Integrated mouthcare systems and oral reservoir devices may be helpful but further research is required to confirm this. Well designed, adequately powered randomised controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care. For many people the symptom of dry mouth is a chronic problem and trials should evaluate whether treatments are palatable, effective in reducing xerostomia, as well as the long-term effects of treatments on quality of life of those with chronic dry mouth symptoms.

Interventions for the management of dry mouth: topical therapies.

BACKGROUND: Many dentists or hygienists provide scaling and polishing for patients at regular intervals, even if those patients are considered to be at low risk of developing periodontal disease. There is debate over the clinical effectiveness and cost effectiveness of 'routine scaling and polishing' and the 'optimal' frequency at which it should be provided for healthy adults.A 'routine scale and polish' treatment is defined as scaling or polishing or both of the crown and root surfaces of teeth to remove local irritational factors (plaque, calculus, debris and staining), that does not involve periodontal surgery or any form of adjunctive periodontal therapy such as the use of chemotherapeutic agents or root planing. OBJECTIVES: The objectives were: 1) to determine the beneficial and harmful effects of routine scaling and polishing for periodontal health; 2) to determine the beneficial and harmful effects of providing routine scaling and polishing at different time intervals on periodontal health; 3) to compare the effects of routine scaling and polishing with or without oral hygiene instruction (OHI) on periodontal health; and 4) to compare the effects of routine scaling and polishing provided by a dentist or dental care professional (dental therapist or dental hygienist) on periodontal health. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 15 July 2013), CENTRAL (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 15 July 2013) and EMBASE via OVID (1980 to 15 July 2013). We searched the metaRegister of Controlled Trials and the US National Institutes of Health Clinical Trials Register (clinicaltrials.gov) for ongoing and completed studies to July 2013. There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials of routine scale and polish treatments (excluding split-mouth trials) with and without OHI in healthy dentate adults, without severe periodontitis. DATA COLLECTION AND ANALYSIS: Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MDs) (standardised mean differences (SMDs) when different scales were reported) and 95% confidence intervals (CIs) for continuous data and, where results were meta-analysed, we used a fixed-effect model as there were fewer than four studies. Study authors were contacted where possible and where deemed necessary for missing information. MAIN RESULTS: Three studies were included in this review with 836 participants included in the analyses. All three studies are assessed as at unclear risk of bias. The numerical results are only presented here for the primary outcome gingivitis. There were no useable data presented in the studies for the outcomes of attachment change and tooth loss. No studies reported any adverse effects.- Objective 1: Scale and polish versus no scale and polish Only one trial provided data for the comparison between scale and polish versus no scale and polish. This study was conducted in general practice and compared both six-monthly and 12-monthly scale and polish treatments with no treatment. This study showed no evidence to claim or refute benefit for scale and polish treatments for the outcomes of gingivitis, calculus and plaque. The MD for six-monthly scale and polish, for the percentage of index teeth with bleeding at 24 months was -2% (95% CI -10% to 6%; P value = 0.65), with 40% of the sites in the control group with bleeding. The MD for 12-monthly scale and polish was -1% (95% CI -9% to 7%; P value = 0.82). The body of evidence was assessed as of low quality.- Objective 2: Scale and polish at different time intervals Two studies, both at unclear risk of bias, compared routine scale and polish provided at different time intervals. When comparing six with 12 months there was insufficient evidence to determine a difference for gingivitis at 24 months SMD -0.08 (95% CI -0.27 to 0.10). There were some statistically significant differences in favour of scaling and polishing provided at more frequent intervals, in particular between three and 12 months for the outcome of gingivitis at 24 months, with OHI, MD -0.14 (95% CI -0.23 to -0.05; P value = 0.003) and without OHI MD -0.21 (95% CI -0.30 to -0.12; P value < 0.001) (mean per patient measured on 0-3 scale), based on one study. There was some evidence of a reduction in calculus. This body of evidence was assessed as of low quality.- Objective 3: Scale and polish with and without OHIOne study provided data for the comparison of scale and polish treatment with and without OHI. There was a reduction in gingivitis for the 12-month scale and polish treatment when assessed at 24 months MD -0.14 (95% CI -0.22 to -0.06) in favour of including OHI. There were also significant reductions in plaque for both three and 12-month scale and polish treatments when OHI was included. The body of evidence was once again assessed as of low quality.- Objective 4: Scale and polish provided by a dentist compared with a dental care professionalNo studies were found which compared the effects of routine scaling and polishing provided by a dentist or dental care professional (dental therapist or dental hygienist) on periodontal health. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of routine scale and polish treatments. High quality trials conducted in general dental practice settings with sufficiently long follow-up periods (five years or more) are required to address the objectives of this review.

/pdf/routine-scale-and-polish-for-periodontal-health-in-adults-3qw0pcocs8.pdf

Routine scale and polish for periodontal health in adults

Background
Xerostomia is the subjective sensation of dry mouth. Common causes of xerostomia include adverse effects of many commonly prescribed medications, disease (e.g. Sjogren's Syndrome) and radiotherapy treatment for head and neck cancers. Non-pharmacological techniques such as acupuncture or mild electrostimulation may be used to improve symptoms.

Objectives
To assess the effects of non-pharmacological interventions administered to stimulate saliva production for the relief of dry mouth.

Search methods
We searched the Cochrane Oral Health Group's Trials Register (to 16th April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), MEDLINE via OVID (1948 to 16th April 2013), EMBASE via OVID (1980 to 16th April 2013), AMED via OVID (1985 to 16th April 2013), CINAHL via EBSCO (1981 to 16th April 2013), and CANCERLIT via PubMed (1950 to 16th April 2013). The metaRegister of Controlled Clinical Trials (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov) were also searched to identify ongoing and completed trials. References lists of included studies and relevant reviews were also searched. There were no restrictions on the language of publication or publication status.

Selection criteria
We included parallel group randomised controlled trials of non-pharmacological interventions to treat dry mouth, where participants had dry mouth symptoms at baseline.

Data collection and analysis
At least two review authors assessed each of the included studies to confirm eligibility, assess risk of bias and extract data using a piloted data extraction form. We calculated mean difference (MD) and 95% confidence intervals (CI) for continuous outcomes or where different scales were used to assess an outcome, we calculated standardised mean differences (SMD) together with 95% CIs. We attempted to extract data on adverse effects of interventions. Where data were missing or unclear we attempted to contact study authors to obtain further information.

Main results
There were nine studies (total 366 participants randomised) included in this review of non-pharmacological interventions for dry mouth which were divided into three comparisons. Eight studies were assessed at high risk of bias in at least one domain and the remaining study was at unclear risk of bias.

Five small studies (total 153 participants, with dry mouth following radiotherapy treatment) compared acupuncture with placebo. Four were assessed at high risk and one at unclear risk of bias. Two trials reported outcome data for dry mouth in a form suitable for meta-analysis. The pooled estimate of these two trials (70 participants, low quality evidence) showed no difference between acupuncture and control in dry mouth symptoms (SMD -0.34, 95% CI -0.81 to 0.14, P value 0.17, I2 = 39%) with the confidence intervals including both a possible reduction or a possible increase in dry mouth symptoms. Acupuncture was associated with more adverse effects (tiny bruises and tiredness which were mild and temporary). There was a very small increase in unstimulated whole saliva (UWS) at the end of 4 to 6 weeks of treatment (three trials, 71 participants, low quality evidence) (MD 0.02 ml/minute, 95% CI 0 to 0.04, P value 0.04, I2 = 57%), and this benefit persisted at the 12-month follow-up evaluation (two trials, 54 participants, low quality evidence) (UWS, MD 0.06 ml/minute, 95% CI 0.01 to 0.11, P value 0.03, I2 = 10%). For the outcome of stimulated whole saliva (SWS, three trials, 71 participants, low quality evidence) there was a benefit favouring acupuncture (MD 0.19 ml/minute, 95% CI 0.07 to 0.31, P value 0.002, I2 = 1%) an effect which also persisted at the 12-month follow-up evaluation (SWS MD 0.28 ml/minute, 95% CI 0.09 to 0.47, P value 0.004, I2 = 0%) (two trials, 54 participants, low quality evidence).

Two small studies, both at high risk of bias, compared the use of an electrostimulation device with a placebo device in participants with Sjogren's Syndrome (total 101 participants). A further study, also at high risk of bias, compared acupuncture-like electrostimulation of different sets of points in participants who had previously been treated with radiotherapy. None of these studies reported the outcome of dry mouth. There was no difference between electrostimulation and placebo in the outcomes of UWS or SWS at the end of the 4-week treatment period in the one study (very low that provided data for these outcomes. No adverse effects were reported.

A single study at high risk of bias, compared the stimulatory effect of powered versus manual toothbrushing and found no difference for the outcomes of UWS or SWS.

Authors' conclusions
There is low quality evidence that acupuncture is no different from placebo acupuncture with regard to dry mouth symptoms, which is the most important outcome. This may be because there were insufficient participants included in the two trials to show a possible effect or it may be that there was some benefit due to 'placebo' acupuncture which could have biased the effect to the null. There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms. It is well known that dry mouth symptoms may be problematic even when saliva production is increased, yet only two of the trials that evaluated acupuncture reported dry mouth symptoms, a worrying reporting bias. There is some low quality evidence that acupuncture results in a small increase in saliva production in patients with dry mouth following radiotherapy.

There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms or saliva production in patients with Sjogren's Syndrome. Reported adverse effects of acupuncture are mild and of short duration, and there were no reported adverse effects from electrostimulation.

/pdf/interventions-for-the-management-of-dry-mouth-non-2gdlsleya3.pdf

Interventions for the management of dry mouth: non-pharmacological interventions.

Pharmacological and non-pharmacological interventions for cough in adults with respiratory and non-respiratory diseases: A systematic review of the literature

Gemma Bryan

Papers

Interventions for treating oral mucositis for patients with cancer receiving treatment.

Interventions for the management of dry mouth: topical therapies.

Routine scale and polish for periodontal health in adults

Interventions for the management of dry mouth: non-pharmacological interventions.

Pharmacological and non-pharmacological interventions for cough in adults with respiratory and non-respiratory diseases: A systematic review of the literature