A rhamnose-binding lectin from Rhodnius prolixus and the impact of its silencing on gut bacterial microbiota and Trypanosoma cruzi.

Lectins are ubiquitous proteins involved in the immune defenses of different organisms and mainly responsible for non-self-recognition and agglutination reactions. This work describes molecular and biological characterization of a rhamnose-binding lectin (RBL) from Rhodnius prolixus, which possesses a 21 amino acid signal peptide and a mature protein of 34.6 kDa. The in-silico analysis of the primary and secondary structures of RpLec revealed a lectin domain fully conserved among previous insects studied. The three-dimensional homology model of RpLec was similar to other RBL-lectins. Docking predictions with the monosaccharides showed rhamnose and galactose-binding sites comparable to Latrophilin-1 and N-Acetylgalactosamine-binding in a different site. The effects of RpLec gene silencing on levels of infecting Trypanosoma cruzi Dm 28c and intestinal bacterial populations in the R. prolixus midgut were studied by injecting RpLec dsRNA into the R. prolixus hemocoel. Whereas T. cruzi numbers remained unchanged compared with the controls, numbers of bacteria increased significantly. The silencing also induced the up regulation of the R. prolixus defC (defensin) expression gene. These results with RpLec reveal the potential importance of this little studied molecule in the insect vector immune response and homeostasis of the gut bacterial microbiota.

James Lind Alliance research priorities: what role do carbohydrates, fats and proteins have in the management of Type 2 diabetes, and are there risks and benefits associated with particular approaches?

AIMS: To assess the role played by carbohydrates, fat and proteins in the management of Type 2 diabetes. BACKGROUND: Diabetes research tends to reflect the interests of academics or the pharmaceutical industry, rather than those of people living with Type 2 diabetes. The James Lind Alliance and Diabetes UK addressed this issue by defining the research priorities of people living with Type 2 diabetes. Three of the top 10 research priority questions focused on lifestyle. METHODS: A narrative review was undertaken with a structured search strategy using three databases. Search terms included the three macronutrients and Type 2 diabetes. No restrictions were placed on macronutrient quantity or length of study follow-up. Outcomes included changes in HbA1c , body weight, insulin sensitivity and cardiovascular risk. RESULTS: There is no strong evidence that there is an optimal ratio of macronutrients for improving glycaemic control or reducing cardiovascular risk. Challenges included defining the independent effect of macronutrient manipulation and identifying the effects of macronutrients, independent of foods and dietary patterns. Extreme intakes of macronutrients may be associated with health risks. CONCLUSIONS: It is challenging to formulate food-based guidelines from studies based on macronutrient manipulation. Structured education should be offered to support individuals in discovering their optimal, individual dietary approach. Recommendations for dietary guidelines should be expressed in terms of foods and not macronutrients.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

Airborne infection control in India: Baseline assessment of health facilities.

BACKGROUND: Tuberculosis transmission in health care settings represents a major public health problem. In 2010, national airborne infection control (AIC) guidelines were adopted in India. These guidelines included specific policies for TB prevention and control in health care settings. However, the feasibility and effectiveness of these guidelines have not been assessed in routine practice. This study aimed to conduct baseline assessments of AIC policies and practices within a convenience sample of 35 health care settings across 3 states in India and to assess the level of implementation at each facility after one year. METHOD: A multi-agency, multidisciplinary panel of experts performed site visits using a standardized risk assessment tool to document current practices and review resource capacity. At the conclusion of each assessment, facility-specific recommendations were provided to improve AIC performance to align with national guidelines. RESULT: Upon initial assessment, AIC systems were found to be poorly developed and implemented. Administrative controls were not commonly practiced and many departments needed renovation to achieve minimum environmental standards. One year after the baseline assessments, there were substantial improvements in both policy and practice. CONCLUSION: A package of capacity building and systems development that followed national guidelines substantially improved implementation of AIC policies and practice.

Alcohol health literacy in young adults with type 1 diabetes and its impact on diabetes management.

AIMS: To investigate the knowledge of alcohol and carbohydrate content of commonly consumed alcoholic drinks among young adults with Type 1 diabetes and to explore alcohol consumption while identifying diabetes self-management strategies used to minimize alcohol-associated risk. METHOD: We conducted an open-access, multiple-choice web survey to investigate knowledge of alcohol and carbohydrate content of typical alcoholic drinks using images. Respondents to the survey also recorded their current alcohol consumption and diabetes self-management strategies when drinking. RESULTS: A total of 547 people aged 18-30 years responded to the survey (341 women; 192 men; mean (sd) age 24.5 (3.7) years), of whom 365 (66.7%) drank alcohol. In all, 84 (32.9%) women and 31 (22.6%) men scored higher than the cut-off score for increased-risk drinking. Knowledge accuracy of alcohol units was poor: only 7.3% (n = 40) correctly identified the alcohol content of six or more out of 10 drinks. Knowledge of carbohydrate content was also poor: no respondent correctly identified the carbohydrate content of six or more out of 10 drinks. Various and inconsistent strategies to minimize alcohol-associated risk were reported. CONCLUSIONS: Alcohol consumption was common among the survey respondents, but knowledge of alcohol and carbohydrate content was poor. Greater alcohol-related health literacy is required to minimize alcohol-associated risk. Further research should help develop effective strategies to improve health literacy and support safe drinking for young adults with Type 1 diabetes.

Kaleidoscope model of diabetes care: time for a rethink?

National Audit Data highlight persistent sub-optimum control among increasing numbers of people living with diabetes, with severe consequences for the individual and the NHS. The aim of the present review was to introduce a new cohesive, holistic model of care, tailored to individual needs to support optimum diabetes outcomes. This model of diabetes is necessary in order to understand the driving forces behind behaviour and their impact on diabetes management. Feelings (an emotional state or reaction) and beliefs (an acceptance that something is true or real) are fundamental behavioural drivers and influence diabetes self-management choices. Individually, these explain some of the complexities of behaviour and, collectively, they impact on personal motivation (rationale/desire to act) to achieve a specific outcome. Inevitably, they independently affect diabetes self-management and the environment in which individuals live. A model of care that proposes the encompassing of environment, intrinsic thought and therapy regimens to provide tailored, personalized healthcare should support enhanced diabetes self-management and outcomes from diagnosis. The Kaleidoscope model of care could be deliverable in routine care, incorporating each of the influences on diabetes self-management, and should benefit both individuals with diabetes and healthcare professionals.

Neuroendocrine breast tumours: breast cancer or neuroendocrine cancer presenting in the breast?

Neuroendocrine tumours (NET) of the breast are rare. Diagnosis depends on close scrutiny of core- or excisional-biopsy specimens for characteristic growth patterns (papillary, nesting or mixed), which should trigger immunohistochemical staining for neuroendocrine markers (in particular chromogranin and synaptophysin). The diagnosis is confirmed if a) >50% of the tissue specimen demonstrate neuroendocrine markers and b) in-situ ductal carcinoma is identified and/or imaging modalities exclude extra-mammary sites. Our literature search including the non-English literature identified 66 articles with data on 123 cases, including our own. Oestrogen receptors are not diagnostic for NET's of the breast as they are found in tumours of non-mammary origin, too. Half of reported cases of neuroendocrine tumours have axillary lymph node involvement. Breast-conserving surgery (wide local excision ± axillary clearance) is commonly performed for suitable tumours. Chemotherapy regimens utilised are commonly either platinum- (as for small-cell cancers) or anthracycline-based (as for primary breast cancers). Best management remains unknown.

Laryngeal cancer management in a small, rural, multidisciplinary team setting: 15-year review.

BACKGROUND: The Cumberland Infirmary, Carlisle, serves a largely remote, rural population of 330 000. The aim of this study was to report the treatment and survival figures for patients treated for laryngeal cancer at this centre. METHODS: The study included 209 consecutive patients with squamous cell carcinoma of the larynx diagnosed between 1996 and 2010 at the Cumberland Infirmary. RESULTS: Disease-specific survival was 100 per cent for stage one, 76 per cent for stage two, 87 per cent for stage three and 46 per cent for stage four. In total, 76 patients (36 per cent) had a laryngectomy, either as primary treatment or as a salvage procedure. CONCLUSION: Our tumour-specific survival rate was very high, and this success may be due in part to high rates of surgical intervention. Survival data compared favourably with other centres, despite less radical radiotherapy regimes. Laryngeal cancer can be managed effectively in a small, relatively remote, multidisciplinary team setting.

Can head and neck cancer patients be discharged after three years?

BACKGROUND: Follow-up surveillance of head and neck cancer patients varies throughout the UK. The heterogeneity of these patients limits the applicability of a standardised protocol. Improvements in our understanding of the natural history of the disease may assist in the tailoring of resources to patients. METHOD: Prospective data collected at the Cumberland Infirmary over a 13-year period were analysed, primarily focusing upon recurrence rates and time to recurrence. RESULTS: In keeping with other studies, recurrence of head and neck squamous cell carcinoma was found to be maximal within the first three years of treatment, regardless of subsite. CONCLUSION: Hospital-based surveillance may be safely discontinued after three years for some patients. Laryngeal carcinoma may require further surveillance due to possible delayed recurrence of a second primary formation. Emphasis must be placed on patient education, accessibility to head and neck services, and the existence of a robust system to facilitate urgent referrals.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

This article summarizes the Diabetes UK evidence-based guidelines for the prevention of Type 2 diabetes and nutritional management of diabetes. It describes the development of the recommendations and highlights the key changes from previous guidelines. The nutrition guidelines include a series of recommendations for the prevention of Type 2 diabetes, nutritional management of Type 1 and Type 2 diabetes, weight management, management of microvascular and macrovascular disease, hypoglycaemia management, and additional considerations such as nutrition support, end-of-life care, disorders of the pancreas, care of the older person with diabetes, nutrition provided by external agencies and fasting. The evidence-based recommendations were graded using the Scottish Intercollegiate Guidelines Network methodology and, in a small number of topic areas, where strong evidence was lacking, the recommendations were reached by consensus. The Diabetes UK 2011 guidelines place an emphasis on carbohydrate management and a more flexible approach to weight loss, unlike previous guidelines which were expressed in terms of recommendations for individual nutrient intakes. Additionally, the guidelines for alcohol have been aligned to national recommendations. The full evidence-based nutrition guidelines for the prevention and management of diabetes are available from: http://www.diabetes.org.uk/nutrition-guidelines.

A transposon insertion single-gene knockout library and new ordered cosmid library for the model organism Streptomyces coelicolor A3(2).

A simple and high-throughput transposon mediated mutagenesis system employing in vitro shuttle transposon mutagenesis has been used to systematically mutagenise the Streptomyces coelicolor genome. To achieve the highest coverage, a new ordered cosmid library was also constructed. Individual cosmids from both the existing and new libraries were disrupted using the Tn5-based mini-transposon Tn5062. A total of 35,358 insertions were sequenced resulting in the disruption of 6,482 genes (83% of the predicted open reading frames). Complete information for both the newly generated cosmids as well as all the insertions has been uploaded onto a central database, StrepDB ( http://strepdb.streptomyces.org.uk/ ). All insertions, new cosmids and a range of transposon exchange cassettes are available for study of individual gene function.

The therapeutics of lifestyle management on obesity.

The global incidence and prevalence of obesity continue to increase, with the fastest rate of increase in the developing world. Obesity is associated with many chronic diseases including type 2 diabetes, cardiovascular disease and some cancers. Weight loss can reduce the risk of developing these diseases and can be achieved by means of surgery, pharmacotherapy and lifestyle interventions. Lifestyle interventions for prevention and treatment of obesity include diet, exercise and psychological interventions. All lifestyle interventions have a modest but significant effect on weight loss, but there is little evidence to indicate that any one intervention is more effective. There is evidence of an additive effect for adjunct therapy, and the combination of diet, exercise and behavioural interventions appears to be most effective for both the prevention and treatment of obesity.

An assessment of lifestyle video education for people newly diagnosed with type 2 diabetes.

BACKGROUND: Education plays a key role in the development of self-management skills for people with type 2 diabetes, although there is limited evidence for the use of video education. AIMS: To develop a video-based lifestyle education programme for people newly diagnosed with type 2 diabetes and to evaluate changes in knowledge, biomedical indices and quality of life. METHODS: Forty-two newly diagnosed type 2 diabetic subjects were recruited and randomly allocated to either a video education or control group. Data were collected at baseline and 6 months after the intervention. Subjects (43% male) had a mean (SD) age of 60.8 (9.6) years, weight 89.5 (15.5) kg, BMI 31.3 (5.1) kg m(2), glycated haemoglobin (A1c) 7.4 (1.7)%, total cholesterol 4.7 (1.2) mmol L(-1), high-density lipoprotein cholesterol 1.15 (0.34) mmol L(-1), triglycerides 1.8 (1.0) mmol L(-1), low-density lipoprotein cholesterol 2.8 (1.0) mmol L(-1), pedometer reading 5721 (3446) steps per day. There were 63.7% correct answers given to the ADKnowl questionnaire and the WHO-5 Well-Being score was 65.8%. RESULTS: At 6 months, the intervention group showed increased knowledge compared to controls (74.3% versus 56.4% correct answers, P < or = 0.0001). Although there were no significant differences in changes over 6 months between the two groups, the intervention group showed improvements in A1c (-0.7%, P = 0.024), total cholesterol (-0.5 mmol L(-1), P = 0.017), low-density lipoprotein cholesterol (-0.5, P = 0.018) and increased physical activity measured by pedometer (1266 steps per day, P = 0.043) from baseline, with no significant changes in the control group. CONCLUSIONS: A brief video intervention increased diabetes knowledge amongst those newly diagnosed with type 2 diabetes and may comprise an effective way of directing education to such individuals.

Streptomyces coelicolor Dps-like proteins: differential dual roles in response to stress during vegetative growth and in nucleoid condensation during reproductive cell division.

The Dps protein, a member of the ferritin family, contributes to DNA protection during oxidative stress and plays a central role in nucleoid condensation during stationary phase in unicellular eubacteria. Genome searches revealed the presence of three Dps-like orthologues within the genome of the Gram-positive bacterium Streptomyces coelicolor. Disruption of the S. coelicolor dpsA, dpsB and dpsC genes resulted in irregular condensation of spore nucleoids in a gene-specific manner. These irregularities are correlated with changes to the spacing between sporulation septa. This is the first example of these proteins playing a role in bacterial cell division. Translational fusions provided evidence for both developmental control of DpsA and DpsC expression and their localization to sporogenic compartments of aerial hyphae. In addition, various stress conditions induced expression of the Dps proteins in a stimulus-dependent manner in vegetative hyphae, suggesting stress-induced, protein-specific protective functions in addition to their role during reproductive cell division. Unlike in other bacteria, the S. coelicolor Dps proteins are not induced in response to oxidative stress.

Bone biomarkers and risk of fracture in two- and three-year-old Thoroughbreds.

The aim of this study was to determine whether bone biomarkers (osteocalcin, PICP, ICTP and CTX-I) could be used to identify 2- and 3-year-olds at increased risk of fracture in the subsequent flat racing season. It was concluded that these bone biomarkers cannot be used to identify 2- and 3-year-olds that sustain a fracture. Whether bone biomarkers have better predictive value in older horses or when measured serially in the same animal remains to be determined.

The effects of trastuzumab on the CD4+CD25+FoxP3+ and CD4+IL17A+ T-cell axis in patients with breast cancer.

In addition to the direct targeting effects on HER2-positive cells, trastuzumab may have a therapeutic role modulating the activity of the cellular immune system in patients with breast cancer. To investigate this further, the balance of T-regulatory (T(reg)), Th17, natural killer (NK) and NK T (NKT) cells before, during and after trastuzumab therapy was investigated. Sequential frequencies of circulating T(reg) cells, Th17 cells, NK and NKT cells were measured in peripheral blood of breast cancer patients and normal controls throughout therapy. Individuals with breast cancer had significantly higher T(reg) frequencies of peripheral blood compared with healthy controls (9.2 or 8.6 vs 6%; P<0.05), and no significant differences in T(reg) frequencies were observed between HER2-positive and HER2-negative individuals. The number of Th17 cells was lowest in HER2-positive patients compared with both healthy controls and HER2-negative patients (0.31 vs 0.75% or 0.84%; P=0.01). There appeared to be an inverse relationship between T(reg) and Th17 frequencies in metastatic breast cancer (MBC) with T(reg) levels significantly reduced during treatment with trastuzumab (P=0.04), whereas Th17 frequencies were concomitantly increased (P=0.04). This study supports earlier data that T(reg) cells are present at higher frequencies in breast cancer patients compared with healthy individuals. For the first time, we show that HER2-positive individuals with breast carcinomas have reduced numbers of circulating Th17 cells, which appear, in turn to have an inverse relationship with T(reg) frequency in MBC. The change in balance of the T(reg) : Th17 ratio appears to characterise the cancer state, and furthermore, is disrupted by trastuzumab therapy.

A review of low and reduced carbohydrate diets and weight loss in type 2 diabetes.

BACKGROUND: Recent evidence from randomized controlled trials of hypocaloric low carbohydrate diets in people without diabetes has shown that they promote significant weight loss over the short term. There is very little evidence for any effects of reduced carbohydrate intakes on body weight, glycaemia and cardiovascular risk in people with type 2 diabetes. METHODS: An electronic search was performed using MEDLINE (1966 to March 2007), EMBASE (1988 to March 2007) and Cochrane Central Register of Controlled Trials (1991 to March 2007) using the keywords low carbohydrate, type 2 diabetes and weight loss. Studies including subjects with type 2 diabetes who adopted a reduced carbohydrate weight loss diet were identified. Data were extracted on study design, weight loss, effects on glycaemia and cardiovascular risk and potential adverse effects. RESULTS: Six studies investigating the effects of hypocaloric reduced carbohydrate diets in people with type 2 diabetes were identified. The studies were heterogenous and most included small numbers, were short-term and provided varying amounts of carbohydrate. No studies were identified that were both low carbohydrate (<50 g day(-1)) and also designed as randomized controlled trials. All studies reported reductions in both body weight and glycated haemoglobin, with no deleterious effects on cardiovascular risk, renal function or nutritional intake. CONCLUSIONS: Conclusions are limited by study design and small numbers, but it appears that reduced carbohydrate diets are safe and effective over the short term for people with type 2 diabetes.

Insulin for type 2 diabetes: choosing a second-line insulin regimen.

UNLABELLED: Guidance has been published on the choice of initial insulin regimen for patients with type 2 diabetes [NPH (isophane) insulin or a long-acting insulin analogue] but not on how to choose a second regimen when glycaemic control becomes unsatisfactory. AIMS: To develop pragmatic clinical guidance for choosing a second-line insulin regimen tailored to the individual needs of patients with type 2 diabetes after failure of first-line insulin therapy. METHODS: Formulation of a consensus by expert panel based on published evidence and best clinical practice, taking into account patient preferences, lifestyle and functional capacity. RESULTS: Six patient-dependent factors relevant to the choice of second-line insulin regimen and three alternative insulin regimens (twice-daily premixed, basal-plus and basal-bolus) were identified. The panel recommended one or more insulin regimens compatible with each factor, emphasising the fundamental importance of a healthy lifestyle that includes exercise and weight reduction. These recommendations were incorporated into an algorithm to provide pragmatic guidance for clinicians. CONCLUSION: The three alternative insulin regimens offer different benefits and drawbacks and it is important to make the right choice to optimise outcomes for patients.