Higher Dietary Vitamin K Intake is Associated with Better Physical Function and Lower Long-Term Injurious Falls Risk in Community-Dwelling Older Women.

BACKGROUND: In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown. OBJECTIVE: To examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women. DESIGN: Cohort study. PARTICIPANTS: 1347 community-dwelling older Australian women ≥70 years. MEASUREMENTS: A new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data. RESULTS: Over 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52-0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59-0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ~70-100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls. CONCLUSION: A higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted.

The role and impact of community health workers in childhood obesity interventions: a systematic review and meta-analysis.

Childhood obesity increases the risk for poor health during childhood, as well as for adult obesity and its associated comorbidities. Children from racial/ethnic minority groups or who live in poverty experience elevated rates of obesity. One potential method for reducing childhood obesity disparities is to involve community health workers (frontline public health workers who are trusted members of and/or have an unusually close understanding of the community served). The purpose of this systematic review and meta-analysis was to explore the role and effectiveness of community health workers in childhood obesity interventions. Eleven studies met inclusion criteria, of which nine were eligible for inclusion in the meta-analysis. Results demonstrated that community health workers played various roles in childhood obesity interventions in the home, clinic, school, and community setting. Interventions focused primarily on children from underserved populations. Meta-analytic findings demonstrated a small but significant impact on BMIz and BMI percentile (BMIz [7 studies]: -0.08, 95% CI: -0.15, -0.01, p = 0.03, I2  = 39.4%; BMI percentile [2 studies]: -0.25, 95% CI: -0.38, -0.11, p < 0.01, I2  = 0%). Findings from this review demonstrate that partnering with community health workers may be an important strategy for reducing childhood obesity disparities and advancing health equity.

Prevalence and treatment of necrotizing ulcerative gingivitis (NUG) in the British Armed Forces: a case-control study.

OBJECTIVES: Necrotizing ulcerative gingivitis (NUG) has been seen in military populations throughout history. This study aims to determine the prevalence, treatment modality and risk factors associated with NUG in the British Armed Forces. MATERIALS AND METHODS: A whole population dataset of the British Armed Forces was searched to determine cases of NUG during the period 1 January to 31 December 2012. Individual case records were identified, and a case-control study undertaken with data gathered and analysed against a randomised control group, matched for age, sex and service. RESULTS: A prevalence rate for NUG of 0.11 % was determined against the whole military population. The majority of cases received (alone or in combination) the following: oral hygiene instruction (66.5 %), antibiotics (64.4 %) and a mouthwash (58.1 %). Of the cases, 48.7 % received debridement. Analgesics were only prescribed in 8.4 % of the cases, and smoking cessation advice was only given in 10.7 % of the cases. Analysis of risk factors against the control group showed an increase in odds ratios for diagnosis of NUG of 3.4 (95 % CI 2.0-5.7) for current smokers and 7.3 (95 % CI 1.9-28.0) for individuals with an overall Basic Periodontal Examination (BPE) score of 3. CONCLUSIONS: Whilst NUG is a rare disease, it is evident from this study that it still occurs within the British Armed Forces. A strong association was shown between NUG and current smokers and those cases with an overall BPE score of 3. CLINICAL RELEVANCE: This study provides prevalence data for NUG in the British Armed Forces and description of its treatment and associated risk factors. Oral hygiene and smoking must be addressed in patients with NUG and prescribing protocols should be carefully followed.

Ecological analyses of the associations between injury risk and socioeconomic status, geography and Aboriginal ethnicity in British Columbia, Canada.

BACKGROUND: The current study examines what factors contribute to higher injury risk among Aboriginal peoples, compared to the total British Columbia (BC) population. We explore socioeconomic, geographic, and cultural factors, and combinations of these factors, that contribute to increased injury risk for Aboriginal peoples. This follows from our previously reported findings of improvements in injury risk over time for both the total and Aboriginal populations. DATA AND METHODS: We use provincial population-based linked health care databases of hospital discharge records. We identify three population groups: total BC population, and Aboriginal populations living off-reserve, or on-reserve. For each group we calculate age and gender-standardized relative risks (SRR) of injury-related hospitalization, relative to the total population of BC, for two 5-year time periods (1999-2003, and 2004-2008). We use custom data from the 2001 and 2006 long-form Censuses that described income, education, employment, housing conditions, proportion of urban dwellers, proportion of rural dwellers, and prevalence of Aboriginal ethnicity. We use multivariable linear regression to examine the associations between the census characteristics and SRR of injury. RESULTS: The best-fitting model was an excellent fit (R(2) = 0.905, p < 0.001) among the three population groups within Health Service Delivery Areas of BC. We find indicators in all three categories (socioeconomic, geographic, and cultural) are associated with disparity in injury risk. While the socioeconomic indicators (income, education, housing, employment) were shown to be highly correlated, only living in housing that needs major repair and occupational hazardousness, along with rural residence and Aboriginal ethnicity, remained in the final model. Our data show that cultural density is not associated with injury risk for Aboriginal peoples, and that living off-reserve is associated with reduced injury by improving socioeconomic and geographic conditions (compared to living on-reserve). Finally, our analyses show that Aboriginal status itself is associated with injury risk. CONCLUSIONS: Our findings confirm previous research indicating that geographical differences differentiate injury risk, including for Aboriginal populations, and that socioeconomic determinants are associated with health risks. Our analyses showing that Aboriginal status itself contributes to injury risk is new, but we can only speculate about pathway, and whether the causes are direct or indirect.

PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer.

Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell's responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention.

Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis.

BACKGROUND: Hepatic osteodystrophy (HO) is a major complication of cirrhosis. However, the prevalence of HO in a general cirrhotic patient population is not well defined as previous studies were in single aetiology or pre-liver transplant patients. AIMS: The aims of this study were to investigate the prevalence of HO and vitamin D deficiency in patients with cirrhosis of mixed aetiology and disease severity and to determine the risk factors for HO. METHODS: This is a single-centre cross-sectional study of all patients newly diagnosed with cirrhosis between September 2009 and December 2012. All patients underwent bone mineral density assessment using dual energy X-ray absorptiometry within 3 months of diagnosis. Demographic and biochemical factors, severity of underlying liver disease, previous fragility fractures, smoking status and alcohol use were collected on diagnosis. Logistic regression analysis was used to assess risk factors for HO. RESULTS: Among the 406 patients (67% males), the median (range) age was 56 years (21-85) and most (84%) were Childs-Pugh A or B with a median (range) model for end-stage liver disease score of 11 (5-40). Alcohol (41%) was the most common underlying aetiology. The prevalence of HO and vitamin D deficiency (≤50 nmol/L) was 56% and 54%, respectively, and previous fragility fractures had occurred in 3%. Increasing age (odds ratio (95% confidence interval): 1.49 per 10 years (1.02-2.18), P = 0.04), excessive alcohol intake (2.34 (1.03-5.32), P = 0.04) and lower body mass index (0.92 per kg/m2 (0.87-0.98), P = 0.009) were independent risk factors for HO. CONCLUSION: There is a high prevalence of HO and vitamin D deficiency in patients with cirrhosis at presentation irrespective of disease severity or underlying aetiology.

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis.

BACKGROUND: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. METHODS: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. RESULTS: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1α and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. CONCLUSIONS: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR-145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines.

The importance of, and the benefits derived from, forward dental peripatetic clinics in Afghanistan.

The majority of dental care for military personnel is carried out in clinics that would be familiar to all dental professionals. In times of conflict, however, dental care is often required to travel to those in need. Dental morbidity has a detrimental effect on a fighting force, both at the personal level and for maintaining combat efficiency. In Afghanistan, two main dental centres provided the majority of emergency care to coalition forces, but from March to September 2012, 23 peripatetic clinics also took place with 472 dental casualties treated. Assessment of these peripatetic clinics demonstrates both quantitative and qualitative benefits. Return travel to main base clinics takes between three to five days. If all personnel during this period had attended a main base and returned to their duty station in only three days, over 1,000 duty days would have been lost. This compares to the 32 days actually lost by attending peripatetic clinics instead and illustrates the considerable time that was saved. Additionally, time spent travelling in a hostile environment is also time at risk of attack. Forty-one anonymous comments about the clinics were left by personnel. All were positive and enthusiastic. The results of this review demonstrate that these clinics save considerable mission time, reduce risk to military personnel, and were greatly valued by those suffering dental problems.

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. METHODS: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in two-dimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. RESULTS: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1α-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. CONCLUSION: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress.

Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasound is a standard of care for higher-risk patients with viral hepatitis. Adherence to screening guidelines is an important quality indicator in hepatology, but multiple studies have demonstrated poor HCC surveillance practices in real-world settings. AIMS: The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients, who fulfilled criteria for screening, associated with a large tertiary hospital. METHODS: Clinical practice improvement principles were utilised. A baseline audit of 22 consecutive viral hepatitis patients was performed. Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced. These included: improved doctor education, system redesign and improved patient education. The effects of interventions were measured by serial random audits of patients. A final audit occurred over 3 years after the initial baseline audit. RESULTS: At baseline, 46% and 0% of patients had appropriate surveillance performed during the prior 6 months (one surveillance cycle) and 2 years (four surveillance cycles) respectively. Three years after initiation of these strategies, a final audit revealed 92% (vs 46% at baseline) and 64% (vs 0% at baseline) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively (P < 0.001 in each case). CONCLUSIONS: Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world settings. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change.

miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.

BACKGROUND: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. METHODS: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. RESULTS: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. CONCLUSION: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.

Integrated surveillance and potential sources of Salmonella enteritidis in human cases in Canada from 2003 to 2009.

Salmonella enteritidis has emerged as the most prevalent cause of human salmonellosis in Canada. Recent trends of S. enteritidis subtypes and their potential sources were described by integrating Salmonella data from several Canadian surveillance and monitoring programmes. A threefold increase in S. enteritidis cases from 2003 to 2009 was identified to be primarily associated with phage types 13, 8 and 13a. Other common phage types (4, 1, 6a) showed winter seasonality and were more likely to be associated with cases linked to international travel. Conversely, phage types 13, 8 and 13a had summer seasonal peaks and were associated with cases of domestically acquired infections. During agri-food surveillance, S. enteritidis was detected in various commodities, most frequently in chicken (with PT13, PT8 and PT13a predominating). Antimicrobial resistance was low in human and non-human isolates. Continued integrated surveillance and collaborative prevention and control efforts are required to mitigate future illness.

Is there a differential in the dental health of new recruits to the British Armed Forces? A pilot study.

BACKGROUND AND AIM: Figures from the British Defence Dental Services reveal that serving personnel in the British Army have a persistently lower level of dental fitness than those in the Royal Navy or the Royal Air Force. No research had been undertaken to ascertain if this reflects the oral health of recruits joining each Service. This study aimed to pilot a process for collecting dental and sociodemographic data from new recruits to each Service and examine the null hypothesis that no differences in dental health existed. METHOD: Diagnostic criteria were developed, a sample size calculated and data collected at the initial training establishments of each Service. RESULTS: Data for 432 participants were entered into the analysis. Recruits in the Army sample had a significantly greater prevalence of dental decay and greater treatment resource need than either of the other two Services. Army recruits had a mean number of 2.59 (2.08, 3.09) decayed teeth per recruit, compared to 1.93 (1.49, 2.39 p <0.01) in Royal Navy recruits and 1.26 (0.98, 1.53 p <0.001) in Royal Air Force recruits. Among Army recruits 62.7% were from the two most deprived quintiles of the Index of Multiple Deprivation compared to 42.5% of Royal Naval recruits and 36.6% of Royal Air Force recruits. CONCLUSION: A significant difference in dental health between recruits to each Service does exist and is a likely to be a reflection of the sociodemographic background from which they are drawn.

Proapoptotic signaling activity of the anti-CD40 monoclonal antibody dacetuzumab circumvents multiple oncogenic transformation events and chemosensitizes NHL cells.

Non-Hodgkin lymphoma (NHL) is a genetically heterogeneous disease with several oncogenic events implicated in the transformation of normal developing B lymphocytes. The objective of this study was to elucidate the signal transduction-based antitumor mechanism(s) of action for the anti-CD40 monoclonal antibody dacetuzumab (SGN-40) in NHL. We report that dacetuzumab activates two distinct proapoptotic signaling pathways, overcoming transformation events key to the pathogenesis of NHL. Dacetuzumab-mediated CD40 signaling constitutively activated the nuclear factor-κB and mitogen-activated protein kinase signaling pathways producing the sustained downregulation of B-cell lymphoma 6 (BCL-6), an oncoprotein implicated in lymphomagenesis. Loss of BCL-6 resulted in c-Myc downregulation and activation of a transcriptional program characteristic of early B-cell maturation, concomitant with reduced proliferation and cell death. In a second mechanism, dacetuzumab signaling induced the expression of the proapoptotic p53 family member TAp63α and downstream proteins associated with the intrinsic and extrinsic apoptotic machinery. Dacetuzumab was synergistic in combination with DNA-damaging chemotherapeutic drugs, correlating with TAp63α upregulation. Furthermore, dacetuzumab augmented the activity of rituximab in combination with multiple chemotherapies in the xenograft models of NHL. The ability of dacetuzumab signaling to circumvent oncogenic events and potentiate the activity of chemotherapy regimens provides a unique therapeutic approach to NHL.

Fetal muscle development, mesenchymal multipotent cell differentiation, and associated signaling pathways.

Enhancing muscle growth while reducing fat accumulation improves the efficiency of animal production. The fetal stage is crucial for skeletal muscle development. Fetal muscle development involves myogenesis, adipogenesis, and fibrogenesis from mesenchymal multipotent cells (MC), which are negatively affected by maternal nutrient deficiencies. Enhancing myogenesis increases the lean-to-fat ratio of animals, enhancing intramuscular adipogenesis increases intramuscular fat that is indispensible for the superior eating properties of meat because fat is the major contributor to meat flavor. The promotion of fibrogenesis leads to the accumulation of connective tissue, which contributes to the background toughness of meat and is undesirable. Thus, it is essential to regulate MC differentiation to enhance lean growth and improve meat quality. To date, our understanding of mechanisms regulating the lineage commitment of MC is limited. In this review, we first discuss the impact of maternal nutrient deficiency on fetal development, offspring body composition, and meat quality. Because maternal nutrition affects fetal muscle through altering MC differentiation, we then review several important extracellular morphogens regulating MC differentiation, including hedgehog, Wingless and Int (Wnt), and bone morphogenic proteins. Possible involvement of epigenetic modifications associated with histone deacetylases class IIa and histone acetyltransferase, p300, in MC differentiation is also discussed.

Third molar-related morbidity in deployed Service personnel.

INTRODUCTION: The minimisation of disease and non-battle injury (DNBI) is essential for maintaining efficiency in a fighting force. Third molar-related morbidity is a common cause of DNBI. With extended lines of communication in current military deployments, travelling for dental care is often subject to significant danger. MATERIAL AND METHODS: Military dental officers in Afghanistan and Iraq recorded data on patients presenting with third molar pathology. Related previous history was obtained from the individual and from the military dental records. RESULTS: Three hundred and three individuals presented during the 23 month study period; 27.7% were unable to access care immediately, most commonly citing work pressure or lack of safe transport. Of those needing to travel, 70% were moved by helicopter. Pericoronitis was diagnosed in 84.4% of cases, 20.6% of these teeth being extracted; 53.5% of patients reported no prior symptoms, 22.7% with two or more episodes. There was documented evidence in military dental records of previous problems in 29.2% of cases. 11.3% had previously been listed for extraction of the presenting tooth. DISCUSSION: Dental treatment for troops in combat situations is fraught with difficulty. Special consideration must be given to the management of third molars in military personnel.

Mouse AMP-activated protein kinase gamma3 subunit R225Q mutation affecting mouse growth performance when fed a high-energy diet.

The Rendement Napole (RN) genotype widely exists in Hampshire pigs. Recently, RN gene was identified as a R200Q mutation in AMP-activated protein kinase (AMPK) gamma3 subunit. The effect of RN genotype on the growth performance of animals and the underlying mechanisms remain controversial. Using transgenic mice carrying an analogous R225Q mutation, the objective of this study was to study the role of RN gene in the growth performance of animals at different energy levels. Wild-type (WT) mice and those with the RN mutation were assigned to 4 groups: 1) WT plus normal diet, 2) RN plus normal diet, 3) WT plus high-energy diet, and 4) RN plus high-energy diet. Mice were weaned at 21 d old and fed the trial diets for 1 mo and then killed for carcass measurements. The pH of postmortem muscle from RN mice was less (P < 0.01) than that from WT mice. No difference in growth performance was observed when mice were fed a normal diet. When fed a high-energy diet, RN mice showed a greater fat accumulation (WT vs. RN, 1.11 vs. 1.63 g for gonadal fat and 1.40 vs. 1.84 g for subcutaneous fat; P < 0.05). Muscle weight was also increased (WT vs. RN, 0.27 vs. 0.30 g for gastrocnemius muscle; P < 0.05). The food consumption was greater in RN compared with WT mice (2.95 vs. 2.49 g; P < 0.05). The AMPK content and its downstream target, acetyl-CoA carboxylase (ACC), content were greater in RN mice (P < 0.05). The phosphorylation of ACC at Ser 79, a site exclusively phosphorylated by AMPK, was increased (P < 0.05), showing greater AMPK activity in RN mouse muscle. No difference in muscle fiber composition and mitochondrial content was observed between WT and RN mice. High fat diet downregulates protein kinase B but upregulates extracellular signal-regulated kinase signaling. In conclusion, the R225Q mutation has no major effect on the growth performance of animals fed a normal diet; a high-energy diet increased fatness in RN mice, likely due to their greater consumption of feed compared with WT mice.

The distribution of general dental practitioners with NHS contract numbers in relation to the distance of their practices from the seven dental undergraduate teaching hospitals in England outside London.

OBJECTIVE: To examine whether the presence of a dental school acts as an influence on the number of dentists practicing in the surrounding area. RESEARCH DESIGN: The project used Geographical Information Systems (GIS) mapping techniques, along with data on the location of NHS dentists, to plot dentist to population rates at selected distances from dental undergraduate teaching hospitals in England. A GIS map of dentist to population rates was then constructed for each of the dental schools and the rate patterns examined and compared. RESULTS: With the exception of Liverpool, the maps demonstrated higher than average rates up to two miles, and up to five miles for Manchester, from the location of the dental school before falling and then varying around the England and Wales average. No clear pattern emerged between dental schools, and no two schools produced a similar 'footprint'. CONCLUSIONS: Within the constraints of the current study, it appears that for graduates from the seven dental undergraduate teaching hospitals in England outside London, who work as general dental practitioners with NHS contracts, factors other than the distance of a practice from their place of training appear to have a greater influence on their choice of geographical location where they work, than its distance from a dental hospital.

Osteoporosis: integrating biomarkers and other diagnostic correlates into the management of bone fragility.

Bone health, characterized by its mass, density, and micro-architectural qualities, is maintained by a balanced system of remodeling. The lack of these qualities, caused by an uncoupling of the remodeling process, leads to bone fragility and an increased risk for fracture. The prime regulator of bone remodeling is the RANK/RANKL/OPG system. The common origin of both bone and immune stem cells is the key to understanding this system and its relationship to the transcription factor nuclear factor kappaB in bone loss and inflammation. Via this coupled osteo-immune relationship, a catabolic environment from heightened proinflammatory cytokine expression and/or a chronic antigen-induced activation of the immune system can initiate a switch-like diversion of osteoprogenitor-cell differentiation away from monocyte-macrophage and osteoblast cell formation and toward osteoclast and adipocyte formation. This disruption in bone homeostasis leads to increased fragility. Dietary and specific nutrient interventions can reduce inflammation and limit this diversion. Common laboratory biomarkers can be used to assess changes in body metabolism that affect bone health. This literature review offers practical information for applying effective strategic nutrition to fracture-risk individuals while monitoring metabolic change through serial testing of biomarkers. As examples, the clinician may recommend vitamin K and potassium to reduce hypercalciuria, _-lipoic acid and N-acetylcysteine to reduce the bone resorption marker N-telopeptide (N-Tx), and dehydroepiandrosterone (DHEA), whey, and milk basic protein (the basic protein fraction of whey) to increase insulin-like growth factor-1 (IGF-1) and create a more anabolic profile.