Conditional deletion of IGF-I in osteocytes unexpectedly accelerates bony union of the fracture gap in mice

This study evaluated the effects of deficient IGF-I expression in osteocytes on fracture healing. Transgenic mice with conditional knockout (cKO) of Igf1 in osteocytes were generated by crossing Dmp1-Cre mice with Igf1 flox mice. Fractures were created on the mid-shaft of tibia of 12-week-old male cKO mice and wild-type (WT) littermates by three-point bending. At 21 and 28 days post-fracture healing, the increases in cortical bone mineral density, mineral content, bone area, and thickness, as well as sub-cortical bone mineral content at the fracture site were each greater in cKO calluses than in WT calluses. There were 85% decrease in the cartilage area and > 2-fold increase in the number of osteoclasts in cKO calluses at 14 days post-fracture, suggesting a more rapid remodeling of endochondral bone. The upregulation of mRNA levels of osteoblast marker genes (cbfa1, alp, Opn, and Ocn) was greater in cKO calluses than in WT calluses. μ-CT analysis suggested an accelerated bony union of the fracture gap in cKO mice. The Sost mRNA level was reduced by 50% and the Bmp2 mRNA level was increased 3-fold in cKO fractures at 14 days post-fracture, but the levels of these two mRNAs in WT fractures were unchanged, suggesting that the accelerated fracture repair may in part act through the Wnt and/or BMP signaling. In conclusion, conditional deletion of Igf1 in osteocytes not only did not impair, but unexpectedly enhanced, bony union of the fracture gap. The accelerated bony union was due in part to upregulation of the Wnt and BMP2 signaling in response to deficient osteocyte-derived IGF-I expression, which in turn favors intramembranous over endochondral bone repair.     

Evaluating the relationship between muscle and bone modeling response in older adults

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD = 1.85 Mpa) than in men (8.02, SD = 1.43 Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R² = 0.187 vs. 0.055 in men; R² = 0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121 Mpa lower (95% CI: − 0.138, − 0.104; p < 0.001) in men and 0.139 Mpa lower (95% CI: − 0.158, − 0.121; p < 0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load.     

The prevalence of dementia in urban and rural areas of China

ObjectiveThe Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.MethodsFor the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures.ResultsThe prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71–5.57), 3.21% (95% CI, 2.87–3.55), and 1.50% (95% CI, 1.26–1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations.ConclusionsA notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban–rural differences.     

Prevalence of nonfatal coronary heart disease among American adults

BACKGROUND: Few national estimates of the prevalence of coronary heart disease in the United States are available. METHODS: By using data from the Third National Health and Nutrition Examination Survey (1988 to 1994), we estimated prevalence of angina pectoris by questionnaire, self-reported myocardial infarction, and electrocardiographically (ECG)-defined myocardial infarction. RESULTS: Among participants aged >/=40 years who attended the medical examination, the age-adjusted prevalence of angina pectoris, self-reported myocardial infarction, and ECG-defined myocardial infarction were 5.8% of 9255, 6.7% of 9250, and 3.0% of 8206 participants, respectively. Among participants aged >/=65 years compared with those aged 40 to 64 years, the prevalence of a self-reported myocardial infarction was more than 3 times higher and that of ECG-defined myocardial infarction more than 4 times higher. The prevalences of self-reported myocardial infarction and ECG-defined myocardial infarction, but not angina pectoris, were higher among men than women. Among women, prevalence of angina pectoris and self-reported myocardial infarction were highest among blacks; among men, these coronary heart diseases were somewhat higher among whites. Prevalence of ECG-defined myocardial infarction were similar for all 3 race or ethnicity groups in either sex. The age-adjusted prevalence of coronary heart disease defined by the presence of any of these conditions was 13.9% among men and 10.1% among women. CONCLUSIONS: Although the management of coronary heart disease has improved during the past 2 decades, it remains an important prevalent disease burden among adults.     

Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence

OBJECTIVES: Assess the relationship between physical activity and risk for falls and osteoporotic fractures among older adults. DESIGN: Review and synthesis of published literature. MEASUREMENTS: We searched the literature using MEDLINE, Current Contents, and the bibliographies of articles identified. We included randomized controlled trials (RCT) of the effects of physical activity on the incidence of falls and case-control and prospective cohort studies of the association of physical activity with osteoporotic fracture risk. We also summarized mechanisms whereby physical activity may influence risk for falls and fractures. RESULTS: Observational epidemiologic studies and randomized clinical trials evaluating the effectiveness of physical activity programs to prevent falls have been inconclusive. However, many studies have lacked adequate statistical power, and recent trials suggest that exercise, particularly involving balance and lower extremity strength training, may reduce risk of falling. There is consistent evidence from prospective and case-control studies that physical activity is associated with a 20-40% reduced risk of hip fracture relative to sedentary individuals. The few studies that have examined the association between physical activity and risk of other common osteoporotic fractures, such as vertebral and wrist fractures, have not found physical activity to be protective. CONCLUSIONS: Epidemiologic studies suggest that higher levels of leisure time physical activity prevent hip fractures and RCTs suggest certain exercise programs may reduce risk of falls. Future research needs to evaluate the types and quantity of physical activity needed for optimal protection from falls and identify which populations will benefit most from exercise.     

Determination of fluoroquinolones in chicken feces – A new liquid–liquid extraction method combined with LC–MS/MS

The application of antibiotics including fluoroquinolones to farming animals is widespread and may lead to the development of antibiotic resistance and other environmental effects. To calculate environmental loads and for a proper risk assessment it is necessary to determine the antibiotic concentration in feces. Therefore, a new liquid–liquid extraction method combined with HPLC–MS/MS for the detection of marbofloxacin, ciprofloxacin, enrofloxacin and difloxacin in chicken feces was developed. Recoveries ranged from 51.0% to 83.5%. LOQs were between 0.10 and 1.09 μg/kg. Feces of chickens treated with an enrofloxacin dosage of 10 mg/kg bodyweight revealed maximum enrofloxacin and ciprofloxacin concentrations of 61.3 and 18.8 mg/kg. Both antibiotics could be detected in feces up to two days after the last application in notable amounts (∼1 mg/kg). Thus, feces of recently medicated chickens should not be used as a fertilizer without any further processing.     

Hepatitis C virus infection in children: How do we prevent it and how do we treat it?

Introduction: Hepatitis C virus (HCV) infection is an important contributor to the worldwide burden of liver-related morbidity and mortality. Mother-to-child transmission of HCV ranges from 6 to 11% in different populations globally, but accurate estimates on the burden of pediatric HCV infection are limited because screening approaches are not consistent.

Areas covered: The advent of new direct-acting antiviral agents that achieve very high rates of sustained virologic response (representing virologic cure) with short (i.e. 8–12 weeks) regimens has revolutionized the field of HCV treatment and led to the development of global elimination goals for HCV transmission and mortality. However, information on their safety during pregnancy and efficacy in preventing mother-to-child transmission is lacking. Currently, there are no approved treatment regimens with these antiviral agents for children younger than 12 years of age.

Expert commentary: If these agents are shown to be safe during pregnancy and effective in preventing transmission to the infant, screening of pregnant women and antenatal treatment of those infected, could pave the way for eliminating pediatric HCV infection- particularly as these drugs become less costly and more accessible. Treatment of infected children when indicated, along with universal safe health care practices, can further pediatric HCV elimination.     

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BackgroundIn 2013–2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients).MethodsSwab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated.ResultsOut of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1–55.3%) against any influenza, and 56.7% (95% CI: 22.8–75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift.ConclusionsThese results suggest a moderate protective effect of the 2013–2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.