Architecture of viral genome-delivery molecular machines.

From the abyss of the ocean to the human gut, bacterial viruses (or bacteriophages) have colonized all ecosystems of the planet earth and evolved in sync with their bacterial hosts. Over 95% of bacteriophages have a tail that varies greatly in length and complexity. The tail complex interrupts the icosahedral capsid symmetry and provides both an entry for viral genome-packaging during replication and an exit for genome-ejection during infection. Here, we review recent progress in deciphering the structure, assembly and conformational dynamics of viral genome-delivery tail machines. We focus on the bacteriophages P22 and T7, two well-studied members of the Podoviridae family that use short, non-contractile tails to infect Gram-negative bacteria. The structure of specialized tail fibers and their putative role in host anchoring, cell-surface penetration and genome-ejection is discussed

Associations between fibrin D-dimer, markers of inflammation, incident self-reported mobility limitation, and all-cause mortality in older men

Objectives<p></p> To examine the independent relationships between fibrin D-dimer, interleukin 6 (IL-6), C-reactive protein (CRP), and fibrinogen and incident mobility limitation and mortality.<p></p> Design<p></p> Prospective.<p></p> Setting<p></p> General practice in 24 British towns.<p></p> Participants<p></p> Men aged 60 to 79 without prevalent heart failure followed up for an average of 11.5 years (N = 3,925).<p></p> Measurements<p></p> All-cause mortality (n = 1,286) and self-reported mobility disability obtained at examination in 1998 to 2000 and in a postal questionnaire 3 to 5 years later in 2003.<p></p> Results<p></p> High D-dimer (top vs lowest tertile: adjusted odds ratio (aOR) = 1.46, 95% confidence interval = 1.02–2.05) and IL-6 (aOR = 1.43, 95% CI = 1.01–2.02) levels (but not CRP or fibrinogen) were associated with greater incident mobility limitation after adjustment for confounders and prevalent disease status. IL-6, CRP, fibrinogen, and D-dimer were significantly associated with total mortality after adjustment for confounders. Only D-dimer and IL-6 predicted total mortality independent of each other and the other biomarkers. The adjusted hazard ratio (aHR) was 1.16 (95% CI = 1.10–1.22) for a standard deviation increase in log D-dimer and 1.10 (95% CI = 1.04–1.18) for a standard deviation increase in log IL-6. D-dimer was independently related to vascular and nonvascular mortality, and IL-6 was independently related to vascular mortality. Risks of mobility limitation and mortality were greatest in those with a combination of high D-dimer and IL-6 levels.<p></p> Conclusion<p></p> D-dimer and IL-6 are associated with risk of mobility limitation and mortality in older men without heart failure. The findings suggest that coagulation leads to functional decline and mortality s that inflammation does not explain

The cut-off point of dual energy X-ray and laser (DXL) of calcaneus osteoporosis diagnosis in postmenopausal women

Background: Dual X-Ray Absorptiometry (DXA) is a method which can extensively be used for bone mineral densitometry (BMD). Another more recent method is DXL, which associate with dual X ray absorptiometry, assisted by laser measure heel thickness. In this study the cut off points for DXL of calcaneus in the diagnosis of osteoporosis in different bone regions in postmenopausal women had been determined. Materials and Methods: In 268 postmenopausal women, BMD of the spinal and femoral regions was measured by DXA, and the value for the calcaneous was measured by DXL. The agreement of the two methods in the diagnosis of osteoporosis and optimal cut-off point for DXL in defining osteoporosis was obtained. What obtained was the agreement of the two methods in the diagnosis of osteoporosis, as well as the optimal cut-off point for DXL in defining osteoporosis. Results: DXA showed osteoporosis in 40.7 of cases with 35.2 in L2-L4, 16.2 in the femoral neck, and 11.7 for the femoral total region. The DXL found osteoporosis, considering -2.5 SD as a threshold, in 26.1 of cases. Agreement of the two methods in the diagnosis of osteoporosis (Kappa score) was 0.443 for the lumbar region, 0.464 for the neck, and, 0.421 for total femur regions (all P values were significant). Using Receiver Operating Characteristic (ROC ) curves, it was found that a T-score of -2.1, -2.6 and -2.4 as the optimal cut-off point of DXL in the diagnosis of osteoporosis in the lumbar spine, the neck and total region of femur, respectively. Conclusion: The results of this study sh owed a moderate agreement between the two methods in the diagnosis of osteoporosis. It seems that the DXL cannot be used as a substitute for the DXA method, but it can be used as a screening method to find (to diagnose) osteoporosis

Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism?

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60–79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores

The Relationships of Dentition, Use of Dental Prothesis and Oral Health Problems with Frailty, Disability and Diet Quality: Results from Population-Based Studies of Older Adults from the UK and USA

Objectives: This study examined the relationships of dental status, use and types of dental prothesis and oral health problems, individually and combined, with diet quality, frailty and disability in two population-based studies of older adults. Design: Cross-sectional study. Setting and Participants: Men form the British Regional Heart Study (BRHS) (aged 85±4 years in 2018; n=1013) and Men and Women from the Health, Aging, and Body Composition (HABC) Study (aged 75±3 years in 1998–99; n=1975). Measurements: Physical and dental examinations and questionnaires were collected with data available for dental status, oral problems related to eating, diet quality, Fried frailty phenotype, disability based on mobility limitations, and activities of daily living (ADL). The associations of dental status and oral health problems, individually and combined, with risk of frailty and disability were quantified. The relationship with diet quality was also assessed. Results: In the BRHS, but not HABC Study, impaired natural dentition without the use of dentures was associated with frailty independently. This relationship was only established in the same group in those with oral problems (OR=3.24; 95% CI: 1.30–8.03). In the HABC Study, functional dentition with oral health problems was associated with greater risk of frailty (OR=2.21; 95% CI: 1.18–4.15). In both studies those who wore a full or partial denture in one or more jaw who reported oral problems were more likely to have disability. There was no association with diet quality in these groups. Conclusion: Older adults with impaired dentition even who use dentures who experience self-report oral problems related to eating may be at increased risk of frailty and disability. Further research is needed to establish whether improving oral problems could potentially reduce the occurrence of frailty and disability

Prospective associations between diet quality, dietary components, and risk of cardiometabolic multimorbidity in older British men

PURPOSE: Cardiometabolic multimorbidity (CMM) is a major public health challenge. This study investigated the prospective relationships between diet quality, dietary components, and risk of CMM in older British men. METHODS: We used data from the British Regional Heart Study of 2873 men aged 60-79 free of myocardial infarction (MI), stroke, and type 2 diabetes (T2D) at baseline. CMM was defined as the coexistence of two or more cardiometabolic diseases, including MI, stroke, and T2D. Sourcing baseline food frequency questionnaire, the Elderly Dietary Index (EDI), which was a diet quality score based on Mediterranean diet and MyPyramid for Older Adults, was generated. Cox proportional hazards regression and multi-state model were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 19.3 years, 891 participants developed first cardiometabolic disease (FCMD), and 109 developed CMM. Cox regression analyses found no significant association between baseline EDI and risk of CMM. However, fish/seafood consumption, a dietary component of the EDI score, was inversely associated with risk of CMM, with HR 0.44 (95% CI 0.26, 0.73) for consuming fish/seafood 1-2 days/week compared to less than 1 day/week after adjustment. Further analyses with multi-state model showed that fish/seafood consumption played a protective role in the transition from FCMD to CMM. CONCLUSIONS: Our study did not find a significant association of baseline EDI with CMM but showed that consuming more fish/seafood per week was associated with a lower risk of transition from FCMD to CMM in older British men

Three-dimensional structure of a viral genome-delivery portal vertex.

DNA viruses such as bacteriophages and herpesviruses deliver their genome into and out of the capsid through large proteinaceous assemblies, known as portal proteins. Here, we report two snapshots of the dodecameric portal protein of bacteriophage P22. The 3.25-Å-resolution structure of the portal-protein core bound to 12 copies of gene product 4 (gp4) reveals a ~1.1-MDa assembly formed by 24 proteins. Unexpectedly, a lower-resolution structure of the full-length portal protein unveils the unique topology of the C-terminal domain, which forms a ~200-Å-long α-helical barrel. This domain inserts deeply into the virion and is highly conserved in the Podoviridae family. We propose that the barrel domain facilitates genome spooling onto the interior surface of the capsid during genome packaging and, in analogy to a rifle barrel, increases the accuracy of genome ejection into the host cell

Influence of neighborhood-level socioeconomic deprivation and individual socioeconomic position on risk of developing type 2 diabetes in older men: a longitudinal analysis in the British Regional Heart Study cohort

INTRODUCTION: Evidence from longitudinal studies on the influence of neighborhood socioeconomic deprivation in older age on the development of type 2 diabetes mellitus (T2DM) is limited. This study investigates the prospective associations of neighborhood-level deprivation and individual socioeconomic position (SEP) with T2DM incidence in older age. RESEARCH DESIGN AND METHODS: The British Regional Heart Study studied 4252 men aged 60-79 years in 1998-2000. Neighborhood-level deprivation was based on the Index of Multiple Deprivation quintiles for participants' 1998-2000 residential postcode. Individual SEP was defined as social class based on longest-held occupation. A cumulative score of individual socioeconomic factors was derived. Incident T2DM cases were ascertained from primary care records; prevalent cases were excluded. Cox proportional hazard models were used to examine the associations. RESULTS: Among 3706 men, 368 incident cases of T2DM were observed over 18 years. The age-adjusted T2DM risk increased from the least deprived quintile to the most deprived: HR per quintile increase 1.14 (95% CI 1.06 to 1.23) (p=0.0005). The age-adjusted T2DM HR in social class V (lowest) versus social class I (highest) was 2.45 (95% CI 1.36 to 4.42) (p=0.001). Both associations attenuated but remained significant on adjustment for other deprivation measures, becoming non-significant on adjustment for body mass index and T2DM family history. T2DM risk increased with cumulative individual adverse socioeconomic factors: HR per point increase 1.14 (95% CI 1.05 to 1.24). CONCLUSIONS: Inequalities in T2DM risk persist in later life, both in relation to neighborhood-level and individual-level socioeconomic factors. Underlying modifiable risk factors continue to need to be addressed in deprived older age populations to reduce disease burden