Physical and psychosocial risk factors for musculoskeletal disorders in Brazilian and Italian nurses

As part of the international CUPID investigation, we compared physical and psychosocial risk factors for musculoskeletal disorders among nurses in Brazil and Italy. Using questionnaires, we collected information on musculoskeletal disorders and potential risk factors from 751 nurses employed in public hospitals. By fitting country-specific multiple logistic regression models, we investigated the association of stressful physical activities and psychosocial characteristics with site-specific and multisite pain, and associated sickness absence. We found no clear relationship between low back pain and occupational lifting, but neck and shoulder pain were more common among nurses who reported prolonged work with the arms in an elevated position. After adjustment for potential confounding variables, pain in the low back, neck and shoulder, multisite pain, and sickness absence were all associated with somatizing tendency in both countries. Our findings support a role of somatizing tendency in predisposition to musculoskeletal disorders, acting as an important mediator of the individual response to triggering exposures, such as work-load.

Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection

Interleukin-18 (IL-18) and interferon-gamma (IFN-?) exert important functions in both innate and adaptive immune responses against intracellular pathogens and viruses. Previous studies suggested that host genetic factors, including cytokines gene polymorphisms, could be involved in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18 promoter and +874T/A of the IFN-? in DNA samples from 98 HTLV-1-infected individuals exhibiting or not clinical symptoms and 150 healthy control individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1 asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than healthy control group. In contrast, the -607AC genotype was significantly higher in HAC and HTLV-1-infected individuals group compared to the healthy control group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy control group, and the -137C/-607C IL-18 haplotype was increased in the healthy control group compared to the others. Finally, the IFN-? polymorphism analysis showed that the HTLV-1-infected individuals with +874AT genotype presented higher proviral load than +874AA genotype. These data indicate that the IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1 infection, whereas the protective effect could be conferred by -607CC genotype and -137C/-607C haplotype. Also, the IFN-? could be implicated on the proviral load levels.

Evaluation of Viral Load Thresholds for Predicting New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

Background: This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). Methods: Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART >= 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. Results: Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. Conclusions: In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.

Psychobiological correlates of allostatic load

Introduction: The term Clinimetric was introduced by Feinstein in 1982, who first noticed that despite all the improvements in the assessment methods, a number of clinical phenomena were still unconsidered during the evaluation process. Yet today clinical phenomena, such as stress, relevant in diseases progression and course, are not completely evaluated. Only recently, according to the clinimetric approach, Fava and colleagues have introduced specific criteria for evaluating the allostatic overload in clinical setting. Methods: Participants were 240 blood donors recruited from May 2007 to December 2009 in 4 different blood Centers (AVIS) in Italy. Blood samples from each participant were collected for laboratory test the same day the self-rating instruments were administered (Psychosocial Index, Symptom Questionnaire, Psychological well-being scales, Temperament and Character inventory, Self-Report Altruism scale). The study explore different aspects describing sample characteristics and correlates of stress in the total sample (part I), new selection criteria applied to existing instruments to identify individuals reporting allostatic load (part II), and differences on biological correlates between subjects with vs without AL. Results: Significant differences according to gender and past illnesses have been found in different dimensions of well-being and distress. Further, distress was explained for more than 60% by 4 main factors such as anxiety, somatic symptoms, environmental mastery and persistence. According to the new criteria, 98 donors reported AL. Allostatic load individuals reported to engage in less altruistic behaviours. Also they differ in personality traits and characters from controls. In the last part, results showed significant differences among donors according to allostatic load on diverse biological parameters (RBC, MCV, immune essay). Conclusion: This study presents obvious limitations due to its preliminary nature. Further research are need to confirm that these new criteria may lead to identify high risk individuals reporting not only stressful situations but also vulnerabilities.

Effects of Alzheimer caregiving on allostatic load

This study aimed to determine if Alzheimer caregivers have increased allostatic load compared to non-caregivers. Potential psychological moderators (mastery, depression, and role overload) of the relationship between caregiving status and allostatic load were also explored. Eighty-seven caregivers and 43 non-caregivers underwent biological assessment of allostatic load and psychological assessments. Caregivers had significantly higher allostatic load compared to non-caregivers ( p < .05). Mastery, but not depression or overload, moderated the relationship between caregiving status and allostatic load. In conclusion, allostatic load may represent a link explaining how stress translates to downstream pathology, but more work is necessary to understand the role of psychological factors.

Neurological outcome, working capacity and prognostic factors of patients with SCIWORA

STUDY DESIGN: Retrospective case review. OBJECTIVES: In the present study, the neurological outcome, retirement and prognostic factors of patients with spinal cord injury without radiographic abnormality (SCIWORA) were evaluated. SETTING: Swiss national work accident insurance database. METHODS: The medical histories of 32 patients who were insured by the Swiss Accident Insurance Fund (SUVA) and had SCIWORA between 1995 and 2004 were evaluated thoroughly. Moreover, all available magnetic resonance imaging (MRI) scans were evaluated. RESULTS: At the last follow-up, none of the patients had complete spinal cord injury, only 4 patients had severe deficits and 12 patients had normal motor and sensory function in the neurological examination. However, only 7 out of 32 patients had returned to full-time work and 10 out of 32 patients were fully retired. Both the presence of spinal cord change (ρ=0.51) and higher maximum spinal cord compression (ρ=0.57) in MRI scan correlated with the likelihood for retirement; older age (ρ=0.38) and physical load of work (ρ=0.4) correlated with retirement to a lesser extent. CONCLUSION: Although the neurological outcome of SCIWORA is mostly good, the retirement rate is high. Presence of spinal cord change and severity of cord compression are the best predictors for the degree of retirement.

Increasing Utilization of US Electric Grids via Smart Technologies: Integration of Load Management, Real Time Pricing, Renewables, EVs and Smart Grid Sensors

Electric power grids throughout the world suffer from serious inefficiencies associated with under-utilization due to demand patterns, engineering design and load following approaches in use today. These grids consume much of the world’s energy and represent a large carbon footprint. From material utilization perspectives significant hardware is manufactured and installed for this infrastructure often to be used at less than 20-40% of its operational capacity for most of its lifetime. These inefficiencies lead engineers to require additional grid support and conventional generation capacity additions when renewable technologies (such as solar and wind) and electric vehicles are to be added to the utility demand/supply mix. Using actual data from the PJM [PJM 2009] the work shows that consumer load management, real time price signals, sensors and intelligent demand/supply control offer a compelling path forward to increase the efficient utilization and carbon footprint reduction of the world’s grids. Underutilization factors from many distribution companies indicate that distribution feeders are often operated at only 70-80% of their peak capacity for a few hours per year, and on average are loaded to less than 30-40% of their capability. By creating strong societal connections between consumers and energy providers technology can radically change this situation. Intelligent deployment of smart sensors, smart electric vehicles, consumer-based load management technology very high saturations of intermittent renewable energy supplies can be effectively controlled and dispatched to increase the levels of utilization of existing utility distribution, substation, transmission, and generation equipment. The strengthening of these technology, society and consumer relationships requires rapid dissemination of knowledge (real time prices, costs & benefit sharing, demand response requirements) in order to incentivize behaviors that can increase the effective use of technological equipment that represents one of the largest capital assets modern society has created.

Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

Correlation of Pullout Force of Kirschner (K-) Wire to Other Factors Indicative of Bone Quality

More than 250,000 hip fractures occur annually in the United States and the most common fracture location is the femoral neck, the weakest region of the femur. Hip fixation surgery is conducted to repair hip fractures by using a Kirschner (K-) wire as a temporary guide for permanent bone screws. Variation has been observed in the force required to extract the K-wire from the femoral head during surgery. It is hypothesized that a relationship exists between the K-wire pullout force and the bone quality at the site of extraction. Currently, bone mineral density (BMD) is used as a predictor for bone quality and strength. However, BMD characterizes the entire skeletal system and does not account for localized bone quality and factors such as lifestyle, nutrition, and drug use. A patient’s BMD may not accurately describe the quality of bone at the site of fracture. This study aims to investigate a correlation between the force required to extract a K-wire from femoral head specimens and the quality of bone. A procedure to measure K-wire pullout force was developed and tested with pig femoral head specimens. The procedure was implemented on 8 human osteoarthritic femoral head specimens and the average pullout force for each ranged from 563.32 ± 240.38 N to 1041.01 ± 346.84 N. The data exhibited significant variation within and between each specimen and no statistically significant relationships were determined between pullout force and patient age, weight, height, BMI, inorganic to organic matter ratio, and BMD. A new testing fixture was designed and manufactured to merge the clinical and research environments by enabling the physician to extract the K-wire from each bone specimen himself. The new device allows the physician to gather tactile feedback on the relative ease of extraction while load history is recorded similar to the previous procedure for data acquisition. Future work will include testing human bones with the new device to further investigate correlations for predicting bone quality.

Effective Length K-Factors For Flexural Buckling Strengths Of Web Members In Open Web Steel Joists

Open web steel joists are designed in the United States following the governing specification published by the Steel Joist Institute. For compression members in joists, this specification employs an effective length factor, or K-factor, in confirming their adequacy. In most cases, these K-factors have been conservatively assumed equal to 1.0 for compression web members, regardless of the fact that intuition and limited experimental work indicate that smaller values could be justified. Given that smaller K-factors could result in more economical designs without a loss in safety, the research presented in this thesis aims to suggest procedures for obtaining more rational values. Three different methods for computing in-plane and out-of-plane K-factors are investigated, including (1) a hand calculation method based on the use of alignment charts, (2) computational critical load (eigenvalue) analyses using uniformly distributed loads, and (3) computational analyses using a compressive strain approach. The latter method is novel and allows for computing the individual buckling load of a specific member within a system, such as a joist. Four different joist configurations are investigated, including an 18K3, 28K10, and two variations of a 32LH06. Based on these methods and the very limited number of joists studied, it appears promising that in-plane and out-of-plane K-factors of 0.75 and 0.85, respectively, could be used in computing the flexural buckling strength of web members in routine steel joist design. Recommendations for future work, which include systematically investigating a wider range of joist configurations and connection restraint, are provided.

CD4+ T-cell count increase in HIV-1-infected patients with suppressed viral load within 1 year after start of antiretroviral therapy

BACKGROUND: CD4+ T-cell recovery in patients with continuous suppression of plasma HIV-1 viral load (VL) is highly variable. This study aimed to identify predictive factors for long-term CD4+ T-cell increase in treatment-naive patients starting combination antiretroviral therapy (cART). METHODS: Treatment-naive patients in the Swiss HIV Cohort Study reaching two VL measurements <50 copies/ml >3 months apart during the 1st year of cART were included (n=1816 patients). We studied CD4+ T-cell dynamics until the end of suppression or up to 5 years, subdivided into three periods: 1st year, years 2-3 and years 4-5 of suppression. Multiple median regression adjusted for repeated CD4+ T-cell measurements was used to study the dependence of CD4+ T-cell slopes on clinical covariates and drug classes. RESULTS: Median CD4+ T-cell increases following VL suppression were 87, 52 and 19 cells/microl per year in the three periods. In the multiple regression model, median CD4+ T-cell increases over all three periods were significantly higher for female gender, lower age, higher VL at cART start, CD4+ T-cell <650 cells/microl at start of the period and low CD4+ T-cell increase in the previous period. Patients on tenofovir showed significantly lower CD4+ T-cell increases compared with stavudine. CONCLUSIONS: In our observational study, long-term CD4+ T-cell increase in drug-naive patients with suppressed VL was higher in regimens without tenofovir. The clinical relevance of these findings must be confirmed in, ideally, clinical trials or large, collaborative cohort projects but could influence treatment of older patients and those starting cART at low CD4+ T-cell levels.

How reliable is an undetectable viral load?

OBJECTIVES: An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? METHODS: We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. RESULTS: With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. CONCLUSIONS: After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability.

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy

BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). CONCLUSION: Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

DXA predictions of human femoral mechanical properties depend on the load configuration

The aim of this study was to evaluate the ability of dual energy X-rays absorptiometry (DXA) areal bone mineral density (aBMD) measured in different regions of the proximal part of the human femur for predicting the mechanical properties of matched proximal femora tested in two different loading configurations. 36 pairs of fresh frozen femora were DXA scanned and tested until failure in two loading configurations: a fall on the side or a one-legged standing. The ability of the DXA output from four different regions of the proximal femur in predicting the femoral mechanical properties was measured and compared for the two loading scenarios. The femoral neck DXA BMD was best correlated to the femoral ultimate force for both configurations and predicted significantly better femoral failure load (R2=0.80 vs. R2=0.66, P<0.05) when simulating a side than when simulating a standing configuration. Conversely, the work to failure was predicted similarly for both loading configurations (R2=0.54 vs. R2=0.53, P>0.05). Therefore, neck BMD should be considered as one of the key factors for discriminating femoral fracture risk in vivo. Moreover, the better predictive ability of neck BMD for femoral strength if tested in a fall compared to a one-legged stance configuration suggests that DXA's clinical relevance may not be as high for spontaneous femoral fractures than for fractures associated to a fall.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.