Is burnout related to allostatic load?

Background: Burnout has a negative impact on physical health, but the mechanisms underlying this relation remain unclear. To elucidate these mechanisms, possible mediating physiological systems or risk factors for adverse health in burned-out employees should be investigated. Goal: The aim of the present study among 290 Dutch managers was to explore whether allostatic load mediates the relationship between burnout and physical health. Method: Burned-out managers, as identified with the Maslach Burnout Inventory General Survey (MBI-GS), were compared with a healthy control group with regard to their allostatic load. The allostatic load index included eight parameters: Body-mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), C-reactive protein (CRP), high-density lipoprotein (HDL), cholesterol, glycosylated hemoglobin (HbA1C) and glucose. Results: Contrary to expectations, burned-out managers did not differ from healthy managers with regard to their scores on the allostatic load index. An additional analysis, using groups of managers in the extreme deciles of exhaustion (the core symptom of burnout), did also not reveal differences in allostatic load. Conclusion: Burnout seems not to be associated with this proxy measure of allostatic load. The mediating physiological mechanisms between burnout and objective physical health remain to be elucidated.     

HIV viral load: the myth of the undetectable?

There is a wealth of data supporting the use of viral load measurements to monitor therapy. Indeed, clinical drug trial endpoints routinely include the proportion of patients with a plasma viral load reduction of greater than 0.5 log(10), or greater than 1 log(10). Since a higher viral load reflects increased amounts of virus replication, it would seem desirable to reduce this replication as far as possible, so that the goal of therapy has become one of viral undetectability in plasma. However, virological suppression to undetectable levels is not an absolute determinant of outcome because recent observational cohort data suggest that any significant reduction of viral load is associated with clinical benefit. There are also technical problems when attempting to measure undetectability, with lower limits of detection of 400 or 50 RNA copies/ml of plasma being driven more by the performance of commercial assays than by any inherent cut-off value with proven prognostic significance. Furthermore, the obsession with undetectability has created the concept of the 'viral blip', or 'intermittent viraemia' commonly defined as a single viral load measurement of between 50 and 400 copies/ml, preceded and followed by consistent measurements of less than 50 copies/ml, in a patient receiving therapy. Such blips should be considered in the context of frequent transient changes in viral load which occur below the lower limit of detection by existing laboratory assays. In my view, there remains a misunderstanding about the importance ascribed to these relatively minor changes in lower detection limits, when considered against the background of virus within the body as a whole. I also consider other possible uses of HIV-1 quantification in clinical practice, such as identifying the inherent potency of antiviral regimens.     

How does skin adapt to repetitive mechanical stress to become load tolerant?

Skin breakdown from mechanical stress application is a difficult health care problem for lower-limb amputees using prosthetic limbs. Post-operative treatments to encourage skin adaptation do exist, but are largely unsuccessful. Potentially, by understanding skin adaptation on a molecular level, appropriate biomolecules can be identified and then delivered to skin to encourage adaptation in at-risk patients. Based from a critical review of the literature, it is expected that adaptation occurs by forming new collagen fibrils with larger diameters as opposed to increasing diameters of existing fibrils. Small collagen fibril breakdown by stress activated metalloproteinases is expected to be followed by increased expressions of decorin, biglycan, fibromodulin, lumican, thrombospondin-2, and collagens I and III, facilitating formation of new fibrils with larger diameters. After remodeling, total collagen fibril cross-sectional area is expected to return to baseline values since increased collagen content would increase mass and be redundant towards the purpose of adaptation.     

Low DNA HTLV-2 proviral load among women in São Paulo City

BACKGROUND: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HIV-1 co-infection. METHODS: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. RESULTS: Six of 53HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 copies/10(4) PBMCs, p<0.05). CONCLUSIONS: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus.     

Heart rate variability in diabetic patients during orthostatic load — A spectral analytic approach

Summary Spectral analysis of heart rate variability (HRV) was used to assess the autonomic nervous control of cardiac function during orthostatic load in insulin-dependent diabetic patients and healthy subjects. The diabetic patients were divided into three groups: diabetics without neuropathy (group 1), diabetics with peripheral neuropathy (group 2), and diabetics with peripheral and autonomic neuropathy (group 3). Resting mid-frequency (MF, 0.05–0.15 Hz) and respiration-related (RF, power around respiration rate) HRV were significantly lower in group 2 and 3 diabetics than in controls, indicating a reduced parasympathetic nervous system influence on the heart. Standing MF and RF spectral power data were significantly lower in all diabetic groups than in controls, suggesting marked alterations in the autonomic cardiovascular control during a mild physical load not only in symptomatic diabetics but also in patients with no signs and symptoms of neuropathy. The difference between supine and standing MF power, an estimate of-adrenergic influence on the heart, was significantly lower in all diabetic subject groups studied than in controls. This suggests a reduced sympathetic nervous system influence on the heart in diabetic patients. Our data suggest that computerized spectral analysis of HRV during orthostatic load seems to be a very sensitive method of evaluating of the autonomie nervous systems influence on the heart in patients suffering from diabetes niellitus.Abbreviations dB decibel - HRV heart rate variability - LF low-frequency component - MF mid-frequency component - RF respiration related frequency component     

Does high load of oxidants in human semen contribute to male factor infertility?

Basal generation of reactive oxygen species (ROS) was essential for male reproductive function, whereas high ROS levels may be linked to low quality of sperm and male infertility. We examined the associations between ROS levels in whole ejaculates and sperm quality among 1092 male factor infertility (MFI) patients and 50 donors with normal semen characteristics. ROS levels were significantly positively correlated with abnormal morphology rate, head defect, and sperm deformity index. Further, we investigated whether seminal plasma from MFI patients with high ROS levels affects sperm motility from donors with normal semen characteristics. After cross-culturing fresh human sperm from donors possessing normal semen characteristics with seminal plasma from infertitle men, sperm motility was measured at different ROS levels. Seminal plasma from MFI patients significantly reduced motility of sperm and the reduction rate increased with increasing ROS levels in seminal plasma. On the other hand, we found MFI patients with the ROS levels in the lowest 25th percentile had similar ROS levels to donors with normal semen characteristics. Collectively, our observations lead to the hypothesis that oxidative stress plays a critical role in the development of MFI among those with high ROS levels, but not those with low ROS levels.     

Fiber reinforced calcium phosphate cements -- on the way to degradable load bearing bone substitutes?

Calcium phosphate cements (CPC) are well-established materials for the repair of bone defects with excellent biocompatibility and bioactivity. However, brittleness and low flexural/tensile strength so far restrict their application to non-load bearing areas. Reinforcement of CPC with fibers can substantially improve its strength and toughness and has been one major strategy to overcome the present mechanical limitations of CPC. Fiber reinforced calcium phosphate cements (FRCPC) thus bear the potential to facilitate the use of degradable bone substitutes in load bearing applications. This review recapitulates the state of the art of FRCPC research with focus on their mechanical properties and their biological evaluation in?vitro and in?vivo, including the clinical data that has been generated so far. After an overview on FRCPC constitutes and processing, some general aspects of fracture mechanics of reinforced cementitious composites are introduced, and their importance for the mechanical properties of FRCPC are highlighted. So far, fiber reinforcement leads to a toughness increase of up to two orders of magnitude. FRCPC have extensively been examined in?vitro and in?vivo with generally good results. While first clinical products focus on the improved performance of FRCPC with regard to secondary processing after injection such as fixation of screws and plates, first animal studies in load bearing applications show improved performance as compared to pure CPCs. Aside of the accomplished results, FRCPC bear a great potential for future development and optimization. Future research will have to focus on the selection and tailoring of FRCPC components, fiber-matrix compatibilization, integral composite design and the adjusted degradation behavior of the composite components to ensure successful long term behavior and make the composites strong enough for application in load bearing defects.     

Tissue transglutaminase is involved in mechanical load–induced osteogenic differentiation of human ligamentum flavum cells

Mechanical load–induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load–induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load–induced and TGM2-induced ALP activity. In summary, mechanical load–induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum.     

Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.     

Plastic alteration of vestibulo-cardiovascular reflex induced by 2 weeks of 3-G load in conscious rats

Previous studies conducted in our laboratory have demonstrated that the vestibular system plays a significant role in controlling arterial pressure (AP) in conscious rats under conditions of transient microgravity. The vestibular system is known to be highly plastic, and on exposure to different gravitational environments, the sensitivity of the vestibular system-mediated AP response might be altered. In order to test this hypothesis, rats were maintained in a 3-G or a normal 1-G environment for 2 weeks, and the AP responses to free drop-induced microgravity were determined. In 1-G rats, the microgravity increased the AP by 37 ± 3 mmHg; this pressor response was significantly attenuated by vestibular lesion (VL) (24 ± 3 mmHg) or body stabilization (29 ± 2 mmHg). Thus, the microgravity-induced pressor response was mediated by both the vestibular and nonvestibular systems; the input of the latter system was blocked by body stabilization. In the 3-G rats, the pressor responses were significantly suppressed compared to those in the corresponding 1-G rats; i.e., the AP increased by 24 ± 2 mmHg in freely moving 3-G rats, by 10 ± 4 mmHg in 3-G rats with VL, and by 13 ± 4 mmHg in stabilized 3-G rats. Furthermore, there was no difference between the 1- and 3-G rats in terms of the pressor response induced by stressors such as a loud noise or an air jet. These results indicate that pre-exposure to 3-G for 2 weeks induces plasticity in both the vestibular- and nonvestibular-mediated AP responses to microgravity.     

Full-length hepatitis B virus sequences from naïve patients with fluctuation of viral load during ADV monotherapy

The reasons for adefovir dipivoxil (ADV) treatment failures appear diverse. Few studies have reported full-length hepatitis B virus (HBV) genome in patients with ADV treatment failures. The patients were from a phase III clinical trial that investigated the antiviral response to ADV in China. Seven patients had increase in HBV-DNA (>1 log₁₀ copies/ml above on-treatment nadir) at week 52. The serum HBV-DNA levels were above 10⁴copies/ml at week 92 in four of them. Sixteen full-length HBV genomes from the four patients at four time points were sequenced using cloning sequencing method. The frequency of substitutions at week 52 was higher than at weeks 28(16 wt) and 92(80). HBV-DNA reduction was correlated negatively with the frequency of substitutions at the three time points. No published ADV-resistant mutations were detected. The mutations, including substitutions in immunogenic epitopes and conserved sites of the polymerase gene, were frequent during ADV treatment. Amino acid deletions in X gene and basal core promoter/pre-core mutations appeared before or during ADV treatment. The substitutions in immunogenic epitopes (mainly of the surface gene) and conserved sites of the polymerase gene other than ADV-resistant mutations may have influenced antiviral efficacy in the study. More potent antiviral drugs may be important to rescue individual patients and for public health safety. It is needed to study how these substitutions influence HBV replication, disease progression, and antiviral treatment efficacy.     

Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?

An unstable CAG triplet repeat expansion encoding a polyglutamine stretch within the ubiquitously expressed protein huntingtin is responsible for causing Huntington's disease (HD). By quantifying the repeat sizes of individual mutant alleles in tissues derived from an accurate genetic mouse model of HD we show that the mutation becomes very unstable in striatal tissue. The expansion-biased changes increase with age, such that some striatal cells from old HD mice contain mutations that have tripled in size. If this pattern of repeat instability is recapitulated in human striatal tissue, the concomitant increased polyglutamine load may contribute to the patterns of selective neuronal cell death in HD. Our findings also suggest that trinucleotide repeat instability can occur by mechanisms that are not replication-based.