Life satisfaction and risk of burnout among men and women working as physiotherapists

Objectives

Recently in Poland as a result of the high rate of aging population and high rates of morbidity, a growing demand for the physiotherapist profession is observed. The results of this study can be used to formulate principles for better organization of physiotherapist’s workplace in order to prevent occurrence of burnout. The aim of this study is to investigate the effect of gender on satisfaction with life and burnout among active physiotherapists.

Material and Methods

The survey was anonymous and voluntary, and involved a group of 200 active physiotherapists working in health care units and educational centers in Po?land. The study group was selected randomly and incidentally. Each respondent received a demographic data sheet and a set of self-rating questionnaires (Life Satisfaction Questionnaire, Burnout Scale Inventory).

Results

Burnout among men decreased along with increasing satisfaction with one’s work and occupation, friends, relatives and acquaintances, sexuality, and increased due to greater satisfaction with one’s housing status. Burnout among women decreased along with increasing satisfaction with one’s health, free time and friends, relatives and acquaintances, and increased due to work at a setting other than a health care unit or educational center. Statistical analysis failed to reveal any significant differences with regard to the BSI domains and with regard to the overall burnout index as well as with regard to the assessment of satisfaction with life between female and male physiotherapists.

Conclusions

Satisfaction with children, marriage and partnership, with one’s work and occupation, interactions with friends, relatives and acquaintances and sexuality may contribute to reduction of burnout among men. Women who are satisfied with their children, family, health, free time and contacts with friends, relatives and acquaintances are less prone to burnout. Weak financial situation among women and deficiency of free time among men can induce burnout. Improving staff happiness may contribute to decreasing burnout.     

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

Replication-dependent histone mRNAs end with a conserved stem loop that is recognized by stem-loop–binding protein (SLBP). The minimal RNA-processing domain of SLBP is phosphorylated at an internal threonine, and Drosophila SLBP (dSLBP) also is phosphorylated at four serines in its 18-aa C-terminal tail. We show that phosphorylation of dSLBP increases RNA-binding affinity dramatically, and we use structural and biophysical analyses of dSLBP and a crystal structure of human SLBP phosphorylated on the internal threonine to understand the striking improvement in RNA binding. Together these results suggest that, although the C-terminal tail of dSLBP does not contact the RNA, phosphorylation of the tail promotes SLBP conformations competent for RNA binding and thereby appears to reduce the entropic penalty for the association. Increased negative charge in this C-terminal tail balances positively charged residues, allowing a more compact ensemble of structures in the absence of RNA.Histone synthesis increases at the beginning of S-phase to package newly replicated DNA with histone proteins, but synthesis must be shut down rapidly and histone mRNA degraded at the end of DNA replication because of the toxicity of surplus histone proteins (1, 2). This cyclic demand for histones requires strict regulation, which is achieved mainly by controlling the synthesis and degradation of histone mRNA (3). Replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated and instead end with a conserved stem loop (4). Histone mRNAs are generated from longer histone pre-mRNAs as a result of an endonucleolytic cleavage between the stem loop and a purine-rich downstream sequence termed the “histone downstream element” (HDE) (5).Stem-loop–binding protein (SLBP), also known as “hairpin-binding protein” (6), binds to the histone mRNA stem loop, and U7 small nuclear ribonucleoprotein binds to the HDE (7). Other factors, including the endonuclease CPSF-73, are involved in both polyadenylation and histone mRNA 3′-end processing (8–11). In mammalian nuclear extracts, SLBP is not absolutely required for the biochemical reaction of processing (12). In contrast, cleavage of histone pre-mRNA in Drosophila cells and nuclear extracts requires the binding of SLBP to the stem loop (10, 13).The minimal histone mRNA processing domain of Drosophila SLBP contains a 72-aa RNA-binding domain (RBD) unique to SLBPs and an 18-aa C-terminal region (Fig. 1A) (14). This RNA-processing domain (RPD) is necessary and sufficient for histone mRNA 3′-end processing in vitro (15). The RBDs of human SLBP (hSLBP) and Drosophila SLBP (dSLBP) are phosphorylated at a Thr residue in a conserved TPNK motif (16, 17). The recent crystal structure of hSLBP RBD in complex with histone mRNA stem loop and 3′ hExo, a 3′–5′ exonuclease required for histone mRNA degradation, provided the first molecular insights into the architecture of this complex, and revealed how the hSLBP RBD forms a new RNA-binding motif to interact with the stem-loop RNA (18). On the other hand, how SLBP alone interacts with the RNA or how this interaction might be affected by phosphorylation of the TPNK motif is not known.Open in a separate windowFig. 1.Schematic of the domain architecture of dSLBP (Upper) and amino acid sequence alignment of RPDs of Drosophila and human SLBP (Lower). Domains of SLBP include the N-terminal domain (NTD), RBD, and C-terminal region (C). Amino acid sequences are shown with the RBD sequence in the top two rows and the C-terminal region in the bottom row. T230 in the TPNK motif and phosphorylation sites in the C-terminal region are indicated with boldface and asterisks, respectively; the residues involved in RNA binding are shown in cyan; and acidic residues in the C-terminal region are shown in red.The C-terminal region of dSLBP contains a motif, SNSDSDSD, whose hyperphosphorylation is required for efficient processing of histone pre-mRNA (15). Despite the similarity of hSLBP and dSLBP RBDs (55% identical residues) and their ability to bind identical stem-loop RNA sequences, neither SLBP can substitute for the other to process histone pre-mRNA in nuclear extracts; in fact, hSLBP inhibits processing of Drosophila histone pre-mRNA (15). This incompatibility results from differences in the C-terminal region (Fig. 1). The sequence C-terminal to the RBD in hSLBP is required for processing, but it is longer, has no similarity to the Drosophila sequence, and lacks phosphorylation sites.Here we focused on dSLBP and showed that phosphorylation greatly increases dSLBP binding affinity for the histone mRNA stem loop. Mimicking phosphorylation of the dSLBP RPD by mutation of phosphorylation sites to Glu residues at both the TPNK motif and the C-terminal region also boosted binding affinity relative to the nonphosphorylated dSLBP RPD. Structural studies of both the human and Drosophila SLBP RPD indicated that phosphorylation of the TPNK motif stabilizes the RNA-binding domain, but the C-terminal region is flexible in the protein:RNA complex and does not contact the RNA. Instead, we show that the increased negative charge in the C-terminal region of the dSLBP RPD results in a more compact ensemble of protein conformations in the absence of RNA, thereby increasing RNA-binding affinity by reducing the entropy of the unbound protein.     

Immunosignature system for diagnosis of cancer

Although the search for disease biomarkers continues, the clinical return has thus far been disappointing. The complexity of the body’s response to disease makes it difficult to represent this response with only a few biomarkers, particularly when many are present at low levels. An alternative to the typical reductionist biomarker paradigm is an assay we call an “immunosignature.” This approach leverages the response of antibodies to disease-related changes, as well as the inherent signal amplification associated with antigen-stimulated B-cell proliferation. To perform an immunosignature assay, the antibodies in diluted blood are incubated with a microarray of thousands of random sequence peptides. The pattern of binding to these peptides is the immunosignature. Because the peptide sequences are completely random, the assay is effectively disease-agnostic, potentially providing a comprehensive diagnostic on multiple diseases simultaneously. To explore the ability of an immunosignature to detect and identify multiple diseases simultaneously, 20 samples from each of five cancer cohorts collected from multiple sites and 20 noncancer samples (120 total) were used as a training set to develop a reference immunosignature. A blinded evaluation of 120 blinded samples covering the same diseases gave 95% classification accuracy. To investigate the breadth of the approach and test sensitivity to biological diversity further, immunosignatures of >1,500 historical samples comprising 14 different diseases were examined by training with 75% of the samples and testing the remaining 25%. The average accuracy was >98%. These results demonstrate the potential power of the immunosignature approach in the accurate, simultaneous classification of disease.Cancer is the most likely disease for which an early diagnostic would be immediately beneficial. Unfortunately, finding specific biomarkers, especially for cancer, has been complicated by the fact that biological molecules (RNA, DNA, proteins, or peptides) that are uniquely released by a small tumor into the bloodstream are extremely dilute. Classical biomarker assays are based on one-to-one molecular recognition events to detect one or a few specific analytes that are often measured by antibody–protein interactions. There are three fundamental limitations with this approach, all of which are confounded by the dilution problem alluded to above. The first is that the cross-reactivity of such interactions poses a formidable problem in distinguishing diseases. Biology’s promiscuous use of a limited number of homologous sequences, folds, and domains makes specificity difficult. The second is that diseases such as cancer are themselves heterogeneous, and individual response to disease, at a molecular level, can vary considerably. It is unlikely that this level of complexity can be quantitatively assessed by one or a few specific proteins or metabolites in a way that supports robust diagnosis. Third, many of the biomarkers that have been proposed are of low stability or require substantial preassay purification or preparation; these aspects introduce substantial variation into the measured values (1, 2). As a result, although considerable effort has been put into the development of biomarkers, only a small fraction of candidates make it to clinical practice, and the utility of those that are used is sometimes only modest (3–5). Here, we explore the ability of the immunosignature technology to address the ideal of a simple, comprehensive diagnostic for multiple cancers.An “immunosignature” is the pattern obtained when circulating antibodies in blood are allowed to bind to a large microarray of randomized-sequence peptides affixed to a solid surface (6). Cancers generate neoantigens by virtue of their mutagenic nature, and they tend to release native proteins and biomolecules not normally encountered by the immune system (7–9). These behaviors can elicit an immune response (6, 10, 11). By virtue of the tremendous amplification afforded by B-cell replication (12), the signal elicited by the disease-specific antigens is massively amplified. In fact, a key aspect of the immunosignature assay is that the blood is greatly diluted before application to the array, such that only the antibodies that have been sufficiently amplified give distinct signals (13).Another somewhat counterintuitive aspect of the method is that the peptide sequences used on the microarray are purposefully not chosen to represent the natural antigens of the antibodies produced in response to disease. In fact, in the arrays of 10,000 peptides used in this study, the peptide sequences were generated with a random number generator. This enables the same microarray to be used for diagnosis of any disease. Despite using random-sequence peptides, monoclonal antibodies generated from a wide variety of antigens show specific patterns of binding on these arrays, to both cognate and noncognate sequences (14, 15). Many of the peptides bound by a monoclonal antibody against a known linear epitope have no obvious sequence similarity to that epitope. Most of the peptides thus identified have demonstrated low affinity in solution for the antibody but are retained on the arrays due to avidity created by close spacing of individual peptides (15).An immunosignature of an individual consists of an overlay of the patterns from the binding signals of many of the most prominent circulating antibodies. Some of the binding signals are present in most individuals (whether sick or healthy), and some are unique to an individual, but if the individual has a disease such as a cancer, a subset of the binding signals will be due to disease-associated antigens that are common to most individuals with the disease (16). An important aspect of this approach is that it senses essentially all antibodies raised to the disease and detects each of the antibodies as separable binding patterns composed of unique molecular recognition elements. This differs from, for example, an ELISA, which might sum the contributions of many different antibodies using a single protein, cell, or virus capsid. Again, from a statistical perspective, the high dimensionality of this readout affords much more specificity than could be obtained from a set of cognate sequences or from an array of the native antigens themselves.Not only does the use of highly dilute blood and random peptide sequences in the immunosignature assay paradoxically give rise to improved sensitivity and specificity but these aspects of the assay also result in several other unique benefits of the immunosignature approach. Because of the dilution (1:500 in these studies), blood proteins other than antibodies do not significantly bind to the arrays, meaning that there is no sample preparation involved other than dilution (17). The dilution ensures the assay is sample-sparing. Finally, the assay is disease-agnostic. The arrays can be used for the simultaneous detection and identification of multiple diseases.It is simultaneous detection and identification of multiple diseases with a single assay that underlies the true potential of this approach as a disruptive force in healthcare. This, combined with the fact that serum antibodies are robust to handling (17, 18) such that a drop of blood can be sent dried on filter paper through the mail (17), should enable frequent, inexpensive monitoring for many different diseases. The goal of the current work is to test the multidisease aspect of immunosignatures rigorously. Although the approach has previously been used to discriminate various subtypes of brain cancer (19), it has not yet demonstrated multiplexed cancer diagnosis. Here, we perform a blinded train/test validation study wherein a group of 120 individuals with five different cancers from various geographic regions was used as a training set to define a multicancer signature. The signature predicted the disease status of a test cohort of equal size and composition. To explore the ability of the approach to discriminate between an even larger set of diseases, 1,516 different individuals spanning 14 different disease cohorts plus a diverse cohort of healthy controls were assayed and the ability to distinguish between these diseases was evaluated.     

Prevalence of malnutrition in systemic sclerosis patients assessed by different diagnostic tools

Clinical Rheumatology - Gastrointestinal complaints of scleroderma (SS) patients are risk factors for impaired nutritional status, so insightful assessment is necessary. The aim was comparison of...     

Widespread Differential Maternal and Paternal Genome Effects on Fetal Bone Phenotype at Mid‐Gestation

Parent‐of‐origin–dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1–6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25‐hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = –0.34 and –0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle‐bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.     

Two-dimensional speckle-tracking echocardiography assessment of left ventricular remodeling in patients after myocardial infarction and primary reperfusion

Introduction

Left ventricular remodeling (LVR) is the most prognostically important consequence of acute myocardial infarction (AMI). The aim of the study was to assess the value of speckle tracking echocardiography in the prediction of left ventricular remodeling in patients after AMI and primary coronary angioplasty (PCI).

Material and methods

Eighty-eight patients (F/M = 31/57 patients; 63.6 ±11 years old) with coronary artery disease (CAD) and successful PCI were enrolled and divided into group I with ST-elevation myocardial infarction or non-ST elevation myocardial infarction and group II with stable angina pectoris. Conventional and speckle tracking echocardiography was performed 3 days (baseline), 30 days and 90 days after PCI. Patients were divided into 2 groups based on the presence of LVR (increase of LV end-diastolic and/or end-systolic volume > 20%) at 3 months follow-up.

Results

At initial presentation, 2-chamber longitudinal strain (9.4 ±3.5% vs. –11.6 ±3.6%, p < 0.04) and 4-chamber transverse strain (10.4 ±8.2% vs. 15.6 ±8%, p < 0.003) were lower in the LVR+ group compared to the LVR– group. LV wall motion score index did not differ between the two groups. After 30 days, circumferential apical and basal strain (–15.58 ±8.9% vs. –25.53 ±8.8%, p < 0.001; –15.02 ±5.6 vs. –19.78 ±6.3, p < 0.008), radial apical strain (9.96 ±8.4% vs. 14.15 ±5.5%, p < 0.03), 4-chamber longitudinal strain (–8.7 ±5.8% vs. –13.47 ±3.9%, p < 0.005), 4-chamber transverse strain (10.5 ±8.1% vs. 16.7 ±8.3%, p < 0.03), apical rotation (3.84 ±2.5° vs, 5.66 ±3.2°, p < 0.04) and torsion (6.15 ±4.1° vs. 8.98 ±4.6°, p < 0.03) were significantly decreased in the LVR+ group compared to the LVR– group. According to ROC analysis, circumferential apical strain > –15.92% (sensitivity 93%, specificity 59%, positive predictive value 90%) was the most powerful predictor of remodeling after primary PCI in AMI.

Conclusions

Our results suggest that impaired indices of LV deformation detected 3 days and 30 days after AMI may provide important predictive value in LV remodeling and patients’ follow-up.     

Incorporation of Optical Density into the Blending Design for a Biocement Solution

The engineering practices for applying the microbial precipitation of carbonates require a design of the blending biocement solution (BCS). The BCS is usually blended with concentrated strains NO-A10, reaction media, such as urea and CaCl₂, and a solvent, i.e., water or seawater. To characterize the BCS, the unknown microbial characteristics, such as the cell viability, are complex factors. Therefore, the optical density (OD) was redefined as Rcv OD*, in which OD* was the tentative OD of the BCS used and Rcv was the conversion rate concerning the cell viability. To determine Rcv values, a standard precipitation curve based on the precipitation rate at 24 h was determined. It was found that the curve was expressed by λ₁ OD+ λ₂ OD², in which λ₁ and λ₂ were 8.46 M and −17.633 M, respectively. With this, the Rcv and OD values of unknown BCS were estimated from the results of precipitation tests using arbitrary OD* values. By extending the testing time, the second order term of OD or OD* was negligible. Accordingly, the precipitation amount is expressed as 8.46 OD, in which the OD can be estimated by precipitation tests using arbitrary OD* values of BCSs. Unless the Ca²⁺ value is dominant, the optimum blending of BCS can be determined by OD. Thus, it is concluded that the blending design of BCS is achieved using 8.46 OD, or 8.46 Rcv OD*, and the standard precipitation curve was defined in this study.     

Studies of adsorption of α,β-unsaturated carbonyl compounds on heterogeneous Au/CeO2, Au/TiO2 and Au/SiO2 catalysts during reduction by hydrogen

Our research focuses on phenomena accompanying adsorption of mesityl oxide (4-methylpent-3-en-2-one) on the surface of heterogeneous supported gold catalysts: Au/CeO₂, Au/TiO₂ and Au/SiO₂. We have studied reduction in the gas phase of (volatile) α,β-unsaturated carbonyl compounds (R-(V)ABUCC) which mesityl oxide is a basic model of. In situ infrared (IR) spectroscopy was employed to establish that the most active catalysts allow adsorption of conjugated ketones or aldehydes in the enolate (i.e. bridge-like adsorption through the oxygen from the carbonyl group and the β-carbon) and carboxylic form or with the ^αC ^βC double bond on a Lewis acidic site. Reductive properties of the catalysts and pure supports were studied by temperature-programmed reduction (TPR). We show that cerium(iv) oxide (CeO₂, ceria) and titanium(iv) oxide (TiO₂, titania) when decorated with gold nanoparticles (AuNP) can interact with hydrogen at temperatures approx. 150 °C lower than typical for pure oxides what includes even cyclic adsorption and instant release of H₂ below 100 °C in the case of gold–ceria system. Morphology and structure characterisation by transmission electron microscopy (TEM) and powder X-ray diffraction (PXRD) confirms that, with the obtained Au loadings, we achieved excellent dispersion of AuNPs while maintaining their small size, preferably below 5 nm, even though the Au/CeO₂ catalyst contained broad distribution of AuNPs sizes.

We deliver spectroscopic IR data describing the adsorption phenomena accompanying reduction of conjugated carbonyl compounds aided by heterogeneous catalysts.