Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans.

The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.

The influence of random-coil chemical shifts on the assessment of structural propensities in folded proteins and IDPs.

In studying secondary structural propensities of proteins by nuclear magnetic resonance (NMR) spectroscopy, secondary chemical shifts (SCSs) serve as the primary atomic scale observables. For SCS calculation, the selection of an appropriate random coil chemical shift (RCCS) dataset is a crucial step, especially when investigating intrinsically disordered proteins (IDPs). The scientific literature is abundant in such datasets, however, the effect of choosing one over all the others in a concrete application has not yet been studied thoroughly and systematically. Hereby, we review the available RCCS prediction methods and to compare them, we conduct statistical inference by means of the nonparametric sum of ranking differences and comparison of ranks to random numbers (SRD-CRRN) method. We try to find the RCCS predictors best representing the general consensus regarding secondary structural propensities. The existence and the magnitude of resulting differences on secondary structure determination under varying sample conditions (temperature, pH) are demonstrated and discussed for globular proteins and especially IDPs.

Sensitization Pathways in NIR-Emitting Yb(III) Complexes Bearing 0, +1, +2, or +3 Charges.

Yb(III) complexes of macrocyclic ligands based on 1,4,7,10-tetraazacyclododecane were synthesized. The ligands carried a carbostyril chromophore for Yb(III) sensitization, and carboxylate or carbamide donors for metal binding, forming complexes of 0, +1, +2, or +3 overall charge. The coordination geometry was little affected by the replacement of carboxylates with amides, as shown by paramagnetic 1H NMR spectroscopy. The Yb(III)/Yb(II) reduction potentials were dependent on the nature of the metal binding site, and the more positively charged complexes were easier to reduce. Carbostyril excitation resulted in Yb(III) luminescence in every complex. The residual carbostyril fluorescence quantum yields were smaller in complexes containing more reducible Yb(III) centers decreasing from 5.9% for uncharged complexes to 3.1-4.4% in +3 charged species, suggesting photoinduced electron transfer (PeT) from the antenna to the Yb(III). The relative Yb(III) luminescence quantum yields were identical within the experimental error, except for the +3 charged complex with fully methylated coordinating amides, which was the most intense Yb(III) emitter of the series in water. Quenching of the Yb(III) excited state by NH vibrations proved to limit Yb(III) emission. No clear improvement of the Yb(III) sensitization efficiency was shown upon faster PeT. This result can be explained by the concomitant sensitization of Yb(III) by phonon-assisted energy transfer (PAEnT) from the antenna triplet excited state, which was completely quenched in all of the Yb complexes. Depopulation of the triplet by PeT quenching of the donor singlet excited state would be compensated by the sensitizing nature of the PeT pathway, thus resulting in a constant overall sensitization efficiency across the series.

Functional diversification of heat shock factors.

Heat shock transcription factors (HSFs) are widely known as master regulators of the heat shock response. In invertebrates, a single heat shock factor, HSF1, is responsible for the maintenance of protein homeostasis. In vertebrates, seven members of the HSF family have been identified, namely HSF1, HSF2, HSF3, HSF4, HSF5, HSFX, and HSFY, of which HSF1 and HSF2 are clearly associated with heat shock response, while HSF4 is involved in development. Other members of the family have not yet been studied as extensively. Besides their role in cellular proteostasis, HSFs influence a plethora of biological processes such as aging, development, cell proliferation, and cell differentiation, and they are implicated in several pathologies such as neurodegeneration and cancer. This is achieved by regulating the expression of a great variety of genes including chaperones. Here, we review our current knowledge on the function of HSF family members and important aspects that made possible the functional diversification of HSFs.

Improved emission of Yb(III) ions in triazacyclononane-based macrocyclic ligands compared to cyclen-based ones.

Yb(III) complexes based on ligands with a 1,4,7-triazacyclononane (tacn) macrocyclic core were synthesised. The complexes carry a 4-methoxymethyl-substituted carbostyril chromophore that serves as a light-harvesting antenna. The ligands supply 5 nitrogen and 3 oxygen donors via 1 methylenecarboxamide and 2 picolinate donors, creating +1 charged complexes with an octadentate binding environment. The electronic properties of the picolinates are modulated by varying the substitution at the 4 position with OMe, H, Cl, or CF3. Cyclic voltammetry indicated that the tacn-based Yb(III) complexes were easier to reduce than the analogous cyclen complexes. The first reductive event is likely picolinate-centred, followed by the formation of further reduced species. Antenna excitation yielded Yb(III) luminescence in the near-infrared (NIR) region in all cases. The antenna photophysical properties were consistent with intraligand photoinduced electron transfer from the excited carbostyril to the picolinate groups. The relative quantum yields of Yb(III) luminescence were determined. The lowest value was obtained for the complex with the most efficient antenna-to-picolinate photoinduced electron transfer. Despite intraligand electron transfer quenching of the antenna, the tacn-based Yb complexes were more emissive than their cyclen analogues, highlighting the influence of the ligand structure on the luminescence properties of NIR emissive lanthanide(III) ions.

Neck-shaft angle measurement in children: accuracy of the conventional radiography-based (2D) methods compared to 3D reconstructions.

Aim of this study was to examine the accuracy of widely used conventional radiography-based (2D) neck-shaft angle measurements compared to 3D reconstruction. In our retrospective study, EOS 2D/3D images of 156 patients (312 limbs) were selected from our database (4-16 years old: 6 girls and 6 boys/year), where no pathology was revealed. Using the 2D modality of the EOS method neck-shaft angle was measured using the "biggest diameter" and "circle fitting" techniques to define the femoral neck axis and 1/3, 1/2 and full femur to determine the femoral shaft axis. EOS 3D reconstructions of same images were also performed and a comparison of 2D and 3D results was made. We did not find any significant difference between accuracy of the four examined 2D methods, although the deviation between 2 and 3D results was considerable (average difference: 5.11-5.58°, p < 0,001). In 31% of the cases, difference was more than 10°. Only femoral torsion showed significant influence on the difference (correlation coefficient: 0.380, p < 0.001). We did not find a clinically significant difference between the examined 2D methods, although their accuracy was highly questionable compared to 3D results. We suggest using any 3D imaging method for surgical planning and in uncertain cases.

The Relevance of Goodness-of-fit, Robustness and Prediction Validation Categories of OECD-QSAR Principles with Respect to Sample Size and Model Type.

We investigated the relevance of the validation principles on the Quantitative Structure Activity Relationship models issued by Organization for Economic and Co-operation and Development. We checked the goodness-of-fit, robustness and predictivity categories in linear and nonlinear models using benchmark datasets. Most of our conclusions are drawn using the sample size dependence of the different validation parameters. We found that the goodness-of-fit parameters misleadingly overestimate the models on small samples. In the case of neural network and support vector models, the feasibility of the goodness-of-fit parameters often might be questioned. We propose to use the simplest y-scrambling method to estimate chance correlation. We found that the leave-one-out and leave-many-out cross-validation parameters can be rescaled to each other in all models and the computationally feasible method should be chosen depending on the model type. We assessed the interdependence of the validation parameters by calculating their rank correlations. Goodness of fit and robustness correlate quite well over a sample size for linear models and one of the approaches might be redundant. In the rank correlation between internal and external validation parameters, we found that the assignment of good and bad modellable data to the training or the test causes negative correlations.

Novel Lysine-Rich Delivery Peptides of Plant Origin ERD and Human S100: The Effect of Carboxyfluorescein Conjugation, Influence of Aromatic and Proline Residues, Cellular Internalization, and Penetration Ability.

The need for novel drug delivery peptides is an important issue of the modern pharmaceutical research. Here, we test K-rich peptides from plant dehydrin ERD14 (ERD-A, ERD-B, and ERD-C) and the C-terminal CPP-resembling region of S100A4 (S100) using the 5(6)-carboxyfluorescein (Cf) tag at the N-terminus. Via a combined pH-dependent NMR and fluorescence study, we analyze the effect of the Cf conjugation/modification on the structural behavior, separately investigating the (5)-Cf and (6)-Cf forms. Flow cytometry results show that all peptides internalize; however, there is a slight difference between the cellular internalization of (5)- and (6)-Cf-peptides. We indicate the possible importance of residues with an aromatic sidechain and proline. We prove that ERD-A localizes mostly in the cytosol, ERD-B and S100 have partial colocalization with lysosomal staining, and ERD-C mainly localizes within vesicle-like compartments, while the uptake mechanism mainly occurs through energy-dependent paths.

Reduced quenching effect of pyridine ligands in highly luminescent Ln(III) complexes: the role of tertiary amide linkers.

Luminescent Eu(III) and Tb(III) complexes were synthesised from octadentate ligands carrying various carbostyril sensitizing antennae and two bidentate picolinate donors. Antennae were connected to the metal binding site via tertiary amide linkers. Antennae and donors were assembled on a 1,4,7-triazacyclononane (tacn) platform. Solution- and solid-state structures were comparable to those of previously reported complexes with tacn architectures, with nine-coordinate distorted tricapped trigonal prismatic Ln(III) centres, and distinct from those based on 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles. In contrast, the photophysical properties of these tertiary amide tacn-based complexes were more comparable to those of previously reported systems with cyclen ligands, showing efficient Eu(III) and Tb(III) luminescence. This represents an improvement over secondary amide-linked analogues, and is due to a greatly increased sensitization efficiency in the tertiary amide-linked complexes. Tertiary amide-linked Eu(III) and Tb(III) emitters were more photostable than their secondary amide-linked analogues due to the suppression of photoinduced electron transfer and back energy transfer.

Lumbar spine abnormalities in patients with obstructive sleep apnoea.

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland-Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0-3.5/ vs. 0/0-1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.

Screening for the presence of scleroedema adultorum of Buschke in patients with diabetes mellitus: newly diagnosed patients had a high prevalence of dyslipidaemia.

BACKGROUND: Scleroedema adultorum of Buschke is a rare disorder characterized by fibromucinous thickening of the dermis that manifests mainly at the nape of the neck and on the upper back and shoulders. This study screened patients with diabetes mellitus for skin hardening caused by scleroedema adultorum of Buschke and characterized the clinical and laboratory findings in patients with newly identified cases, with a focus on lipid metabolism abnormalities and vascular complications. METHODS: Out of 113 consecutive patients with diabetes, 11 (9.7%) new scleroedema patients, all with type 2 diabetes, were found. Their clinical and laboratory data were compared to those of the rest of the screened patients and to those of a cohort of 15 patients with scleroedema and diabetes who were already being treated in a tertiary clinical centre at the University of Pécs. RESULTS: Higher proportions of patients with dyslipidaemia, hypertriglyceridemia (P < 0.05) and increased mean levels of non-high-density lipoprotein cholesterol (non-HDL-C) were found (P < 0.01) in both scleroedema groups than in the group without scleroedema. Stroke and venous thromboembolism (VTE) were more frequently found in the histories of both the newly identified scleroedema group (each 3/11; 27.3%) and the treated cohort (each 6/15; 40.0%) than in the group without scleroedema (6/102; 5.9% in cases of stroke P = 0.021, P < 0.001; and 14/102; 13.7%; P < 0.05 in cases of VTE, respectively). Based on binary logistic regression, a high non-HDL-C level (odds ratio (OD): 3.338, confidence interval (CI): 1.77-6.28; P < 0.001) and insulin treatment (OR 7.64, CI 1.9-29.3; P = 0.003) were independent predictors of scleroedema in patients with diabetes mellitus. CONCLUSIONS: Diabetes patients with scleroedema had more severe dyslipidaemia and higher occurrence of vascular complications compared to those without scleroedema. In addition to poorly controlled type 2 diabetes mellitus requiring insulin treatment, high non-HDL-C levels may be another contributing factor to the development of scleroedema. TRIAL REGISTRATION: NCT04335396 .

Electron transfer pathways in photoexcited lanthanide(iii) complexes of picolinate ligands.

A series of luminescent lanthanide(iii) complexes consisting of 1,4,7-triazacyclononane frameworks and three secondary amide-linked carbostyril antennae were synthesised. The metal binding sites were augmented with two pyridylcarboxylate donors yielding octadentate ligands. The antennae carried methyl, methoxymethyl or trifluoromethyl substituents in their 4-positions, allowing for a range of excited state energies and antenna electronic properties. The 1H NMR spectra of the Eu(iii) complexes were found to be analogous to each other. Similar results were obtained in the solid-state by single-crystal X-ray crystallography, which showed the structures to have nine-coordinate metal ions with heavily distorted tricapped trigonal prismatic geometries. Steady-state and time-resolved luminescence spectroscopy showed that the antennae could sensitize both Tb(iii) and Eu(iii), however, quantum yields were lower than in other octadentate complexes lacking pyridylcarboxylate. Complexes with more electron-poor pyridines were less emissive even when equipped with the same antenna. The oxidation and reduction potentials of the antennae and the pyridinecarboxylates, respectively, were determined by cyclic voltammetry. The obtained values were consistent with electron transfer from the excited antenna to the pyridine providing a previously unexplored quenching pathway that could efficiently compete with energy transfer to the lanthanide. These results show the crucial impact that photophysically innocent ligand binding sites can have on lanthanide luminescence.

Effects of Individualized Ischemic Preconditioning on Protection Against Eccentric Exercise-Induced Muscle Damage: A Randomized Controlled Trial.

BACKGROUND: The effects of ischemic preconditioning (IPC) versus a deceptive sham protocol on indirect markers of exercise-induced muscle damage (EIMD) after the application of individualized occlusion pressure were examined. The goal of using a sham protocol is to control for the potential effect of placebo. HYPOTHESIS: IPC would surpass the sham protocol in protecting against EIMD. STUDY DESIGN: A randomized, double-blinded, clinical trial. LEVEL OF EVIDENCE: Level 1. METHODS: Thirty healthy young men were randomly assigned to an eccentric exercise for the knee extensor muscles preceded by IPC (4 × 5 minutes of individualized total occlusion pressure) or sham protocol (4 × 5 minutes using 20 mm Hg). Maximal voluntary isometric torque (MVIT), rate of torque development, muscle soreness, pressure pain threshold, knee range of motion, thigh girth, and creatine kinase (CK) activity were assessed before IPC or sham protocol and up to 72 hours after the eccentric EIMD. Affective valence and perceived exertion were also evaluated. RESULTS: MVIT decreased 17.1% in the IPC and 18.1% in the sham groups, with no differences between groups. Differences from baseline were observed in the sham group for muscle soreness at 48 hours (P < 0.001) and 72 hours (P = 0.02), and for CK activity at 72 hours (P = 0.04). Muscle soreness was reduced in the IPC group at 48 hours compared with the sham group (∆ = 15.8 mm; P = 0.008) but without achieving the minimal clinically important difference. IPC induced a smaller perceived exertion than the sham protocol (∆ = 1.1 a.u.; P = 0.02). The remaining outcomes were not statistically different in both groups. CONCLUSION: IPC does not surpass the sham protocol to protect against mild EIMD of the knee extensors muscles. CLINICAL RELEVANCE: Although IPC is a noninvasive, low-cost, and easy-to-administer intervention, the IPC effects can, in part, be explained by the placebo effect. In addition, individualized IPC promotes attenuation in perceived exertion during eccentric exercise.

In Situ Rolling Circle Amplification Förster Resonance Energy Transfer (RCA-FRET) for Washing-Free Real-Time Single-Protein Imaging.

Fluorescence signal enhancement via isothermal nucleic acid amplification is an important approach for sensitive imaging of intra- or extracellular nucleic acid or protein biomarkers. Rolling circle amplification (RCA) is frequently applied for fluorescence in situ imaging but faces limitations concerning multiplexing, dynamic range, and the required multiple washing steps before imaging. Here, we show that Förster resonance energy transfer (FRET) between fluorescent dyes and between lanthanide (Ln) complexes and dyes that hybridize to ß-actin-specific RCA products in HaCaT cells can afford washing-free imaging of single ß-actin proteins. Proximity-dependent FRET could be monitored directly after or during (real-time monitoring) dye or Ln DNA probe incubation and could efficiently distinguish between photoluminescence from ß-actin-specific RCA and DNA probes freely diffusing in solution or nonspecifically attached to cells. Moreover, time-gated FRET imaging with the Ln-dye FRET pairs efficiently suppressed sample autofluorescence and improved the signal-to-background ratio. Our results present an important proof of concept of RCA-FRET imaging with a strong potential to advance in situ RCA toward easier sample preparation, higher-order multiplexing, autofluorescence-free detection, and increased dynamic range by real-time monitoring of in situ RCA.

Lanthanide(III) Complexes of Cyclen Triacetates and Triamides Bearing Tertiary Amide-Linked Antennae.

The coordination compounds of the trivalent lanthanide ions (Ln(III)) have unique photophysical properties. Ln(III) excitation is usually performed through a light-harvesting antenna. To enable Ln(III)-based emitters to reach their full potential, an understanding of how complex structure affects sensitization and quenching processes is necessary. Here, the role of the linker between the antenna and the metal binding fragment was studied. Four macrocyclic ligands carrying coumarin 2 or 4-methoxymethylcarbostyril sensitizing antennae linked to an octadentate macrocyclic ligand binding site were synthesized. Complexation with Ln(III) (Ln = La, Sm, Eu, Gd, Tb, Yb and Lu) yielded species with overall -1, 0, or +2 and +3-charge. Paramagnetic 1H NMR spectroscopy indicated subtle differences between the coumarin- and carbostyril-carrying Eu(III) and Yb(III) complexes. Cyclic voltammetry showed that the effect of the linker on the Eu(III)/Eu(II) apparent reduction potential was dependent on the electronic properties of the N-substituent. The Eu(III), Tb(III) and Sm(III) complexes were all luminescent. Coumarin-sensitized complexes were poorly emissive; photoinduced electron transfer was not a major quenching pathway in these species. These results show that seemingly similar emitters can undergo very different photophysical processes, and highlight the crucial role the linker can play.

Our initial experiences with MR arthrography / Kezdeti tapasztalataink az MR-artrográfiával.

INTRODUCTION: The gold standard method for shoulder surgery imaging is magnetic resonance imaging (MRI). The sensitivity of the conventional MRI for full thickness tears is way above 85%, for partial rotator cuff lesions this number is less than 40%. Diagnostic accuracy is equally low in detecting different variations of anterior labrum lesion and also in injury of the glenohumeral ligaments. Contrast agent given directly into the joint can improve these diagnostic inaccuracies. METHOD: We made the first shoulder joint related MR arthrography in February 2018 at the Semmelweis University. The studied period lasted for 17 months; during that time 29 examinations were performed. For the injection we used gadolinium-based contrast substance. RESULTS: In the case of 26 patients (89.9%), the contrast substance had a good position and distended well. From all of the shoulder MRI examinations, 9 (31%) surgical interventions were made, and 8 surgical findings had the same diagnosis as the radiologic description. CONCLUSION: The contrast substance given into the intraarticular space makes it easier to identify and detect the structures in the joint. The injection under X-ray screening is safe, it is absorbed from the joint in short time, and so far - based on our experience - there has not been any complication. It can help to identify injuries which are difficult to diagnose with conventional MRI, and helps planning before surgery. Orv Hetil. 2020; 161(36): 1514-1521.

Coordination Environment-Controlled Photoinduced Electron Transfer Quenching in Luminescent Europium Complexes.

The quenching of sensitized Eu(III) luminescence by photoinduced electron transfer from the excited light-harvesting antenna to Eu(III) was investigated. A series of complexes incorporating different metal binding sites and thus having varying Eu(III)/Eu(II) reduction potentials were prepared. The complexes were fully characterized using a combination of single-crystal X-ray crystallography and paramagnetic 1H NMR spectroscopy, the results of which support the structural similarity of the complexes. The redox and photophysical behavior of the Eu(III) center and the light-harvesting antenna were studied using cyclic voltammetry and steady-state and time-resolved emission spectroscopy on the nanosecond and millisecond time scales. The contribution of photoinduced electron transfer to the overall reduction of the Eu(III) luminescence quantum yield was found to be comparable and, in many cases, larger than the quenching caused by well-established processes such as coupling to X-H oscillators. These results suggest that the elimination or mitigation of photoinduced electron transfer could substantially improve the emissive properties of the widely used Eu(III)-based emitters.

The Impact of Early Epidural Discontinuation on Pain, Opioid Usage, and Length of Stay After Periacetabular Osteotomy.

BACKGROUND: Periacetabular osteotomy (PAO) is the standard of care for treatment of symptomatic acetabular dysplasia. Patients undergoing PAO for acetabular dysplasia have postoperative pain that can be managed with epidural analgesia. The purpose of this study was to evaluate the impact of the timing of the discontinuation of epidural analgesia on pain, opioid usage, and hospital length of stay (LOS). The study hypothesis was that removal of the epidural catheter on postoperative day 1 (POD1) would lead to reduced overall opioid usage and LOS compared with removal on POD2. METHODS: This is a retrospective before-and-after observational review of the impact of discontinuing epidural analgesia on POD1 versus POD2 in terms of in-hospital pain, opioid usage, and LOS. Baseline patient factors such as age, sex, and body mass index (BMI) as well as outcomes including mean and median of daily pain, total oral morphine milligram equivalents (MMEs) used per day, and LOS were recorded. Descriptive and comparative statistical analyses including multivariable main-effects linear regression modeling were performed to evaluate the impact of the timing of epidural removal on outcomes. RESULTS: Directly comparing outcomes for the day of epidural removal, patients with removal on POD1 had significantly less pain (mean of 4.6 versus 5.1 on the numeric rating scale [NRS], p = 0.033) and opioid usage (130.7 versus 200.4 MMEs, p < 0.001) than patients with removal on POD2. Additionally, LOS (3.3 versus 4.6 days, p < 0.001) and total opioid usage (333.0 versus 674.8 MMEs, p < 0.001) were significantly reduced in patients with epidural removal on POD1. These results persisted in multivariable analyses that were adjusted for age, sex, and BMI. CONCLUSIONS: This study demonstrated that patients with epidural removal on POD1 have significantly lower pain and an overall decrease in opioid usage on the date of epidural removal compared with patients undergoing epidural removal on POD2. Additionally, they have a shorter LOS as well as lower total opioid usage. Decreasing the duration of epidural usage may reduce pain, opioid usage, and LOS in patients undergoing PAO. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.