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Background: Improving the quality of care relies on understanding patients' perceptions and expectations based on their experiences. The study aimed to determine the gaps between patients’ perceived value and expected value, and to identify critical areas for outpatient service improvement. Method: This cross-sectional study was conducted in China from November 2020 to February 2021. A sample of 572 outpatients, randomly selected from a comprehensive tertiary public hospital, was surveyed using a validated patient perceived value questionnaire. Importance-performance analysis was used to evaluate the differences between patients' perceived and expected value. Results: The scores of patients’ expected value for outpatient services were significantly higher than their perceived value in all 29 items and 8 dimensions. The items with the highest and lowest gaps were “short waiting time” (−1.52) and “hospital reputation and popularity” (−0.24) respectively, and the dimensions of price and efficiency (functional value) were located in the quadrant of high expectation and low perception. Conclusion: Our findings are useful for hospital administrators and policymakers to identify strategic focus areas and allocate resources rationally and effectively. We suggest healthcare providers should take measures to narrow the gaps, especially in terms of service efficiency and price.

Abstract Background Focusing on patients’ perceived values is essential for patient-centered health care. Only by identifying the patient’s preferred values can we better meet their needs and provide them with valuable medical services. This study aimed to construct and validate a research model to obtain an overall quantification of patient value during outpatient encounters. Methods The development of the research model was based on the reviewed literature, and an initial theoretical framework was formed by an expert panel discussion. A scale questionnaire for all the items was adapted from previous research related to patient value, verified using a presurvey, and thus used for data collection for this study. The structural equation model was used to determine and evaluate the research model of the values patients perceived during outpatient encounters. Results 572 eligible respondents who completed outpatient visits from a typical public hospital in China participated in this study from November 2020 to February 2021. We constructed the patient perceived value (PPV) model to identify core values, which includes eight dimensions and 29 items in terms of functional value (installation, efficiency, price, service quality), emotional value (interactive, control), and social value (accessibility, image) from two subgroups of patient value outside and in the outpatient visit process. Cronbach’s alpha for the whole model was 0.950. The confirmatory factor analysis showed that the PPV model fits well, with a correlation of 0.83 between the two subgroups. Conclusion It is essential to recognize the values based on patients’ perceptions and experiences throughout the entire visit process. Our findings offer targeted insights for healthcare administrators, enabling them to holistically optimize outpatient service processes and continually enhance the quality of outpatient medical services from the patient’s perspective.

In this note, we establish an integral inequality for compact and orientable real hypersurfaces in complex two-plane Grassmannians G2ℂm+2, involving the shape operator A and the Reeb vector field ξ. Moreover, this integral inequality is optimal in the sense that the real hypersurfaces attaining the equality are completely determined. As direct consequences, some new characterizations of the real hypersurfaces in G2ℂm+2 with isometric Reeb flow can be presented.

BackgroundPrevious studies, often simply using either objective workload or mental workload as a measure of physician workload in various healthcare settings might have failed to comprehensively reflect the real workload among physicians. Despite this, there is little research that further explores a comprehensive workload evaluation framework with the integration of objective workload and mental workload to describe their comprehensive workload.MethodsA comprehensive evaluation framework for physician workload was proposed based on the combination of objective workload and task-level mental workload also with the consideration of quality of provided medical services and served patient complexity; and accordingly, an integrated evaluation model for physician comprehensive workload (PCW) tethered to outpatient practice was developed and further applied to perform a PCW analysis using cross-sectional data on outpatient workload of 1,934 physicians mainly from 24 hospitals in 6 provinces in Eastern, Central, and Western China. Multiple linear regression and multinomial logistic regression analyses were established to identify significant factors influencing the PCW.ResultsOverall, the average score of PCW tethered to outpatient practice Chinese physicians experienced was 811.30 (SD=494.98) with concentrating on between 200 and 1,200. Physicians who were female, from Eastern or Western China, and those who worked >60 h per week and longer outpatient hours per week were more likely to experience a higher PCW. 11.2% of participating physicians were identified as very high PCW physicians, compared with 11.6% as low PCW physicians, 45.5% as medium PCW physicians and 30.7% as high PCW physicians. Those who were female, older, from Western China, those who had lower educational levels, lower professional titles and longer working years in the current institution, and those who worked in tertiary A hospitals and Internal or Surgical, and worked >60 h per week and longer outpatient hours per week were more likely to be very high PCW physicians.ConclusionsOur work has a potential application for comprehensively assessing physician workload tethered to outpatient practice and could provide a solid foundation for hospital managers to further accurately determine and identify physicians with high workload, who would otherwise be missed in either objective workload or mental workload.

BackgroundWorkflow interruptions are frequent in hospital outpatient clinics. Eventually, not only reducing the work efficiency and quality, but also further threatening patient safety. Over the last 10–15 years, research on workflow interruptions in inpatient care has increased, but there is a lack of research on the interruptions in outpatient clinics. The present study aimed to study the differences in physicians' workflow interruptions among outpatient departments in the tertiary hospital in China.MethodsIn a tertiary hospital, a standardized observational study of 32 doctors' workflow in outpatient department of four typical clinical specialties was conducted. The record of workflow interruptions was based on a self-made observation instrument after verifying its reliability and validity. Linear regression methods were used to assess outpatient characteristics as predictors of the number of interruptions. The Kruskal-Wallis test was used to analyze the difference about the duration of interruptions among specialties, and the Chi-Square Test was used to examine the sources of interruptions among different specialties, to determine whether interruption source is associated with specialty.ResultsThe number of patients was the significant independent predictor of the number of interruptions (p < 0.001). In terms of work tasks being interrupted, the highest interruption rate occurred when physicians were asking health history: 19.95 interruptions per hour. The distribution of interruption sources among the four clinical specialties were statistically different (X2 = 16.988, p = 0.049).ConclusionThe findings indicate that physicians' workflow interruptions are connected with many contents in the work system. Further emphasis should be placed on the effective application of hospital management measures in an interrupted environment to promote a safe and efficiency outpatient care.

BackgroundPhysician dissatisfaction with more time spent on related paperwork but less time available for direct interaction with patients is increasing internationally. Increased physician workload resulting from paperwork might negatively affect their interaction with patients and increase the risk for burnout. This study aimed to investigate the level of physician workload tethered to paperwork during outpatient encounters and explore its latent workload subgroups among Chinese physicians.MethodsA cross-sectional survey was conducted via online questionnaire primarily in 24 hospitals in 6 provinces in Eastern, Central, and Western China from November 2020 to February 2021. The Chinese physician mental workload scale developed by our research team was used for assessment of physician workload tethered to paperwork. Physicians were categorized into different subgroups of workload via latent profile analysis. Multinomial logistic regression was subsequently performed to examine how demographic variables differ among physicians belonging to different subgroups.ResultsA total of 1,934 valid questionnaires were received. Chinese physicians reported medium levels of workload while performing non-physician-patient communication work tasks characterized by paperwork during outpatient encounters. Four latent workload subgroups were identified: “low workload group” (8.8%), “medium workload group” (34.0%), “high workload group” (42.1%) and “very high workload group” (15.1%). Compared with the other latent workload subgroups, physicians belonging to the “very high workload group” were more likely to be younger, married, those who had worse health status, lower educational levels and lower average monthly incomes, those who worked more years in the current institution, more hours per week and longer outpatient hours per week, and those who worked in public general hospitals, tertiary B hospitals and Obstetrics and Gynecology, and saw more than 50 outpatients per day, with more time spent on per patient.ConclusionsThere exit four latent workload subgroups among Chinese physicians tethered to paperwork during outpatient encounters along with great individual variations among these subgroups. The characteristics of the latent “very high workload group” can help permit more targeted guidance for developing interventions with optimized human resource allocation to, in turn, increase the time available for direct interaction with patients, thereby resulting in improved quality of physician-patient interactions and decreased risk for physician burnout.

Background: The aim of this study is to develop a scale and evaluate its' validity and reliability to measure the joy in work of doctors.Methods: Based on literature review and panel discussion, the scale framework and item pool were determined. Next, the items were modified by two rounds of expert consultation. Then the pre-investigation was applied and the formal version of scale was formed. Last, the reliability and validity of the scale were tested with 426 physicians.Results: The scale was composed of four dimensions: work autonomy needs, competency identification needs, competency perception needs and work relationship needs. Each dimension had 7 items, and both reliability and validity were acceptable. The Cronbach α coefficient and half-reliability coefficient of the whole scale were 0.954 (>0.9) and 0.974 (>0.9). The Spearman correlations of item-total score ranged from 0.556 to 0.749, indicating a good-item total score correlation. The χ 2/ df, RMSEA, RMR, GFI, CFI, and TLI, CFA of the maximum likelihood method supported a good fit with the model.Conclusions: Based on the self-determination theory, this study develops a scale to measure the joy in work of doctors. It has good validation and reliability, which is useful for doctors and medical institutions to take steps to improve happiness.

Objective: The purpose of this study is to investigate the mental workload level of physicians in outpatient practice since the normalization of prevention and control of the COVID-19 pandemic in China and explore the subtypes of physicians regarding their mental workload.Methods: A cross-sectional survey of 1,934 physicians primarily in 24 hospitals in 6 provinces in Eastern, Central, and Western China was conducted from November 2020 to February 2021. A latent profile analysis was performed to identify clusters based on the six subscales of the Chinese version of physician mental workload scale developed by our research team. Chi-square tests were performed to explore the differences in demographic characteristics of the subtypes among the subgroups, and multinomial logistic regression analysis was further conducted to identify the determinants of the subtypes of physicians.Results: Overall, the participating physicians reported high levels of task load but with high self-assessed performance (68.01 ± 14.25) while performing communication work tasks characterized by direct patient interaction in outpatient clinics. About 33.8% of the participating physicians were identified as “high workload and high self-assessment” subtype, compared to 49.7% “medium workload and medium self-assessment” subtype and 16.4% “low workload and low self-assessment” subtype. Physicians in “high workload and high self-assessment” subtype had the highest mean mental workload score. Physicians who were female, younger, married, worse health status, those who had lower educational level and an average monthly income of 5,001–10,000 RMB, those who worked in tertiary A hospitals, more hours per week and more than 40 h per week in outpatient clinics, and those who saw more outpatients per day, and spent more time per patient but with higher outpatient satisfaction were more likely to belong to “high workload and high self-assessment” subtype.Conclusion: Our findings can help provide a solid foundation for developing targeted interventions for individual differences across physicians regarding their mental workload. We suggest the hospital managers should pay more attention to those physicians with characteristics of the “high workload and high self-assessment” subtype and strengthen the management of the workload of this subtype of physicians to reduce the risks of their mental health, and to maintain their high work performance in outpatient clinics.

In this paper, we classified the paracontact metric κ,μ-manifold satisfying the Miao-Tam critical equation with κ>−1. We proved that it is locally isometric to the product of a flat n+1-dimensional manifold and an n-dimensional manifold of negative constant curvature −4.

Let Mn,g,f be a complete gradient shrinking Ricci soliton of dimension n≥3. In this paper, we study the rigidity of Mn,g,f with pointwise pinching curvature and obtain some rigidity results. In particular, we prove that every n-dimensional gradient shrinking Ricci soliton Mn,g,f is isometric to ℝn or a finite quotient of Sn under some pointwise pinching curvature condition. The arguments mainly rely on algebraic curvature estimates and several analysis tools on Mn,g,f, such as the property of f-parabolic and a Liouville type theorem.

It is known that there does not exist any Hopf hypersurface in complex Grassmannians of rank two of complex dimension 2m with constant sectional curvature for m≥3. The purpose of this article is to extend the above result, and without the Hopf condition, we prove that there does not exist any locally conformally flat real hypersurface for m≥3.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent and often associated with chronic hypoxia. Previous studies have shown alterations of cerebral oxygenation and cardiac repolarization in COPD patients (GOLD stage II-IV). Airplane travel is common in patients with COPD; however, the clinical effects of a diminished oxygen partial pressure in aircraft cabin environments at cruising altitude remain elusive. The aim of this study was to assess changes of cerebral oxygenation as well as parameters of cardiac repolarization during a hypoxia altitude simulation combined with mild physical activity in these patients. METHODS: Patients with COPD and healthy subjects (10 per group) randomly selected from the Charité outpatient clinic conducted a hypoxia altitude simulation test which consisted of three phases. The regional cerebral oxygen saturation (rSO₂) of the frontal cortex was measured at rest using near-infrared spectroscopy (NIRS). Furthermore, oxygen saturation (S p O₂), blood pressure, and heart rate values, as well as a 12-lead-ECG, were recorded. Subsequently, a mild treadmill exercise program (25 W) was divided into 10 min of normoxia (pre-hypoxia), 30 min of mild hypoxia (F I O₂ = 0.15), followed by a second 10-min period of normoxia (post-hypoxia). Meanwhile, mentioned parameters were recorded in 2-min intervals. P, PQ, QRS, QT, QTc, QTd, T-peak-T-end interval (TpTe), and corrected TpTe (TpTec) were measured on three ECG complexes, each at baseline, at the end of the normoxic phase, and at the end of the hypoxic phase. RESULTS: A total of 10 patients with COPD and 10 control subjects were included in this study. S p O₂ was significantly lower in COPD patients throughout the whole test. Frontal cerebral rSO₂ was significantly lower in the left hemisphere during hypoxia altitude simulation in COPD patients (59.5 ± 8.5 vs. 67.5 ± 5.7). CONCLUSIONS: We show reduced left frontal cerebral oxygenation during hypoxia and mild exercise in patients with COPD, suggesting diminished altitude resilience and altitude capabilities. Preflight hypoxia assessment might be recommended to patients with severe COPD. Dehe L, Hohendanner F, Gültekin E, Werth G, Wutzler A, Bender TO. Hypoxia altitude simulation and reduction of cerebral oxygenation in COPD patients . Aerosp Med Hum Perform. 2023; 94(3):102-106.

Background: Emerging evidences indicate that glucocorticoid receptors (GR) play a regulatory role in cardiac function, particularly with regard to the autonomic nervous system. Therefore, this study aimed to demonstrate the expression and the precise anatomical location of GR in relation to the parasympathetic and sympathetic innervations of the heart., Methods: The present study used tissue samples from rat heart atria to perform conventional reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, and double immunofluorescence confocal analysis of GR with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) as well as the mineralocorticoid receptor (MR)., Results: Double immunofluorescence labeling revealed that GRs were co-expressed with VAChT in parasympathetic principal neuronal somata and nerve terminals innervating atrium. Also, GR colocalized with the sympathetic neuronal marker TH in a cluster of small intensely fluorescent (SIF) cells, on intracardiac nerve terminals and in the atrial myocardium. GR immunoreactivity was scarcely identified on CGRP-immunoreactive sensory nerve terminals. Approximately 20% of GR immunoreactive neuronal somata co-localized with MR. Finally, conventional RT-PCR and Western blot confirmed the presence of GR and MR in rat heart atria., Conclusion: This study provides evidence for the existence of GR predominantly on cardiac parasympathetic neurons and TH-immunoreactive SIF cells suggesting a functional role of cardiac GR on cardiovascular function by modulation of the cardiac autonomic nervous system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mousa, Dehe, Aboryag, Shaqura, Beyer, Schäfer and Treskatsch.)

In previous studies, upregulation of myocardial opioid receptors as well as the precursors of their endogenous ligands were detected in the failing heart due to chronic volume overload. Moreover, opioid receptor blockade by naltrexone improved left ventricular function. In parallel, inflammatory processes through cytokines have been confirmed to play an important role in the pathogenesis of different forms of heart failure. Thus, the present study examined the systemic and myocardial inflammatory response to chronic volume overload and its modulation by chronic naltrexone therapy. Chronic volume overload was induced in male Wistar rats by applying an infrarenal aortocaval fistula (ACF) for 28 days during which the selective opioid receptor antagonist naltrexone ( n = 6) or vehicle ( n = 6) were administered via a subcutaneously implanted Alzet minipump. The ultrastructural, morphometric and hemodynamic characterization of ACF animals were performed using an intraventricular conductance catheter in vivo and electron microscopy in vitro . Co-localization of mu-, delta- and kappa-opioid receptor subtypes (MOR, DOR, and KOR respectively) with the voltage gated L-type Ca2+ channel (Cav1.2), the ryanodine receptor (RyR), and mitochondria in cardiomyocytes as well as IL-6, IL-12, TNF-alpha, and Malondialdehyde (MDA) were determined using double immunofluorescence confocal microscopy, RT-PCR and ELISA, respectively. In rat left ventricular myocardium, three opioid receptor subtypes MOR, DOR, and KOR colocalized with Cav1.2, RyR and mitochondria suggesting a modulatory role of the excitation-contraction coupling. In rats with ACF-induced volume overload, signs of heart failure and myocardial ultrastructural damage, chronic naltrexone therapy improved cardiac function and reversed the systemic and myocardial inflammatory cytokine expression as well as lipid peroxidation. In conclusion, antagonism of the cardiodepressive effects of the myocardial opioid system does not only improve left ventricular function but also blunts the inflammatory response and lipid peroxidation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dehe, Mousa, Shaqura, Shakibaei, Schäfer and Treskatsch.)

Recent interest has focused on the mineralocorticoid receptor (MR) and its impact on the myocardium and the performance of the heart. However, there is a lack of evidence about MR expression and its endogenous ligand aldosterone synthesis with specific regard to the intrinsic cardiac nervous system. Therefore, we looked for evidence of MR and aldosterone in sympathetic and parasympathetic neurons of intracardiac ganglia. Tissue samples from rat heart atria were subjected to conventional reverse-transcriptase polymerase chain reaction (PCR), Western blot, and double immunofluorescence confocal analysis of MR, corticosterone-inactivating enzyme 11β-hydroxysteroid-dehydrogenase-2 (11β-HSD2), aldosterone, and its processing enzyme CYP11B2 together with the neuronal markers vesicular acetylcholine transporter (VAChT) and tyrosine hydroxylase (TH). Our results demonstrated MR, 11β-HSD2, and CYP11B2 specific mRNA and protein bands in rat heart atria. Double immunofluorescence labeling revealed coexpression of MR immunoreactivity with VAChT in large diameter parasympathetic principal neurons. In addition, MR immunoreactivity was identified in TH-immunoreactive small intensely fluorescent (SIF) cells and in nearby VAChT- and TH-immunoreactive nerve terminals. Interestingly, the aldosterone and its synthesizing enzyme CYP11B2 and 11β-HSD2 colocalized in MR- immunoreactive neurons of intracardiac ganglia. Overall, this study provides first evidence for the existence of not only local expression of MR, but also of 11β-HSD2 and aldosterone with its processing enzyme CYP11B2 in the neurons of the cardiac autonomic nervous system, suggesting a possible modulatory role of the mineralocorticoid system on the endogenous neuronal activity on heart performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dehe, Mousa, Aboryag, Shaqura, Beyer, Schäfer and Treskatsch.)

Purpose: Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation-contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure., Methods: Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls., Results: In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls., Conclusion: Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.

Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

Background: This study investigated histopathological changes and apoptotic factors that may be involved in the renal damage caused by congestive heart failure in a rat model of infrarenal aortocaval fistula (ACF)., Methods: Heart failure was induced using a modified approach of ACF in male Wistar rats. Sham-operated controls and ACF rats were characterized by their morphometric and hemodynamic parameters and investigated for their histopathological, ultrastructural, and apoptotic factor changes in the kidney., Results: ACF-induced heart failure is associated with histopathological signs of congestion and glomerular and tubular atrophy, as well as nuclear and cellular degeneration in the kidney. In parallel, overexpression of proapoptotic Bax protein, release of cytochrome C from the outer mitochondrial membrane into cell cytoplasm, and nuclear transfer of activated caspase 3 indicate apoptotic events. This was confirmed by electron microscopic findings of apoptotic signs in the kidney such as swollen mitochondria and degenerated nuclei in renal tubular cells., Conclusions: This study provides morphological evidence of renal injury during heart failure which may be due to caspase-mediated apoptosis via overexpression of proapoptotic Bax protein, subsequent mitochondrial cytochrome C release, and final nuclear transfer of activated caspase 3, supporting the notion of a cardiorenal syndrome.

Cardiac function is one important determinant to maintain tissue oxygenation and is thus highly regulated. In this context, it is interesting that centrally mediated opioidergic influence on cardiac function has long been known. Only recently, KOR and DOR have been found to be expressed in healthy left ventricular myocardium in rats and colocalized with parts of the excitation-contraction-coupling system. However, several comments in literature exist doubting the existence of MOR in cardiac tissue. We, therefore, aimed to detect MOR in rat left ventricular cardiomyocytes, and to evaluate whether MOR and POMC are regulated during heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics and the existence of MOR and POMC was investigated by means of radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Membrane MOR selective binding sites were detected in the left ventricular myocardium, however, they were lower in abundance than KOR- and DOR-specific binding sites and B max of MOR could not be determined. In left ventricular cardiomyocytes, MOR colocalized with parts of the excitation-coupling mechanism, e.g., Cav1.2 of the cell membrane and invaginated T-tubules as well as the ryanodine receptor of the sarcoplasmatic reticulum. More importantly, MOR strongly colocalized with mitochondria of left ventricular cardiomyocytes. Volume overload was not associated with an altered expression of MOR and POMC on both mRNA and protein level. These findings provide evidence for the existence of MOR on the cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular cardiomyocytes in rats. However, heart failure does not result in an altered expression of the cardiac MOR-opioid system. Thus, MOR agonist treatment-commonly used in the clinical setting-might directly affect cardiac function, which needs to be evaluated in greater detail in the near future.

The role of the cardiac opioid system in congestive heart failure (CHF) is not fully understood. Therefore, this project investigated the cellular localization of delta opioid receptors (DOR) in left ventricle (LV) myocardium and adaptive changes in DOR and its endogenous ligand, the precursor peptide proenkephalin (PENK), during CHF. Following IRB approval, DOR localization was determined by radioligand binding using [H(3)]Naltrindole and by double immunofluorescence confocal analysis in the LV of male Wistar rats. Additionally, 28 days following an infrarenal aortocaval fistula (ACF) the extent of CHF and adaptions in left ventricular DOR and PENK expression were examined by hemodynamic measurements, RT-PCR, and Western blot. DOR specific membrane binding sites were identified in LV myocardium. DOR were colocalized with L-type Ca(2+)-channels (Cav1.2) as well as with intracellular ryanodine receptors (RyR) of the sarcoplasmatic reticulum. Following ACF severe congestive heart failure developed in all rats and was accompanied by up-regulation of DOR and PENK on mRNA as well as receptor proteins representing consecutive adaptations. These findings might suggest that the cardiac delta opioid system possesses the ability to play a regulatory role in the cardiomyocyte calcium homeostasis, especially in response to heart failure.

Opioids have long been known for their analgesic effects and are therefore widely used in anesthesia and intensive care medicine. However, in the last decade research has focused on the opioidergic influence on cardiovascular function. This project thus aimed to detect the precise cellular localization of kappa opioid receptors (KOR) in left ventricular cardiomyocytes and to investigate putative changes in KOR and its endogenous ligand precursor peptide prodynorphin (PDYN) in response to heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics. In addition, the existence and localization as well as adaptive changes of KOR and PDYN were investigated using radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Similar to the brain and spinal cord, [(3)H]U-69593 KOR selective binding sites were detected the left ventricle (LV). KOR colocalized with Cav1.2 of the outer plasma membrane and invaginated T-tubules and intracellular with the ryanodine receptor of the sarcoplasmatic reticulum. Interestingly, KOR could also be detected in mitochondria of rat LV cardiomyocytes. As a consequence of heart failure, KOR and PDYN were up-regulated on the mRNA and protein level in the LV. These findings suggest that the cardiac kappa opioidergic system might modulate rat cardiomyocyte function during heart failure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

When magnetic compass orientation of migratory robins was tested, the birds proved well oriented under low intensity monochromatic light of shorter wavelengths up to 565 nm green; from 583 nm yellow onward, they were disoriented. In the present study, we tested robins under bichromatic lights composed (1) of 424 nm blue and 565 nm green and (2) of 565 nm green and 583 nm yellow at two intensities. Under dim blue-green light with a total quantal flux of ca. 8 × 10(15)quanta/sm(2), the birds were well oriented in their migratory direction by their inclination compass; under blue-green light of twice this intensity, their orientation became axial. In both cases, the magnetic directional information was mediated by the radical pair processes in the eye. When green and yellow light were combined, however, the nature of the behavior changed. Under green-yellow light of the higher intensity, the birds showed a 'fixed direction' response that was polar, no longer controlled by the normal inclination compass; under dim green-yellow light, the response became axial. Under these two light conditions, the respective directional information was mediated by the magnetite-based receptors in the skin of the upper beak. Apparently, yellow light leads to a change from one magnetoreception system to the other. How this change is effected is still unknown; it appears to reflect complex interactions between the visual and the two magnetoreception systems., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Under 502 nm turquoise light combined with 590 nm yellow light and in total darkness, European robins, Erithacus rubecula, no longer prefer their migratory direction, but exhibit so-called fixed direction responses that do not show the seasonal change between spring and autumn. We tested robins under these light conditions in the local geomagnetic field of 46 microT, a field of twice this intensity, 92 microT, and a field of three times this intensity, 138 microT. Under all three magnetic conditions, the birds preferred the same easterly direction under turquoise-and-yellow light and the same northwesterly direction under dark, while they were oriented in their seasonally appropriate direction under control conditions. "Fixed direction" responses are thus not limited to a narrow intensity window as has been found for normal compass orientation. This can be attributed to their origin in the magnetite-based receptor in the upper beak, which operates according to fundamentally different principles than the radical pair mechanism in the retina mediating compass orientation. "Fixed direction" responses are possibly a relict of a receptor mechanism that changed its function, now mainly providing information on magnetic intensity.