Hemoglobin (Hb) serves as the main oxygen transporter in erythrocytes, but it is also expressed in nonhematopoietic organs, where it serves an unknown function. In this study, microarray and proteomic analyses demonstrated Hb expression in the kidney. Rat kidneys were perfused extensively with saline, and glomeruli were isolated by several techniques (sieving, manual dissection, and laser capturemicrodissection). Reverse transcriptase-PCR revealed glomerular ␣-and ␤-globin expression, and immunoblotting demonstrated expression of the protein. In situ hybridization studies showed expression of the globin subunits in the mesangium, and immunostaining confirmed this localization of Hb. Furthermore, globin mRNA expression was detected in primary cultures of rat mesangial cells but not in cultured glomerular endothelial or epithelial cells. For investigation of Hb function in mesangial cells, the SV40-MES13 murine mesangial cell line was transfected with a vector expressing ␣-and ␤-globins; this overexpression reduced production of hydrogen peroxide-induced intracellular radical oxygen species and enhanced cell viability against oxidative stress. In summary, Hb is expressed by rat mesangial cells, and its potential functions may include antioxidative defense.

Renal senescence is characterized by interstitial fibrosis and loss of peritubular capillaries. In this study, we provided evidence of tubulointerstitial hypoxia and the operation of hypoxia-inducible factor (HIF) in the aging kidney. Using two distinct methods, pimonidazole immunostaining and the expression of the "hypoxia-responsive" reporter of the transgenic rats, we identified the age-related expansion of hypoxia in all areas of the kidney. Expansion was most prominent in the cortex. Clusters of hypoxic tubules were observed in the superficial cortical zones, areas adjacent to the outer nephrons and expanded in the medullary rays. The degree of hypoxia was positively correlated with the age-related tubulointerstitial injury (R(2) = 0.88, p <.01), which was associated with the upregulation of HIF-regulated genes, such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (GLUT1) (real-time polymerase chain reaction). These findings point to the involvement of hypoxia and highlight the pathological relevance of HIF and its target genes in the aging kidney.

BackgroundPatient-centered care has been one of the most frequently discussed principles in medical practice. However, there is a serious concern that the patient-centered attitudes of physicians diminish over the course of their medical education. This longitudinal study examined changes in resident physicians’ patient-centered attitudes and their confidence in communicating with patients, and explored the relationship between the two traits.MethodsThe study participants were resident physicians at a university hospital in Tokyo. Participants’ patient-centered attitudes (as measured by the Patient–Practitioner Orientation Scale [PPOS]), and their confidence in communicating with patients (as per the Physician Confidence in the Medical Interview scale: [PCMI]) were assessed through self-reported questionnaires completed at the beginning of residency (n = 204) and again at the end of the first year (n = 95).ResultsPPOS scores declined significantly during the year, both in terms of attitude toward sharing information and decision-making with patients, and attitude of caring for patients’ expectations and emotions. The shift in caring attitude differed significantly by gender. The increase in PCMI score was greater for those with a smaller decrease in PPOS score.ConclusionsAs seen in previous studies of medical students, resident physicians’ patient-centered attitudes declined during their first year of residency, while there may be a gender-based difference within the shift. The increase in physicians’ confidence in communicating with patients was greater for those who showed a smaller decline in patient-centered attitude. Additional studies are needed to detail the changes in physicians’ attitudes, confidence, and communication skills over the course of their medical training, and to develop systematic assessment and training programs.

Son D, Kojima I, Inagi R, Matsumoto M, Fujita T, Nangaku M. Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis. Am J Physiol Renal Physiol 294: F62-F72, 2008. First published October 24, 2007 doi:10.1152/ajprenal.00113.2007.-Accumulating evidence suggests a pathogenic role of chronic hypoxia in various kidney diseases. Chronic hypoxia in the kidney was induced by unilateral renal artery stenosis, followed 7 days later by observation of tubulointerstitial injury. Proteomic analysis of the hypoxic kidney found various altered proteins. Increased proteins included lipocortin-5, calgizzarin, ezrin, and transferrin, whereas the decreased proteins were ␣ 2u-globulin PGCL1, eukaryotic translation elongation factor 1␣ 2, and Cu/Zn superoxide dismutase (SOD1). Among these proteins, we focused on Cu/Zn-SOD, a crucial antioxidant. Western blot analysis and real-time quantitative PCR analysis confirmed the downregulation of Cu/Zn-SOD in the chronic hypoxic kidney. Furthermore, our laser capture microdissection system showed that the expression of Cu/Zn-SOD was predominant in the tubulointerstitium and was decreased by chronic hypoxia. The tubulointerstitial injury estimated by histology and immunohistochemical markers was ameliorated by tempol, a SOD mimetic. This amelioration was associated with a decrease in levels of the oxidative stress markers 4-hydroxyl-2-nonenal and nitrotyrosine. Our in vitro studies utilizing cultured tubular cells revealed a role of TNF-␣ in downregulation of Cu/Zn-SOD. Since the administration of anti-TNF-␣ antibody ameliorated Cu/Zn-SOD suppression, TNF-␣ seems to be one of the suppressants of Cu/Zn-SOD. In conclusion, our proteomic analysis revealed a decrease in Cu/Zn-SOD, at least partly by TNF-␣, in the chronic hypoxic kidney. This study, for the first time, uncovered maladaptive suppression of Cu/Zn-SOD as a mediator of a vicious cycle of oxidative stress and subsequent renal injury induced by chronic hypoxia. chronic kidney failure; oxidative stress ONCE RENAL DAMAGE REACHES a certain threshold, the progression of renal disease is consistent, irreversible and largely independent of the initial insult. The final common pathway in this process has been closely studied. The chronic hypoxia hypothesis, proposed by Fine et al. (11), emphasizes chronic ischemic damage in the tubulointerstitium as a final common pathway in end-stage kidney injury. Since its introduction, this fascinating hypothesis has been intensively investigated by many investigators (9,20,24). Despite intensive efforts to elucidate the pathomechanisms of chronic hypoxia on kidney damage, however, their complexity has hampered investigations and details remain scarce. Among others, mechanisms proposed to date include transdifferentiation (22), cell death (40 -42), production of extracellular matrix (26,27), and so on.Advances in proteomics technology offer promise to substantially improve our understanding and treatment of the molecular basis of disease. In particular, deciphering the a...

Introduction: This study aimed to verify the internal consistency and validity of the Japanese version of the 9-item Shared Decision-Making Questionnaire (SDM-Q-9) and investigate the association among patient factors, shared decision-making experienced by patients, and patients’ decision conflict during the treatment decision process in primary outpatient settings in Japan. Methods: Patients who visited a primary care outpatient unit for the first time and completed the Japanese version of SDM-Q-9 and the Decisional Conflict Scale (DCS) immediately after consultation were included. The internal consistency of SDM-Q-9 was assessed using Cronbach’s alpha coefficient. Factor analysis and structural equation modeling were used to investigate structural construct validity. The relationship among patient-perceived experiences of shared decision-making, decision conflict, and patient factors was evaluated using correlation analysis. Results: A total of 131 patients with chronic diseases (55.0% females, 28.2% aged ≥ 70 years) were included in this analysis. Cronbach’s alpha for the Japanese version of SDM-Q-9 was 0.917, indicating a high degree of internal consistency. Confirmatory factor analysis indicated that the Japanese version of SDM-Q-9 had a one-factor structure. Spearman’s rank correlation analysis indicated that the correlation between SDM-Q-9 and DCS was −0.577 ( p < 0.05), indicating a significant inverse correlation and convergent validity. Older age was positively associated with perceived support of the physician in understanding all information. Conclusions: We confirmed that the Japanese version of SDM-Q-9 was both reliable and valid for use in Japanese primary care settings. In addition, we found a clear association between shared decision-making and decisional conflict of patients.

IntroductionMedical and healthcare professionals’ empathy for patients is crucially important for patient care. Some studies have suggested that a significant decline in empathy occurs during clinical training years in medical school as documented by self-assessed empathy scales. Moreover, a recent study provided qualitative evidence that communication skills training in an examination context, such as in an objective structured clinical examination, might stimulate perspective taking but inhibit the development of compassionate care. Therefore, the current study examined how perspective taking and compassionate care relate to medical students’ willingness to show empathic behaviour and how these relations may change with communication skills training.MethodsA total of 295 fourth-year Japanese medical students from three universities completed the Jefferson Empathy Scale and a newly developed set of items on willingness to show empathic behaviour twice after communication skills training, pertaining to post-training and retrospectively for pre-training.ResultsThe findings indicate that students’ willingness to show empathic behaviour is much more correlated with perspective taking than with compassionate care. Qualitative descriptive analysis of open-ended question responses revealed a difficulty of feeling compassion despite showing empathic behaviour.DiscussionThese findings shed light on the conceptual structure of empathy among medical students and generate a number of hypotheses for future intervention and longitudinal studies on the relation between communication skills training and empathy.Electronic supplementary materialThe online version of this article (10.1007/s40037-018-0431-z) contains supplementary material, which is available to authorized users.

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BackgroundSharing information is crucial for discussion of problems and treatment decision making by patients and physicians. However, the focus of communication skills training in undergraduate medical education has been on building the relationship and gathering information; thus, resident physicians tend to be less confident about sharing information and planning treatment.This study evaluated the medical interviews conducted by resident physicians with a focus on information giving, and investigated its relationships with their confidence in communication and simulated patient (SP) satisfaction.MethodsAmong 137 junior resident physicians at a university hospital in Japan who participated in a survey of communication skills, 25 volunteered to conduct simulated medical interviews. The medical interviews were video-recorded and analyzed using the Roter Interaction Analysis System, together with additional coding to explore specific features of information giving. The SPs evaluated their satisfaction with the medical interview.ResultsResident physicians who were more confident in their communication skills provided more information to the patients, while SP satisfaction was associated only with patient-prompted information giving. SPs were more satisfied when the physicians explained the rationales for their opinions and recommendations.ConclusionOur findings underscore the importance of providing relevant information in response to the patient requests, and explaining the rationales for the opinions and recommendations. Further investigation is needed to clinically confirm our findings and develop an appropriate communication skills training program.