Mapping scientific research on the negative aspects of the medical school learning environment.

OBJECTIVE: We sought to understand the landscape of published articles regarding medical schools' learning environments (LE) worldwide, with an explicit focus on potentially harmful aspects of the LE as an effort to identify areas specifically in need of remediation or intervention that could prevent future unprofessional behaviors, burnout, violence and mistreatment among students and physicians. METHODS: A bibliometric analysis was conducted in six electronic databases (PubMed/Medline, Web of Science, Cochrane Library, SCOPUS, ERIC-ProQuest, and PsycINFO) up to December 31, 2016, including 12 themes: learning environment - general, hidden curriculum (harmful), unethical behaviors, bullying/hazing, violence, sexual discrimination, homophobia, racism, social discrimination, minorities discrimination, professional misconduct, and other negative aspects. RESULTS: Of the 9,338 articles found, 710 met the inclusion criteria. The most common themes were general LE (233 articles), unprofessional behaviors (91 articles), and sexual discrimination (80 articles). Approximately 80% of articles were published in the 21st century. CONCLUSION: There is a definite increase in scientific articles on negative aspects of the medical school LE in high-quality journals, especially in the 21st century. However, more studies are needed to investigate negative LE aspects with greater attention to experimental, longitudinal, and cross-cultural study designs.

Mapping scientific research on the negative aspects of the medical school learning environment

SUMMARY OBJECTIVE: We sought to understand the landscape of published articles regarding medical schools' learning environments (LE) worldwide, with an explicit focus on potentially harmful aspects of the LE as an effort to identify areas specifically in need of remediation or intervention that could prevent future unprofessional behaviors, burnout, violence and mistreatment among students and physicians. METHODS: A bibliometric analysis was conducted in six electronic databases (PubMed/Medline, Web of Science, Cochrane Library, SCOPUS, ERIC-ProQuest, and PsycINFO) up to December 31, 2016, including 12 themes: learning environment - general, hidden curriculum (harmful), unethical behaviors, bullying/hazing, violence, sexual discrimination, homophobia, racism, social discrimination, minorities discrimination, professional misconduct, and other negative aspects. RESULTS: Of the 9,338 articles found, 710 met the inclusion criteria. The most common themes were general LE (233 articles), unprofessional behaviors (91 articles), and sexual discrimination (80 articles). Approximately 80% of articles were published in the 21st century. CONCLUSION: There is a definite increase in scientific articles on negative aspects of the medical school LE in high-quality journals, especially in the 21st century. However, more studies are needed to investigate negative LE aspects with greater attention to experimental, longitudinal, and cross-cultural study designs.

RESUMO OBJETIVO: Buscou-se entender o panorama dos artigos publicados sobre os ambientes de aprendizagem (AA) das escolas médicas em todo o mundo, com um foco explícito nos aspectos potencialmente negativos do AA como um esforço para identificar áreas especificamente necessitadas de remediação ou intervenção que poderiam evitar futuros comportamentos não profissionais, violência e maus-tratos entre estudantes e médicos. MÉTODOS: Foi realizada uma análise bibliométrica em seis bases de dados eletrônicas (PubMed / Medline, Web of Science, Biblioteca Cochrane, SCOPUS, ERIC-ProQuest e PsycINFO) até 31 de dezembro de 2016, incluindo 12 temas: ambiente de aprendizagem - geral, currículo oculto (negativo), comportamentos antiéticos, bullying/trote, violência, discriminação sexual, homofobia, racismo, discriminação social, discriminação de minorias, má conduta profissional e "outros" aspectos negativos. RESULTADOS: Dos 9.338 artigos encontrados, 710 preencheram os critérios de inclusão. Os temas mais comuns foram LE geral (233 artigos), comportamentos não profissionais (91 artigos) e discriminação sexual (80 artigos). Aproximadamente 80% dos artigos foram publicados no século XXI. CONCLUSÃO: Há um claro aumento em artigos científicos sobre aspectos negativos da escola de medicina LE em periódicos de alta qualidade, especialmente no século XXI. No entanto, mais estudos são necessários para investigar aspectos negativos do LE com maior atenção aos desenhos de estudos experimentais, longitudinais e transculturais.

Mapping the scientific research on the negative aspects of the medical school learning environment.

OBJECTIVE: We sought to understand the landscape of published articles regarding medical schools' learning environments (LE) worldwide, with an explicit focus on potentially negative aspects of the LE as an effort to identify areas specifically in need of remediation or intervention that could prevent future unprofessional behaviours, burnout, violence and mistreatment among students and physicians. METHODS: A bibliometric analysis was conducted in six electronic databases (PubMed/Medline, Web of Science, Cochrane Library, SCOPUS, ERIC-ProQuest and PsycINFO) through December 31, 2016, including 12 themes: learning environment - general, hidden curriculum (negative), unethical behaviours, bullying/hazing, violence, sexual discrimination, homophobia, racism, social discrimination, minorities' discrimination, professional misconduct, and "other" negative aspects. RESULTS: Of 9,338 articles found, 710 met the inclusion criteria. The most common themes were general LE (233 articles), unprofessional behaviours (91 articles), and sexual discrimination (80 articles). Approximately 80% of articles were published in the 21st century. CONCLUSION: There is a clear increase in scientific articles on negative aspects of the medical school LE in high-quality journals, especially in the 21st century. However, more studies are needed to investigate negative LE aspects with greater attention paid to experimental, longitudinal, and cross-cultural study designs.

Mapping the scientific research on the negative aspects of the medical school learning environment

SUMMARY Objective: We sought to understand the landscape of published articles regarding medical schools' learning environments (LE) worldwide, with an explicit focus on potentially negative aspects of the LE as an effort to identify areas specifically in need of remediation or intervention that could prevent future unprofessional behaviours, burnout, violence and mistreatment among students and physicians. Methods: A bibliometric analysis was conducted in six electronic databases (PubMed/Medline, Web of Science, Cochrane Library, SCOPUS, ERIC-ProQuest and PsycINFO) through December 31, 2016, including 12 themes: learning environment - general, hidden curriculum (negative), unethical behaviours, bullying/hazing, violence, sexual discrimination, homophobia, racism, social discrimination, minorities' discrimination, professional misconduct, and "other" negative aspects. Results: Of 9,338 articles found, 710 met the inclusion criteria. The most common themes were general LE (233 articles), unprofessional behaviours (91 articles), and sexual discrimination (80 articles). Approximately 80% of articles were published in the 21st century. Conclusion: There is a clear increase in scientific articles on negative aspects of the medical school LE in high-quality journals, especially in the 21st century. However, more studies are needed to investigate negative LE aspects with greater attention paid to experimental, longitudinal, and cross-cultural study designs.

RESUMO OBJETIVO: Buscou-se entender o panorama dos artigos publicados sobre os ambientes de aprendizagem (AA) das escolas médicas em todo o mundo, com um foco explícito nos aspectos potencialmente negativos do AA como um esforço para identificar áreas específicamente necessitadas de remediação ou intervenção que poderiam evitar futuros comportamentos não profissionais, violência e maus-tratos entre estudantes e médicos. Métodos: Foi realizada uma análise bibliométrica em seis bases de dados eletrônicas (PubMed/Medline, Web of Science, Biblioteca Cochrane, Scopus, Eric-ProQuest e PsycInfo) até 31 de dezembro de 2016, incluindo 12 temas: ambiente de aprendizagem - geral, currículo oculto (negativo), comportamentos antiéticos, bullying/trote, violência, discriminação sexual, homofobia, racismo, discriminação social, discriminação de minorias, má conduta profissional e "outros" aspectos negativos. Resultados: Dos 9.338 artigos encontrados, 710 preencheram os critérios de inclusão. Os temas mais comuns foram LE geral (233 artigos), comportamentos não profissionais (91 artigos) e discriminação sexual (80 artigos). Aproximadamente 80% dos artigos foram publicados no século XXI. Conclusão: Há um claro aumento em artigos científicos sobre aspectos negativos da escola de medicina LE em periódicos de alta qualidade, especialmente no século XXI. No entanto, mais estudos são necessários para investigar aspectos negativos do LE com maior atenção aos desenhos de estudos experimentais, longitudinais e transculturais.

Flow cytometry assessment of graft-infiltrating lymphocytes can accurately identify acute rejection in kidney transplants.

BACKGROUND: Previously, we have reported that flow cytometry analysis of fine-needle aspirates can accurately predict rejection in kidney transplants treated with cyclosporine-azathioprine-prednisolone. In this study, we examined this technique's accuracy using current immunosuppression. METHODS: Kidney transplant recipients were treated with calcineurin inhibitors, mycophenolate mofetil, and prednisolone: 92 remained rejection-free - Group I - and 37 developed acute rejection - Group II. An allograft aspiration specimen and peripheral blood were collected from Group I on post-transplant day 7 and from Group II on the day of clinical rejection. RESULTS: Significant changes were seen in both aspiration and peripheral blood samples in several T cell subsets when comparing Groups I and II. A sensitivity of 94.6%, specificity of 85%, and AUC = 0.966 were observed through combining CD8DR with CD3CD69 values from aspiration specimen; the corresponding AUC in peripheral blood was 0.847. Irreversible rejections displayed a significantly higher activation score (p = 0.024). CONCLUSIONS: Flow cytometry analysis of aspiration specimen achieved high diagnostic performance in renal transplants through studying CD8DR and CD3CD69 under current immunosuppressive therapy. Peripheral blood analysis, although not significant, showed the same trend. The activation score anticipated the irreversibility of rejection. The data suggest this test, through an easily tolerated technique, merits further diagnostic use.

Postrenal transplantation body composition: different evolution depending on gender.

OBJECTIVE: Patients receiving regular hemodialysis have a lower body mass index, which is mainly caused by the reduction of fat mass and body cell mass (BCM) and the accompanying extracellular water (ECW) expansion. Kidney transplant (Tx) recipients normally regain subnormal renal filtration, and they must cope with significant therapeutic-associated metabolic side effects, which may compromise the recovery of normal nutritional status. We investigated the influence of renal function recovery on body fluid composition during the first period post-Tx, when immunosuppressive drugs doses are at their highest. We also analyzed the differences between males and females and compared them with healthy controls. METHODS: Eighteen patients (11 males and 7 females) were studied. Biolectric impedance analysis was done pre-Tx and at months 1 and 3 post-Tx. We considered the following parameters: total body water, ECW, intracellular water, Na:K exchangeable ratio, phase angle, and BCM. The healthy group was evaluated three times in a year interval. RESULTS: We observed differences between genders. Compared with healthy males, resistance, reactance, intracellular water, and BCM were greater and ECW was lower among Tx males at pre-Tx time. At months 1 and 3, we observed only different total body water in males compared with controls. Females did not display any differences in biolectric impedance analysis parameters compared with healthy controls, with the exception of lower reactance at month 1. CONCLUSIONS: Compared with healthy subjects, uremic males presented body water disturbances pre-Tx. During the first 3 months post-Tx, males showed an incomplete recovery of bioelectric impedance analysis parameters with a greater total body water, probably the result of drug therapy side effects. Pre-Tx, Tx females at pre-Tx time had no differences as compared with healthy females.

Body composition assessed by impedance changes very early with declining renal graft function.

BACKGROUND: Kidney transplant (Tx) restores renal filtration, although it does not achieve the function of two native kidneys, and with time it may variably involute back to chronic renal failure. We hypothesized that bioelectrical impedance analysis (BIA) might highlight differences for body compartments among Tx with different filtration rates, and we compared them with healthy controls. METHODS: 38 Tx patients (25 males, 13 females) were studied at 75.9 +/- 37.8 months postsurgery and divided into three groups: good creatinine clearance (CrCl, ml/min/1.73 m2; > 65.0), borderline (35.0 < CrCl < 60.0) and bad (CrCl < 35.0). BIA was assessed three times in a year. Total body water, extracellular water (ECW), intracellular water (ICW), Na:K exchange rate (Nae:Ke) and phase angle were studied. Healthy (n = 11) and hemodialysis (n = 11) groups were also studied. RESULTS: BIA showed no differences between healthy controls and good Tx while both borderline and bad Tx presented a significantly higher ECW and lower ICW than either good Tx or normal controls. Only good CrCl was different from predialysis. CONCLUSIONS: A good kidney graft manages to restore and maintain normal body composition, even with potential disturbances brought about by steroids and cyclosporine. With mild renal dysfunction a change in body compartments was observed, moving towards the composition of that with chronic renal failure patients.

Humoral immune response after kidney transplantation is enhanced by acute rejection and urological obstruction and is down-regulated by mycophenolate mofetil treatment.

The anti-allograft immune response may have a cellular and a humoral component. Lymphocytotoxic antibodies (Ab) and anti-human leucocyte antigen (HLA) Ab present before kidney transplantation carry an enhanced risk of acute rejection. Current immunosuppressive drugs act predominantly upon the cellular immune pathway which may leave unopposed the humoral mechanisms of anti-allograft response. We studied the production of lymphocytotoxic Ab and anti-HLA Ab after kidney transplantation under different drug therapies. Two hundred and sixty-four consecutive kidney transplant recipients treated with different immunosuppressive drugs, either stable and or with previous acute rejection or acute urologic obstruction, entered this study. Lymphocytotoxic Ab and anti-HLA Ab were evaluated by complement-dependent cytotoxicity and by ELISA. Ab donor-specificity was determined by flow cytometry. Both lymphocytotoxic Ab and anti-HLA Ab were significantly increased in acute rejection whatever the immunosuppressive regimen and almost significantly in urologic obstruction treated with azathioprine (AZA) groups. The presence of antidonor-specific Ab was associated with a significantly higher rate of graft loss. Mycophenolate mofetil (MMF) therapy significantly down-regulated Ab synthesis in all patients groups when compared with AZA. The development of humoral antidonor response post-transplantation is associated with a dismal graft prognosis. This is the first report that acute urologic obstruction may be followed by unspecific lymphocytotoxic and anti-HLA Ab synthesis, surmising that a protracted obstruction may promote renal fibrosis through antibody mediation. The significant down-regulation of the humoral response by MMF when compared with AZA may herald a lower risk to mount a chronic rejection process.

Cyclosporine enhances salt sensitivity of body water composition as assessed by impedance among psoriatic patients with normal renal function.

OBJECTIVE: Cyclosporine (CsA) therapy may be accompanied by a significant increase in blood pressure, either sodium (Na+) independent or Na+ dependent. The relationship between Na+ intake and body water distribution among patients treated with CsA has not been evaluated. We report the study, by bioelectrical impedance analysis (BIA), of water composition changes after dietary salt manipulations both before and during CsA treatment of psoriatic patients. METHODS: Ten normotensive psoriatic patients, ages 37 +/- 12 years (range, 19 to 54), with normal renal function were included. Each patient was assessed by BIA in 2 phases, before (phase 1) and during (phase 2) CsA therapy (3 mg/kg/day). In both phases, each patient was assessed in basal conditions (basal1 and basal2), on day 7 of a low-sodium diet (LS1 and LS2; 20 mEq/day) and on day 7 of a high-sodium diet (HS1 and HS2; 350 mEq/day). Plasma creatinine (Pcr), urinary volume excretion (Uv), urinary sodium (UNa+), urinary potassium (UK+), urinary osmolality (UOsmo), weight (Wt), resistance (R), reactance (Xc), total body water (TBW), extracellular water (ECW), intracellular water (ICW), Na:K exchangeable (Nae:Ke), phase angle (PA), and body cell mass (BCM) were evaluated. Blood pressure was monitored during 24 hours on the last day of each diet. Paired Student's t-test was used to analyze the different phases. RESULTS: Before CsA treatment, Wt, TBW and Nae:Ke were lower during LS1 than during basal1, whereas TBW was higher during HS1 than during LS1. During CsA, Wt, TBW, ECW, and Nae:Ke were lower during LS2 than during basal2, whereas ICW and PA were higher during LS2 than during basal2. HS2 showed higher TBW, ECW, and Nae:Ke and lower ICW, PA, and BCM than during LS2. Systolic blood pressure was higher during HS2 than during LS2 or HS1. In addition, diastolic blood pressure was higher during HS2 than during HS1. CONCLUSION: Body hydration status was more sensitive to dietary salt fluctuations during CsA treatment than without CsA, and a high-sodium diet seemed to enhance the CsA-induced hypertension side effect. Moreover, patients on low sodium intake under CsA treatment displayed neither any disturbance of body water composition nor any blood pressure change. Our data suggest that a low sodium intake might be very useful in preventing undesirable pressure and volume changes brought about by CsA treatment.

Bioimpedance analysis highlights changes in body composition at the early stages of impairment of kidney transplant function.

OBJECTIVE: Kidney transplantation restores renal filtration, although it does not achieve the function of 2 native kidneys, and with time it may involute back to chronic renal failure. We hypothesized that bioelectrical impedance analysis (BIA) might highlight differences for body compartments among kidney transplants (Tx) with different filtration rates. METHODS: Thirty transplantation patients (19 male, 11 female) were studied at 62.4+/-26.6 months postsurgery and were divided into 3 groups: good creatinine clearance (crCl, mL/min/1.73 m2; >65.0), borderline (35.0

Estradiol receptor binding to the epithelium of uterine lumen and glands: region- and time-related changes during preimplantation and periimplantation periods studied by autoradiography.

The presence and changes of estradiol nuclear binding and related functions in uterine luminal and glandular epithelium were studied before and after blastocyst implantation using receptor autoradiography with (3)H-estradiol-17beta in association with (3)H-thymidine incorporation and immunocytochemical binding of antibody to estrogen receptor ER-alpha. (3)H-estradiol nuclear binding is present but variable during days 1.5-7.5 of pregnancy. Sites of strong nuclear binding of (3)H-estradiol exhibit strong immunocytochemical staining with ER-alpha antibody. Qualitative and quantitative evaluation of autoradiograms reveal that there is a general increase of nuclear (3)H-estradiol binding during the first 3 days after fertilization in both luminal and glandular epithelium. The binding of estradiol is stronger in glandular epithelium from day 2.5 to day 7.5, paralleled by a rise in (3)H-thymidine incorporation on day 2.5. By comparison, in the epithelium of the uterine lumen (3)H-estradiol nuclear binding is low, but relatively high in epithelial cells at lateral branching of the lumen where the increase in (3)H-estradiol binding corresponds to an increased labeling index with (3)H-thymidine. A highly differentiated binding of (3)H-estradiol to luminal and glandular epithelium was demonstrated with region- and time-specific changes of related effects on cell proliferation, differentiation, and secretion, probably involving involution and remodeling. The strong (3)H-estradiol binding to glandular epithelium suggests that estradiol exerts pronounced effects on glandular activities in the periimplantation period.

Mitotracker green is a P-glycoprotein substrate.

P-glycoprotein has a widespread expression on normal tissues. The protein has also been strongly associated with the multidrug resistance phenotype (MDR) on tumor cells. The employment of flow cytometry and confocal microscopy has contributed to the discovery and application of new particular fluorescent dyes. Nevertheless, several studies are being performed in different cellular types neglecting the expression/activity of MDR proteins. Because many fluorochromes have been reported as P-glycoprotein substrates, an especial attention must be given to the properties of new dyes in the presence of MDR proteins. Flow cytometric analyzes of Mitotracker Green (MTG) fluorescence profile were performed in a human erythroleukemic cell line and its resistant counterpart. In this report we demonstrated that MTG, a probe used to evaluate the mitochondrial mass, is a P-glycoprotein substrate and its staining profile is dependent on the activity of this protein. In vitro studies on a human erythroleukemic cell line and its resistant counterpart revealed that MDR modulators (Cyclosporin A, Verapamil, and Trifluoperazine) alter the MTG fluorescence pattern on a resistant cell line. The findings suggest that attention should be given to the expression of P-glycoprotein when performing an evaluation of mitochondria properties with MTG.

Compared to mycophenolate mofetil, rapamycin induces significant changes on growth factors and growth factor receptors in the early days post-kidney transplantation.

BACKGROUND: The new immunosuppressive drug Rapamycin (Rapa) is endowed with a mechanism of action that is distinct from that of calcineurin inhibitors. It has been claimed that Rapa does not significantly modulate either the cytokine expression or the transcription of several growth factors in mitogen-activated T cells. Previously, we reported that fine-needle aspiration biopsy (FNAB) sample cultures synthesize a large array of cytokines, and some of them may be powerful predictors of acute rejection in renal transplants. We hypothesized that Rapa may induce significant changes on cytokine production by FNAB sample cultures and on serum cytokine receptors when compared to other immunosuppressive drugs. METHODS: Kidney transplants treated with CsA-Rapa-Pred (Rapa group) were compared with transplants treated with CsA-mycophenolate mofetil-Pred (MMF group). They were studied on day 7 posttransplantation, and they remained rejection free for at least the first 6 months. FNAB samples were cultured and the supernatants were collected at 48 hr of incubation and analyzed by ELISA for interleukin 1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-10, IL-18, monocyte chemotactic protein 1 (MCP-1), soluble tumor necrosis factor I, and transforming growth factor (TGF)-beta(1). The soluble receptors for IL-1, IL-2, IL-6, and tumor necrosis factor alpha, together with IL-2 and IL-18 were also measured in serum. RESULTS: Significant differences were observed when comparing Rapa with the MMF group. IL-18 and TGF-beta(1) synthesis were up-regulated, whereas IL-6 and MCP-1 were down-regulated in FNAB sample cultures. The Rapa group showed a significant down-regulation of each cytokine receptor and of IL-2 in serum. CONCLUSIONS: Rapa was associated with a decreased synthesis of primarily monocyte-derived cytokines and enhanced production of TGF-beta(1), which in an appropriate cytokine milieu may promote allograft tolerance. The down-regulation of cytokine receptors and IL-2 may be associated with a depressed immune response towards the kidney allograft.