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Background: Babesiosis poses significant risks of adverse outcomes in individuals with immunocompromising conditions (IC) and asplenia/hyposplenia (AH). This study compares clinical outcomes between these vulnerable groups and immunocompetent patients., Methods: A multicenter retrospective cohort study included adult patients with laboratory-confirmed babesiosis from 2009 to 2023. Complications, management, and outcomes were compared between patients with IC/AH (ICAH) and without ICAH (immune intact cohort)., Results: Of 225 patients (mean age 66 years, 36% female), 112 were ICAH. ICAH patients had higher median peak parasitemia (2.8% vs. 0.9%, p<0.0001) and higher rates of complications, including acute kidney injury (24% vs. 11%, p=0.016), acute respiratory distress syndrome (11% vs. 4%, p=0.041), and were more likely to undergo packed red blood cell transfusion (31% vs. 17%, p=0.023) and exchange transfusion (18% vs. 6%, p=0.008). Treatment duration was longer in the ICAH cohort (median 27 vs. 10 days, p<0.001), particularly in those with both IC and AH (median 43 days, p=0.003). ICAH patients had higher 12-month all-cause mortality (7% vs. 1%, p=0.019) and recurrence rates (8% vs. 0%, p=0.001). Hematologic malignancy (OR=7.0, p=0.023) and B-cell-depleting therapies (OR=9.4, p=0.015) were significant predictors of recurrence. Despite most patients undergoing follow-up testing with blood smears and PCR, these did not reliably predict recurrence., Conclusion: Patients with ICAH with babesiosis experience more severe disease and higher complication rates. Follow-up testing, including blood smear and PCR, did not reliably predict recurrence, highlighting the need for more effective monitoring strategies in these high-risk populations., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The transition from medical school to residency is a critical developmental phase; coaching may help students prepare for this role transition., Aims: We explored whether near-peer coaching could improve a specific workplace skill prior to residency., Methods: A resident-as-coach program was piloted for the medicine sub-internship, an advanced acting internship rotation. Between March and June 2021, 26 students were assigned a resident coach ( n  = 16). Resident coaches completed one training session, and student-coach dyads met for one coaching session on 'pre-rounding'- gathering patient data before rounds. The program was evaluated through surveys and focus groups., Results: 20/26 students and 14/16 residents completed the survey. 19/20 students identified a pre-rounding challenge and reported increased pre-rounding efficiency; all committed to one actionable step for improvement. All 16 residents felt their coaching skills improved. In focus groups, students valued the program's focus on honing a relevant skill in a safe, near-peer setting. Residents expressed their intent to incorporate coaching into their future work., Conclusions: A resident-as-coach model can be effective in preparing students for residency, while concurrently building residents' coaching skills.

Purpose: This study examines how internal medicine clerkship faculty and leadership conceptualize professionalism and professional behaviors and attitudes, identifies whether and how faculty use metrics to assess professionalism and factor it into clerkship grades, and describes barriers that prevent faculty from feeling prepared to support the development of professional behaviors in students., Method: The Clerkship Directors in Internal Medicine opened a call for thematic survey section proposals to its physician-faculty members, blind-reviewed all submissions, and selected 4 based on internal medicine clinical clerkship training experience relevance. The survey launched on October 5 and closed on December 7, 2021. Data were analyzed using descriptive statistics., Results: Of 137 core clerkship directors (CDs) at Liaison Committee on Medical Education-accredited medical schools, 103 (75.2%) responded to the survey. Of 102 respondents (1 nonrespondent), 84 (82.4%) identified professional behavior lapses in involvement and 60 (58.8%) identified introspection lapses. Of 103 respondents, 97 (94.2%) reported that their clerkships ask clinical faculty and residents to formally evaluate professionalism, and 64 (62.1%) reported that they factor professionalism assessments into final clerkship grades. CDs reported multiple barriers to addressing professionalism directly with students, including logistical barriers, professionalism assessment subjectivity concerns, and the possible adverse effect of an unprofessional label for students., Conclusions: Professionalism assessment and remediation in medical education currently center on a deficit model that seeks to identify and remediate professionalism lapses, rather than a developmental model that seeks to nurture growth. This dichotomous characterization of behaviors as professional or unprofessional limits assessment and can adversely affect the learning environment. The authors propose a shift to a developmental model that considers professionalism as a continuous process parallel to the acquisition of clinical skills and medical knowledge., (Copyright © 2023 the Association of American Medical Colleges.)

Background: In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab-a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody-has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking., Case Presentation: We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri's during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts < 200 cells/mm 3 ; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts < 200 cells/mm 3 , three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor-12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died., Conclusions: In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts < 200 cells, are warranted to assess infectious and other outcomes after IL-6ri use, particularly in the context of co-administered corticosteroids., (© 2022. The Author(s).)

Background: Gender inequity is widespread in academic medicine, including in the promotion, academic recognition, and compensation of female faculty., Objective: To assess whether these inequities extend to the GME intern selection process, this study examines differences in the interview scores assigned to male and female applicants at one large internal medicine residency program., Methods: Subjects include 1399 applicants who completed 3099 interviews for internship positions for the Brigham and Women's Hospital internal medicine residency in Electronic Residency Application Service (ERAS) cycles 2015-2016, 2017-2018, 2018-2019, and 2019-2020. Unadjusted and multivariable linear regressions were used to assess the simultaneous effect of applicant gender, interviewer gender, and applicant academic characteristics on pre-interview, post-interview, and change in interview scores., Results: Our analysis included 3027 interviews (97.7%) of 1359 applicants (97.1%). There were no statistically significant differences in the interview scores assigned to female versus male applicants. This was true across pre-interview scores (difference = 0.03, P = .61), post-interview scores (difference = 0.00, P = .98), and change in interview scores (difference = 0.01, P = .24) as well as when adjusting for the baseline academic characteristics of both male and female applicants. This was also true when analyzing individual application years, individual residency tracks, and accounting for the gender of the faculty interviewers., Conclusions: The findings do not support the presence of gender inequity in the interview scores assigned to male and female applicants included in this study., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background: People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting., Methods: Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization., Results: There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes., Conclusions: Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression., Clinical Trials Registration: NCT04333953., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections., Methods: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment., Results: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported., Conclusions: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Infective endocarditis (IE) among people who inject drugs is associated with high rates of mortality and repeat episodes of endocarditis. We sought to report on longer-term clinical outcomes of patients with IE who were offered buprenorphine or methadone treatment for opioid use disorder (OUD) at their initial hospital admission., Methods: Individuals with OUD hospitalized between 2013 and 2015 with IE were included for the retrospective study. The following data were extracted from the medical record: sociodemographic data, mortality, repeat episodes of endocarditis, and evidence of ongoing buprenorphine and methadone treatment. The impact of medication use on mortality and repeat episode of endocarditis was examined using survival analysis., Results: Overall, 26 individuals were included in the study. The mean duration of follow-up was 45.0 months (SD 7.2, range 34.0-56.0). During the index admission, 8 received buprenorphine, 8 received methadone, and 10 declined medications. During the follow-up period, 4 (15.4%) individuals died and 10 (38.5%) individuals experienced a repeat episode of endocarditis. Survival analysis of mortality (log-rank P = 0.066) and repeat episode of endocarditis (log-rank P = 0.86) comparing those who received buprenorphine, received methadone, and declined medication did not differ significantly., Conclusions: Initiation of medication treatment alone may not be sufficient to impact long-term mortality and rates of repeat episode of endocarditis. More research is needed to identify optimal treatment strategies for people who inject drugs with IE.

In 2017, state health departments notified the Centers for Disease Control and Prevention about 4 patients with shigellosis who experienced persistent illness after treatment with oral third-generation cephalosporins. Given increasing antibiotic resistance among Shigella , these cases highlight the need to evaluate the efficacy of oral cephalosporins for shigellosis., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

Background and Objectives: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown., Methods: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84)., Results: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P  = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98)., Conclusion and Scientific Significance: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159)., (© 2020 American Academy of Addiction Psychiatry.)

Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (P<0.001) and had positive direct antiglobulin tests for IgG and complement component 3; warm autoantibodies were identified in all these patients. No alternative explanation for clinical hemolysis was found. WAHA required immunosuppressive treatment in 4 of the 6 patients. Conclusions We documented post-babesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.

Background: "Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States., Objectives: The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively., Methods: A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures., Results: Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution., Conclusions: We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios., Level of Evidence: 5 Therapeutic., (© 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (K(ATP)) channels. Acutely instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of the area at risk (AAR) for infarction in control, diabetic (3 wk after streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs, respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10 +/- 1% of AAR, P < 0.05) but did not produce protection in the presence of diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl; 23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3, 15 +/- 3 (P < 0.05), and 11 +/- 2% (P < 0.05), respectively]. There were no differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by radioactive microspheres) between groups. The results indicate that diabetes or hyperglycemia impairs activation of mitochondrial K(ATP) channels.

Unlabelled: We tested the hypothesis that levosimendan, a new positive inotropic drug that activates adenosine triphosphate-regulated potassium (K(ATP)) channels in vitro, decreases myocardial infarct size in vivo. Myocardial infarct size was measured after a 60-min left anterior descending coronary artery occlusion and 3 h of reperfusion in dogs receiving either IV vehicle (0.9% saline) or levosimendan (24 microg/kg bolus followed by an infusion of 0.4 microg x kg(-1) x min(-1)) in the presence or absence of glyburide (a K(ATP) channel antagonist) pretreatment (100 microg/kg). Levosimendan increased (P < 0.05) the maximal rate of increase of left ventricular pressure and decreased myocardial infarct size from 24%+/-2% (control experiments) to 11%+/-2% of the left ventricular area at risk for infarction. Glyburide did not alter the hemodynamic effects of levosimendan but blocked levosimendan-induced reductions of infarct size. Subendocardial collateral blood flow was similar among groups. However, levosimendan increased subepicardial and midmyocardial collateral perfusion in the absence, but not in the presence, of glyburide. Levosimendan exerts cardioprotective effects via activation of K(ATP) channels at a dose that simultaneously enhances myocardial contractility., Implications: Levosimendan may be advantageous in patients requiring inotropic support who are also at risk of myocardial ischemia. Activation of adenosine triphosphate-regulated potassium channels during infusion of levosimendan may produce cardioprotective effects while simultaneously enhancing ventricular contractile function.

Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. Significant (p < 0.05) increases in heart rate (HR) and decreases in systemic vascular resistance (SVR) occurred 15 min after CPB in patients receiving placebo. Later increases in mean arterial pressure (MAP) and cardiac output (CO) and decreases in stroke volume (SV) and pulmonary vascular resistance also were observed. HR was greater in patients receiving high- but not low-dose levosimendan versus placebo immediately after CPB. MAP also was lower in patients treated with either dose of levosimendan compared with placebo after CPB. Levosimendan increased CO and decreased SVR (4.2 +/- 0.4 to 7.9 +/- 0.4 L/min and 1,150 +/- 99 to 512 +/- 42 dyn/s/cm5, respectively, 15 min after CPB; mean +/- SEM). CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.

An unselected group of right hemisphere, semi-acute stroke patients (n = 30) was run on a laboratory test of naturalistic action production and was found to commit errors of action at a higher rate than what was previously reported for recovering head injury patients [Schwartz et al., Naturalistic action impairment in closed head injury. Neuropsychology, 1997, 8, 59-72]. There were strong similarities in how these two patient groups responded to variations in task demands and in the pattern of errors they produced. Hemispatial biases were evident in the errors of right hemisphere patients with neglect but not those without neglect; and neglect patients also many errors that were unrelated to the spatial layout. We argue that a non-specific resource limitation--which might translate as reduced arousal or effort--is central to the breakdown of naturalistic action production after brain damage, and right hemisphere patients are especially vulnerable to this resource limitation and its behavioral consequences.

RSR13 (2-[4-[[(3, 5-dimethylanilino)carbonyl]methyl]phenoxyl]-2-methylpropr ionic acid) is a synthetic allosteric modifier of oxygen (O2)-hemoglobin affinity that increases O2 release to tissue by allosterically stabilizing deoxyhemoglobin. We tested the hypothesis that RSR13 enhances the functional recovery of stunned myocardium in barbiturate-anesthetized dogs instrumented for measurement of left ventricular (LV) and aortic blood pressure, LV +dP/dtmax and subendocardial segment shortening (%SS) in ischemic [left anterior descending (LAD) coronary artery] and normal (left circumflex coronary artery) zones. The partial pressure of oxygen and the Hill coefficient at 50% saturation (P50 and n50, respectively) were determined in arterial blood samples by multiple point tonometry and nonlinear regression analysis. Coronary collateral blood flow in the LAD zone was quantified with radioactive microspheres. Dogs received intravenous vehicle (0.45% saline) or one of two doses of RSR13 (100 or 150 mg.kg-1 bolus followed by a 0.50 or 0.75 mg.kg-1.min-1 infusion, respectively) in a random manner. All dogs were subjected to five 5-min periods of LAD occlusion separated by 5-min periods of reperfusion and followed by 180 min of final reperfusion during which hemodynamics, %SS, arterial blood gases, P50 and n50 were determined at selected intervals. RSR13 caused no hemodynamic effects and coronary collateral blood flow was equivalent among groups. RSR13 increased P50 (+40 +/- 4% for the high dose) and decreased n50 (-31 +/- 2% for the high dose). LAD occlusion caused regional dyskinesia during each 5-min occlusion. Enhanced recovery of %SS by 180 min after final reperfusion was observed in dogs treated with high-dose RSR13 (47 +/- 9% of base line) but not low-dose RSR13 (10 +/- 18% of base line) or vehicle alone (2 +/- 16% of base line). The results suggest that high-dose RSR13 improves the recovery of stunned myocardium throughout reperfusion in open-chest dogs. These findings may be related to increases in O2 availability to ischemic myocardium resulting from RSR13-induced stabilization of the deoxy form of hemoglobin.

The authors sought to determine whether errors of action committed by patients with closed head injury (CHI) would conform to predictions derived from frontal lobe theories. In Study 1, 30 CHI patients and 18 normal controls performed routine activities, such as wrapping a present, under conditions of graded complexity. CHI patients committed more errors even on the simplest condition; but, except for a higher proportion of omitted actions, their error profile was very similar to that of controls. Study 2 involved a subset of patients whose performance in Study 1 was within normal limits. When these high functioning patients were asked to perform the routine tasks under still more taxing conditions, they, too, committed errors in excess of the control group. Accounts based on frontal mechanisms have a difficult time explaining the overall pattern of findings. An alternative based on limited-capacity resources is suggested.

Previous investigations have suggested that object-based neglect may reflect an impairment in attentional allocation that occurs relative to the intrinsic left and right of objects. We report a patient with apparent "object-based" neglect of 90 degrees rotated stimuli for whom the pattern of neglect was a function of task strategy. When the patient was instructed to visualize the rotated stimuli as if they were upright, i.e. mentally rotate them, he showed apparent "object-based" neglect to the left of the principal axes of the stimuli. In contrast, when instructed to refrain from mental rotation, neglect was apparent only with respect to his left, but not the left of the stimuli. Thus, the apparent "object-based" neglect of this patient may be attributed to a process of mental rotation of objects to upright, and subsequent neglect in viewer-centered or environment-centered coordinates. These data suggest a mechanism whereby object-based and viewer/environment-centered reference frames may be aligned, thereby causing viewer/environment-centered neglect to appear as if object-based.

Polyphenol oxidase (PPO) was extensively purified to homogeneity from d'Anjou pear (Pyrus communis L.) by extraction in the presence of the phenolic binder AG 2-X8 andTriton X-100. Chlorophyll pigment was removed by chromatography resulting in a clear, colorless enzyme extract. Purification of pear PPO was achieved after chromatography on Phenyl Sepharose CL-4B, DEAE-cellulose, and hydroxylapatite columns. Only after the columns were run at room temperature rather than at 4 degrees C were sharp peaks and good resolution obtained. Reproducibility of the entire scheme was excellent with chromatography on the hydrophobic resin as a key to successful purification. Three separate fractions of pear PPO were homogeneous when stained for protein with the silver stain after polyacrylamide slab gel electrophoresis and corresponded to relative mobilities of 0.41, 0.43, and 0.73. The effect of dimethylsulfoxide on enzyme activity was investigated and found to increase significantly the activity of purified pear PPO over the control.

According to the present study, crude preparations of rainbow trout liver and rabbit muscle lactate dehydrogenase (LDH,EC 1.1.1.27) were not inhibited by methyl sterculate and oleate, while trout liver glucose-6-phosphate dehydrogenase (G6PDH,EC 1.1.1.49) was activated by these esters. Methyl sterculate inhibited purified preparations of trout liver, rabbit muscle, and bovine heart LDH in contrast to methyl oleate which inhibited only a portion of the activity of purified rabbit muscle LDH and had no appreciable effect on the activities of the other purified LDH preparations. Trout liver LDH preparations were not inhibited by p-Chloromercuribenzoate (pCMB), while rabbit muscle and bovine heart LDH were sensitive to the presence of this inhibitor. Trout liver G6PDH was activated at the lower concentrations of pCMB. These data suggest that the reduction of the activities of liver dehydrogenases in the rainbow trout fed a diet containing methyl sterculate was not due to inhibition of these dehydrogenases by this cyclic fatty acid.

Cyclopropenoid fatty acids in the diet of rainbow trout caused significant reductions in liver protein and activity of glucose-6-phosphate dehydrogenase, NADP-linked isocitrate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase. Changes in total activity were usually accompanied by similar changes in specific activity. The activity of glucose-6-phosphate dehydrogenase appeared to be more sensitive to the ingestion of cyclopropenoid fatty acids than the other dehydrogenases studied. Feeding 20 ppb aflatoxin B(1) to rainbow trout did not significantly change the activity of the dehydrogenases except for a small increase in the activity of glucose-6-phosphate dehydrogenase after 21 days of feeding. Relationships of these changes to the cocarcinogenicity of cyclopropenoid fatty acids and the carcinogenicity of aflatoxin are discussed.

Egg white trypsin inhibitor activated coagulase clotting when added to a final concentration between 2 and 60 mg/ml. The greatest increase in clotting rate was observed in reaction mixtures containing the lowest concentrations of serum and plasma. Maximal activation was reached with 40 mg of trypsin inhibitor per ml when either serum or plasma was used as the source of coagulase-reacting factor (CRF). The increased rate of clotting is partly due to inhibition of plasmin. Freezing and thawing reduced plasma clotting inhibition. Soybean trypsin inhibitor also activated the coagulase reaction. The increased rate of clotting was observed with a coagulase preparation from organisms which produced plasminogen activators and with the culture supernatant fraction from organisms which did not activate plasminogen to plasmin. The tube test for coagulase could be made more sensitive for some strains of staphylococci by increasing the concentration of CRF (added as plasma or serum) by adding trypsin inhibitor, or both.

Assay of the esterase activity of sonically treated cell-free extracts, whole cell suspensions, and supernatant fluid of Pseudomonas fragi cultures with a differential respirometer revealed that the esterases were intracellular. Polyacrylamide-gel electrophoresis demonstrated six bands of esterase activity, which revealed substrate specificity differences. Band 1 exhibited slow mobility, bands 2, 3, and 4 moderate mobility, and bands 5 and 6 rapid mobility. Six bands were active with alpha-naphthyl acetate, four bands with alpha-naphthyl propionate, and 5 bands with alphanaphthyl butyrate. These esterases appeared to be more active with aromatic esters than with aliphatic esters.