Adaptive Evolution of Nearctic Deepwater Fish Vision: Implications for Assessing Functional Variation for Conservation.

Intraspecific functional variation is critical for adaptation to rapidly changing environments. For visual opsins, functional variation can be characterized in vitro and often reflects a species' ecological niche but is rarely considered in the context of intraspecific variation or the impact of recent environmental changes on species of cultural or commercial significance. Investigation of adaptation in postglacial lakes can provide key insight into how rapid environmental changes impact functional evolution. Here, we report evidence for molecular adaptation in vision in 2 lineages of Nearctic fishes that are deep lake specialists: ciscoes and deepwater sculpin. We found depth-related variation in the dim-light visual pigment rhodopsin that evolved convergently in these 2 lineages. In vitro characterization of spectral sensitivity of the convergent deepwater rhodopsin alleles revealed blue-shifts compared with other more widely distributed alleles. These blue-shifted rhodopsin alleles were only observed in deep clear postglacial lakes with underwater visual environments enriched in blue light. This provides evidence of remarkably rapid and convergent visual adaptation and intraspecific functional variation in rhodopsin. Intraspecific functional variation has important implications for conservation, and these fishes are of conservation concern and great cultural, commercial, and nutritional importance to Indigenous communities. We collaborated with the Saugeen Ojibway Nation to develop and test a metabarcoding approach that we show is efficient and accurate in recovering the ecological distribution of functionally relevant variation in rhodopsin. Our approach bridges experimental analyses of protein function and genetics-based tools used in large-scale surveys to better understand the ecological extent of adaptive functional variation.

A Sticky Situation: Variable Agreement Between Platelet Function Tests Used to Assess Anti-platelet Therapy Response.

Background: Platelet function testing to monitor antiplatelet therapy is important for reducing thromboembolic complications, yet variability across testing methods remains challenging. Here we evaluated the agreement of four different testing platforms used to monitor antiplatelet effects of aspirin (ASA) or P2Y12 inhibitors (P2Y12-I). Methods: Blood and urine specimens from 20 patients receiving dual antiplatelet therapy were analyzed by light transmission aggregometry (LTA), whole blood aggregometry (WBA), VerifyNow PRUTest and AspirinWorks. Result interpretation based on pre-defined cutoff values was used to calculate raw agreement indices, and Pearson's correlation coefficient determined using individual units of measure. Results: Agreement between LTA and WBA for P2Y12-I-response was 60% (r = 0.65, high-dose ADP; r = 0.75, low-dose ADP). VerifyNow agreed with LTA in 75% (r = 0.86, high-dose ADP; r = 0.75, low-dose ADP) and WBA in 55% (r = 0.57) of cases. Agreement between LTA and WBA for ASA-response was 45% (r = 0.09, high-dose collagen WBA; r = 0.19, low-dose collagen WBA). AspirinWorks agreed with LTA in 60% (r = 0.32) and WBA in 35% (r = 0.02, high-dose collagen WBA; r = 0.08, low-dose collagen WBA) of cases. Conclusions: Overall agreement varied from 35 to 75%. LTA and VerifyNow demonstrated the highest agreement for P2Y12-I-response, followed by moderate agreement between LTA and WBA. LTA and AspirinWorks showed moderate agreement for aspirin response, while WBA showed the weakest agreement with both LTA and AspirinWorks. The results from this study support the continued use of LTA for monitoring dual antiplatelet therapy, with VerifyNow as an appropriate alternative for P2Y12-I-response. Integration of results obtained from these varied testing platforms with patient outcomes remains paramount for future studies.

Assessment of Coagulation and Hemostasis Biomarkers in a Subset of Patients With Chronic Cardiovascular Disease.

Measurement of a single marker of coagulation may not provide a complete picture of hemostasis activation and fibrinolysis in patients with chronic cardiovascular diseases. We assessed retrospective orders of a panel which included prothrombin fragment 1.2 (PF1.2), thrombin: antithrombin complexes, fibrin monomers, and D-dimers in patients with heart assist devices, cardiomyopathies, atrial fibrillation and intracardiac thrombosis (based on ordering ICD-10 codes). During 1 year there were 117 panels from 81 patients. Fifty-six (69%) patients had heart assist devices, cardiomyopathy was present in 17 patients (21%) and 29 patients (36%) had more than 1 condition. PF1.2 was most frequently elevated in patients with cardiomyopathy (61.1%) compared to those with cardiac assist devices (15.7%; P = 0.0002). D-dimer elevation was more frequent in patients with cardiac assist devices (98.8%) compared to those patients with cardiomyopathy (83.3%; P = 0.014). Patients with cardiomyopathy show increases of PF1.2 suggesting thrombin generation. In contrast, elevations of D-dimers without increase in other coagulation markers in patients with cardiac assist devices likely reflect the presence of the intravascular device and not necessarily evidence of hemostatic activation.

Anticoagulation Therapy Reduces Recurrent Stroke in Embolic Stroke of Undetermined Source Patients With Elevated Coagulation Markers or Severe Left Atrial Enlargement.

Background: The objective of this study was to evaluate if anticoagulation therapy reduces recurrent stroke in embolic stroke of undetermined source (ESUS) patients with left atrial enlargement (LAE) or abnormal markers of coagulation and hemostatic activity (MOCHA) compared to antiplatelet therapy. Methods: ESUS patients from January 1, 2017, to June 30, 2019, underwent outpatient cardiac monitoring and the MOCHA profile (serum d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). Anticoagulation was offered to patients with abnormal MOCHA (≥2 elevated markers) or left atrial volume index 40 mL/m2. Patients were evaluated for recurrent stroke or major hemorrhage at routine clinical follow-up. We compared this patient cohort (cohort 2) to a historical cohort (cohort 1) who underwent the same protocol but remained on antiplatelet therapy. Results: Baseline characteristics in cohort 2 (n = 196; mean age = 63 ± 16 years, 59% female, 49% non-White) were similar to cohort 1 (n = 42) except that cohort 2 had less diabetes (43 vs. 24%, p = 0.01) and more tobacco use (26 vs. 43%, p = 0.04). Overall, 45 patients (23%) in cohort 2 initiated anticoagulation based on abnormal MOCHA or LAE. During mean follow-up of 13 ± 10 months, cohort 2 had significantly lower recurrent stroke rates than cohort 1 (14 vs. 3%, p = 0.009) with no major hemorrhages. Conclusions: Anticoagulation therapy in a subgroup of ESUS patients with abnormal MOCHA or severe LAE may be associated with a reduced rate of recurrent stroke compared to antiplatelet therapy. A prospective, randomized study is warranted to validate these results.

Validation of an admission coagulation panel for risk stratification of COVID-19 patients.

BACKGROUND: There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications. METHODS: Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality. MAIN RESULTS: Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2-8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint. CONCLUSIONS: An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.

The Utility of the Markers of Coagulation and Hemostatic Activation Profile in the Management of Embolic Strokes of Undetermined Source.

BACKGROUND: Potential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke. METHODS: We prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up. RESULTS: Of 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively. DISCUSSION: The MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS.

Development of iron deficiency anemia in patients undergoing extracorporeal photopheresis: Comparison of the UVAR and CELLEX instruments.

INTRODUCTION: Extracorporeal photopheresis (ECP) is a procedure used to influence T-cell activity in patients suffering from immune-mediated cellular damage secondary to activated lymphocytes. Although well-tolerated, iron deficiency anemia (IDA) has been described. The goal herein is to describe IDA in patients who received extracorporeal photopheresis (ECP) treatment using UVAR (Therakos Inc) and CELLEX (Therakos Inc) instruments. DESIGN AND METHODS: Patients treated with ECP from 2015 to 2019 were retrospectively analyzed. IDA was defined by a decrease in hemoglobin following treatment with concomitant decrease in mean cell volume, mean corpuscular hemoglobin concentration, increased RBC distribution width, and/or iron studies compatible with IDA. RESULTS: During the four-year study period, thirty-four patients received ECP. Thirteen (38%) underwent treatment with the previous UVAR device while 21 (62%) received treatment on the newer CELLEX instrument. Nineteen (56%) of the cohort developed clinical and laboratory evidence of IDA with an average of 3.2 g/dL decrease in hemoglobin. Patients who developed IDA treated on the CELLEX instrument experienced a significantly greater drop in hemoglobin (P = .04) than those treated on the UVAR. Examining the CELLEX-treated patients, those who received the procedure at greater frequency experienced significantly greater drops in hemoglobin (P = .03). CONCLUSIONS: IDA is a risk of chronic ECP therapy and is likely secondary to retained blood components in the instrument. The temporal relationship between anemia and ECP treatment has a direct correlation with the treatment schedule. Patients undergoing ECP treatment should be closely monitored for the development of IDA.

Retrospective Analyses Associate Hemostasis Activation Biomarkers With Poor Outcomes in Patients With COVID-19.

OBJECTIVES: Patients with coronavirus disease 2019 (COVID-19) have thromboembolic complications. Assessment of coagulation and other markers could be useful to understand their coagulopathy. METHODS: We performed a retrospective study of inflammatory and coagulation parameters, including prothrombin fragment 1.2 (PF1.2), thrombin-antithrombin complexes (TATs), fibrin monomers, and D-dimer, in hospitalized patients with COVID-19. We compared the markers in patients with thrombosis, admission to the intensive care unit (ICU), and poor outcome. RESULTS: Of the 81 patients, 9 (11%) experienced an acute thrombotic event (4 with pulmonary embolism, 3 with venous thrombosis, and 2 with stroke). PF1.2 was elevated in 32 (39%) patients, TATs in 54 (67%), fibrin monomers in 49 (60%), and D-dimer in 76 (94%). Statistically significant elevation in PF1.2 and TATs was seen in patients admitted to the ICU, while D-dimer and fibrin monomers were significantly elevated in patients with poor outcomes. The presence of multiple abnormal coagulation parameters was associated with ICU admission. Other parameters with statistically significant results included abnormal WBC counts and elevated C-reactive protein, which were associated with ICU admission and poor outcomes. CONCLUSIONS: Our data demonstrate that abnormalities of biomarkers of hemostasis activation and inflammatory markers are associated with poor outcomes in patients with COVID-19.

Therapeutic plasma exchange for COVID-19-associated hyperviscosity.

BACKGROUND: Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID-19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID-19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID-19-associated hyperviscosity. STUDY DESIGN AND METHODS: Six critically ill COVID-19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4-1.8 cP) underwent daily TPE for 2-3 treatments. RESULTS: TPE decreased plasma viscosity in all six patients (Pre-TPE median 3.75 cP, range 2.6-4.2 cP; Post-TPE median 1.6 cP, range 1.5-1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre-TPE median 739 mg/dL, range 601-1188 mg/dL; Post-TPE median 359 mg/dL, range 235-461 mg/dL); D-dimer levels in all six patients (Pre-TPE median 5921 ng/mL, range 1134-60 000 ng/mL; Post-TPE median 4893 ng/mL, range 620-7518 ng/mL); and CRP levels in five of six patients (Pre-TPE median 292 mg/L, range 136-329 mg/L; Post-TPE median 84 mg/L, range 31-211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. CONCLUSIONS: This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID-19-associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID-19.

Disease Burden in Patients with Glanzmann's Thrombasthenia: Perspectives from the Glanzmann's Thrombasthenia Patient/Caregiver Questionnaire.

PURPOSE: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder caused by a mutation in the αIIbß3 integrin essential for optimal platelet function and hemostasis. The aim of this study was to identify the burden of GT on patients and caregivers through better understanding of the management and psychosocial impact of this disorder. PATIENTS AND METHODS: Participants for this online survey were recruited using a rare disease specialty recruiter from Comprehensive Health Education Services. Data were collected from January 31 through March 12, 2019. The questionnaire was designed to collect information regarding demographics, diagnosis, treatment, and psychosocial impact. RESULTS: Of the 45 respondents (24 patients and 21 caregivers), the majority were female (58%), white (64%), and employed full-time (53%) and had no family history of GT (64%). Many patients reported significant bruising at birth (76%), and the mean age at diagnosis was 2.6 years. About half of the patients experienced 1 bleed per day, and 13% had over 500 bleeds of any severity per year. Most bleeds were skin bruising or mouth bleeds, but patients also reported joint/muscle and gastrointestinal bleeds. Most patients reported receiving a platelet transfusion (82%), and some had developed platelet refractoriness (38%) or antibodies (32%). Common treatments were antifibrinolytics (82%) and recombinant activated factor VII (rFVIIa) (42%), likely due to the presence of antibodies. Many (58%) patients experienced issues with excessive bleeding at school; 38% reported missing school as a result. Female patients struggled to find a gynecologist with knowledge of the management of GT. Most patients were satisfied with the support they receive from their current partner (65%) and their friends (76%). CONCLUSION: Most patients with GT are diagnosed early. Patients experience considerable psychosocial impact. Patient and physician education concerning treatment alternatives and the support of the GT community are critical.

Psychosocial Impact and Disease Management in Patients with Congenital Factor VII Deficiency.

PURPOSE: Congenital factor VII (FVII) deficiency is a rare bleeding disorder of variable phenotype with predominantly mucocutaneous bleeding. The aim of this study was to identify the burden of FVII deficiency on patients and caregivers through a better understanding of the management and psychosocial impact of this disease. MATERIALS AND METHODS: A rare disease specialty recruiter from Comprehensive Health Education Services recruited participants for this online survey, which was conducted from January 31 to March 12, 2019. A moderator-assisted questionnaire was used to collect data on demographics, diagnosis, treatment, and psychosocial impact. RESULTS: Of the 45 respondents (25 patients and 20 caregivers), the majority were female (56%). Respondents reported a wide variety of initial bleeding symptoms, including bruising (58%), epistaxis (56%), and menorrhagia (36% of females). Because symptoms varied between individuals and were not always severe, diagnosis was often delayed. Mean time to obtain a diagnosis was 6.5 years and mean age at first diagnosis was 12.9 years. One-quarter (24%) of the respondents reported more than 100 bleeds of any severity over the previous year. When treating bleeds, 44% of patients reported using antifibrinolytics, and 42% reported using recombinant activated factor VII. Almost 31% of respondents reported missing schooldays as children, and 16% reported losing or resigning from a job in adulthood as a direct result of their disease. Notably, 29% of caregivers and 10% of their partners had also experienced issues with employment. Forty percent of respondents reported not participating in contact sports during childhood, and 22% continued to avoid contact sports in adulthood. CONCLUSION: Overall, FVII deficiency has a substantial psychosocial impact, but most patients are satisfied with their disease management and are optimistic about their future. Patients desire additional educational, social, and financial support.

Cracking under Internal Pressure: Photodynamic Behavior of Vinyl Azide Crystals through N2 Release.

When exposed to UV light, single crystals of the vinyl azides 3-azido-1-phenylpropenone (1a), 3-azido-1-(4-methoxyphenyl)propenone (1b), and 3-azido-1-(4-chlorophenyl)propenone (1c) exhibit dramatic mechanical effects by cracking or bending with the release of N2. Mechanistic studies using laser flash photolysis, supported by quantum mechanical calculations, show that each of the vinyl azides degrades through a vinylnitrene intermediate. However, despite having very similar crystal packing motifs, the three compounds exhibit distinct photomechanical responses in bulk crystals. While the crystals of 1a delaminate and release gaseous N2 indiscriminately under paraffin oil, the crystals of 1b and 1c visibly expand, bend, and fracture, mainly along specific crystallographic faces, before releasing N2. The photochemical analysis suggests that the observed expansion is due to internal pressure exerted by the gaseous product in the crystal lattices of these materials. Lattice energy calculations, supported by nanoindentation experiments, show significant differences in the respective lattice energies. The calculations identify critical features in the crystal structures of 1b and 1c where elastic energy accumulates during gas release, which correspond to the direction of the observed cracks. This study highlights the hitherto untapped potential of photochemical gas release to elicit a photomechanical response and motility of photoreactive molecular crystals.

Passenger Lymphocyte Syndrome; a Review of the Diagnosis, Treatment, and Proposed Detection Protocol.

Passenger lymphocyte syndrome (PLS) is caused by the transfer of B-lymphocytes present in the donor graft into the recipient circulation following solid organ or hematopoietic stem cell transplantation. These cells may produce antibodies against the recipient's red blood cells, thereby triggering antibody dependent cytotoxicity and erythroid clearance, with potential resulting hemolysis and jaundice. Although uncommon, the true incidence is unknown because many cases are subclinical, with only serologic findings or with non significant levels of hemolysis detectable clinically or by laboratory monitoring. Thus, these cases may not be detected in the immediate perioperative period. No standardized consensus exists on screening for PLS in patients. Through a review of the literature from 2009 to 2019, we aim to approximate the incidence of this condition in different solid organ transplant settings, as well as to streamline recognition, detection, and management of PLS early in the disease course to prevent adverse outcomes and minimize invasive therapy. The resultant literature review yielded 22 case reports and 8 case series comprising 71 solid organ transplant patients. Hematopoietic stem cell transplant cases were excluded, as PLS cases related to solid organ transplant were the primary focus of this review. Our institution has traditionally handled PLS on a case-by-case basis, although we hope to improve this process through an introduction of an algorithm based on review of the literature and formalized communication with primary caregivers.

Validation of PLASMIC score: an academic medical center case series (2012-present).

BACKGROUND: The PLASMIC score is a rapid and inexpensive tool for predicting severe ADAMTS13 deficiency (activity <10%) in patients with suspected thrombotic thrombocytopenic purpura (TTP) by analyzing seven parameters (platelet count; combined hemolysis variable; absence of active neoplasia; absence of an organ or stem-cell transplant; mean corpuscular value; international normalized ratio; and serum creatinine). The purpose of this study was to validate the PLASMIC score at a large multi-institutional academic medical center. METHODS: An internal database of consultations to the transfusion medicine service, which oversees therapeutic apheresis at our institution, was reviewed to identify patients who were evaluated for and/or received plasma exchange for suspected TTP. These consultations covered the time period of January 2012 to February 2019. PLASMIC scoring criteria and ADAMTS13 assay results were abstracted from the electronic medical record, the PLASMIC score was calculated, and cases stratified into risk categories (low, intermediate, high risk) based on the score value. RESULTS: Of 58 patients identified, 46 met inclusion criteria, and 27 demonstrated ADAMTS13 activity <10%. Correlation of severe ADAMTS13 deficiency with risk-stratified groups resulted in 78% sensitivity, 63% specificity, 75% positive predictive value (PPV), and 67% negative predictive value (NPV). DISCUSSION: These findings paralleled those from validation studies performed at other institutions. They provided insufficient evidence to recommend routine use of the PLASMIC score to rule out TTP among patients at our hospitals. Nonetheless, these results reinforce the importance of early ADAMTS13 testing as a diagnostic triage tool for patients with suspected TTP.

Markers of coagulation and hemostatic activation aid in identifying causes of cryptogenic stroke.

OBJECTIVE: To test the hypothesis that markers of coagulation and hemostatic activation (MOCHA) help identify causes of cryptogenic stroke, we obtained serum measurements on 132 patients and followed them up to identify causes of stroke. METHODS: Consecutive patients with cryptogenic stroke who met embolic stroke of undetermined source (ESUS) criteria from January 1, 2017, to October 31, 2018, underwent outpatient cardiac monitoring and the MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) obtained ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. Prespecified endpoints monitored during routine clinical visits included new atrial fibrillation (AF), malignancy, venous thromboembolism (VTE), or other defined hypercoagulable states (HS). RESULTS: Overall, 132 patients with ESUS (mean age 64 ± 15 years, 61% female, 51% nonwhite) met study criteria. During a median follow-up of 10 (interquartile range 7-14) months, AF, malignancy, VTE, or HS was identified in 31 (23%) patients; the 53 (40%) patients with ESUS with abnormal MOCHA were significantly more likely than patients with normal levels to have subsequent new diagnoses of malignancy (21% vs 0%, p < 0.001), VTE (9% vs 0%, p = 0.009), or HS (11% vs 0%, p = 0.004) but not AF (8% vs 9%, p = 0.79). The combination of 4 normal MOCHA and normal left atrial size (n = 30) had 100% sensitivity for ruling out the prespecified endpoints. CONCLUSION: The MOCHA profile identified patients with cryptogenic stroke more likely to have new malignancy, VTE, or HS during short-term follow-up and may be useful in direct evaluation for underlying causes of cryptogenic stroke.

Habenular TCF7L2 links nicotine addiction to diabetes.

Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signalling in the mHb increases nicotine intake in mice and rats. Nicotine increases levels of blood glucose by TCF7L2-dependent stimulation of the mHb. Virus-tracing experiments identify a polysynaptic connection from the mHb to the pancreas, and wild-type rats with a history of nicotine consumption show increased circulating levels of glucagon and insulin, and diabetes-like dysregulation of blood glucose homeostasis. By contrast, mutant Tcf7l2 rats are resistant to these actions of nicotine. Our findings suggest that TCF7L2 regulates the stimulatory actions of nicotine on a habenula-pancreas axis that links the addictive properties of nicotine to its diabetes-promoting actions.

Development, Implementation, and Evaluation of a Fourth-Year Medical School Elective Course in Blood Banking and Transfusion Medicine.

Objectives: Knowledge of transfusion medicine by medical students is limited. Transfusion medicine physicians developed, implemented, and evaluated a half-day elective on transfusion medicine for fourth-year medical students. Methods: The course included a didactic lecture with integrated audience response questions and role-playing, as well as a "Jeopardy"-style game to review the material. The same 10-question knowledge quiz was administered before and after the elective. Results: Both knowledge quizzes were taken by 102 students. An average score of 3.3 was obtained on the initial quiz, with only three (3%) students having a passing score (≥6 correct questions). The average score after the elective was 6.6, with 83 (81%) students having a passing score. Students found the elective was informative (62 students, 60.8%), very useful (56, 54.9%), and practical (51, 50%), although some thought it was challenging (22, 21.6%). Conclusions: A short course for medical students that allowed repetition of concepts using several teaching modalities improved their knowledge in transfusion medicine.

Coagulation markers and echocardiography predict atrial fibrillation, malignancy or recurrent stroke after cryptogenic stroke.

We evaluated the utility of left atrial volume index (LAVI) and markers of coagulation and hemostatic activation (MOCHA) in cryptogenic stroke (CS) patients to identify those more likely to have subsequent diagnosis of atrial fibrillation (AF), malignancy or recurrent stroke during follow-up.Consecutive CS patients who met embolic stroke of undetermined source (ESUS) who underwent transthoracic echocardiography and outpatient cardiac monitoring following stroke were identified from the Emory cardiac registry. In a subset of consecutive patients, d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex and fibrin monomer (MOCHA panel) were obtained ≥2 weeks post-stroke and repeated ≥4 weeks later if abnormal; abnormal MOCHA panel was defined as ≥2 elevated markers which did not normalize when repeated. We assessed the predictive abilities of LAVI and the MOCHA panel to identify patients with subsequent diagnosis of AF, malignancy, recurrent stroke or the composite outcome during follow-up.Of 94 CS patients (mean age 64 ± 15 years, 54% female, 63% non-white, mean follow-up 1.4 ± 0.8 years) who underwent prolonged cardiac monitoring, 15 (16%) had new AF. Severe LA enlargement (vs normal) was associated with AF (P < .06). In 42 CS patients with MOCHA panel testing (mean follow-up 1.1 ± 0.6 years), 14 (33%) had the composite outcome and all had abnormal MOCHA. ROC analysis showed LAVI and abnormal MOCHA together outperformed either test alone with good predictive ability for the composite outcome (AUC 0.84).We report the novel use of the MOCHA panel in CS patients to identify a subgroup of patients more likely to have occult AF, occult malignancy or recurrent stroke during follow-up. A normal MOCHA panel identified a subgroup of CS patients at low risk for recurrent stroke on antiplatelet therapy. Further study is warranted to evaluate whether the combination of an elevated LAVI and abnormal MOCHA panel identifies a subgroup of CS patients who may benefit from early anticoagulation for secondary stroke prevention.