Quantitative susceptibility mapping in the brain reflects spatial expression of genes involved in iron homeostasis and myelination.

Quantitative susceptibility mapping (QSM) is an MRI modality used to non-invasively measure iron content in the brain. Iron exhibits a specific anatomically varying pattern of accumulation in the brain across individuals. The highest regions of accumulation are the deep grey nuclei, where iron is stored in paramagnetic molecule ferritin. This form of iron is considered to be what largely contributes to the signal measured by QSM in the deep grey nuclei. It is also known that QSM is affected by diamagnetic myelin contents. Here, we investigate spatial gene expression of iron and myelin related genes, as measured by the Allen Human Brain Atlas, in relation to QSM images of age-matched subjects. We performed multiple linear regressions between gene expression and the average QSM signal within 34 distinct deep grey nuclei regions. Our results show a positive correlation (p < .05, corrected) between expression of ferritin and the QSM signal in deep grey nuclei regions. We repeated the analysis for other genes that encode proteins thought to be involved in the transport and storage of iron in the brain, as well as myelination. In addition to ferritin, our findings demonstrate a positive correlation (p < .05, corrected) between the expression of ferroportin, transferrin, divalent metal transporter 1, several gene markers of myelinating oligodendrocytes, and the QSM signal in deep grey nuclei regions. Our results suggest that the QSM signal reflects both the storage and active transport of iron in the deep grey nuclei regions of the brain.

Unplanned cesarean sections in advanced maternal age: A predictive model.

INTRODUCTION: As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. MATERIAL AND METHODS: This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40-44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. RESULTS: A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72-0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. CONCLUSIONS: Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section.

Framed, Interactive Theory-Driven Texting: Effects of Message Framing on Health Behavior Change for Weight Loss.

More approaches to support weight control are needed, especially among racial minorities who shoulder a disproportionate obesity burden. Using an approach influenced by regulatory fit theory, we conducted a 28-day, 4-arm experimental trial with 89 obese adults recruited from urban, predominantly African American churches to ascertain the efficacy of framed text messages to motivate behaviors conducive to weight loss. Participants were assigned to receive message framing that was matched versus mismatched to their motivational orientation. Results were mixed overall; however, matched texts elicited greater motivation to change eating and exercise behavior, suggesting promise in using motivational approaches to tailor messages.

Management of Asymptomatic Bacteriuria in Non-Catheterized Adults.

Understanding the management of asymptomatic bacteriuria (ASB) is important given the prevalence of the condition, associated risks in certain patient populations, and the risks associated with inappropriate antibiotic administration. Generally, screening and treatment is only recommended in pregnant women and in those undergoing urologic procedures that will violate the urothelium. Knowing the appropriate time to screen and treat ASB is critical for managing high-risk patients and preventing the growth of antibiotic resistance. Recent research into the protective nature of avirulent strains of Escherichia coli might offer a new approach to management of ASB.

The effect of clinical face shields on aerosolized particle exposure.

Background: Face shields protect healthcare workers (HCWs) from fluid and large droplet contamination. Their effect on smaller aerosolized particles is unknown. Materials & methods: An ultrasonic atomizer was used to simulate particle sizes equivalent to human breathing and forceful cough. Particles were measured at positions correlating to anesthetic personnel in relation to a patient inside an operating theatre environment. The effect of the application of face shields on HCW exposure was measured. Results & Conclusion: Significant reductions in particle concentrations were measured after the application of vented and enclosed face shields. Face shields appear to reduce the concentration of aerosolized particles that HCWs are exposed to, thereby potentially conferring further protection against exposure to aerosolized particles in an operating theatre environment.

Face shields protect health workers from splash contamination. We do not know if they protect against smaller invisible aerosol drops that can carry diseases like coronavirus 2019/COVID-19. The authors tested whether face shields can stop floating droplets using different types of face shields. This included one that was designed and made by a 3D printer, and traditional face shields. The shields were tested in a hospital operating room. A machine was designed that made invisible saltwater droplets. A monitor was used to measure the droplets present at a doctor's or nurse's mouth and then if this changed when a face shield was used. The face shield might be helpful in stopping health workers from catching diseases by stopping the flow of aerosol drops.

An audit of perioperative end-of-life care practices and documentation relating to patients who died in a surgical unit in three Victorian hospitals.

The number of older, frail patients undergoing surgery is increasing, prompting consideration of the benefits of intensive treatment. Despite collaborative decision-making processes such as advance care planning being supported by recent Australian legislation, their role in perioperative care is yet to be defined. Furthermore, there has been little evaluation of the quality of end-of-life care in the surgical population. We investigated documentation of the premorbid functional status, severity of illness, intensity of treatment, operative management and quality of end-of-life care in patients who died in a surgical unit, with a retrospective study of surgical mortality which was performed across three hospitals over a 23-month period in Victoria, Australia. Among 99 deceased patients in the study cohort, 68 had a surgical operation. Preoperative functional risk assessment by medical staff was infrequently documented in the medical notes (5%) compared with activities of daily living (69%) documented by nursing staff. Documented preoperative discussions regarding the risk of death were rarely and inconsistently done, but when done were extensive. Documented end-of-life care discussions were identified in 71%, but were frequently brief, inconsistent, and in 60% did not occur until 48 hours from death. In 35.4% of instances, documented discussions involved junior staff (registrars or residents), and 43.4% involved intensive care unit staff. Palliative or terminal care referrals also occurred late (1-2 days prior to death). Not-for-resuscitation orders were frequently changed when approaching the end of life. Overall, 57% of deceased patients had a documented opportunity for farewell with family. We conclude that discussions and documentation of end-of-life care practices could be improved and recommend that all surgical units undertake similar audits to ensure that end-of-life care discussions occur for high-risk and palliative care surgical patients and are documented appropriately.

Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.

OBJECTIVE: We tested the hypothesis that both chronic and acute inflammatory processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM. MATERIALS AND METHODS: Twelve- to thirteen-week-old male Zucker Diabetic Fatty (ZDF) rats vs. Zucker Lean Controls (ZLC) rats were tested at baseline and after middle cerebral artery occlusion (ischemia) and reperfusion (I-R). Neutrophil adhesion to the cerebral microcirculation, neutrophil expression of CD11b, infarction size, edema, neurologic function, sICAM, and cerebral expression of neutrophil-endothelial inflammatory genes were measured. RESULTS: At baseline, CD11b and sICAM were significantly increased in ZDF vs. ZLC animals (p < 0.05). After I-R, significantly more neutrophil adhesion and cell aggregates were observed in ZDF vs. ZLC (p < 0.05); infarction size, edema, and neurologic function were significantly worse in ZDF vs. ZLC (p < 0.05). CD11b and sICAM-1 remained significantly increased in ZDFs (p < 0.05), and cerebral expression of IL-1ß, GRO/KC, E-selectin, and sICAM were significantly induced in ZDF, but not ZLC groups (p < 0.05) after 2.5 hours of reperfusion. CONCLUSION: Both sides of the neutrophil-endothelial interface appear to be primed prior to I-R, and remain significantly more activated during I-R in an experimental model of T2DM. Consequently, reperfusion injury appears to play a significant role in poor stroke outcome in T2DM.

Caspase inhibition of platelet activation.

The role of caspases in platelet function is not well understood. When platelets are activated, they express phosphatidylserine on the outer plasma membrane, form platelet microparticles, and aggregate (Pag). The aims of this study were to determine if caspases play a role in the platelet activation seen in type 2 diabetes. Diabetic rats (Zucker diabetic fatty) were treated with a broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone, in vivo and platelets were evaluated for phosphatidylserine expression, platelet microparticle formation, and Pag. We found a decreased phosphatidylserine exposure in zVAD-Zucker diabetic fatty rats compared to Zucker diabetic fatty-phosphate-buffered saline when activated with 20 micromol/l ADP. Zucker diabetic fatty rats treated with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone decreased platelet microparticle numbers compared to phosphate-buffered saline control Zucker diabetic fatty rats. Further, treatment with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone significantly decreased Pag. These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role of these proteases and perhaps the underlying mechanisms involved in the chronic platelet activation observed in type 2 diabetes.

Caspase inhibition decreases both platelet phosphatidylserine exposure and aggregation: caspase inhibition of platelets.

Apoptosis of nucleated cells is regulated by caspases, a group of cysteine proteases, and is characterized by phosphatidylserine expression on the outer leaflet of the plasma membrane. Reports indicate that platelets contain caspases. However, the role of caspases in platelet function is not well understood. When platelets become activated, they express phosphatidylserine (PS) on the outer leaflet of the plasma membrane. In addition, platelets aggregate when activated. The aims of this study were to determine if caspase inhibition (using the pan-caspase inhibitor zVAD-fmk): (1) decreased PS expression and (2) decreased platelet aggregation following activation. Flow cytometry was used to determine PS expression and a platelet aggregometer was used to assess aggregation. We found that platelets treated with zVAD-fmk significantly decreased both A23187-induced PS exposure (total fluorescence index, TFI: A23187=791.42+/-174; zVAD+A23187=92.97+/-57, p<==0.05) and ADP-induced PS exposure (TFI: ADP=669.24+/-145, zVAD+ADP=174.6+/-151, p<==0.05). Further, treatment with zVAD-fmk significantly decreased ADP-induced platelet aggregation (%: untreated=80+/-1.5, zVAD treated=69+/-3.0, p<==0.05). These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role for these proteases.

Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation.

Diabetics suffer from many complications including a prothrombotic condition. Activated platelet membrane provides an anchor, phosphatidylserine, for the attachment of the prothrombinase complex, which allows increased thrombin formation. This study aimed to further elucidate the interrelationship between coagulation proteins and activated platelets in type 2 diabetic blood. We found that there was a significant increase (30 x) in thrombin activity in the type 2 diabetic (ZDF) blood as compared to age-matched (ZL) controls (p<0.001). There was also a significant increase in the number of platelet microparticles in the type 2 diabetic rat compared to the lean control (p<0.001). Further, there were significant increases in caspase-3, -6, and -8 activities in the type 2 diabetic rats as compared to the lean controls (p<0.05). The combination of increased thrombin activity, increased PMP formation and increased caspase activity may contribute to the hypercoagulability of the diabetic blood. These results give more insight into the mechanisms underlying the interrelationship between diabetic platelets and coagulation proteins causing a prothrombotic condition in this patient population at increased risk from thromboembolic events.

Inflammablog: peer-to-peer online learning in immunology.

Is it possible for students in different courses, at different academic levels, and at different universities to learn immunology together using the Internet? We teach a colloquium on inflammation for undergraduates at the University of Arizona and a lecture course on human immunology for graduate students and clinical and basic science fellows at the University of Colorado Anschutz Medical Campus. Students in these programs, being scattered about large campuses, have little time for student-directed discussion and peer interactions, and they never have the opportunity to meet students in the course in the other state. Instead of requiring the usual essays and term papers, we set up a blog (an online discussion group) for the two courses, and required all students to post, and comment on other posts, within and between the courses. Student writing is normally directed at a single reader, the instructor, which seems like a waste of talent; we encouraged peer exchanges. Furthermore, we were interested in observing the interactions between the Colorado students, who were older and sometimes experienced professionals, and the younger Arizonans. We used a blog because it is administratively impossible to enroll the students in two universities in a single courseware (learning management system) site. Blogging has offered insights into students' comfort with this form of social medium, and into the potential for this approach in light of the rapid adoption of blended and massively open online courses.

How microRNAs influence both hereditary and inflammatory-mediated colon cancers.

MicroRNAs have emerged as important post-translational regulators of gene expression and are involved in several physiological and pathological states including the pathogenesis of human colon cancers. In regards to tumor development, microRNAs can act as oncogenes or tumor suppressors. Two hereditary predispositions (i.e., Lynch syndrome and familial adenomatous polyposis) contribute to the development of colon cancer. In addition, individuals who suffer from inflammatory bowel diseases such as Crohn's disease or ulcerative colitis have a higher risk of developing colon cancer. Here, we discuss the occurrence of the deregulated expression of microRNAs in colon cancer that arise as a result of hereditary predisposition and inflammatory bowel disease.

Whole blood aggregation, coagulation, and markers of platelet activation in diet-induced diabetic C57BL/6J mice.

AIMS: Type 2 diabetes in humans is associated with hypercoaguability; however, little is known about platelet function in mouse models of type 2 diabetes used to study this disorder. Therefore, the purpose of this study was to examine platelet aggregation, coagulation, and markers of platelet activation in a diet-induced mouse model of type 2 diabetes. METHODS: Four week old, male, C57BL/6J mice were randomized to a standard chow or high fat (60% beef lard) diet for 4 months. To examine platelet function we measured ADP-induced whole blood aggregometry, whole blood coagulation by thromboelastography, tail bleeding times, platelet microparticle and platelet expression of p-selectin and platelet expression of CD61 by flow cytometry. RESULTS: Diabetic mice exhibited less aggregation (p<0.05), less coagulation (p<0.01), prolonged tail bleeding times (n.s.), and lower agonist stimulated platelet CD61 expression (p<0.001) compared to non-diabetic mice. There was no difference in platelet microparticle and platelet p-selectin expression. CONCLUSIONS: Diet-induced type 2 diabetic mouse do not demonstrate the hypercoagulability and platelet activation typically observed in humans with this disorder. More studies are warranted to further explore platelet function in this mouse model; to determine their applicability for studying these alterations in type 2 diabetes.

Neutrophil activation by murine retroviral infection during chronic ethanol consumption.

AIMS: Neutrophil adhesion molecule CD11b and reactive oxygen species (ROS) are neutrophil activation markers for evaluating the functional activity of neutrophils. The aim of this study was to determine if neutrophils are activated in murine AIDS and/or chronic ethanol consumption and if neutrophil CD11b expression and ROS production vary when progressive retrovirus infection occurs. METHODS: Four groups were studied: control, murine AIDS, ethanol and ethanol plus murine AIDS. Neutrophil activation was assessed by CD11b expression and ROS production using flow cytometry. RESULTS: We found that neutrophils lost their responsiveness to fMLP due to retrovirus or ethanol exposure. In the murine AIDS group, neutrophil CD11b expression was up-regulated along with a significant increase in ROS after 1 month of retroviral infection. After 2 months, neutrophil CD11b and ROS decreased. However, neutrophil CD11b expression further increased after 3 months. In the ethanol consumption group, neutrophil CD11b expression was down-regulated after 2 months, whereas ROS production increased in the first and third months. In the murine AIDS plus ethanol group, there were significant increases in both ROS and CD11b expression during the 3-month observation period. CONCLUSIONS: These findings suggest that neutrophil function is impaired by LP-BM5 retrovirus infection and/or chronic ethanol consumption. The pattern of neutrophil CD11b expression and ROS production might help to predict the stage of murine AIDS. Ethanol may further compromise neutrophil function in AIDS.