Selective Computed Tomography (CT) Imaging is Superior to Liberal CT Imaging in the Hemodynamically Normal Pediatric Blunt Trauma Patient.

BACKGROUND: The optimal imaging strategy in hemodynamically stable pediatric blunt trauma remains to be defined. The purpose of this study was to determine the differences between selective and liberal computed tomography (CT) strategy in a pediatric trauma population with respect to radiation exposure and outcomes. METHODS: We performed a retrospective analysis of hemodynamically stable blunt pediatric trauma patients (≤16 y) who were admitted to a Level I trauma center between 2013-2016. Patients were stratified into selective and liberal imaging cohorts. Univariate and multivariate regression analyses were used to compare outcomes between the groups. Outcomes included radiation dose, hospital and ICU length of stay, complications and mortality. RESULTS: Of the 485 patients included, 176 underwent liberal and 309 selective CT imaging. The liberal cohort were more likely to be severely injured (ISS>15: 34.1 versus 8.4%, P< 0.001). The odds of exposure to a radiation dose of >15 mSv were higher with liberal scanning in patients with both ISS > 15 (OR 2.78, 95% CI 1.76-5.19, P< 0.001) and ISS ≤ 15 (OR 3.41, 95% CI 2.19-8.44, P < 0.001). Adjusted outcomes regarding mortality, ICU length of stay, and complications were similar between the cohorts. CONCLUSION: Selective CT imaging in hemodynamically stable blunt pediatric trauma patients was associated with reduced radiation exposure and similar outcomes when compared to a liberal CT strategy.

Increased Incidence of COVID-19 Infections Amongst Interpersonal Violence Patients.

OBJECTIVE: To investigate whether any specific acute care surgery patient populations are associated with a higher incidence of COVID-19 infection. BACKGROUND: Acute care providers may be exposed to an increased risk of contracting the COVID-19 infection since many patients present to the emergency department without complete screening measures. However, it is not known which patients present with the highest incidence. METHODS: All acute care surgery (ACS) patients who presented to our level I trauma center between March 19, 2020, and September 20, 2020 and were tested for COVID-19 were included in the study. The patients were divided into two cohorts: COVID positive (+) and COVID negative (-). Patient demographics, type of consultation (emergency general surgery consults [EGS], interpersonal violence trauma consults [IPV], and non-interpersonal violence trauma consults [NIPV]), clinical data and outcomes were analyzed. Univariate and multivariate analyses were used to compare differences between the groups. RESULTS: In total, 2177 patients met inclusion criteria. Of these, 116 were COVID+ (5.3%) and 2061 were COVID- (94.7%). COVID+ patients were more frequently Latinos (64.7% versus 61.7%, P = 0.043) and African Americans (18.1% versus 11.2%, P < 0.001) and less frequently Caucasian (6.0% versus 14.1%, P < 0.001). Asian/Filipino/Pacific Islander (7.8% versus 7.2%, P = 0.059) and Native American/Other/Unknown (3.4% versus 5.8%, P = 0.078) groups showed no statistical difference in COVID incidence. Mortality, hospital and ICU lengths of stay were similar between the groups and across patient populations stratified by the type of consultation. Logistic regression demonstrated higher odds of COVID+ infection amongst IPV patients (OR 2.33, 95% CI 1.62-7.56, P < 0.001) compared to other ACS consultation types. CONCLUSION: Our findings demonstrate that victims of interpersonal violence were more likely positive for COVID-19, while in hospital outcomes were similar between COVID-19 positive and negative patients.

Increased Use of Prehospital Tourniquet and Patient Survival: Los Angeles Countywide Study.

BACKGROUND: Recent trends in prehospital tourniquet use remain underreported. In addition, the impact of prehospital tourniquet use on patient survival has not been evaluated in a population-level study. We hypothesized that prehospital tourniquets were used more frequently in Los Angeles County and their use was associated with improved patient survival. STUDY DESIGN: This is a retrospective cohort study using a database maintained by the Los Angeles County Emergency Medical Services Agency. We included patients who sustained extremity vascular injuries between October 2015 and July 2019. Patients were divided into the following study groups: prehospital tourniquet and no-tourniquet group. Our primary end point was in-hospital mortality. The secondary outcomes included 4- and 24-hour transfusion requirements and delayed amputation. RESULTS: A total of 944 patients met our inclusion criteria. Of those, 97 patients (10.3%) had prehospital tourniquets placed. The rate of tourniquet use increased linearly throughout our study period (goodness of fit, p = 0.014). In multivariable analysis, prehospital tourniquet use was significantly associated with improved mortality (adjusted odds ratio 0.32; 95% CI, 0.16 to 0.85; p = 0.032). Similarly, transfusion requirements were significantly lower within 4 hours (regression coefficient -547.76; 95% CI, -762.73 to -283.49; p < 0.001) and 24 hours (regression coefficient -1,389.82; 95% CI, -1,824.88 to -920.97; p < 0.001). There was no significant difference in delayed amputation rates (adjusted odds ratio 1.07; 95% CI, 0.21 to 10.88; p < 0.097). CONCLUSIONS: Prehospital tourniquet use has been on the rise in Los Angeles County. Our results suggest that the use of prehospital tourniquets for extremity vascular injuries is associated with improved patient survival and decreased blood transfusion requirements, without an increase in delayed amputations.

Utility of the Laboratory Risk Indicator for Necrotizing Fasciitis Score: Comorbid Conditions Do Matter.

Background: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) has been proposed as a diagnostic tool for necrotizing soft tissue infection (NSTI). However, its utility remains underreported, particularly in patients with comorbid conditions. The purpose of this study was to identify the test characteristics of LRINEC for patients with various comorbid conditions. Patients and Methods: We conducted a retrospective study including patients with suspected NSTI. Our study patients were then relegated into the subgroups; intravenous drug use (IVDU), end-stage liver disease (ESLD), and diabetes mellitus (DM). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a positive LRINEC score (≥ 6 or 8) were calculated in reference to intra-operative findings or results of the pathologic examination. Area under the curve (AUC) using receiver operating characteristic (ROC) plots were compared between each subgroup and the overall study population using DeLong test. Results: A total of 220 patients were included for the analysis. Overall, the sensitivity was 76%, specificity of 52%, PPV of 32%, and NPV of 88%. The subgroup analysis showed low PPVs in all subgroups. The DM and ESLD groups had a high NPV (90.5% and 88.0%, respectively), whereas NPV in the IVDU group was 70.6%. The AUC and DeLong test for the subgroups were 0.649 (p = 0.902) for ESLD, 0.699 (p = 0.683) for DM, and 0.565 (p = 0.034) for IVDU. Conclusions: The LRINEC can be a useful adjunct to rule out the diagnosis of NSTI with exception of IVDU. In contrast, further diagnostic workup might be still required in those patients with positive LRINEC.

Validation of a Novel Clinical Criteria to Predict Candidacy for Aortic Occlusion: An Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery Study.

For trauma patients with noncompressible truncal hemorrhage (NCTH), aortic occlusion (AO) is attempted with either resuscitative thoracotomy (RT) or the resuscitative endovascular balloon occlusion of the aorta (REBOA). However, it is often challenging to identify the group of patients who would benefit from AO procedures. We hypothesized that patients who met simple clinical criteria would have better outcomes following AO procedures. This is a retrospective cohort study using the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery database (November 2013-August 2019) which included patients who arrived with signs of life and underwent AO procedures (RT or zone 1 REBOA). Outcomes were compared between patients who met the criteria (admission vital signs: Glasgow Coma Scale (GCS) ≥9 and systolic blood pressure <90 mm Hg) and those who did not. Subgroup analyses were then conducted on patients who had a REBOA placed and those who underwent RT. A total of 998 patients met our inclusion criteria. Of those, a REBOA was placed in 364 patients (37%), while 634 (64%) underwent RT. The overall mortality rate in the criteria (+) group was significantly lower than that in the criteria (-) group (62 vs. 79%, P < .001). In patients who survived beyond the emergency department following AO procedures, those who met the criteria underwent hemorrhage control procedures more frequently (83% vs. 57%, P < .001). Our data suggest that simple clinical criteria could guide the provider for proceeding with AO in patients with suspected NCTH.

Who Would Have Benefited from the Prehospital Use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA)? An Autopsy Study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been increasingly used as part of damage control resuscitation for patients with non-compressible truncal hemorrhage. We hypothesized that there might be a select group of patients that could have benefited from prehospital placement of the REBOA. STUDY DESIGN: This was a retrospective cohort study including patients who presented to a Level I trauma center with cardiac arrest between January 2014 and March 2018. The findings of a full autopsy were reviewed for the details of internal injuries. A patient was determined to be a REBOA candidate if the patient sustained abdominal organ injuries or pelvic fractures and no associated severe head injuries. The candidate group was compared with the non-candidate group based on prehospital vital signs and other patient characteristics. A multiple logistic regression analysis was performed to identify certain prehospital factors associated with candidacy for prehospital REBOA. RESULTS: A total of 198 patients met our inclusion criteria. Of those, 27 (13.6%) patients were deemed REBOA candidates. Median Injury Severity Score was 22 (interquartile range 17 to 29). Patients in the candidate group were more likely to have a Glasgow Coma Scale score ≥9 (48% vs 15%; p = 0.012), oxygen saturation >90% (56% vs 35%; p = 0.03), and systolic blood pressure <90 mmHg (48% vs 26%; p = 0.04) in the field. Logistic regression showed that these 3 clinical parameters of prehospital vital signs were significantly associated with REBOA candidacy. CONCLUSIONS: Our data suggest that >10% of trauma patients who presented with cardiac arrest could have benefited from prehospital REBOA. Additional prospective studies are warranted to validate the use of field vital signs in selecting candidates.

The effectiveness of non-surgical interventions for common plantar digital compressive neuropathy (Morton's neuroma): a systematic review and meta-analysis.

BACKGROUND: Morton's neuroma (MN) is a compressive neuropathy of the common plantar digital nerve. It is a common compressive neuropathy often causing significant pain which limits footwear choices and weight bearing activities. This paper aims to review non-surgical interventions for MN, to evaluate the evidence base for the clinical management of MN. METHODS: Electronic biomedical databases (CINAHL, EMBASE, MEDLINE and Cochrane) were searched to January 2018 for studies evaluating the effectiveness of non-surgical interventions for Morton's neuroma. Outcome measures of interest were treatment success rate (SR) (binary) and pain as measured using 100-point visual analogue scale (VAS) (continuous). Studies with and without control groups were included and were evaluated for methodological quality using the Downs and Black Quality Index. Results from randomised controlled trials (RCT) were compared between-groups, and case series were compared pre- versus post-treatment. Effect estimates are presented as odds ratios (OR) for binary data or mean differences (MD) for continuous data. Random effects models were used to pool effect estimates across studies where similar treatments were used. Heterogeneity was assessed using the I 2 statistic. RESULTS: A total of 25 studies met the inclusion criteria, seven RCTs and 18 pre/post case series. Eight different interventions were identified, with corticosteroid or sclerosing injections being the most often reported (seven studies each). Results from a meta-analysis of two RCTs found corticosteroid injection decreased pain more than control on VAS (WMD: -5.3, 95%CI: -7.5 to - 3.2). Other RCTs reported efficacy of: manipulation/mobilisation versus control (MD: -15.3, 95%CI: -29.6 to - 1.0); extracorporeal shockwave therapy versus control (MD: -5.9, 95%CI: -21.9 to 10.1). Treatment success was assessed for extracorporeal shockwave therapy versus control (OR: 0.3, 95%CI: 0.0 to 7.1); and corticosteroid injection vs footwear/padding (OR: 6.0, 95%CI: 1.9 to 19.2). Sclerosing and Botox injections, radiofrequency ablation and cryoneurolysis have been investigated by case series studies, however these were of limited methodological quality. CONCLUSIONS: Corticosteroid injections and manipulation/mobilisation are the two interventions with the strongest evidence for pain reduction, however high-quality evidence for a gold standard intervention was not found. Although the evidence base is expanding, further high quality RCTs are needed.

Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.

Recent advances in genome editing have facilitated the generation of nonhuman primate (NHP) models, with potential to unmask the complex biology of human disease not revealed by rodent models. However, their broader use is hindered by the challenges associated with generation of adult NHP models as well as the cost of their production. Here, we describe the generation of a marmoset model of severe combined immunodeficiency (SCID). This study optimized zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) to target interleukin-2 receptor subunit gamma (IL2RG) in pronuclear stage marmoset embryos. Nine of 21 neonates exhibited mutations in the IL2RG gene, concomitant with immunodeficiency, and three neonates have currently survived from 240 days to 1.8 years. Our approach demonstrates highly efficient production of founder NHP with SCID phenotypes, with promises of multiple pre-clinical and translational applications.

The use of social media in dental hygiene programs: a survey of program directors.

PURPOSE: The use of social media and social networking sites has become increasingly common by the current generation of students. Colleges and universities are using social media and social networking sites to advertise, engage and recruit prospective students. The purpose of this study was to evaluate how social media is being used in dental hygiene program admissions and policy. METHODS: Researchers developed a survey instrument investigating the use of social media. The survey included questions about demographic information, personal use of social media, program use of social media, social media use in admissions and social media policies. An email was sent to 321 dental hygiene program directors asking them to complete the survey. All participants were provided 4 weeks to complete the survey, and 2 reminder emails were sent. RESULTS: A total of 155 responses were received (48.3% response rate). While 84% of respondents indicated their program had a web page, only 20% had an official Facebook page for the program and 2% had a Twitter page. Thirty-five percent had a program policy specifically addressing the use of social media and 31% indicated that their university or institution had a policy. Only 4% of programs evaluate a potential student's Internet presence, mostly by searching on Facebook. Statistically significant differences (p≤0.05) were noted between those respondents with more personal social media accounts and those with fewer accounts, as those with more accounts were more likely to evaluate a potential student's Internet presence. Open ended responses included concern about social media issues, but some uncertainty on how to handle social media in the program. The concern for social media and professionalism was evident and more research and discussion in this area is warranted. CONCLUSION: Social media is currently being used in a variety of ways in dental hygiene programs, but not in the area of admissions. There is some uncertainty about the role social media should play in a professional environment.

A survey of social media policies in U.S. dental schools.

Since social media sites began to appear in the 1990s, their popularity has increased dramatically, especially among younger individuals. With this widespread use of social media, institutions of higher education are finding the need to implement social media policies. The purpose of this study was to gather information from accredited U.S. dental schools on their social media policies. A survey sent to academic deans asked questions related to social media policies and violations of policies. The survey yielded a 35.9 percent (n=23) response rate. Social media policies at the university level were reported by 47.8 percent (n=11) of respondents, and 34.8 percent (n=8) had social media policies specifically in the dental school. Schools that had an institutional social media policy were more likely to have a social media policy in the dental school (p=0.01), and dental schools were more likely to have a policy if the academic dean had been in the position less than five years (p=0.01). All twenty-three responding dental schools have official social media pages. Dental educators and administrators may want to look for opportunities to raise awareness of social media professionalism in their dental schools.

Examination of social networking professionalism among dental and dental hygiene students.

Becoming a dental professional requires one to apply ethical decision making skills and demonstrate high standards of professionalism in practice, including the way professionals present themselves to the public. With social media as an evergrowing part of personal and professional communications, this study aimed to determine the accessibility, amount, and type of unprofessional content on Facebook profiles of dental hygiene and dental students in a college of dentistry. The authors evaluated the online profiles of all 499 dental and dental hygiene students at The Ohio State University using objective measures that included existence of a profile, current privacy settings, and access to personally identifiable information. A sample of profiles were evaluated for unprofessional content including photos, comments, and wall posts. The majority of these students were found to use Facebook, with 61 percent having Facebook profiles. Dental hygiene students were more likely to have a Facebook profile than were dental students: 72.6 percent and 59.1 percent, respectively (p=0.027). The majority of the students' profiles had some form of privacy setting enabled, with only 4 percent being entirely open to the public. Fewer than 2 percent of the students allowed non-friends access to personal information. Based on in-depth analysis of the profiles, fourteen (5.8 percent) instances of unprofessionalism were recorded; the most common unprofessional content involved substance abuse. This study found that these dental and dental hygiene students frequently possessed an identifiable Facebook account and nearly half had some kind of personal information on their profile that could potentially be shared with the public. In some instances, the students gave patients, faculty, and potential employers access to content that is not reflective of a dental professional. Academic institutions should consider implementing policies that bring awareness to and address the use of social media in a professional environment.

Whole-rat conditional gene knockout via genome editing.

Animal models with genetic modifications under temporal and/or spatial control are invaluable to functional genomics and medical research. Here we report the generation of tissue-specific knockout rats via microinjection of zinc-finger nucleases (ZFNs) into fertilized eggs. We generated rats with loxP-flanked (floxed) alleles and a tyrosine hydroxylase promoter-driven cre allele and demonstrated Cre-dependent gene disruption in vivo. Pronuclear microinjection of ZFNs, shown by our data to be an efficient and rapid method for creating conditional knockout rats, should also be applicable in other species.

A survey of US dental practices' use of social media.

AIM: Social media is becoming the way for businesses, including health care professionals, to communicate with consumers. The study examines the use of social media by dental practices in the US. MATERIALS AND METHODS: An electronic survey was sent to 22,682 dentists in the United States. The survey consisted of questions related to the use of social media in the dental practice. Data was analyzed using descriptive statistics and comparisons were made using a Fisher's exact test. RESULTS: A total of 573 responses were received. Social media was used in 52% of dental practices, the most common being Facebook. The use of social media was most commonly for marketing purposes (91%). Dentists younger than 45 years old were more likely to use social media in their practice than dentists 45 years or older (p > 0.001). CONCLUSION: Dental practices actively use social media for marketing and communication. Many dentists are unsure how to measure the success of social media in their practice. Additional research is needed to measure the success of social media in a dental practice. CLINICAL SIGNIFICANCE: Social media is a common way practices market and interact with their patients. There are some difficulties in determining what appropriate content for social media is and how to evaluate the success.

Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes.

Eliminating autoantigen-specific B cells is an attractive alternative to global B-cell depletion for autoimmune disease treatment. To identify the potential for targeting a key autoimmune B-cell specificity in type 1 diabetes, insulin-binding B cells were tracked within a polyclonal repertoire using heavy chain B-cell receptor (BCR) transgenic (VH125Tg) mice. Insulin-specific B cells are rare in the periphery of nonautoimmune VH125Tg/C57BL/6 mice and WT/NOD autoimmune mice, whereas they clearly populate 1% of mature B-cell subsets in VH125Tg/NOD mice. Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells. Endogenous insulin occupies anti-insulin BCR beginning with antigen commitment in bone marrow parenchyma, as identified by a second anti-insulin monoclonal antibody. Administration of this monoclonal antibody selectively eliminates insulin-reactive B cells in vivo and prevents disease in WT/NOD mice. Unexpectedly, developing B cells are less amenable to depletion, despite increased BCR sensitivity. These findings exemplify how a critical type 1 diabetes B-cell specificity escapes immune tolerance checkpoints. Disease liability is corrected by eliminating this B-cell specificity, providing proof of concept for a novel therapeutic approach for autoimmune disease.

A comparison of millennial dental hygiene student and faculty classroom expectations.

PURPOSE: Research has shown that Millennial students are different than students in previous generations. This study compares the expectations of the didactic environment of faculty and students in a baccalaureate dental hygiene program. Expectations of faculty and students were examined, and comparisons between Millennial and non-Millennial students and faculty were made in order to improve the educational experience of dental hygiene students. METHODS: Students and faculty completed a survey adapted from McCargar's role expectations survey. Items were chosen from the survey to cover such areas as technology, group work and authority. The survey consisted of a Likert-type scale including strongly agree, agree, neutral, disagree and strongly disagree. Data was entered into SPSS 15.0 database. Scoring on negative questions was reversed so that the score would be positive. Individual answers are given the following scoring assignments: Strongly Agree (+2), Agree (+1), Neutral (0), Disagree (-1) and Strongly Disagree (-2). Scores were added together to create a summative score for each item. Descriptive statistics and an unpaired t-test comparing responses were used to analyze data. Cronbach's alpha was run to measure the internal consistency of the instrument. RESULTS: Twelve faculty and 94 students returned surveys. Students felt strongly that copies of course notes should be available online and faculty should return emails within 24 hours. Statistically significant differences in the expectations of Millennial and non-Millennial students were found in regards to issues of authority, community service, attendance and evaluation. The majority of significant differences were found between Millennial students and faculty. Significant differences were found in interaction, community service, technology and homework. CONCLUSION: Faculty should examine the expectations of their students and should use the findings to create learning experiences that are more effective for students. Expectations change with each generation, and it is important to change techniques and methodologies in order to meet the needs of current students and the profession.

CXCL13 blockade disrupts B lymphocyte organization in tertiary lymphoid structures without altering B cell receptor bias or preventing diabetes in nonobese diabetic mice.

Lymphocytes that invade nonlymphoid tissues often organize into follicle-like structures known as tertiary lymphoid organs (TLOs). These structures resemble those found in spleen or lymph nodes, but their function is unknown. TLOs are recognized in many autoimmune diseases, including the NOD mouse model of type 1 diabetes. In some cases, TLOs have been associated with the B lymphocyte chemoattractant, CXCL13. Studies presented in this article show that CXCL13 is present in inflamed islets of NOD mice. Ab blockade of this chemokine unraveled B lymphocyte organization in islet TLOs, without reducing their proportion in the islets. These chaotic milieus contained B lymphocytes with the same distinct repertoire of B cell receptors as those found in mice with well-organized structures. Somatic hypermutation, associated with T-B interactions, was not impaired in these disorganized insulitis lesions. Finally, loss of B lymphocyte organization in islets did not provide disease protection. Thus, B lymphocytes infiltrating islets in NOD mice do not require the morphology of secondary lymphoid tissues to support their role in disease.

Vkappa polymorphisms in NOD mice are spread throughout the entire immunoglobulin kappa locus and are shared by other autoimmune strains.

The diversity of immunoglobulin (Ig) and T cell receptor (TCR) genes available to form the lymphocyte repertoire has the capacity to produce a broad array of both protective and harmful specificities. In type 1 diabetes (T1D), the presence of antibodies to insulin and other islet antigens predicts disease development in both mice and humans, and demonstrate that immune tolerance is lost early in the disease process. Anti-insulin T cells isolated from T1D-prone non-obese diabetic (NOD) mice use polymorphic TCRalpha chains, suggesting that the available T cell repertoire is altered in these autoimmune mice. To probe whether insulin-binding B cells also possess polymorphic V genes, Ig light chains were isolated and sequenced from NOD mice that harbor an Ig heavy chain transgene. Three insulin-binding Vkappa genes were identified, all of which were polymorphic to the closest germline sequence matches present in the GenBank database. Additional analysis of over 300 light chain sequences from multiple sources, including germline DNA, shows that polymorphisms are spread throughout the entire NOD Igkappa locus, as these polymorphic sequences represent 43 distinct Vkappa genes which belong to 14 Vkappa families. Database searches reveal that a majority of polymorphic Vkappa genes identified in NOD are identical to Vkappa genes isolated from SLE-prone NZBxNZW F1 or MRL strains of mice, suggesting that a shared Igkappa haplotype may be present. Predicted amino acid changes preferentially occur in CDR, and thus could alter antigen recognition by the germline B cell repertoire of autoimmune versus non-autoimmune mouse strains.

Functional silencing is initiated and maintained in immature anti-insulin B cells.

Mechanisms of B cell tolerance act during development in the bone marrow and periphery to eliminate or restrict autoreactive clones to prevent autoimmune disease. B cells in the spleens of mice that harbor anti-insulin BCR transgenes (125Tg) are maintained in a functionally silenced or anergic state by endogenous hormone, but it is not clear when and where anergy is induced. An in vitro bone marrow culture system was therefore used to probe whether small protein hormones, a critical class of autoantigens, could interact with the BCR to induce anergy early during B cell development. Upon exposure to insulin, anti-insulin (125Tg) immature B cells show similar hallmarks of anergy as those observed in mature splenic B cells. These include BCR down-regulation, impaired proliferative responses to anti-CD40, and diminished calcium mobilization upon stimulation with BCR-dependent and independent stimuli. Inhibition of calcineurin also results in reduced immature B cell proliferation in a similar manner, suggesting a potential mechanism through which reduced intracellular calcium mobilization may be altering cellular proliferation. Signs of impairment appear after short-term exposure to insulin, which are reversible upon Ag withdrawal. This suggests that a high degree of functional plasticity is maintained at this stage and that constant Ag engagement is required to maintain functional inactivation. These findings indicate that tolerance observed in mature, splenic 125Tg B cells is initiated by insulin in the developing B cell compartment and thus highlight an important therapeutic window for the prevention of insulin autoimmunity.

Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus.

Diverse families of viruses bind immunoglobulin superfamily (IgSF) proteins located in tight junctions (TJs) and adherens junctions of epithelium and endothelium. However, little is known about the roles of these receptors in the pathogenesis of viral disease. Junctional adhesion molecule-A (JAM-A) is an IgSF protein that localizes to TJs and serves as a receptor for mammalian reovirus. We inoculated wild-type (WT) and isogenic JAM-A(-/-) mice perorally with reovirus and found that JAM-A is dispensable for viral replication in the intestine but required for systemic dissemination. Reovirus replication in the brain and tropism for discrete neural regions are equivalent in WT and JAM-A(-/-) mice following intracranial inoculation, suggesting a function for JAM-A in reovirus spread to extraintestinal sites. JAM-A promotes reovirus infection of endothelial cells, providing a conduit for the virus into the bloodstream. These findings indicate that a broadly expressed IgSF viral receptor specifically mediates hematogenous dissemination in the host.

Intraindividual stability of human erythrocyte cholinesterase activity.

BACKGROUND: Erythrocyte cholinesterase (RBC-ChE) activities serve as useful and sensitive biomarkers to monitor exposure to cholinesterase-inhibiting substances, such as chemical warfare nerve agents and pesticides. Although the interindividual variation of RBC-ChE is well characterized, the magnitude of intraindividual variation for RBC-ChE remains controversial. An accurate measure of intraindividual variation is critical for establishing the appropriate frequency of RBC-ChE testing. METHODS: We retrospectively tracked the intraindividual variation of RBC-ChE activities among 46 male nerve agent workers from a single US Army depot that participated in a medical surveillance program requiring periodic RBC-ChE monitoring. All RBC-ChE analysis was performed by the same medical laboratory technician by the delta pH method. RESULTS: A mean of 38 and a median of 37 RBC-ChE measurements were available for each worker. The mean duration of employment for these workers was 20 years (median, 21 years). The mean CV for RBC-ChE in this set of 46 workers was 3.9%. Linear regression analysis of the data for each worker resulted in a mean slope of 0.0010 delta pH units/h per year. CONCLUSIONS: RBC-ChE activities increased in each person by a mean of 0.01 delta pH units/h every 10 years, which is a negligible rate. These findings highlight the stability of RBC-ChE activities over time in a given individual and may have important policy implications regarding the appropriate frequency of RBC-ChE testing.