Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

RATIONALE & OBJECTIVE: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined pre- versus post-KT cognition in patients waitlisted for KT at an academic center. PREDICTORS: Transplant status. We measured cognitive function before KT (n=101), 3 months after KT (n=78), and 1 year after KT (n = 83). OUTCOMES: Our primary outcome was change in cognitive function before versus after KT. We used standard neuropsychological tests to assess global cognition (Mini-Mental State Exam [MMSE]), episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test [DSST], Trail Making Test [TMT] A), working memory/attention (Digit Span), executive function (TMT B), and semantic memory/verbal fluency/language (Category Fluency). ANALYTICAL APPROACH: Using linear mixed model analysis, we evaluated the changes in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments. RESULTS: Before KT, Logical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low compared with normative values from the National Alzheimer's Coordinating Center data. Logical Memory I and II scores improved after KT (pre- vs post-KT, estimated group difference [d]=3.3, P<0.001 for Logical Memory I; d=4.27, P<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs normative values, d = -0.37, P=0.06 for Logical Memory I; d = -0.89, P=0.08 for Logical Memory II). Category Fluency (animal naming; d=2.4, P<0.001) and DSST (d=3.12, P=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs normative values, d = -5.17, P<0.001). MMSE, Digit Span, and TMT A and B scores did not change after KT. LIMITATIONS: Single-center study. CONCLUSIONS: Episodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is therefore at least partly reversible with KT. PLAIN-LANGUAGE SUMMARY: Cognitive impairment in kidney disease affects self-esteem, vocational abilities, quality of life, health care costs, and mortality. It is not clear whether kidney transplantation (KT) improves cognition and whether the improvement is uniform across cognitive domains. The distinction between reversible and irreversible cognitive impairment has important implications in the clinical care of patients before and after KT. We assessed cognition before KT and 3 months and 12 months after KT and discovered that episodic and verbal declarative memory normalized with KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function also improved with KT but did not reach normal levels. Cognitive impairment in kidney disease is therefore at least partly reversible.

Demographically-adjusted normative data among Latinos for the version 3 of the Alzheimer's Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

INTRODUCTION: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). METHODS: Healthy Latino adults (N = 437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). RESULTS: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. DISCUSSION: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. HIGHLIGHTS: We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.

First-Line Immunotherapy with Check-Point Inhibitors: Prospective Assessment of Cognitive Function.

Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to (1) demonstrate the feasibility of prospective recruitment, retention, and neurocognitive assessment for older adults receiving first-line CPI(s) and (2) provide preliminary evidence of changes in cognitive function associated with CPI(s). Patients receiving first-line CPI(s) (CPI Group) were assessed at baseline (n = 20) and 6 months (n = 13) for self-report of cognitive function and neurocognitive test performance. Results were compared to age-matched controls without cognitive impairment assessed annually by the Alzheimer's Disease Research Center (ADRC). Plasma biomarkers were measured at baseline and 6 months for the CPI Group. Estimated differences for CPI Group scores prior to initiating CPIs (baseline) trended to lower performance on the Montreal Cognitive Assessment-Blind (MOCA-Blind) test compared to the ADRC controls (p = 0.066). Controlling for age, the CPI Group's 6-months MOCA-Blind performance was lower than the ADRC control group's 12-months performance (p = 0.011). No significant differences in biomarkers were detected between baseline and 6 months, although significant correlations were noted for biomarker change and cognitive performance at 6 months. IFNγ, IL-1ß, IL-2, FGF2, and VEGF were inversely associated with Craft Story Recall performance (p < 0.05), e.g., higher levels correlated with poorer memory performance. Higher IGF-1 and VEGF correlated with better letter-number sequencing and digit-span backwards performance, respectively. Unexpected inverse correlation was noted between IL-1α and Oral Trail-Making Test B completion time. CPI(s) may have a negative impact on some neurocognitive domains and warrant further investigation. A multi-site study design may be crucial to fully powering prospective investigation of the cognitive impact of CPIs. Establishment of a multi-site observational registry from collaborating cancer centers and ADRCs is recommended.

Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.

BACKGROUND: Lowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition. METHODS: This is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms. RESULTS: Mean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention. CONCLUSIONS: Intensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP.

Contaminated Airway Task Training: How to Adapt an Existing Airway Manikin Head for Active Airway Soiling.

The massively contaminated airway is an important and often daunting entity for airway providers. Although massively contaminated airways are considered high acuity, low-occurrence presentations in emergency medicine and pre-hospital settings, formal training in the management of contaminated airways is heterogeneous and infrequent. To facilitate training and augment simulation, an airway task trainer is critical. To our knowledge, this is the first readily accessible, peer-reviewed, detailed technical report to build a low-cost, high-fidelity, contaminated airway task trainer. This trainer can be seamlessly integrated into simulated resuscitation scenarios and/or airway training workshops, reinforcing skill acquisition and retention for the management of the massively contaminated airway.

AIM™ platform: A new immunotherapy approach for viral diseases.

In addition to complications of acute diseases, chronic viral infections are linked to both malignancies and autoimmune disorders. Lack of adequate treatment options for Epstein-Barr virus (EBV), Human T-lymphotropic virus type 1 (HTLV-1), and human papillomavirus (HPV) remains. The NexImmune Artificial Immune Modulation (AIM) nanoparticle platform can be used to direct T cell responses by mimicking the dendritic cell function. In one application, AIM nanoparticles are used ex vivo to enrich and expand (E+E) rare populations of multi-antigen-specific CD8+ T cells for use of these cells as an AIM adoptive cell therapy. This study has demonstrated using E+E CD8+ T cells, the functional relevance of targeting EBV, HTLV-1, and HPV. Expanded T cells consist primarily of effector memory, central memory, and self-renewing stem-like memory T cells directed at selected viral antigen peptides presented by the AIM nanoparticle. T cells expanded against either EBV- or HPV-antigens were highly polyfunctional and displayed substantial in vitro cytotoxic activity against cell lines expressing the respective antigens. Our initial work was in the context of exploring T cells expanded from healthy donors and restricted to human leukocyte antigen (HLA)-A*02:01 serotype. AIM Adoptive Cell Therapies (ACT) are also being developed for other HLA class I serotypes. AIM adoptive cell therapies of autologous or allogeneic T cells specific to antigens associated with acute myeloid leukemia and multiple myeloma are currently in the clinic. The utility and flexibility of the AIM nanoparticle platform will be expanded as we advance the second application, an AIM injectable off-the-shelf nanoparticle, which targets multiple antigen-specific T cell populations to either activate, tolerize, or destroy these targeted CD8+ T cells directly in vivo, leaving non-target cells alone. The AIM injectable platform offers the potential to develop new multi-antigen specific therapies for treating infectious diseases, cancer, and autoimmune diseases.

Validity of In-Home Teleneuropsychological Testing in the Wake of COVID-19.

OBJECTIVE: Teleneuropsychology (TNP) has been shown to be a valid assessment method compared with in-person neuropsychological evaluations. Interest in delivering TNP directly to patients' homes has arisen in response to the coronavirus disease 2019 (COVID-19) pandemic. However, prior research has typically involved patients tested in clinical settings, and the validity of in-home TNP testing has not yet been established. The present study aims to explore the validity and clinical utility of in-home TNP testing in a mixed clinical sample in the wake of COVID-19. METHODS: Test profiles for 111 in-home TNP patients were retrospectively compared with 120 patients who completed in-person evaluations. The TNP test battery consisted of tests measuring attention/processing speed, verbal memory, naming, verbal fluency, and visuoconstruction. TNP scores of cognitively normal (CN) patients were compared with patients with neurocognitive disorders (NCD), and score profiles were examined among suspected diagnostic groups of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular disease (VaD). RESULTS: TNP test scores did not significantly differ from in-person testing across all tests except the Hopkins Verbal Learning Test-Revised Discrimination Index. Within the TNP group, significant differences between the CN and NCD groups were found for all tests, and the memory and semantic fluency tests yielded large effect sizes (d ≥ 0.8). Score profiles among the AD, PD, and VaD groups were explored. CONCLUSIONS: These findings support the validity of in-home TNP testing compared with in-person neuropsychological testing. Practice considerations, limitations, and future directions are discussed.

λ Recombineering Used to Engineer the Genome of Phage T7.

Bacteriophage T7 and T7-like bacteriophages are valuable genetic models for lytic phage biology that have heretofore been intractable with in vivo genetic engineering methods. This manuscript describes that the presence of λ Red recombination proteins makes in vivo recombineering of T7 possible, so that single base changes and whole gene replacements on the T7 genome can be made. Red recombination functions also increase the efficiency of T7 genome DNA transfection of cells by ~100-fold. Likewise, Red function enables two other T7-like bacteriophages that do not normally propagate in E. coli to be recovered following genome transfection. These results constitute major technical advances in the speed and efficiency of bacteriophage T7 engineering and will aid in the rapid development of new phage variants for a variety of applications.

Barriers and enablers that influence guideline-based care of geriatric fall patients presenting to the emergency department.

BACKGROUND: Geriatric patients commonly present to the ED after a fall. Recent evidence suggests that ED physicians are poorly adherent to published ED-specific geriatric fall guidelines. This study applied a theoretical domains framework (TDF) approach to systematically investigate barriers and enablers in the provision of guideline-based care to ED geriatric fall patients. METHODS: From June to September 2017, semistructured interviews of staff ED physicians practising in Ontario, Canada, were conducted and analysed. An interview guide based on the TDF was used to capture 14 domains influencing provision of guideline-based care. Relevant domains were identified based on frequencies of beliefs, existence of conflicting beliefs and evidence of strong beliefs that would influence provision of guideline-based care. RESULTS: Eleven interviews were conducted with practising ED physicians. Thirty belief statements were identified across 13 relevant TDF domains (all except Optimism). Prominent themes included lack of knowledge, paucity of evidence, heterogeneous self-perceived skills, perceived increased time and workload, importance of allied health support, inconsistently available allied health workers, lack of positive reinforcement, emotions negatively impacting these clinical encounters and support for memory aids. Overall, ED physicians were supportive of guideline implementation, and believe it will lead to better outcomes for geriatric fall patients. CONCLUSION: This study identified important barriers and enablers to provision of guideline-based care in geriatric ED fall patients. Based on these findings, future implementation of guidelines nationally and internationally should focus on improving knowledge and training on guidelines, improving positive reinforcement for guideline-appropriate management, greater allied health support and further research to support guidelines.

Diffuse Lewy body disease manifesting as corticobasal syndrome: A rare form of Lewy body disease.

OBJECTIVE: To describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS). METHODS: In 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex. RESULTS: DLBD patients with antemortem features of CBS were significantly younger at disease onset and less likely to have REM sleep behavior disorder than DLBD cases who met clinical criteria for DLB during life. Patients with DLBD manifesting as CBS had more Lewy bodies in the motor cortex than DLBD manifesting as clinically probable DLB. Three cases had concomitant progressive supranuclear palsy and 4 cases had concomitant Alzheimer disease as probable correlates of CBS. CONCLUSION: The neuropathology underlying CBS is heterogeneous, including corticobasal degeneration, Alzheimer disease, and progressive supranuclear palsy. This study suggests that atypical variants of Lewy body disease with severe peri-Rolandic Lewy-related pathology can present clinically as CBS. Patients with DLBD who present as CBS tend to have an earlier age at onset and are less likely to have clinical features of DLB, such as dream enactment behavior during sleep, visual hallucinations, and levodopa-responsive parkinsonism. Future studies with biofluid or molecular imaging biomarkers for α-synuclein will permit better recognition of this uncommon pathologic substrate of CBS.

Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype.

Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlapping clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to elucidate whether transactive response DNA-binding protein of 43 kDa (TDP-43) pathology contributes to clinicopathologic heterogeneity of CBD. Paraffin-embedded sections of the midbrain, pons, subthalamic nucleus, and basal forebrain from 187 autopsy-confirmed CBD cases were screened with immunohistochemistry for phospho-TDP-43. In cases with TDP-43 pathology, additional brain regions (i.e., precentral, cingulate, and superior frontal gyri, hippocampus, medulla, and cerebellum) were immunostained. Hierarchical clustering analysis was performed based on the topographical distribution and severity of TDP-43 pathology, and clinicopathologic and genetic features were compared between the clusters. TDP-43 pathology was observed in 45% of CBD cases, most frequently in midbrain tegmentum (80% of TDP-43-positive cases), followed by subthalamic nucleus (69%). TDP-43-positive CBD was divided into TDP-limited (52%) and TDP-severe (48%) by hierarchical clustering analysis. TDP-severe patients were more likely to have been diagnosed clinically as PSP compared to TDP-limited and TDP-negative patients (80 vs 32 vs 30%, P < 0.001). The presence of downward gaze palsy was the strongest factor for the antemortem diagnosis of PSP, and severe TDP-43 pathology in the midbrain tectum was strongly associated with downward gaze palsy. In addition, tau burden in the olivopontocerebellar system was significantly greater in TDP-positive than TDP-negative CBD. Genetic analyses revealed that MAPT H1/H1 genotype frequency was significantly lower in TDP-severe than in TDP-negative and TDP-limited CBD (65 vs 89 vs 91%, P < 0.001). The homozygous minor allele frequencies in GRN rs5848 and TMEM106B rs3173615 were not significantly different between the three groups. In conclusion, the present study indicates that CBD with severe TDP-43 pathology is a distinct clinicopathologic subtype of CBD, characterized by PSP-like clinical presentations, severe tau pathology in the olivopontocerebellar system, and low frequency of MAPT H1 haplotype.

Cognitive impairment in progressive supranuclear palsy is associated with tau burden.

BACKGROUND: Cognitive impairment is one of the core features of progressive supranuclear palsy. This study aimed to clarify the profile of cognitive impairment and its underlying pathology in progressive supranuclear palsy. METHODS: We retrospectively reviewed medical records to evaluate the pattern and severity of cognitive impairment in 121 autopsy-confirmed progressive supranuclear palsy patients. A subset of 37 patients underwent neuropsychological evaluation as part of their clinical workup. The burden of progressive supranuclear palsy-related tau pathology (neurofibrillary tangles/pretangles, coiled bodies, tufted astrocytes, and threads) was semiquantitatively scored in 20 vulnerable brain regions. Concurrent pathologies potentially associated with cognitive impairment, such as Alzheimer's-type pathology, were also assessed. To evaluate possible genetic risk factors for cognitive impairment, genetic analysis for APOE and MAPT was performed. RESULTS: Ninety patients (74%) had documented cognitive impairment based on neurologic evaluation. In a subgroup with neuropsychological testing (n = 37), executive functioning was the most severely impaired cognitive domain. A global cognitive impairment index (Spearman's rho, -0.49; P = 0.005) and executive functioning were negatively correlated with total tau burden (Spearman's rho, -0.51; P = 0.003), but not correlated with the Alzheimer's-type pathology. APOE ɛ4 carriers had more severe amyloid pathology, but total tau burden and a global cognitive impairment index did not differ from APOE ɛ4 noncarriers. CONCLUSION: Cognitive impairment in progressive supranuclear palsy, most notably executive dysfunction, is associated with severity of progressive supranuclear palsy-related tau pathology. © 2017 International Parkinson and Movement Disorder Society.

Detecting feigned postconcussional and posttraumatic stress symptoms with the structured inventory of malingered symptomatology (SIMS).

The Structured Inventory of Malingered Symptomatology (SIMS) is a standalone symptom validity test (SVT) designed as a screening measure to detect a variety of exaggerated psychological symptoms. A number of studies have explored the accuracy of the SIMS in litigious and clinical populations, yet few have examined the validity of the SIMS in detecting feigned symptoms of postconcussional disorder (PCD) and posttraumatic stress disorder (PTSD). The present study examined the sensitivity of the SIMS in detecting undergraduate simulators (N = 78) feigning symptoms of PCD, PTSD, and the comorbid presentation of both PCD and PTSD symptomatologies. Overall, the SIMS Total score produced the highest sensitivities for the PCD symptoms and PCD+PTSD symptoms groups (.89 and .85, respectively), and to a lesser extent, the PTSD symptoms group (.69). The Affective Disorders (AF) subscale was most sensitive to the PTSD symptoms group compared to the PCD and PCD+PTSD symptoms groups. Additional sensitivity values are presented and examined at multiple scale cutoff scores. These findings support the use of the SIMS as a SVT screening measure for PCD and PTSD symptom exaggeration in neuropsychological assessment.

Profile of cognitive impairment and underlying pathology in multiple system atrophy.

BACKGROUND: The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. METHODS: We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer's disease, hippocampal sclerosis, and cerebrovascular pathology. RESULTS: Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia. CONCLUSIONS: The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA. © 2016 International Parkinson and Movement Disorder Society.

tCRISPRi: tunable and reversible, one-step control of gene expression.

The ability to control the level of gene expression is a major quest in biology. A widely used approach employs deletion of a nonessential gene of interest (knockout), or multi-step recombineering to move a gene of interest under a repressible promoter (knockdown). However, these genetic methods are laborious, and limited for quantitative study. Here, we report a tunable CRISPR-cas system, "tCRISPRi", for precise and continuous titration of gene expression by more than 30-fold. Our tCRISPRi system employs various previous advancements into a single strain: (1) We constructed a new strain containing a tunable arabinose operon promoter PBAD to quantitatively control the expression of CRISPR-(d)Cas protein over two orders of magnitude in a plasmid-free system. (2) tCRISPRi is reversible, and gene expression is repressed under knockdown conditions. (3) tCRISPRi shows significantly less than 10% leaky expression. (4) Most important from a practical perspective, construction of tCRISPRi to target a new gene requires only one-step of oligo recombineering. Our results show that tCRISPRi, in combination with recombineering, provides a simple and easy-to-implement tool for gene expression control, and is ideally suited for construction of both individual strains and high-throughput tunable knockdown libraries.

Effect of a point-of-care ultrasound protocol on the diagnostic performance of medical learners during simulated cardiorespiratory scenarios.

BACKGROUND: Goal-directed point-of-care ultrasound (PoCUS) protocols have been shown to improve the diagnostic accuracy of the initial clinical assessment of the critically ill patient. The diagnostic impact of the Abdominal and Cardiac Evaluation with Sonography in Shock (ACES) protocol was assessed in simulated emergency medical scenarios. METHODS: Following a focused PoCUS training program, the diagnostic accuracy, confidence, and precision of 12 medical learners participating in standardized scenarios were tested using high-fidelity clinical and ultrasound simulators. Participants were assessed during 72 simulated cardiorespiratory scenarios. Differential diagnoses were collected from participants before and after PoCUS in each scenario, and confidence surveys were completed. Data were analysed using R software. RESULTS: Prior to PoCUS, 45 (62.5%) correct primary diagnoses were made compared with 64 (88.9%) following PoCUS (χ2=14, 1df, p=0.0002). PoCUS was also shown to increase participants' confidence in their diagnoses. The mean confidence in diagnosis score pre-PoCUS was 52.2 (SD=14.7), whereas post-PoCUS it was 81.7 (SD=9.5). The estimated difference in means (-28.36) was significant (t=-7.71, p<0.0001). Using PoCUS, participants were further able to narrow their differential diagnoses. The median number of diagnoses for each patient pre-PoCUS was 3.5 (interquartile range [IQR]=3.8, 3.0) with a median of 2.3 (IQR=2.9,1.5) diagnoses post-PoCUS. The difference was significant (W=0, p<0.001). CONCLUSION: This pilot study suggests that, in medical learners newly competent in PoCUS, the addition of an ACES PoCUS protocol to standard clinical assessment improves diagnostic accuracy, confidence, and precision in simulated cardiorespiratory scenarios. This is consistent with clinical studies and supports the use of ultrasound during medical simulation.

Bacteriophage λ N protein inhibits transcription slippage by Escherichia coli RNA polymerase.

Transcriptional slippage is a class of error in which ribonucleic acid (RNA) polymerase incorporates nucleotides out of register, with respect to the deoxyribonucleic acid (DNA) template. This phenomenon is involved in gene regulation mechanisms and in the development of diverse diseases. The bacteriophage λ N protein reduces transcriptional slippage within actively growing cells and in vitro. N appears to stabilize the RNA/DNA hybrid, particularly at the 5' end, preventing loss of register between transcript and template. This report provides the first evidence of a protein that directly influences transcriptional slippage, and provides a clue about the molecular mechanism of transcription termination and N-mediated antitermination.

Bacteriophages lytic for Salmonella rapidly reduce Salmonella contamination on glass and stainless steel surfaces.

A cocktail of six lytic bacteriophages, SalmoFresh™, significantly (p < 0.05) reduced the number of surface-applied Salmonella Kentucky and Brandenburg from stainless steel and glass surfaces by > 99% (2.1-4.3 log). Both strains were susceptible to SalmoFresh™ in the spot-test assay. Conversely, SalmoFresh™ was unable to reduce surface contamination with a Salmonella Paratyphi B strain that was not susceptible to the phage cocktail in the spot-test assay. However, by replacing two SalmoFresh™ component phages with two new phages capable of lysing the Paratyphi B strain in the spot-test assay, the target range of the cocktail was shifted to include the Salmonella Paratyphi B strain. The modified cocktail, SalmoLyse™, was able to significantly (p < 0.05) reduce surface contamination of the Paratyphi B strain by > 99% (2.1-4.1 log). The data show that both phage cocktails were effective in significantly reducing the levels of Salmonella on hard surfaces, provided the contaminating strains were susceptible in the spot-test (i.e., spot-test susceptibility was indicative of efficacy in subsequent surface decontamination studies). The data also support the concept that phage preparations can be customized to meet the desired antibacterial application.