Using mycobacterium cell wall fraction to decrease equine chorionic gonadotropin after abortion.

BACKGROUND: Equine embryonic loss following the development of endometrial cups delays return to cyclicity due to the production of equine chorionic gonadotropin (eCG). Natural degradation of endometrial cups coincides with an influx of immune cells at 100-120 days of gestation, but therapeutic stimulation of reduced eCG production has been relatively unsuccessful. Recently, we observed an increase in pro-inflammatory cytokine production following the use of the immunostimulant mycobacterium cell wall fraction (MCWF). OBJECTIVES: To evaluate the efficacy of hysteroscopic-guided injection of MCWF on the accelerated decline of eCG secretion. STUDY DESIGN: In vivo experiment. METHODS: Mares were pharmacologically aborted at 40-45 days of gestation, and then divided into groups: MCWF-treated (6 mg MCWF suspended in 20 mL LRS; n = 10) and Control (20 mL LRS; n = 6). Five days after abortion, hysteroscopic-guided injection of endometrial cups was performed, with 1 mL of volume placed into each visible endometrial cup. This was repeated 7 days later. Trans-rectal ultrasonography was performed to monitor ovarian activity, and serum was obtained to assess eCG and cytokine concentrations. RESULTS: Concentrations of eCG decreased in the MCWF-treated group (p < 0.01) with a significant suppression noted as early as 14 days after onset of treatment and remained suppressed for the duration of the study. This coincided with an increase in peripheral IFN-γ (p < 0.01) and IL-1ß (p < 0.01) concentrations. Eight out of ten MCWF-treated mares (80%) developed pre-ovulatory follicles, in comparison to 2/6 controls (33%). A pre-ovulatory follicle was noted 23 ± 4 days after onset of treatment. MAIN LIMITATIONS: No pregnancy data was obtained following treatment. CONCLUSIONS: This is the first report of a treatment for the accelerated reduction of eCG following abortion. Stimulation of this process allowed mares to develop a pre-ovulatory follicle within a month of MCWF treatment onset, granting repeat attempts at breeding within the confines of a single breeding season.

Chest CT at X-Ray Dose Using a Noise-Mitigating Weighted Projection: The Thoracic Tomogram. Diagnostic Performance for Pneumonia Detection in Hemato-Oncology Patients.

PURPOSE: To compare the diagnostic performance of a thick-slab reconstruction obtained from an ultra-low-dose CT (termed thoracic tomogram) with standard-of-care low-dose CT (SOC-CT) for rapid interpretation and detection of pneumonia in hemato-oncology patients. METHODS: Hemato-oncology patients with a working diagnosis of pneumonia underwent an SOC-CT followed by an ultra-low-dose CT, from which the thoracic tomogram (TT) was reconstructed. Three radiologists evaluated the TT and SOC-CT in the following categories: (I) infectious/inflammatory opacities, (II) small airways infectious/inflammatory changes, (III) atelectasis, (IV) pleural effusions, and (V) interstitial abnormalities. The TT interpretation time and radiation dose were recorded. Sensitivity, specificity, diagnostic accuracy, ROC, and AUC were calculated with the corresponding power analyses. The agreement between TT and SOC-CT was calculated by Correlation Coefficient for Repeated Measures (CCRM), and the Shrout-Fleiss intra-class correlations test was used to calculate interrater agreement. RESULTS: Forty-seven patients (mean age 58.7 ± 14.9 years; 29 male) were prospectively enrolled. Sensitivity, specificity, accuracy, AUC, and Power for categories I/II/III/IV/V were: 94.9/99/97.9/0.971/100, 78/91.2/86.5/0.906/100, 88.6/100/97.2/0.941/100, 100/99.2/99.3/0.995/100, and 47.6/100/92.2/0.746/87.3. CCRM between TT and SOC-CT for the same categories were .97/.81/.92/.96/.62 with an interobserver agreement of .93/.88/.82/.96/.61. Mean interpretation time was 18.6 ± 5.4 seconds. The average effective radiation dose of TT was similar to a frontal and lateral chest X-ray (0.27 ± 0.08 vs 1.46 ± 0.64 mSv for SOC-CT; P < .01). CONCLUSION: Thoracic tomograms provide comparable diagnostic information to SOC-CT for the detection of pneumonia in immunocompromised patients at one-fifth of the radiation dose with high interobserver agreement.

Optimizing Outpatient Oral Contrast Use in Abdominal CT-A Radiology Pandemic Response Initiative to Reduce Patient Time in the Waiting Room and Reduce Costs, While Improving Patient Experience.

Purpose: The aim was to reduce outpatient wait time and improve patient experience by optimising oral contrast use. Methods: Our multidisciplinary stakeholder collaboration implemented two simultaneous interventions: (1) Creation of 'oral contrast policy', limiting recommended indications. (2) Creation of a new shorter oral contrast regime (30 vs 60 min). We conducted a retrospective service evaluation of oral contrast use in outpatient (OP) abdominal CT at baseline and post-intervention. Patient wait times were measured and per-patient cost-savings were reported. An image quality review was performed by 2 blinded abdominal radiologists. Patient experience was evaluated with a standard voluntary survey. Statistical analysis was performed comparing baseline and evaluation outcomes using Chi-square or Fisher Exact test for categorical variables and Student's t-test or ANOVA for continuous data. Results: Over 1-month periods, OP CT scans were assessed in baseline (pre-pandemic) n = 575, baseline (pandemic) n = 495 and post-intervention n = 545 groups. Oral contrast use reduced from 420/575, 73.0% at baseline to 178/545, 32.7% post intervention. The turn-around time reduced by 15.8 minutes per patient from 70.3 to 54.5 minutes, P < .001 (Interventions 1 and 2). The diagnostic quality did not differ between the oral contrast regimes (Intervention 2, P = 1.0, P = .08). No repeat CTs were needed due to lack of oral contrast (Intervention 1) or poor opacification (Intervention 2). There was oral contrast cost reductions of 69.1-78.4% (P < .001). Patients reported their overall experience was improved post-intervention (Interventions 1 and 2). Conclusions: Optimising the CT oral contrast service through judicious use and a shorter regime, reduced patient wait times, improved patient experience and preserved diagnostic quality.

Formation of a ß-barrel membrane protein is catalyzed by the interior surface of the assembly machine protein BamA.

The ß-barrel assembly machine (Bam) complex in Gram-negative bacteria and its counterparts in mitochondria and chloroplasts fold and insert outer membrane ß-barrel proteins. BamA, an essential component of the complex, is itself a ß-barrel and is proposed to play a central role in assembling other barrel substrates. Here, we map the path of substrate insertion by the Bam complex using site-specific crosslinking to understand the molecular mechanisms that control ß-barrel folding and release. We find that the C-terminal strand of the substrate is stably held by BamA and that the N-terminal strands of the substrate are assembled inside the BamA ß-barrel. Importantly, we identify contacts between the assembling ß-sheet and the BamA interior surface that determine the rate of substrate folding. Our results support a model in which the interior wall of BamA acts as a chaperone to catalyze ß-barrel assembly.

Substrate binding to BamD triggers a conformational change in BamA to control membrane insertion.

The ß-barrel assembly machine (Bam) complex folds and inserts integral membrane proteins into the outer membrane of Gram-negative bacteria. The two essential components of the complex, BamA and BamD, both interact with substrates, but how the two coordinate with each other during assembly is not clear. To elucidate aspects of this process we slowed the assembly of an essential ß-barrel substrate of the Bam complex, LptD, by changing a conserved residue near the C terminus. This defective substrate is recruited to the Bam complex via BamD but is unable to integrate into the membrane efficiently. Changes in the extracellular loops of BamA partially restore assembly kinetics, implying that BamA fails to engage this defective substrate. We conclude that substrate binding to BamD activates BamA by regulating extracellular loop interactions for folding and membrane integration.

Clinicopathological correlations in behavioural variant frontotemporal dementia.

Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data.

Precipitous Deterioration of Motor Function, Cognition, and Behavior.

A 72-year-old woman developed new-onset depression, sustained an unexplained fall, and started walking cautiously. After 1 year, her depression resolved but she developed a dry cough. One year later, she experienced a more rapid decline in her gait with parkinsonism, visual difficulties with restricted vertical gaze, slowed horizontal and vertical saccades, dysphagia, apathy, and progressive cognitive decline, which led to her death 2 years later. The differential diagnosis, neuroimaging, and pathological findings are discussed, as well as their public health implications.

Frontotemporal Dementia and Psychiatric Illness: Emerging Clinical and Biological Links in Gene Carriers.

OBJECTIVE: To describe psychiatric presentations in individuals with genetic mutations causing frontotemporal dementia (FTD). DESIGN: Case descriptions from five carriers of FTD-related gene mutations with symptoms associated with non-neurodegenerative psychiatric disease. SETTING: A comprehensive research program investigating genetic and non-genetic FTD at the University of California, San Francisco Memory and Aging Center. PARTICIPANTS: Three proband and two non-proband gene carriers. MEASUREMENTS: Medical history and neurological examination, neuropsychological testing, magnetic resonance and/or positron emission tomography imaging, and a genetic analysis to screen for dementia-related mutations. Genetic status was unknown at the time of initial evaluation. RESULTS: The chosen cases are illustrative of the variety of presentations of psychiatric symptoms in FTD gene carriers. In some cases, a non-neurodegenerative psychiatric illness was diagnosed based on specific symptoms, but the diagnosis may have been inappropriate based on the overall syndrome. In other cases, symptoms closely resembling those seen in non-neurodegenerative psychiatric illness did occur, in some cases immediately preceding the development of dementia, and in other cases developing a decade prior to dementia symptoms. CONCLUSIONS: Psychiatric symptoms in FTD gene carriers can be very similar to those seen in non-neurodegenerative psychiatric illness. Psychiatric symptoms with atypical features (e.g., late-life onset, insidiously worsening course) should prompt careful assessment for neurodegenerative disease. Guidelines for such an assessment should be established.

Young-onset frontotemporal dementia in a homozygous tau R406W mutation carrier.

Microtubule-associated protein tau mutations result in 10-20% of cases of genetic frontotemporal lobar degeneration. Tau mutation carriers typically develop behavioral variant frontotemporal dementia with or without parkinsonism. Unlike most frontotemporal dementia gene mutations, heterozygous R406W tau mutation carriers most often develop clinical Alzheimer's disease. We report a homozygous tau R406W mutation carrier with behavioral variant frontotemporal dementia who developed symptoms 20 years before mean family symptom onset. Voxel-based morphometry showed frontoinsular, frontal, and mesial temporal cortical atrophy. Homozygous tau R406W mutations appear to accelerate symptom onset and drive a behavioral variant frontotemporal dementia syndrome.

Prodromal posterior cortical atrophy: clinical, neuropsychological, and radiological correlation.

We present longitudinal clinical, cognitive, and neuroimaging data from a 63-year-old woman who enrolled in research as a normal control and evolved posterior cortical atrophy (PCA) over 5 year follow-up. At baseline she reported only subtle difficulty driving and performed normally on cognitive tests, but already demonstrated atrophy in left visual association cortex. With follow-up she developed insidiously progressive visuospatial and visuoperceptual deficits, correlating with progressive atrophy in bilateral visual areas. Amyloid PET was positive. This case tracks the evolution of PCA from the prodromal stage, and illustrates challenges to early diagnosis as well as the utility of imaging biomarkers.

Esophagectomy outcomes at a mid-volume cancer center utilizing prospective multidisciplinary care and a 2-surgeon team approach.

BACKGROUND: Esophagectomy is associated with high morbidity and mortality, leading to calls for restricted performance at high-volume centers. METHODS: Patients with esophageal cancer were evaluated prospectively in a multidisciplinary tumor board from January 2012 - December 2012. A 2-surgeon team was utilized and detailed outcomes were assessed prospectively. RESULTS: Thirty-one patients underwent esophagectomy, 20 patients underwent laparoscopic transhiatal (65%) approach, and 11 patients underwent laparoscopically assisted Ivor-Lewis (35%) approach. Eighty-one percent of the patients were male, with a median age of 64 years (range: 35 to 83 years) and 73% of the patients had adenocarcinoma. Neoadjuvant chemoradiation was performed in 79% of the patients. R0 resection was achieved in 29 (94%) patients, median nodes identified were 15. Major complications (grade III to V) occurred in 13 (42%) patients and did not correlate with surgical techniques, anastomotic leak occurred in 5 (16%) patients, and significant pulmonary complications occurred in 11 (35%) patients. The length of stay at the hospital was 10 days, readmission rate 23%, and 30-day mortality rate 6%. CONCLUSIONS: High-quality esophagectomy can be performed safely at a mid-volume cancer center. Our outcomes question the reliance on volume alone as an indicator of cancer surgical quality.

Gastrointestinal nurse navigation: implementation of a novel role.

Gastrointestinal (GI) cancer is the second most frequent cancer diagnosis in the United States, and the care for patients with GI cancer is multifaceted, with each clinical encounter impacting patients' overall experience. Patients and families often navigate this complicated journey on their own with limited resources and knowledge; therefore, innovative, patient-centered, and quality-focused programs must be developed. The purpose of this article is to discuss the development of GI nurse navigators (NNs) and the important role they have in providing coordinated evidence-based cancer care and in the benchmarking of quality metrics to allow more transparency and improve GI cancer care. This article provides a foundation for developing a GI NN role within the context of a newly developed multidisciplinary GI cancer program, and identifies the importance of tracking specific quality metrics. This innovative model is useful for healthcare organizations and nursing practice because it identifies the importance of a nurse in the navigator role, as well as highlights the numerous functions the NN can provide to the GI multidisciplinary team and patients.

Solvent-Free Synthesis and Fluorescence of a Thiol-Reactive Sensor for Undergraduate Organic Laboratories.

A green organic laboratory experiment was developed in which students synthesize a sensor for thiols using a microscale, solventless Diels-Alder reaction at room temperature or 37 °C. The molecular probe is easily purified by column chromatography in a Pasteur pipet and characterized by thin-layer chromatography and NMR spectroscopy. The thiol-reactive sensor becomes intensely fluorescent upon exposure to thiols from N-acetylcysteine, bovine serum albumin, or human hair (pretreated with a reducing agent to reveal cysteine thiols in α-keratin). This fluorescence is observable even with micrograms of probe.

Laryngeal cancer involving a branchial cleft cyst.

BACKGROUND: Benign secondary neck lesions in the setting of laryngeal cancer have been described, but not with branchial cleft cysts. This article describes a branchial cleft cyst in a laryngectomy/neck dissection specimen. METHODS AND RESULTS: A 44-year-old woman presented to our emergency department with an obstructing laryngeal tumor that was staged as a T4N0M0 squamous cell cancer on the basis of clinical and radiographic findings. After laryngectomy with bilateral neck dissections, the neck specimen contained a right-sided branchial cleft cyst, which was directly invaded by tumor. In addition, the location of the cyst relative to the larynx suggested that this was a third branchial cleft cyst. CONCLUSION: This is the first report of a laryngeal carcinoma invading a branchial cleft cyst. Staging discrepancies may result from concurrent head and neck lesions, altering treatment plans, or changing the prognosis for the patient. Lesions such as this are nearly impossible to diagnose preoperatively, and a high index of suspicion for advanced cancer should be maintained.

Pleasurable emotional response to music: a case of neurodegenerative generalized auditory agnosia.

Recent functional neuroimaging studies implicate the network of mesolimbic structures known to be active in reward processing as the neural substrate of pleasure associated with listening to music. Psychoacoustic and lesion studies suggest that there is a widely distributed cortical network involved in processing discreet musical variables. Here we present the case of a young man with auditory agnosia as the consequence of cortical neurodegeneration who continues to experience pleasure when exposed to music. In a series of musical tasks, the subject was unable to accurately identify any of the perceptual components of music beyond simple pitch discrimination, including musical variables known to impact the perception of affect. The subject subsequently misidentified the musical character of personally familiar tunes presented experimentally, but continued to report that the activity of 'listening' to specific musical genres was an emotionally rewarding experience. The implications of this case for the evolving understanding of music perception, music misperception, music memory, and music-associated emotion are discussed.

Outcome analysis of patients with squamous cell carcinoma of the head and neck and hepatitis C virus.

OBJECTIVE/HYPOTHESIS: Infection with the hepatitis C virus (HCV) is a global problem with over 170 million people infected. Recently, we have noticed that a large number of patients diagnosed with squamous cell carcinoma of the head and neck (SCCHN) have also been diagnosed with HCV. A review of the literature reveals little information concerning this patient population. The objective of this study was to compare the outcome of SCCHN patients who have been exposed to HCV with naïve SCCHN patients. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review from June 1991 through December 2002 was performed to identify patients diagnosed with SCCHN who were screened for HCV. Patients were stratified into two groups (HCV positive and HCV negative). Data were recorded on patients for status of disease at last clinic visit, pretreatment serum albumin and hematocrit levels, and RNA quantities of HCV. Statistical analysis was performed using paired t test to compare serum albumin and hematocrit levels. Kaplan-Meier survival curves were used to compare outcomes. The log-rank test was used to determine significance. Cox regression was used to examine the association of prognostic predictor variables with overall survival and disease-free survival. RESULTS: There was no difference noted in 5 year survival between hepatitis C positive and hepatitis C negative groups in overall outcomes (66.7% vs. 67.9%, P = 1.000) or 5 year disease-free survival (90.5% vs. 80.8%, P = .514). The two groups, HCV positive versus HCV negative, also had similar serum albumin levels (3.62 g/dL vs. 3.72 g/dL, P = .37) as well as serum hematocrit levels (42.9% vs. 41.0%, P = .12). Serum levels of hepatitis C RNA were obtained in seven patients, with only one being undetectable. The only prognostic predictor variable that was significantly associated with overall survival was age. None of the predictor variables were significantly associated with disease-free survival. CONCLUSION: Co-infection with HCV, although prevalent in the Veterans Administration Hospital population, did not affect patient outcome as defined by disease-free survival. Patients who were seropositive for HCV had comparable serum albumin levels as well as serum hematocrit when compared with HCV negative patients.