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Background Gastric adenocarcinoma is common and consequent mortality high. Presentation and mortality are increased in obese individuals, many of whom have elevated circulating insulin concentrations. High plasma insulin concentrations may promote, and increase mortality from, gastric adenocarcinoma. Tumour promotion activities of insulin and its receptor are untested in gastric cancer cells. Methods Tumour gene amplification and expression were computed from sequencing and microarray data. Associations with patient survival were assessed. Insulin-dependent signal transduction, growth, apoptosis and anoikis were analysed in metastatic cells from gastric adenocarcinoma patients and in cell lines. Receptor involvement was tested by pharmacological inhibition and genetic knockdown. RNA was analysed by RT-PCR and proteins by western transfer and immunofluorescence. Results INSR expression was higher in tumour than in normal gastric tissue. High tumour expression was associated with worse patient survival. Insulin receptor was detected readily in metastatic gastric adenocarcinoma cells and cell lines. Isoforms B and A were expressed. Pharmacological inhibition prevented cell growth and division, and induced caspase-dependent cell death. Rare tumour INS expression indicated tumours would be responsive to pancreatic or therapeutic insulins. Insulin stimulated gastric adenocarcinoma cell PI3-kinase/Akt signal transduction, proliferation, and survival. Insulin receptor knockdown inhibited proliferation and induced programmed cell death. Type I IGF receptor knockdown did not induce cell death. Conclusions The insulin and IGF signal transduction pathway is dominant in gastric adenocarcinoma. Gastric adenocarcinoma cell survival depends upon insulin receptor. That insulin has direct cancer-promoting effects on tumour cells has implications for clinical management of obese and diabetic cancer patients.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork‐Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus. This article is protected by copyright. All rights reserved.

PF-06881894 is a proposed biosimilar to pegfilgrastim (Neulasta®). This study evaluated the pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of PF-06881894 vs pegfilgrastim reference products (US- and EU-Neulasta®) in healthy volunteers. A phase 1, open-label, randomized, crossover study was conducted to assess the pharmacologic equivalence and safety of a single 6-mg dose of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU. The primary PD endpoints were area under the effect-versus-time curve for absolute neutrophil count (ANC) from dose administration to 288 h postdose, and maximum observed ANC value among subjects confirmed negative for anti-pegfilgrastim antibodies. Primary PK variables included area under the serum pegfilgrastim-versus-time curve from the time of dose administration to time infinity and maximum observed serum pegfilgrastim concentration. A second phase 1, open-label, randomized (1:1), parallel-group, non-inferiority study was conducted to assess the immunogenicity and safety of multiple 6-mg doses of PF-06881894 versus pegfilgrastim-US. The primary endpoint for the immunogenicity study was the proportion of subjects with both negative baseline and confirmed positive postdose anti-pegfilgrastim antibodies at any time during the study. Across the single- and multiple-dose studies (N = 153 and N = 420 treated subjects, respectively), demographics for age (18–65 years), male gender (n = 264/573), and white race (n = 423/573) were similar. Three-way PD/PK equivalence of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU was demonstrated with the primary PD endpoints and primary PK variables being completely contained within the predefined 90% confidence interval acceptance limits (80–125%). The non-inferiority of PF-06881894 versus pegfilgrastim-US in terms of immunogenicity was established according to the prespecified non-inferiority margin (≤10%). Overall, there were no clinically meaningful differences in safety profiles among or between study groups. Single-dose PF-06881894 demonstrated PD/PK equivalence and comparable safety with US- and EU-pegfilgrastim reference products. Multiple-dose PF-06881894 demonstrated immunogenicity non-inferiority to pegfilgrastim-US with comparable safety. Both studies contributed to the totality of evidence supporting biosimilarity. ClinicalTrials.gov identifiers: NCT02629289 (C1221001); NCT03273842 (C1221005).

Irrigation water sources have been shown to harbor foodborne pathogens and could contribute to the outbreak of foodborne illness related to consumption of contaminated produce. Determining the probability of and the degree to which these irrigation water sources contain these pathogens is paramount. The purpose of this study was to determine the prevalence of Salmonella enterica and Listeria monocytogenes in alternative irrigation water sources. Water samples (n = 188) were collected over 2 years (2016 to 2018) from 2 reclaimed water plants, 3 nontidal freshwater rivers, and 1 tidal brackish river on Maryland’s Eastern Shore (ESM). Samples were collected by filtration using modified Moore swabs (MMS) and analyzed by culture methods. Pathogen levels were quantified using a modified most probable number (MPN) procedure with three different volumes (10 liters, 1 liter, and 0.1 liter). Overall, 65% (122/188) and 40% (76/188) of water samples were positive for S. enterica and L. monocytogenes, respectively. For both pathogens, MPN values ranged from 0.015 to 11 MPN/liter. Pathogen levels (MPN/liter) were significantly (P

Metastatic spread of invasive lobular breast carcinoma to stomach is rare especially before diagnosis of primary breast cancer. Incorrect diagnosis might result in delay of appropriate treatment for breast cancer. Recognition of this possibility enables better clinical management. A 62-year-old female presented with upper gastrointestinal symptoms and weight loss and was referred to a gastroenterologist for investigation. At the time of initial diagnosis of stomach cancer, patient was asymptomatic for breast cancer. Multiple gastric biopsies taken showed features suspicious of metastatic breast cancer. Consequently, the initial provisional diagnosis of stomach cancer changed into metastatic invasive lobular breast carcinoma. These findings were corroborated radiologically. The patient was treated with letrozole and zoledronic acid as first-line therapy for one year. Residual metastatic breast cancer was present in the gastric mucosa. The patient was treated with endocrine therapy containing ribociclib and treatment was ineffective confirmed by PET-CT scan. But her symptoms have resolved completely despite her presentation with stage IV. We present rare case of initial presentation of gastric metastasis before diagnosis of a primary invasive lobular breast carcinoma. Correct diagnosis and appropriate treatment were accomplished through initial clinical suspicion, accurate histological examination, and endoscopy together with analysis of disease-specific biomarkers.

Background: Studies have shown conflicting results on the efficacy of tocilizumab (TCZ) for patients with COVID-19, with many confounders of clinical status and limited duration of the observation. Here, we evaluate the real-world long-term efficacy of TCZ in COVID-19 patients. Methods: We conducted a retrospective study of hospitalized adult patients with COVID-19 using a large US-based multicenter COVID-19 database (Cerner Real-World Data; updated in September, 2020). The TCZ group was defined as patients who received at least one dose of the drug. Matching weight (MW) and a propensity score weighting method were used to balance confounding factors. Results: A total of 20,399 patients were identified. 1,510 and 18,899 were in the TCZ and control groups, respectively. After MW adjustment, no statistically significant differences in all-cause mortality were found for the TCZ vs. control group (Hazard Ratio [HR]:0.76, p=0.06). Survival curves suggested a better trend in short-term observation, driven from a subgroup of patients requiring oxygen masks, BIPAP or CPAP. Conclusion: We observed a temporal (early) benefit of TCZ, especially in patients on non-invasive high-flow supplemental oxygen. However, the benefit effects faded with longer observation. The long-term benefits and risks of TCZ should be carefully evaluated with follow-up studies.

Background Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists’ experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett’s esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions. Methods We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking. Results Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 μm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up. Conclusions Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Background Acute odontogenic infections are a common surgical emergency managed by public hospitals in Australia which cause considerable patient morbidity and occasionally, mortality. Despite posing a significant public health burden, Australian data evaluating the cost of the management of these patients are lacking. This study assessed the patient and treatment variables associated with inpatient management of deep odontogenic infections, and their respective financial impact, at a statewide Oral & Maxillofacial service. Methods A retrospective audit was carried out of patients with deep odontogenic infections at our institution, over a 7-year period. The primary outcome was the total cost of admission. Secondary outcomes included treatment received, operating room time, return-to-theatre, length of admission (LOS), and intensive care unit (ICU) use. Cost variables were assessed against the total LOS and ICU use to determine clinical predictors affecting outcome. Results Four hundred and sixty two patients met the inclusion criteria. The average cost per patient was $12 228 Australian Dollars. After multivariate analysis, variables most significantly associated with increased cost of care and LOS were high-risk infections with airway compromise, high admission white cell count and age. Conclusion Hospital-based management of deep-space odontogenic infections engender significant costs compared to early primary care intervention such as a dental extraction ($181/extraction).

In den letzten Jahren hat sich im therapeutischen Bereich der stabilen koronaren Herzkrankheit (KHK) die folgende Erkenntnis kontinuierlich konsolidiert: Die Bypass-Chirurgie bleibt der Goldstandard bei komplexer KHK, insbesondere bei Dreigefaserkrankung mit oder ohne Hauptstammbeteiligung. Sie ist die einzige Therapieform, die nach den aktuellen Daten das Potenzial birgt, das Leben des Patienten zu verlangern. Die Bypass-Operation kann damit eine prognostische Indikation haben. Die 2018 neu erschienenen Leitlinien zur Myokardrevaskularisation haben die Unterscheidung zur perkutanen Koronarintervention (PCI) jetzt genauer differenziert und geben erstmals Empfehlungen zu operativen Details der Revaskularisation. Der Fokus dieser Literaturubersicht liegt auf den chirurgisch relevanten Aspekten. Weitere therapierelevante Informationen zu Diagnostik und medikamentoser Therapie sind ebenfalls ubersichtlich zusammengefasst. Die aus dem Jahr 2018 masgebliche Literatur zur chirurgischen Revaskularisation lasst sich in folgende Punkte untergliedern: 1. PCI vs. Bypass-Chirurgie, 2. neue diagnostische Verfahren fur die Bypass-Chirurgie, 3. Rolle der medikamentosen Therapie fur die Bypass-Chirurgie und 4. technische Aspekte der Bypass-Chirurgie.

Background Little is known about the perceptions of older adults with end-stage kidney disease (ESKD) on chronic hemodialysis (HD) even though this could potentially influence how treatment is received. This study explores the perceptions of older adults with ESKD on HD, specifically their decision to initiate HD, preconceptions and expectations of HD, perceived difficulties with HD, and coping strategies. Design: Cross–sectional Setting: Outpatient chronic dialysis units Participants: Older adults with ESKD on HD Intervention: Open-ended interviews were conducted with 15 participants. Inclusion criteria were age 60 years and older, HD duration of at least three months, and ability to consent and participate in the interview process. Results: We report on four identified domains: decision to initiate HD; preconceptions and expectations of HD; drawback of HD; and coping strategies. All participants were reluctant to initiate HD, but made the decision on advice from their physicians for varying reasons. Trust in physicians’ opinions also played a role for some. Some participants had positive preconceptions of HD, while a few had negative preconceptions or unrealistic expectations. Even though the majority of participants identified several difficulties with being on HD, they also had positive coping strategies, and the majority indicated that they would make the same decision to initiate HD. Conclusion: As clinicians are turning more to patient-centered medicine, understanding patients’ perceptions of HD is of crucial importance. Our study highlights the importance of improving pre-hemodialysis education to ensure that patients’ expectations are realistic, as well as identifying individualized coping strategies by patients.

The microbial quality of irrigation water has increasingly become a concern as a source of contamination for fruits and vegetables. Non-traditional sources of water are being used by more and more growers in smaller, highly diversified farms in the Mid-Atlantic region of the U.S. Shiga-toxigenic E. coli (STEC) have been responsible for several outbreaks of infections associated with the consumption of leafy greens. Our study evaluated the prevalence of the “big seven” STEC serogroups and the associated enterohemorrhagic E. coli (EHEC) virulence factors (VF) genes in conventional and nontraditional irrigation waters in the Mid-Atlantic region of the U.S. Water samples (n = 510) from 170 sampling events were collected from eight untreated surface water sites, two wastewater reclamation facilities, and one vegetable processing plant, over a 12-month period. Ten liters of water were filtered through Modified Moore swabs (MMS); swabs were then enriched into Universal Pre-enrichment Broth (UPB), followed by enrichment into non-O157 STEC R&F broth and isolation on R & F non-O157 STEC chromogenic plating medium. Isolates (n = 2489) from enriched MMS from water samples were screened for frequently reported STEC serogroups that cause foodborne illness: O26, O45, O103, O111, O121, O145, and O157, along with VF genes stx1, stx2, eae, and ehxA. Through this screening process, STEC isolates were found in 2.35% (12/510) of water samples, while 9.0% (46/510) contained an atypical enteropathogenic E. coli (aEPEC) isolate. The eae gene (n = 88 isolates) was the most frequently detected EHEC VF of the isolates screened. The majority of STEC isolates (stx1 or stx2) genes mainly came from either a pond or reclamation pond water site on two specific dates, potentially indicating that these isolates were not spatially or temporally distributed among the sampling sites. STEC isolates at reclaimed water sites may have been introduced after wastewater treatment. None of the isolates containing eae were determined to be Escherichia albertii. Our work showed that STEC prevalence in Mid-Atlantic untreated surface waters over a 12-month period was lower than the prevalence of atypical EPEC.

Three comparative clinical studies assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of PF-06881893 (filgrastim-aafi; Nivestym™), a filgrastim biosimilar, versus US-licensed reference product (filgrastim; US-Neupogen®) in healthy volunteers (HVs). Two separate open-label, crossover-design PK/PD studies were conducted: a single-dose study (n = 24) and a multiple-dose study (n = 60). In each study, HVs were randomized to Nivestym followed by US-Neupogen, or vice versa. Study drug (5 μg/kg) was administered subcutaneously as a single injection or as five consecutive daily injections. Primary PK and PD endpoints were area under the filgrastim serum concentration–time curve, maximum observed concentration, area under the effect curve (AUEC) for absolute neutrophil count (ANC), maximum observed ANC, AUEC for cluster of differentiation (CD)-34+ count, and maximum observed CD34+ count. In an open-label, parallel-design, non-inferiority, comparative immunogenicity study, HVs were randomized (n = 128/treatment) to Nivestym or US-Neupogen. The primary endpoint was the proportion of subjects with a negative baseline antidrug antibody (ADA) test result and one or more confirmed post-dose positive ADA result. Overall demographics were as follows: female (n = 162/340); White (n = 274/340), Black (n = 58/340), and other (n = 8/340); age (18–65 years); and weight (50.8–96.5 kg). All primary PK and PD endpoints met the pre-specified criteria for PK and PD equivalence. The primary endpoint in the comparative immunogenicity study met pre-specified criteria for non-inferiority. Nivestym demonstrated PK and PD equivalence in single and multiple subcutaneous-dose settings and non-inferiority for immunogenicity to US-Neupogen, with a comparable safety profile, supporting the demonstration of biosimilarity. ClinicalTrials.gov C1121002 (NCT02766647); C1121003 (NCT02766634); C1121012 (NCT02923791).

INTRODUCTION Oral bisphosphonates are first-line agents for treating osteoporosis in men, but there are no studies regarding efficacy of oral bisphosphonates for treatment of osteoporosis in ambulatory male adults with intellectual disability. METHODS Nine adult males with intellectual disability and increased fracture risk had been treated with weekly or monthly oral bisphosphonates, vitamin D and calcium for 1-3 years. Post-treatment bone mineral density (BMD), serum 25(OH)D, parathyroid hormone and C-telopeptide of type I collagen were then determined for the first time. RESULTS Weekly or monthly oral bisphosphonates were well tolerated and led to significant increases in BMD in all 9 individuals. Serum 25(OH)D level enhanced the "pecent increase of BMD" that occurred in response to bisphosphonate treatment (p

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Background Understanding factors influencing retention in care (RIC) and viral load improvement (VLI) in people with HIV (PWH) who are out of care and hospitalized will assist in intervention development for this vulnerable population. Methods The study was a post hoc analysis of prospectively collected data. Hospitalized participants were enrolled if they were newly diagnosed with HIV during the hospitalization or out of HIV care. Participants completed surveys at baseline and 6 months postenrollment and laboratory studies of viral load (VL). Outcomes were RIC (2 completed visits, 1 within 30 days of discharge) and VLI (VL Results The study cohort included 417 participants enrolled between 2010 and 2013. The population was 73% male, 67% non-Hispanic black, 19% Hispanic, and 70% uninsured. Sixty-five percent had a baseline CD4 400 copies/mL or missing, and the population was generally poor with low educational attainment. After discharge from the hospital, 60% did not meet the definition for RIC, and 49% did not have VLI. Modifiable factors associated with the outcomes include drug use (including marijuana alone and other drugs), life instability (eg, housing, employment, and life chaos), and using avoidance coping strategies in coping with HIV. Conclusions Hospitalized out-of-care PWH in the United States are at high risk of poor re-engagement in care after discharge. Interventions for this population should focus on improving socioeconomic stability and coping with HIV and reducing drug use.

Background The aims of this study were to evaluate the microbiological trends in severe odontogenic infections requiring hospital admission in the South Australian Oral and Maxillofacial Surgery Unit. Rates of antibiotic resistance to empirical antibiotic regimens were determined to quantify the clinical implications of antibiotic-resistant odontogenic infections. Methods A retrospective case audit was performed on all odontogenic infections admitted to the Royal Adelaide Hospital over a 9-year period. Data was collected regarding demographics, microbiological culture and sensitivity results, and clinical outcome variables. Results Of a total of 672 patients, microbiology data was available for 447 cases. Penicillin-resistant organisms were identified in 10.8% of patients, who required a significantly longer length of hospital admission (mean, 9.93 days) and higher rates of non-response to initial surgical therapy (40%). Conclusions There were moderate rates of antibiotic-resistant odontogenic infections within the South Australian population. Patients within this subgroup demonstrate markedly poorer clinical outcomes. Effective treatment of odontogenic infections involves early operative intervention, with adjunctive use of appropriate antibiotic therapy that involves close monitoring of response to removal of the cause and use of first-line antibiotic agents. Cases that fail to respond require urgent specialist review in order to reduce morbidity and mortality outcomes.

Background Changes in the organization of medical practice have impeded humanistic practice and resulted in widespread physician burnout and dissatisfaction. Objective To identify organizational factors that promote or inhibit humanistic practice of medicine by faculty physicians. Design From January 1, 2015, through December 31, 2016, faculty from eight US medical schools were asked to write reflectively on two open-ended questions regarding institutional-level motivators and impediments to humanistic practice and teaching within their organizations. Participants Sixty eight of the 92 (74%) study participants who received the survey provided written responses. All subjects who were sent the survey had participated in a year-long small-group faculty development program to enhance humanistic practice and teaching. As humanistic leaders, subjects should have insights into motivating and inhibiting factors. Approach Participants’ responses were analyzed using the constant comparative method. Key Results Motivators included an organizational culture that enhances humanism, which we judged to be the overarching theme. Related themes included leadership supportive of humanistic practice, responsibility to role model humanism, organized activities that promote humanism, and practice structures that facilitate humanism. Impediments included top down organizational culture that inhibits humanism, along with related themes of non-supportive leadership, time and bureaucratic pressures, and non-facilitative practice structures. Conclusions While healthcare has evolved rapidly, efforts to counteract the negative effects of changes in organizational and practice environments have largely focused on cultivating humanistic attributes in individuals. Our findings suggest that change at the organizational level is at least equally important. Physicians in our study described the characteristics of an organizational culture that supports and embraces humanism. We offer suggestions for organizational change that keep humanistic and compassionate patient care as its central focus. Electronic supplementary material The online version of this article (10.1007/s11606-018-4470-2) contains supplementary material, which is available to authorized users.

Background Identification of people with HIV from electronic health record (EHR) data is an essential first step in the study of important HIV outcomes, such as risk assessment. This task has been historically performed via manual chart review, but the increased availability of large clinical data sets has led to the emergence of phenotyping algorithms to automate this process. Existing algorithms for identifying people with HIV rely on a combination of International Classification of Disease codes and laboratory tests or closely mimic clinical testing guidelines for HIV diagnosis. However, we found that existing algorithms in the literature missed a significant proportion of people with HIV in our data. Objective The aim of this study is to develop and evaluate HIV-Phen, an updated criteria-based HIV phenotyping algorithm. Methods We developed an algorithm using HIV-specific laboratory tests and medications and compared it with previously published algorithms in national and local data sets to identify cohorts of people with HIV. Cohort demographics were compared with those reported in the national and local surveillance data. Chart reviews were performed on a subsample of patients from the local database to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the algorithm. Results Our new algorithm identified substantially more people with HIV in both national (up to an 85.75% increase) and local (up to an 83.20% increase) EHR databases than the previously published algorithms. The demographic characteristics of people with HIV identified using our algorithm were similar to those reported in national and local HIV surveillance data. Our algorithm demonstrated improved sensitivity over existing algorithms (98% vs 56%-92%) while maintaining a similar overall accuracy (96% vs 80%-96%). Conclusions We developed and evaluated an updated criteria-based phenotyping algorithm for identifying people with HIV in EHR data that demonstrates improved sensitivity over existing algorithms.

Open communication between healthcare professionals about care concerns, also known as 'speaking up', is essential to patient safety.Compare interns' and residents' experiences, attitudes and factors associated with speaking up about traditional versus professionalism-related safety threats.Anonymous, cross-sectional survey.Six US academic medical centres, 2013-2014.1800 medical and surgical interns and residents (47% responded).Attitudes about, barriers and facilitators for, and self-reported experience with speaking up. Likelihood of speaking up and the potential for patient harm in two vignettes. Safety Attitude Questionnaire (SAQ) teamwork and safety scales; and Speaking Up Climate for Patient Safety (SUC-Safe) and Speaking Up Climate for Professionalism (SUC-Prof) scales.Respondents more commonly observed unprofessional behaviour (75%, 628/837) than traditional safety threats (49%, 410/837); p0.001, but reported speaking up about unprofessional behaviour less commonly (46%, 287/628 vs 71%, 291/410; p0.001). Respondents more commonly reported fear of conflict as a barrier to speaking up about unprofessional behaviour compared with traditional safety threats (58%, 482/837 vs 42%, 348/837; p0.001). Respondents were also less likely to speak up to an attending physician in the professionalism vignette than the traditional safety vignette, even when they perceived high potential patient harm (20%, 49/251 vs 71%, 179/251; p0.001). Positive perceptions of SAQ teamwork climate and SUC-Safe were independently associated with speaking up in the traditional safety vignette (OR 1.90, 99% CI 1.36 to 2.66 and 1.46, 1.02 to 2.09, respectively), while only a positive perception of SUC-Prof was associated with speaking up in the professionalism vignette (1.76, 1.23 to 2.50).Interns and residents commonly observed unprofessional behaviour yet were less likely to speak up about it compared with traditional safety threats even when they perceived high potential patient harm. Measuring SUC-Safe, and particularly SUC-Prof, may fill an existing gap in safety culture assessment.

Background The Veterans’ Health Administration (VHA), currently mandates that every spinal cord injury and disorder (SCI/D) patient receives a screening urinalysis and urine culture (UC) during the annual evaluation (AE). Our pilot study at a single VHA center showed that 87% of the UCs obtained during the AE represented asymptomatic bacteriuria (ASB), and that 35% of those UC were treated with antibiotics unnecessarily. The objective of the current study is to determine the association between UC and antibiotic use using a national VHA sample of SCI/D patients. Methods Retrospective cohort of Veterans who presented to a VHA SCI/D clinic for their AE in FY18 or FY19. Demographic and clinical characteristics as well as information on primary outcomes (receipt of urine culture and antibiotics) were extracted from the VHA Corporate Data Warehouse. Associations between covariates and outcomes were assessed using logistic regression. P values < 0.05 were considered significant. Results 9447 veterans with SCI/D were included, of whom 5088 (54%) had a UC obtained. Of those with a UC, 2910 (57%) were classified as positive (Figure 1). 1054 (11%) veterans were prescribed antibiotics within 7 days of their AE. Of these, 515 had a positive UC, 202 had a negative UC, and 2878 did not have a UC obtained during the AE. Age, ethnicity, neurologic level of injury (NLI), comorbidity score, frequently identified organism on positive culture, and receipt of antibiotics within 7 days of AE were significantly associated with obtaining a UC during the AE. Race, NLI, bladder management strategy, comorbidity score, frequently identified organism on positive culture, and having a UC obtained during the AE were significantly associated with receipt of antibiotics within 7 days of AE. Flowchart of SCI/D Veterans who had a urine culture and/or received antibiotics during their FY18/19 AE Conclusion Over half of Veterans with SCI/D presenting for their AE receive a screening UC, contrary to other national guidelines recommending against this practice. Age and type or organism identified on UC drive antibiotic use, which was similar to our previous findings and reflect themes identified during our qualitative interviews with SCI/D providers. The knowledge gained from this national VA study will assist the development of interventions to reduce unnecessary urine testing and antibiotic use in the SCI/D population. Disclosures All Authors: No reported disclosures

OBJECTIVES Individuals with intellectual disabilities (IDs) are at increased risk for low bone mass and fragility fractures, and those who are nonambulatory may be at even higher risk. Patients with IDs often are vitamin D deficient, but there is little information concerning how vitamin D treatment of patients with IDs affects markers of bone formation and resorption. METHODS We performed a retrospective analysis of 23 institutionalized individuals with IDs who were the subject of a performance improvement continuing medical education project designed to reduce risk for fracture by optimizing serum vitamin D levels. Patients were divided into those with normal weight-bearing (NWB) physical activity (15 patients: 14 men, 1 woman) and those with low weight-bearing (LWB) physical activity (8 patients: 7 men, 1 woman). All of the subjects received 50,000 IU of vitamin D3 weekly for 4 to 8 weeks, followed by a maintenance dose of 50,000 IU monthly for 3 to 6 months. Bone turnover markers (type 1 cross-linked C-telopeptide [CTX], type 1 N-terminal propeptide [P1NP], and parathyroid hormone [PTH]) and 25(OH)-vitamin D levels were measured before and after vitamin D supplementation. RESULTS At baseline, there were no significant differences in the serum levels of 25OH-D, PTH, P1NP, or CTX between the two groups (NWB and LWB). Vitamin D levels were increased to a higher value in LWB subjects than in NWB subjects (61 ± 4.1 vs 48.4 ± 2.2 ng/mL, P < 0.001). Vitamin D treatment suppressed PTH (20.5% ± 14.3% vs 31.4% ± 7.7%, P = not significant) and P1NP (33.0% ± 6.2% vs 29.4% ± 6.9%, P = not significant) similarly in both groups. Although CTX levels declined by 26.4% ± 5.3% (P = 0.0002) in NWB individuals (as anticipated), vitamin D supplementation resulted in an unexpected 25.8% ± 8% increase (P = 0.01) in CTX in LWB individuals, suggesting osteoclast activation. CONCLUSIONS Although high-dose vitamin D appeared to suppress osteoclast activity in NWB adults with IDs, the increase in serum CTX levels in those with LWB activity implies activation of osteoclasts that could exacerbate their unique low bone mass and increase fracture risk. The results support the use of a lower-dose vitamin D regimen in this patient group with LWB.

We evaluated long-term outcomes for patients with Wilson disease (WD) after liver transplantation (LT) and searched for risk factors for poor survival. Retrospective analysis of UNOS/OPTN data identified 156 pediatric and 515 adult cases of LT for WD between 1987 and 2016. Comparison cases were 10 442 pediatric and 104 874 adult non-WD transplant recipients. Survival was calculated using Kaplan-Meier analysis. Recipient, donor, and surgical variables were compared by Cox regression. Survival rates 3, 5, and 10 years after LT for adult WD patients (87.5%, 85.4%, and 80.5%, respectively) were significantly higher than those for non-WD patients (P < 0.001); survival rates for pediatric WD patients (90.5%, 89.7%, and 86.5%, respectively) did not differ significantly from non-WD patients. Graft survival in adult and pediatric patients followed similar trends. Regression analysis identified older age, female gender, and use of life support at the time of transplant as risk factors for decreased survival for adults with WD, and younger age, male gender, obesity, and high serum creatinine at the time of transplant as risk factors for poor survival in pediatric recipients with WD. Presentation with fulminant liver failure was not associated with survival in WD patients. No donor characteristic predicted poor survival. Long-term patient and graft survival after LT is excellent for both adult and pediatric WD patients.

Background: Circulating miRNAs have potential as surrogate measures of tumor burden to monitor treatment response in clinical trials due to their association with cancer and high stability in blood. Greystoke et al (PMID: 26654130) showed that 10 miRNAs (miRs-200a, 200b, 200c, 141, 429, 95, 195, 210, 335, 375) were elevated in plasma of patients with a range of solid tumors compared to in plasma of healthy volunteers (HVs). The miRNA levels decreased after treatment, especially in patients with larger clinical responses. In the present study, the same 10 miRNAs, and 3 breast cancer (BC) related miRNAs identified in a literature search (miRs-18b, 21, 148b), were analysed to determine if their measurement i) is more sensitive in plasma or serum, ii) distinguishes BC patients from HVs, and iii) changes after surgery or systemic therapy. Methods: The 13-miRNA panel (13-plex) was analysed by qPCR in plasma and serum from 12 BC patients and 8 HVs, and in plasma from 19 BC patients pre- and 4 hours post-surgery with a multiplex of TaqManTM MiRNA Assays. Expression of the 13-plex was measured with custom TaqManTM Low Density Array (TLDA) cards after pre-amplification, in serum collected at cycle 1, day 1 (C1D1) and day 8 (C1D8) from 44 BC patients starting adjuvant chemotherapy on the B-AHEAD 2 study (ISRCTN04156504). Endogenous miR-16 and exogenous ath-miR-159a provided standards to assess miRNA extraction efficiency. Results are reported as the geometric means of the 40-Ct values for the 13 miRNAs (geomean13). Results: Expression of the 13-plex was significantly higher in plasma compared to in matched serum. TLDA analysis of 381 miRNAs confirmed that the plasma to serum superiority was a general effect not restricted to the 13-plex. The superiority of plasma was reduced however by pre-amplification; in the 381-miRNA TLDA analysis, detection in serum improved compared to in the multiplex qPCR assay. The 13-plex was elevated in plasma of BC patients compared to HVs (p = 0.015). There was a trend towards a reduction after surgery, but the difference did not reach statistical significance. However, miR-195, a BC specific marker, was significantly lower after surgery (p = 0.0001). In the B-AHEAD 2 study cohort, the 13-plex was decreased at C1D8 compared to C1D1 (p = 0.0002). The three patients who relapsed within 5 years of diagnosis had geomean13 values at C1D1 of 10.3, 10.6 and 11.8 compared to the median of 10.3 for all patients. Given the low event rate, either a larger patient cohort or a cohort with a higher event rate is required to assess association with clinical outcome. Conclusions: This study shows that plasma is better than serum for miRNA evaluation but that measures in serum are useful if cDNA is pre-amplified after reverse transcription. The 13-plex is elevated in BC, has a trend towards a fall after surgery and is reduced after chemotherapy. The 13-plex has potential as a biomarker of tumor burden in BC trials. Citation Format: Edward B. Amankwatia, Alexandra Bennett, David Ou, David Jamieson, Nicola Cresti, Henry Cain, Rosie McNeillis, Jonathan Womack, Sacha Howell, Michelle Harvie, Felicity May, Alastair Greystoke. Are circulating microRNAs (miRNAs) ready for inclusion as biomarkers in breast cancer clinical trials [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1406.

Irrigation water contaminated with Salmonella enterica and Listeria monocytogenes may provide a route of contamination of raw or minimally processed fruits and vegetables. While previous work has surveyed specific and singular types of agricultural irrigation water for bacterial pathogens, few studies have simultaneously surveyed different water sources repeatedly over an extended period of time. This study quantified S. enterica and L. monocytogenes levels (MPN/L) at 6 sites, including river waters: tidal freshwater river (MA04, n = 34), non-tidal freshwater river, (MA05, n = 32), one reclaimed water holding pond (MA06, n = 25), two pond water sites (MA10, n = 35; MA11, n = 34), and one produce wash water site (MA12, n = 10) from September 2016—October 2018. Overall, 50% (84/168) and 31% (53/170) of sampling events recovered S. enterica and L. monocytogenes, respectively. Results showed that river waters supported significantly (p < 0.05) greater levels of S. enterica than pond or reclaimed waters. The non-tidal river water sites (MA05) with the lowest water temperature supported significantly greater level of L. monocytogenes compared to all other sites; L. monocytogenes levels were also lower in winter and spring compared to summer seasons. Filtering 10 L of water through a modified Moore swab (MMS) was 43.5 (Odds ratio, p < 0.001) and 25.5 (p < 0.001) times more likely to recover S. enterica than filtering 1 L and 0.1 L, respectively; filtering 10 L was 4.8 (p < 0.05) and 3.9 (p < 0.05) times more likely to recover L. monocytogenes than 1L and 0.1 L, respectively. Work presented here shows that S. enterica and L. monocytogenes levels are higher in river waters compared to pond or reclaimed waters in the Mid-Atlantic region of the U.S., and quantitatively shows that analyzing 10 L water is more likely recover pathogens than smaller samples of environmental waters.

Background Unmet needs among hospitalized patients with HIV may prevent engagement in HIV care leading to worse clinical outcomes. Our aim was to examine the role of unmet subsistence needs (eg, housing, transportation, and food) and medical needs (eg, mental health and substance abuse treatment) as barriers for retention in HIV care and viral load (VL) suppression. Methods We used data from the Mentor Approach for Promoting Patients' Self-Care intervention study, the enrolled hospitalized HIV patients at a large publicly funded hospital between 2010 and 2013, who were out-of-care. We examined the effect of unmet needs on retention in HIV care (attended HIV appointments within 0-30 days and 30-180 days) and VL suppression, 6 months after discharge. Results Four hundred seventeen participants were enrolled, 78% reported having ≥1 unmet need at baseline, most commonly dental care (55%), financial (43%), or housing needs (34%). Participants with unmet needs at baseline, compared to those with no needs, were more likely to be African American, have an existing HIV diagnosis and be insured. An unmet need for transportation was associated with lower odds of retention in care [odds ratio (OR): 0.5; 95% confidence interval (CI): 0.34 to 0.94, P = 0.03], even after adjusting for other factors. Compared to participants with no need, those who reported ≥3 unmet subsistence needs were less likely to demonstrate VL improvement (OR: 0.51; 95% CI: 0.28 to 0.92; P = 0.03) and to be retained in care (OR: 0.52; 95% CI: 0.28 to 0.95; P = 0.03). Conclusion Broader access to programs that can assist in meeting subsistence needs among hospitalized patients could have significant individual and public health benefits.

The quality of irrigation water used to cultivate produce that is consumed raw is an important issue with regard to food safety. In this study, the microbiological quality of potential irrigation water sources in Arizona was evaluated by testing for the presence of indicator and pathogenic bacteria. Reclaimed water samples were collected from two wastewater treatment plants and return flow samples were collected from two drainage canals and one return flow pond. Standard membrane filtration methods were used for detection of indicator bacteria. Water samples (n = 28) were filtered through cellulose ester membrane filters and bacterial populations were enumerated by placing the filters on selective agar. For detection of pathogens (Salmonella enterica, Listeria monocytogenes and Shiga toxin-producing E. coli (STEC)), water samples were filtered through Modified Moore swabs and enriched in Universal Pre-enrichment Broth, followed by selective enrichment broth for each pathogen. The enriched broth was streaked onto agar media selective for each pathogen. Presumptive colonies were confirmed by PCR/real-time PCR. Among the 14 reclaimed water samples from two sites, the ranges of recovered populations of E. coli, total coliforms, and enterococci were 0–1.3, 0.5–8.3 × 103, and 0–5.5 CFU/100 mL, respectively. No L. monocytogenes, Salmonella or STEC were found. In the 13 return flow water samples from 3 sites, the ranges of recovered populations of E. coli, total coliforms and enterococci were 1.9–5.3 × 102, 6.5 × 102−9.1 × 104, and 2.9–3.7× 103 CFU/100 mL, respectively. All samples were negative for L. monocytogenes. One (7.1%) of the return flow samples was positive for E. coli O145. Nine (64.3%) of the samples were positive for Salmonella. Both real-time PCR and culture-based methods were used for the detection of Salmonella and L. monocytogenes, and the results from the two methods were comparable. The findings of this study provide evidence that irrigation waters in Arizona, including reclaimed water and return flows, could be potential sources of bacterial contamination of produce. Additional work is needed to evaluate whether bacteria present in irrigation water sources transfer to the edible portion of irrigated plants and are capable of persisting through post-harvest activities.

Few interventions have been shown to improve retention in HIV care. We recently completed a randomized, controlled trial of a peer mentoring intervention, which failed to increase retention in care or HIV suppression. We sought to gain insight into this negative result and elicit suggestions for future interventions. We conducted semi-structured one-on-one interviews with a sub-sample of participants and all available interventionists after completion of the primary study. Interviews were coded by two researchers and thematically analyzed. Participants in the intervention arm (N = 16) reported good rapport with and benefit from peer mentoring and found the mentors helpful in facilitating the transition from hospital to out-patient clinic. Control arm participants (N = 9) reported similar emotional and social support benefits from the health educators. In both arms, ongoing challenges including completing paperwork, securing transportation, and rescheduling missed appointments were cited, along with internalized stigma and lack of will to seek care, despite the mentors' best efforts. Suggested improvements to the intervention included: more frequent contact with interventionists; additional support for mental health problems; and targeting overall health rather than a more selective focus on HIV. Mentors and health educators agreed with the participant-reported barriers and added that some participants were too sick to meaningfully participate in the intervention, while others appeared unwilling to engage with the interventionists in a meaningful way. Mentoring was highly acceptable and felt to be impactful, however it was not sufficient to overcome structural barriers or stigma and low motivation in some participants. The attention control intervention may have had an unintended positive impact. Future interventions should focus on broad aspects of health and well-being.

In brief Thirty-two professional female ballet dancers were studied by means of a gynecological questionnaire to determine the prevalence of menstrual dysfunction. Thirty-seven percent had a history of amenorrhea (p

To develop and test the psychometric properties of two new survey scales aiming to measure the extent to which the clinical environment supports speaking up about (a) patient safety concerns and (b) unprofessional behaviour.Residents from six large US academic medical centres completed an anonymous, electronic survey containing questions regarding safety culture and speaking up about safety and professionalism concerns.Confirmatory factor analysis supported two separate, one-factor speaking up climates (SUCs) among residents; one focused on patient safety concerns (SUC-Safe scale) and the other focused on unprofessional behaviour (SUC-Prof scale). Both scales had good internal consistency (Cronbach's α0.70) and were unique from validated safety and teamwork climate measures (r0.85 for all correlations), a measure of discriminant validity. The SUC-Safe and SUC-Prof scales were associated with participants' self-reported speaking up behaviour about safety and professionalism concerns (r=0.21, p0.001 and r=0.22, p0.001, respectively), a measure of concurrent validity, while teamwork and safety climate scales were not.We created and provided evidence for the reliability and validity of two measures (SUC-Safe and SUC-Prof scales) associated with self-reported speaking up behaviour among residents. These two scales may fill an existing gap in residency and safety culture assessments by measuring the openness of communication about safety and professionalism concerns, two important aspects of safety culture that are under-represented in existing metrics.

The stratification of breast cancer patients for endocrine therapies by oestrogen or progesterone receptor expression is effective but imperfect. The present study aims were to validate microarray studies that demonstrate TFF3 regulation by oestrogen and its association with oestrogen receptors in breast cancer, to evaluate TFF3 as a biomarker of endocrine response, and to investigate TFF3 function. Microarray data were validated by quantitative RT-PCR and northern and western transfer analyses. TFF3 was induced by oestrogen, and its induction was inhibited by antioestrogens, tamoxifen, 4-hydroxytamoxifen and fulvestrant in oestrogen-responsive breast cancer cells. The expression of TFF3 mRNA was associated with oestrogen receptor mRNA in breast tumours (Pearson's coefficient=0.762,P=0.000). Monoclonal antibodies raised against the TFF3 protein detected TFF3 by immunohistochemistry in oesophageal submucosal glands, intestinal goblet and neuroendocrine cells, Barrett's metaplasia and intestinal metaplasia. TFF3 protein expression was associated with oestrogen receptor, progesterone receptor and TFF1 expression in malignant breast cells. TFF3 is a specific and sensitive predictive biomarker of response to endocrine therapy, degree of response and duration of response in unstratified metastatic breast cancer patients (P=0.000,P=0.002 andP=0.002 respectively). Multivariate binary logistic regression analysis demonstrated that TFF3 is an independent biomarker of endocrine response and degree of response, and this was confirmed in a validation cohort. TFF3 stimulated migration and invasion of breast cancer cells. In conclusion, TFF3 expression is associated with response to endocrine therapy, and outperforms oestrogen receptor, progesterone receptor and TFF1 as an independent biomarker, possibly because it mediates the malign effects of oestrogen on invasion and metastasis.

Purpose The aim of this tutorial is to support speech-language pathologists (SLPs) undertaking assessments of multilingual children with suspected speech sound disorders, particularly children who speak languages that are not shared with their SLP. Method The tutorial was written by the International Expert Panel on Multilingual Children's Speech, which comprises 46 researchers (SLPs, linguists, phoneticians, and speech scientists) who have worked in 43 countries and used 27 languages in professional practice. Seventeen panel members met for a 1-day workshop to identify key points for inclusion in the tutorial, 26 panel members contributed to writing this tutorial, and 34 members contributed to revising this tutorial online (some members contributed to more than 1 task). Results This tutorial draws on international research evidence and professional expertise to provide a comprehensive overview of working with multilingual children with suspected speech sound disorders. This overview addresses referral, case history, assessment, analysis, diagnosis, and goal setting and the SLP's cultural competence and preparation for working with interpreters and multicultural support workers and dealing with organizational and government barriers to and facilitators of culturally competent practice. Conclusion The issues raised in this tutorial are applied in a hypothetical case study of an English-speaking SLP's assessment of a multilingual Cantonese- and English-speaking 4-year-old boy. Resources are listed throughout the tutorial.

The hospital setting provides an opportunity to re-engage people living with HIV (PLWH) in HIV care. We developed and implemented a protocol to identify PLWH in a hospital setting. The aim of the current study was to report on our strategy to recruit hospitalized HIV patients into an intervention study, and to report on lessons learned for future studies.Our protocol was developed based on experience of our research staff in recruiting HIV patients as well as clinical input from providers and administrators on delivering care in hospitalized settings. We identified hospitalized PLWH between 2010 and 2013 who were potentially eligible for an intervention study. Patients were identified by review of electronic medical records and clinician referral, followed by in-person screening to confirm eligibility. We examined factors related to identifying and enrolling hospitalized patients, and documented lessons learned.Key strategies included systematic medical record review followed by in-person screening, collaboration with staff, and flexibility in recruitment logistics. We identified 1801 PLWH hospitalized during the 3-year study period. Eighty-four percent (n = 1514) met the met the inclusion criteria based on medical record review. Of these, 48% (n = 733) were ineligible. Among eligible patients, 59% (n = 460) were enrolled. Only 3% (n = 23) of eligible patients declined; 84% (n = 321) were not enrolled because they were discharged before enrollment. Lessons learned included (1) needing to identify patients and deliver the intervention before hospital discharge, (2) limiting the complexity of the intervention, and (3) having research staff available on weekends and after hours.Targeted recruitment of hospitalized populations is a feasible and productive approach for finding and engaging PLWH who are newly diagnosed or out of routine care.

The primary objective of this study was to evaluate changes in student confidence resulting from completion of the American Pharmacists Association (APhA) certification course, an immunization-based simulation, and practical experience in influenza immunization clinics during an Introductory Pharmacy Practice Experience (IPPE). Secondary objectives included evaluation of influences on student confidence such as campus location, prior APhA certification, and prior experience in preparing injectable medications. Methods An eight-question survey was administered to third-year pharmacy students in Fall 2011 to measure confidence in immunization skills and knowledge at four time points; before APhA certification, after APhA certification, after participation in the simulation, and after 12 hours of practical experience in influenza-based immunization clinics. The simulation consisted of case-based scenarios and a skill assessment. Results Upon IPPE completion, at least 86.6% of students reported either confidence or extreme confidence for all survey items. Student confidence increased significantly between time points and from baseline to IPPE completion. Students certified prior to Fall 2011 were significantly less confident at baseline in some of the legal issues and response to anaphylactic reactions; however, this difference became non-significant after completion of the simulation. Conclusions All three training modules are important in preparing students for immunization delivery in their future practice. Schools of pharmacy should consider increasing opportunities for development of student confidence in this area. The lack of initial confidence regarding legal requirements in students certified prior to Fall 2011 may indicate the need for recertification or mandatory immunization-based continuing professional development for immunizing pharmacists.

Two 6-year-old male fraternal twins each received 8 weeks of morphosyntactic and phonological intervention in counterbalanced order. Progress occurred for most targets and measures, with each child making greater progress for either phonology or morphosyntax during the corresponding unitary-domain block. Gains were maintained during the subsequent alternate treatment block. Possible indirect changes in the non-treated domain were also observed in global measures. The data suggest that at least some school-aged children with concomitant difficulties in morphosyntax and phonology, perhaps those with significant constraints in each domain, can benefit from sequences of unitary-domain intervention. This study invites further research concerning many unresolved clinical issues for school-aged children with protracted development in both phonology and morphosyntax.

The objectives of this project were to create a program that would expose underrepresented minority (URM) and low income (LI) high school students to dental professions and provide an opportunity for dental and dental hygiene students from URM/LI groups to be engaged in teaching activities. Data were collected from participants during the school years 2009-10 (high school students: N=23, dental students: N=21, dental hygiene students: N=5) and 2010-11 (N=27, N=11, N=3, respectively). The students participated in fifteen Saturday sessions from October through March each year. The data showed that, from the beginning, mentees and mentors were very interested in participating in the program and getting to know each other. Lectures, general program activities, and patient-related events such as organizing a health fair and shadowing during two outreach clinics were evaluated positively by mentees and mentors. The end of program evaluations showed that the program and the mentee-mentor relationships were rated very positively and that the mentees had an increased interest in oral health-related careers. In conclusion, creating opportunities for URM/LI high school students to explore dental careers and for dental and dental hygiene students to engage in teaching resulted in positive experiences for both groups.

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0−6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.

The objectives of this study were to explore whether Dental Admission Test (DAT) training in an enrichment program for potential dental students increases the participants' Perceptual Achievement Test (PAT) and academic average (AA) scores and whether the length of the program and personal factors such as the number of disadvantages correlate with the DAT scores. Data were collected from 361 students in the summer enrichment program at one dental school between 1994 and 2011. Their baseline, midpoint, and end of program PAT and AA DAT scores were collected. Seventy students self-reported official scores. These students' PAT scores increased from 14.40 at baseline to 17.09 at midpoint to 17.84 at program end (p

A pool of dynein anchored to the nuclear surface mediates many processes at G2/M, although its spatial and temporal regulation is poorly understood. Asunder, a critical regulator of dynein recruitment to the nuclear envelope, works in the nucleus as part of Integrator, an snRNA-processing complex, to mediate this event., We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus–centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3′-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN–small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing.

An adolescent with a persistent frontal lisp participated in a two-part 11-session intervention case study. The first phase used ultrasound imagery and acoustic, phonetic and voice education to provide information about articulatory setting (AS) and general awareness of the speech production process. The second phase used traditional articulation therapy, online visual-acoustic biofeedback and fluency strategies to target the frontal lisp directly (specifically /s/, /z/, /ʃ/ and /ʧ/). Trained listener evaluations of pre-intervention, post-phase 1 and post-phase 2 assessments showed no improvement after phase 1, but notable improvement in all treatment targets immediately after phase 2. These improvements were substantially maintained at assessment 4 months post-intervention. The outcomes suggest that direct training was more effective than the AS approach; however, the client's ability to self-monitor in phase 2, rapid acquisition of the targets and maintenance at 4 months post-intervention possibly reflected the knowledge gained in phase 1 about AS.

The purpose of the current study was to determine the obesogenic practices in all-day child-care centers caring for preschool-aged children. This study used a cross-sectional, self-reported survey mailed to centers across Oklahoma (n=314). Frequency of responses and χ 2 were calculated comparing region and star rating. Items where the majority of centers frequently report best practices include: daily fruits served (76%), daily nonfried vegetables served (71%), rarely/never served sugary drinks (92%), rarely/never used food to encourage good behaviors (88%), staff join children at table most of the time (81%), staff rarely eat different foods in view of children (69%), visible self-serve or request availability of water (93%), regular informal communication about healthy eating (86%), opportunities for outdoor play (95%), not withholding activity for punishment (91%), accessible play equipment (59% to 80% for different types of equipment), and minimization of extended sitting time (78%). Practices where centers can improve include increasing variety of vegetables (18%), reducing frequency of high-fat meats served (74% serve more than once per week), increasing high-fiber and whole-grain foods (35% offer daily), serving style of "seconds" (28% help kids determine whether they are still hungry), nonfood holiday celebrations (44% use nonfood treats), having toys and books that encourage healthy eating (27%) and physical activity (25%) in all rooms in the center, a standard nutrition (21%) and physical education (50%) curriculum, and following a written physical activity policy (43%). Practitioners can use these data to develop benchmarks and interventions, as this was the first study to assess statewide obesogenic practices in child care.

Trefoil factor 1 (TFF1) is a stable secretory protein expressed widely in the gastrointestinal mucosa that is also expressed in pancreatic ductal adenocarcinoma (PDAC). In the current study, we documented the extent and timing of TFF1 expression and investigated the effects of TFF1 on PDAC cells and stellate cells, the primary cells of the PDAC stroma.Trefoil factor 1 expression in pancreatic cancer tissues and cell lines was analyzed using microarray, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry. The effects of recombinant TFF1 on cell growth, migration, and invasion of pancreatic cancer cell lines and immortalized human pancreatic stellate cells (HPSCs) were analyzed using MTS and Matrigel-coated invasion chambers. In vivo studies were also conducted in which Mpanc-96 cells stably expressing TFF1 were implanted orthotopically into nude mice.Trefoil factor 1 was highly increased in preneoplastic lesions. Recombinant TFF1 stimulated motility of both cancer and HPSCs. In contrast, only HPSC cell growth was increased by TFF1. In vivo studies showed that overexpression of TFF1 in PDAC cells did not affect primary tumor growth but greatly increased metastasis.The present data demonstrate that TFF1 influences both PDAC cells and stellate cells and stimulates metastasis.

Striped bass Morone saxatilis were studied in order to characterize their immune responses over the short term following challenge with Mycobacterium marinum. The expression of immunity-related genes (IL-1beta, TNF-alpha, Nramp and TGF-beta) quickly increased following infection with M. marinum, but these genes were subsequently down-regulated despite the fact that bacterial counts remained high. The number of monocytes and neutrophils also initially increased at 1 d postinfection. This confirms the importance of these types of cells in initial inflammation and mycobacterial infection in striped bass. The phagocytic index of splenic leukocytes over these same time frames did not change significantly following infection. The discrete window in which inflammatory mechanisms were stimulated in striped bass may be related to the intracellular nature of this pathogen.

Background: The tissue diagnosis of lymphoma and metastases is commonly obtained from affected lymph nodes. The lymph nodes chosen for biopsy are often the consequence of their appearance on ultrasound, which determines their risk of malignancy. Two frequently used percutaneous sampling techniques are core biopsy and fine needle aspiration (FNA). While core biopsy obtains a larger tissue sample and provides a degree of architectural information, FNA is considered less invasive and has the advantage of immediate confirmation of adequacy by the attending cytologist. Anecdotally, core biopsy is more commonly used when a lymph node is suspected of harboring neoplasia, however a feature of malignancy is hypercellularity, which theoretically should increase the diagnostic yield of FNA. Aim: The aim of this project was to compare the diagnostic capability of FNA and core biopsy in lymph nodes of different malignant potential, as defined by ultrasound, and determine if the radiologic appearance can guide clinicians in their choice of sampling technique. The project also reviewed the role of clinical experience in both the choice of sampling technique and diagnostic yield. Methods: Retrospective study of percutaneous lymph node biopsies performed at a large tertiary hospital between July 2016 and March 2018. The associated ultrasounds were reviewed and the lymph nodes were classified as high or low risk of malignancy by their sonographic appearance. The end point for analysis was the capacity for FNA or core biopsy to provide a definitive diagnosis. The diagnostic yield was then separately assessed for lymph nodes of high and low malignant potential. The effect of clinical experience on diagnostic yield was also examined, by comparing the outcomes of radiology consultants and radiology trainees. Results: 296 lymph node biopsies were reviewed and statistical analysis was performed using logistic regression analysis. Core biopsy, in comparison with FNA, was used twice as often in lymph nodes of high malignant potential, supporting the aforementioned anecdotal evidence. Core biopsy demonstrated superior diagnostic yield in comparison with FNA, providing a diagnostic sample 45% ( P = 0.313) more often in low-risk lymph nodes and 209% ( P = < 0.05) more often in high-risk lymph nodes. Consultant radiologists used FNA 81% more often than core biopsy in lymph nodes of high malignant potential, while radiology trainees used core biopsy 104% more often than FNA in the same group. In high-risk lymph nodes, trainees were 117% ( P = 0.105) more likely to obtain a diagnostic sample than consultants. Conclusion: Core biopsy is superior to FNA in the tissue sampling of lymph nodes regardless of ultrasound determined risk of malignancy. Biopsies obtained by radiology trainees provided a diagnosis twice as often as those obtained by radiology consultants. This appeared to be the consequence of consultant preference for FNA over core biopsy.