Barriers and motivators to national board certification as a certified anticoagulation care provider.

Professionals voice confusion between the distinctions of board certification and educational certificate courses, and note barriers and motivators in obtaining national anticoagulation board certification. To identify barriers vs. motivators in obtaining board certification and detail the differences in board certification and educational certificate courses, an IRB-approved electronic survey was sent to professionals completing the University of Southern Indiana (USI) Anticoagulation Therapy educational certificate course (n = 491) and existing Certified Anticoagulation Care Providers (CACP, n = 622). A total of 1049 surveys were delivered successfully, with a 26% response rate (USI = 62, CACP = 211.) Respondents identified as a nurse (n = 52, 19%), advanced practice nurse (n = 14, 5.1%), pharmacist (n = 206, 75.5%) or physician (n = 5, 1.8%). Overall, respondents indicated board certification via CACP has significant impact on patient/organizational outcomes (n = 118, 43.2%). Top motivators for board certification include personal accomplishment (n = 147, 53%) and professional growth (n = 139, 50.9%). Top barriers include lack of time to prepare (n = 102, 37.3%,) board certification exam cost (n = 95, 34.8%), and for CACP recertification, and requirement to recertify by examination (n = 74, 35.1%). Of board-certified respondents, 45.4% indicated they were not employed at an Anticoagulation Center of Excellence (ACE), 34.8% employed at an ACE and 16.8% were unsure of ACE status. Narrative comments were obtained and evaluated. Significant personal and professional barriers exist in completing, and subsequently maintaining, board certification in anticoagulation. This offers great insight for NCBAP to invoke changes to support clinicians and healthcare organizations in seeking and maintaining CACP credentialing, a component of ACE attainment.

Using the EM algorithm for Bayesian variable selection in logistic regression models with related covariates.

We develop a Bayesian variable selection method for logistic regression models that can simultaneously accommodate qualitative covariates and interaction terms under various heredity constraints. We use expectation-maximization variable selection (EMVS) with a deterministic annealing variant as the platform for our method, due to its proven flexibility and efficiency. We propose a variance adjustment of the priors for the coefficients of qualitative covariates, which controls false-positive rates, and a flexible parameterization for interaction terms, which accommodates user-specified heredity constraints. This method can handle all pairwise interaction terms as well as a subset of specific interactions. Using simulation, we show that this method selects associated covariates better than the grouped LASSO and the LASSO with heredity constraints in various exploratory research scenarios encountered in epidemiological studies. We apply our method to identify genetic and non-genetic risk factors associated with smoking experimentation in a cohort of Mexican-heritage adolescents.

Leading indicators of community-based violent events among adults with mental illness.

BACKGROUND: The public health, public safety and clinical implications of violent events among adults with mental illness are significant; however, the causes and consequences of violence and victimization among adults with mental illness are complex and not well understood, which limits the effectiveness of clinical interventions and risk management strategies. This study examined interrelationships between violence, victimization, psychiatric symptoms, substance use, homelessness and in-patient treatment over time. METHOD: Available data were integrated from four longitudinal studies of adults with mental illness. Assessments took place at baseline, and at 1, 3, 6, 9, 12, 15, 18, 24, 30 and 36 months, depending on the parent studies' protocol. Data were analysed with the autoregressive cross-lag model. RESULTS: Violence and victimization were leading indicators of each other and affective symptoms were a leading indicator of both. Drug and alcohol use were leading indicators of violence and victimization, respectively. All psychiatric symptom clusters - affective, positive, negative, disorganized cognitive processing - increased the likelihood of experiencing at least one subsequent symptom cluster. Sensitivity analyses identified few group-based differences in the magnitude of effects in this heterogeneous sample. CONCLUSIONS: Violent events demonstrated unique and shared indicators and consequences over time. Findings indicate mechanisms for reducing violent events, including trauma-informed therapy, targeting internalizing and externalizing affective symptoms with cognitive-behavioral and psychopharmacological interventions, and integrating substance use and psychiatric care. Finally, mental illness and violence and victimization research should move beyond demonstrating concomitant relationships and instead focus on lagged effects with improved spatio-temporal contiguity.

Response to an exercise intervention after endometrial cancer: differences between obese and non-obese survivors.

OBJECTIVE: The objective of this paper is to describe baseline differences between obese and non-obese endometrial cancer survivor in anthropometrics, exercise behavior, fitness, heart rate and blood pressure, and quality of life, and to analyze whether the effect of a home-based exercise intervention on these outcomes differed for obese and non-obese participants. METHODS: One hundred post-treatment Stage I-IIIa endometrial cancer survivors participated in a single arm 6month study in which they received a home-based exercise intervention. Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured every two months, and quality of life (QOL) and psychological distress were measured at baseline and 6months. RESULTS: Adjusting for potential confounders, at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher systolic blood pressure (p=.018), and lower physical functioning (p<.001) and ratings of general health (p=.002), and more pain (p=.037) and somatization (.002). Significant improvements were seen in exercise behavior, resting heart rate, systolic blood pressure, and multiple QOL domains over the course of the intervention. Obese survivors had less improvement in exercise behavior and cardiorespiratory fitness than non-obese survivors, but there were no differences with regard to improvements in QOL and stress. CONCLUSIONS: Home based exercise interventions are beneficial to endometrial cancer survivors, including those whose BMI is in the obese range. While obese survivors have lower levels of physical activity and fitness, they experienced similar activity, fitness, quality of life and mental health benefits. Exercise should be encouraged in endometrial cancer survivors, including those who are obese.

A systematic review of the gut microbiome, metabolites, and multi-omics biomarkers across the colorectal cancer care continuum.

The gut microbiome and the microbial metabolome contribute to treatment efficacy and treatment outcomes across the cancer care spectrum. This study systematically reviewed the existing literature between 2007 to March 2022 to elucidate the role of gut microbiota-metabolite biomarkers in colorectal cancer (CRC) care and treatment-related outcomes. Using Covidence, all studies identified were screened by title and abstract, followed by a full-text review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extraction. We analysed 13 non-experimental and 9 experimental CRC studies and found that, usually, the α-diversity of the gut microbiome and short-chain fatty acids decreased in CRC patients, while amino acids (e.g. glutamate) increased in CRC patients. Correlations between specific gut microbial taxa and metabolites were identified, with amino acids, fatty acids, and glycerol positively associated with certain gut microbes. Interventions promoting gut microbes and microbial metabolites associated with better health outcomes (e.g. Bifidobacterium, Lactobacillus, butyric acid, and bile acid) can potentially promote treatment efficacy and improve cancer care outcomes. Gut microbial metabolism should be integrated into targeted cancer interventions for CRC patients, given the confirmed role of the gut microbiome and metabolome pathways across the CRC care continuum.

Staff happiness and work satisfaction in a tertiary psychiatric centre.

BACKGROUND: Mental health professionals are at a high risk of burnout. Positive psychology outcomes of staff in acute in-patient psychiatric wards are poorly researched and unclear. AIMS: To quantify the satisfaction with life and work-life satisfaction of mental health staff at a large university-affiliated tertiary psychiatric centre. METHODS: We utilized the Satisfaction with Life Scale (SWLS) and the Work-Life Satisfaction Questionnaire (WLSQ). RESULTS: Two hundred and nine out of 450 staff members (46%) participated; mean age 48.2 + 9.9 years; 63% were male. On average the participants had been practising their speciality for 21.1 + 9.8 years (range: 2-48). The mean total SWLS scores differed significantly between professions (P < 0.05). The highest levels of happiness were reported by psychologists and social workers, followed by the administrative staff, the psychiatrists and finally the nursing staff. Staff scored the highest for work as a 'calling' followed by work as a 'career' and the lowest rating for work as a 'job'. The mean total WLSQ score differed between professions, (P < 0.01). The highest levels of work as a calling were reported by psychiatrists (mean 2.87 of possible 5.0), followed by psychologists and social workers, nursing staff and finally administrative staff. CONCLUSIONS: Satisfaction with life and work orientation do not correlate among mental health professionals. Although highly motivated and perceiving psychiatry as a 'calling' psychiatrists score low on levels of satisfaction with life. Improving staff happiness may contribute to increase in moral and counter burnout.

Hyperplasia of lymphatic vessels in VEGF-C transgenic mice.

No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis.

Design, fabrication, and characterization of a composite scaffold for bone tissue engineering.

Poly(lactide-co-glycolide) (PLGA) scaffolds have been successfully used in bone tissue engineering, with or without hydroxyapatite (HA) and with a macroporosity given either by simple PLGA sphere packaging and/or by leaching out NaCl. The objective of this work was the optimization of the design parameters for bone tissue engineering scaffolds made by sintering microspheres of PLGA, HA nanocrystals for matrix reinforcement and osteoconduction, and salt crystals for macroporosity and control of matrix pore size. Microsphere fabrication by a single-emulsion and solvent evaporation technique was first optimized to obtain a high yield of PLGA microspheres with a diameter between 80 and 300 microm. The influence of the sintering process and matrix composition on the scaffold structure was then evaluated morphologically and mechanically. Three scaffold types were tested for biocompatibility by culturing with human fibroblasts for up to 14 days. The most important parameters to obtain microspheres with the selected diameter range were the viscosity ratio of the dispersed phase to the continuous phase and the relative volume fraction of the 2 phases. The Young's modulus and the ultimate strength of the sintered matrices ranged between 168-265 MPa and 6-17 MPa, respectively, within the range for trabecular bone. Biocompatibility was demonstrated by fibroblast adhesion, proliferation, and spreading throughout the matrix. This work builds upon previous work of the PLGA/HA sintering technique to give design criteria for fabricating a bone tissue engineered matrix with optimized morphological, functional, and biological properties to fit the requirements of bone replacements.

Mechanisms of photodynamic inactivation of herpes simplex viruses: comparison between methylene blue, light plus electricity, and hematoporhyrin plus light.

Herpes simplex virus (HSV) types 1 and 2 have been inactivated in vitro using low concentrations of methylene blue (MB), light (lambda) plus electricity (E), or hematoporphyrin derivative (HPD) plus lambda. Both techniques introduce single strand interruptions into viral DNA, but do not make double strand ruptions into viral DNA, but do not make double strand breaks. MB, lambda plus E-treated virions adsorb normally to and penetrate susceptible cells, whereas HSV inactivated with HPC and light does not. This difference is emphasized by the induction of new viral and cell DNA synthesis after infection with MB, lambda plus E-treated virions, whereas only cell, DNA but no HSV DNA, is made subsequent to HPD and lambda exposure. These observations reflect disparate mechanisms of viral inactivation. A block(s) in viral maturation, subsequent to viral DNA synthesis, occurs as a result of treatment with MB, lambda and E, whereas HPD plus lambda-treated particles fail to enter a susceptible cell, and therefore do not initiate an infection.

Aminoglycoside-inactivating enzymes in clinical isolates of Streptococcus faecalis. An explanation for resistance to antibiotic synergism.

Clinical isolates of enterococci (Streptococcus faecalis) with high-level resistance to both streptomycin and kanamycin (minimal inhibitory concentration >2,000 mug/ml), and resistant to synergism with penicillin and streptomycin or kanamycin were examined for aminoglycoside-inactivating enzymes. All of the 10 strains studied had streptomycin adenylyltransferase and neomycin phosphotransferase activities; the latter enzyme phosphorylated amikacin as well as its normal substrates, such as kanamycin. Substrate profiles of the neomycin phosphotransferase activity suggested that phosphorylation occurred at the 3'-hydroxyl position, i.e., aminoglycoside 3'-phosphotransferase. A transconjugant strain, which acquired high-level aminoglycoside resistance and resistance to antibiotic synergism after mating with a resistant clinical isolate, also acquired both enzyme activities. Quantitative phosphorylation of amikacin in vitro by a sonicate of the transconjugant strain inactivated the antibiotic, as measured by bioassay, and the phosphorylated drug failed to produce synergism when combined with penicillin against a strain sensitive to penicillin-amikacin synergism.No differences were found in the sensitivity of ribosomes from a sensitive and resistant strain when examined in vitro using polyuridylic acid directed [(14)C]-phenylalanine incorporation in the presence of streptomycin, kanamycin, or amikacin. Therefore, we conclude that aminoglycoside-inactivating enzymes are responsible for the aminoglycoside resistance, and resistance to antibiotic synergism observed in these strains.

Plasmid-mediated resistance to antibiotic synergism in enterococci.

Mating experiments have shown that high-level resistance (minimal inhibitory concentration greater than 2,000 microgram/ml) to streptomycin and kanamycin, and resistance to penicillin-streptomycin and penicillin-kanamycin synergism are transferable by conjugation from resistant clinical isolates of enterococci to a sensitive recipient strain. Cesium chloride-ethidium bromide ultracentrifugation revealed a satellite (plasmid) band in resistant clinical isolates and the transconjugant strains but not in the sensitive recipient. Examination of these satellite bands by agarose gel electrophoresis and electron microscopy demonstrated a common plasmid with a weight of 45 megadaltons. Novobiocin treatment of a resistant clinical isolate produced simultaneous loss of high-level resistance to streptomycin and kanamycin, and of resistance to penicillin-aminoglycoside synergism. These results suggest that (a) high-level resistance to streptomycin and kanamycin among some clinical isolates of enterococci is associated with a 45 megadalton plasmid, and (b) the same plasmid is also responsible for the resistance to penicillin-aminoglycoside synergism observed in these strains.

Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder.

The purpose of this study was to determine if patients with schizophrenia or schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are at higher risk for suicidality than patients without comorbid PTSD. Participants were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective disorder. Those with comorbid PTSD reported higher rates of suicidal ideation and suicidal behaviors compared to those without comorbid PTSD. These findings suggest that patients with comorbid PTSD are at higher risk for suicidality. Enhanced screening and targeted interventions may be warranted to address comorbid PTSD and increased suicide risk in this population.

Role of extracellular matrix assembly in interstitial transport in solid tumors.

The extracellular matrix (ECM) may contribute to the drug resistance of a solid tumor by preventing the penetration of therapeutic agents. We measured differences in interstitial resistance to macromolecule (IgG) motion in four tumor types and found an unexpected correspondence between transport resistance and the mechanical stiffness. The interstitial diffusion coefficient of IgG was measured in situ by fluorescence redistribution after photobleaching. Tissue elastic modulus and hydraulic conductivity were measured by confined compression of excised tissue. In apparent contradiction to an existing paradigm, these functional properties are correlated with total tissue content of collagen, not glycosaminoglycan. An extended collagen network was observed in the more penetration-resistant tumors. Collagenase treatment of the more penetration-resistant tumors significantly increased the IgG interstitial diffusion rate. We conclude that collagen influences the tissue resistance to macromolecule transport, possibly by binding and stabilizing the glycosaminoglycan component of the ECM. These findings suggest a new method to screen tumors for potential resistance to macromolecule-based therapy. Moreover, collagen and collagen-proteoglycan bonds are identified as potential targets of treatment to improve macromolecule delivery.

Depressive symptoms and depressive diagnoses in a community population. Use of a new procedure for analysis of psychiatric classification.

A multivariate classification technique was used to examine whether depressive symptoms and symptoms frequently associated with depressive disorders would cluster into recognizable syndromes that parallel traditional DSM-III psychiatric diagnoses. An analysis was made of all respondents in the Epidemiologic Catchment Area (ECA) project of the Piedmont region of North Carolina who reported suffering from depressive symptoms (n = 406) at the second wave of the ECA study. The analysis identified five profiles of symptoms that adequately described the interrelationships of the symptoms as reported in the population. One profile included a set of symptoms nearly identical to the symptoms associated with the DSM-III classification of major depression. Other depressive syndromes emerged and included a premenstrual syndrome among younger women and a mixed anxiety/depression syndrome. The existence of these other depressive syndromes may explain the present discrepancy in the epidemiologic literature between a high prevalence of depressive symptoms and a low prevalence of traditional depressive diagnoses in community populations.

Circulating immune complexes in prosthetic valve endocarditis.

Using the Raji cell radioimmunoassay, we have determined circulating immune complex (CIC) levels in 36 patients with prosthetic valves during 38 episodes of fever. Fever resulted from prosthetic valve endocarditis (PVE) in 27 instances and from other causes in 11 instances. Peak initial CIC levels higher than 100 micrograms/mL occurred more frequently in the group with PVE, while peak initial CIC values less than 30 micrograms/mL were more frequent in the control group. Circulating immune complex levels fell substantially with completion of antibiotic therapy in 28 (78%) of the patients with PVE. Late CIC elevations were associated with drug-related rashes and replacement of persistently infected prostheses. Our data suggest that the predictive value of measurement of CIC levels in patients with fever and prosthetic valves is in excluding PVE in patients with CIC levels persisting below 30 micrograms/mL.

A multistate outbreak of Escherichia coli O157:H7 infections associated with consumption of mesclun lettuce.

BACKGROUND: An outbreak of Escherichia coli O157:H7 infections in Connecticut and Illinois during May 28 to June 27, 1996, was investigated to determine the source of infections. METHODS: Independent case-control studies were performed in both states. Pulsed-field gel electrophoresis (PFGE) was performed on E. coli O157:H7 isolates. A case-patient was defined as a Connecticut or northern Illinois resident with diarrhea whose stool culture yielded E. coli O157:H7 of the outbreak-associated PFGE subtype. Controls were town-, age-, and sex-matched to case-patients. We traced implicated lettuce to the farm level and performed environmental investigations to identify unsafe lettuce production practices. RESULTS: In Connecticut and Illinois, infection was associated with consumption of mesclun lettuce (Connecticut matched odds ratio [MOR], undefined; 95% confidence interval [CI], 3.4 to infinity; and Illinois MOR, undefined; 95% CI, 1.4 to infinity). We traced implicated lettuce to a single grower-processor. Cattle, a known E. coli O157:H7 reservoir, were found near the lettuce fields. Escherichia coli (an indicator of fecal contamination) was cultured from wash water and finished lettuce. A trace-forward investigation identified 3 additional states that received implicated lettuce; E. coli O157:H7 isolates from patients in 1 of these states matched the outbreak-associated PFGE subtype. CONCLUSIONS: This multistate outbreak of E. coli O157:H7 infections was associated with consumption of mesclun lettuce from a single producer. Molecular subtyping facilitated the epidemiological investigation. This investigation increased the knowledge about current production practices that may contribute to the contamination of lettuce by microbial pathogens. Lettuce production practices should be monitored for microbiological safety.

An in vitro model of the tumor-lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion.

The most common cancers, including breast and skin, disseminate initially through the lymphatic system, yet the mechanisms by which tumor cells home towards, enter and interact with the lymphatic endothelium remain poorly understood. Transmural and luminal flows are important biophysical cues of the lymphatic microenvironment that can affect adhesion molecules, growth factors and chemokine expression as well as matrix remodeling, among others. Although microfluidic models are suitable for in vitro reconstruction of highly complex biological systems, the difficult assembly and operation of these systems often only allows a limited throughput. Here we present and characterize a novel flow chamber which recapitulates the lymphatic capillary microenvironment by coupling a standard Boyden chamber setup with a micro-channel and a controlled fluidic environment. The inclusion of luminal and transmural flow renders the model more biologically relevant, combining standard 3D culture techniques with advanced control of mechanical forces that are naturally present within the lymphatic microenvironment. The system can be monitored in real-time, allowing continuous quantification of different parameters of interest, such as cell intravasation and detachment from the endothelium, under varied biomechanical conditions. Moreover, the easy setup permits a medium-high throughput, thereby enabling downstream quantitative analyses. Using this model, we examined the kinetics of tumor cell (MDA-MB-231) invasion and transmigration dynamics across lymphatic endothelium under varying flow conditions. We found that luminal flow indirectly upregulates tumor cell transmigration rate via its effect on lymphatic endothelial cells. Moreover, we showed that the addition of transmural flow further increases intravasation, suggesting that distinct flow-mediated mechanisms regulate tumor cell invasion.

The physiology of the lymphatic system.

This paper presents an overview of the anatomy, physiology, and biology of the lymphatic system specifically relevant to lymphatic drug delivery. We will briefly review the classic fluid and solute transport literature, and also examine the current research in lymphatic endothelial cell biology and tumor metastasis in the lymphatics because of the increasing potential for targeted delivery of immunomodulators, chemotherapeutics, and genetic material to specific lymph nodes (Refs. [1-7]).

Oscillations of attachment in borderline personality disorder.

The authors propose that oscillations of attachment in borderline personality disorder stem from a central problem with regulation of interpersonal distance. This problem derives from borderline patients' conflicts between fears of abandonment and domination. When they move closer to others, they fear that they will be dominated; when they move away, they fear that they will be abandoned. Whichever direction they move, they experience negative feedback. This gives rise to recurrent oscillations between attachment to and detachment from others. Because the oscillations are reinforced by the ambivalent reactions of significant others and the involvement of third parties, family therapy is often indicated.

Somatization disorder in a community population.

The data recently collected in the Piedmont region of North Carolina as part of the National Institute of Mental Health Epidemiologic Catchment Area Program were used to examine somatization disorder in a community population. The authors found an adjusted prevalence of 0.38% for somatization disorder diagnosed according to the Diagnostic Interview Schedule and DSM-III. Respondents with somatization disorder demonstrated demographic characteristics (female, unmarried, nonwhite, from a rural area, less educated) that are consistent with findings from past clinical and epidemiologic studies of somatization disorder. The adjusted prevalence is higher than that of other Epidemiologic Catchment Area sites, and possible explanations for this findings are discussed.