Search

Charlotte L Haley,1 Betsy D Kennard,1,2 David W Morris,1 Ira H Bernstein,3 Thomas Carmody,4 Graham J Emslie,1,2 Taryn L Mayes,1 A John Rush5– 7 1Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Children’s Health, Children’s Medical Center of Dallas, Dallas, TX, USA; 3Department of Psychology, The University of Texas at Arlington, Arlington, TX, USA; 4Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Department of Psychiatry and Clinical Sciences, Duke-National University of Singapore, Singapore, Singapore; 6Department of Psychiatry and Behavioral Sciences, Texas Tech University – Health Sciences Center, Permian Basin, TX, USA; 7Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USACorrespondence: Betsy D Kennard, University of Texas Southwestern Medical Center, Child Psychiatry, 5323 Harry Hines Blvd, Dallas, TX, 75390-8589, USA, Tel +1 214.645.8680, Fax +1 214.648.3914, Email beth.kennard@utsouthwestern.eduObjective: The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children’s Depression Rating Scale-Revised (CDRS-R).Methods: Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of adolescents (QIDS-A17-C (Adolescent)) and of parents (QIDS-A17-C (Parent)) were combined to create the QIDS-A17-C(Composite) and the CDRS-R.Results: All QIDS-A17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses.Conclusion: The psychometric properties of the self-report and composite versions of the QIDS-A17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices.Keywords: pediatric depression, rating scale, psychometric properties, self-report measures

Abstract Background Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. Methods This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. Discussion This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. Trial registration Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Abstract Background This study leverages a large retrospective cohort of head and neck cancer patients in order to develop machine learning models to predict radiation induced hyposalivation from dose-volume histograms of the parotid glands. Methods The pre and post-radiotherapy salivary flow rates of 510 head and neck cancer patients were used to fit three predictive models of salivary hypofunction, (1) the Lyman-Kutcher-Burman (LKB) model, (2) a spline-based model, (3) a neural network. A fourth LKB-type model using literature reported parameter values was included for reference. Predictive performance was evaluated using a cut-off dependent AUC analysis. Results The neural network model dominated the LKB models demonstrating better predictive performance at every cutoff with AUCs ranging from 0.75 to 0.83 depending on the cutoff selected. The spline-based model nearly dominated the LKB models with the fitted LKB model only performing better at the 0.55 cutoff. The AUCs for the spline model ranged from 0.75 to 0.84 depending on the cutoff chosen. The LKB models had the lowest predictive ability with AUCs ranging from 0.70 to 0.80 (fitted) and 0.67 to 0.77 (literature reported). Conclusion Our neural network model showed improved performance over the LKB and alternative machine learning approaches and provided clinically useful predictions of salivary hypofunction without relying on summary measures.

It is common within Ontario’s educational context to hear the term ‘special needs’ or ‘special education’. However, the relationship between language, definitions, and discourse in the treatment of students with disabilities in Ontario's elementary and secondary schools is understudied. Drawing on an extensive body of literature from the sociology of education, disability studies, and special needs education, this paper aims to recognize the profound influence of language and labels on societal perceptions and the treatment of students with disabilities. While investigating the historical definitions of disability, literature in this area highlights the continuous debate and inconsistencies surrounding terminology in academic and educational contexts. By focusing on the often-used term "special needs", this research examines the potential negative impact of this label on reinforcing ableism and prejudices for students with disabilities. Moreover, language, definitions, and discourse have the power to shape perceptions and, if not used thoughtfully, may inadvertently perpetuate negative stereotypes and hinder students' academic and social development. Therefore, educational terminology should be altered to reflect equitable decision-making and dignity throughout supports for students.

Abstract Glycans are the most abundant fundamental biomolecules, but profiling glycans is challenging due to their structural complexity. To address this, a novel glycan detection platform is developed by integrating surface‐enhanced Raman spectroscopy (SERS), boronic acid receptors, and machine learning tools. Boronic acid receptors bind with glycans, and the reaction influences molecular vibrations, leading to unique Raman spectral patterns. Unlike prior studies that focus on designing a boronic acid with high binding selectivity toward a target glycan, this sensor is designed to analyze overall changes in spectral patterns using machine learning algorithms. For proof‐of‐concept, 4‐mercaptophenylboronic acid (4MBA) and 1‐thianthrenylboronic acid (1TBA) are used for glycan detection. The sensing platform successfully recognizes the stereoisomers and the structural isomers with different glycosidic linkages. The collective spectra that combine the spectra from both boronic acid receptors improve the performance of the support vector machine model due to the enrichment of the structural information of glycans. In addition, this new sensor could quantify the mole fraction of sialic acid in lactose background using the machine learning regression technique. This low‐cost, rapid, and highly accessible sensor will provide the scientific community with another option for frequent comparative glycan screening in standard biological laboratories.

Complex biophysical, social, and human behavioral factors influence population vulnerability to vector-borne diseases. Spatially and temporally dynamic environmental and anthropogenic patterns require sophisticated mapping and modeling techniques. While many studies use environmental variables to predict risk, human population vulnerability has been a challenge to incorporate into spatial risk models. This study demonstrates and applies dasymetric mapping techniques to map spatial patterns of vulnerable human populations and characterize potential exposure to mosquito vectors of West Nile Virus across Chesapeake, Virginia. Mosquito vector abundance is quantified and combined with a population vulnerability index to evaluate exposure of human populations to mosquitoes. Spatial modeling is shown to capture the intersection of environmental factors that produce spatial hotspots in mosquito vector abundance, which in turn poses differential risks over time to humans. Such approaches can help design overall mosquito pest management and identify high-risk areas in advance of extreme weather.

Abstract Background Weight gain is commonly observed during psychotropic treatments for chronic forms of severe mental illness and is most rapid during the early treatment phases. All formats of behavioural weight intervention programmes have suggested that weight gain can be prevented or reversed in some patients. There is no data on these programmes in acutely unwell inpatients whom may be the major beneficiaries. Methods A modular behavioural intervention programme (Solutions for Wellness) used in SMI outpatients since 2002 in Ireland has been adapted for inpatient use. Preliminary data is reported from 5 centres in Ireland. Results In 47 inpatients the mean weight change was +0.26 kg (SD 2.02) with a median change of 0 kg. Mean follow-up was 23.7 (SD 21.6) days, and median 14 days (range 6–98 days). There was no difference in mean weight change in those patients involved for > 35 days compared with < 35 days (+0.26 kg; 0.25 kg; p = 0.5). Weight loss or maintenance was seen in 70% of patients. Conclusion These preliminary data are supportive of the concept that acutely unwell inpatients with SMI may engage with a behavioural weight programme. Weight change observed contrasts with the significant weight gain often seen in most subjects. Further clinical trials are warranted.

Objective: The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A 17 ) and the clinician-rated Children's Depression Rating Scale-Revised (CDRS-R)., Methods: Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A 17 -SR. Clinician interviews of adolescents (QIDS-A 17 -C (Adolescent)) and of parents (QIDS-A 17 -C (Parent)) were combined to create the QIDS-A 17 -C(Composite) and the CDRS-R., Results: All QIDS-A 17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses., Conclusion: The psychometric properties of the self-report and composite versions of the QIDS-A 17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices., Competing Interests: Dr. Kennard receives royalties from Guilford Press and is on the board of the Jerry M. Lewis MD Research Foundation and the George G. and Alva Hudson Smith Foundation. Dr. Kennard has research support from American Foundation for Suicide Prevention (AFSP), the National Institutes of Health, Patient-Centered Outcomes Research Institute (PCORI), and the State of Texas. Dr. Carmody is a consultant for Alkermes, Inc. Dr. Emslie is a consultant for Lundbeck and Neuronetics. Dr. Emslie has research support from American Foundation for Suicide Prevention (AFSP), Janssen Pharmaceuticals, Janssen Research & Development, the National Institutes of Health, Patient-Centered Outcomes Research Institute (PCORI), and the State of Texas. Dr. A. John Rush has received consulting fees from Compass Inc., Curbstone Consultant LLC, Emmes Corp., Evecxia Therapeutics, Inc., Holmusk Technologies, Inc., ICON, PLC, Johnson and Johnson (Janssen), Liva-Nova, MindStreet, Inc., Neurocrine Biosciences Inc., Otsuka-US; speaking fees from Liva-Nova, Johnson and Johnson (Janssen); and royalties from Wolters Kluwer Health, Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on two patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S. The authors report no other conflicts of interest in this work., (© 2023 Haley et al.)

Objective: This study aims to examine potentially inappropriate medication (PIM) prevalence and factors that affect the use of PIMs in a military treatment facility. Method: Admission and discharge medication lists of 60 patients aged ≥65 years were retrospectively reviewed by a clinical pharmacist and a member of the study team for the presence of PIM using the 2012 Beers Criteria. Patients included were those discharged between December 2012 and September 2013 from the Womack Army Medical Center, Internal Medicine unit. Results: Among the 60 patients evaluated, 44 (73%) were on at least one PIM at admission, whereas the prevalence of PIM at discharge (30 patients) was 50% ( p < .001). The top three classes of PIM at admission were antihistamines (11, 15.3%), nonsteroidal anti-inflammatory drugs (10, 13.9%), and benzodiazepines (6, 8.3%). Patients on >10 medications at admission (37, 62%) were 4 times more likely to have a PIM ( p < .001). Conclusion: Data showed a high and a previously unknown PIM prevalence among older adults in a U.S. military treatment facility., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute carpal tunnel syndrome is a rare diagnosis in orthopedic medicine. This article describes a 35-year-old man who presented to the ED with complaints of discomfort and paresthesias in his right wrist after a fall, and was subsequently diagnosed with acute carpal tunnel syndrome. The article reviews the pathophysiology of the syndrome and suggested treatment.

In this paper, expressions are derived for the expected number of spurious peaks in a spectrum estimate, that is, crossings above a given significance level per frequency unit, as well as the expected width of these peaks. In numerous scientific applications, spectrum estimates are used for the purpose of identifying sinusoidal or modal components, often thinning large sets of candidate frequencies with coincidence detection. Because one always expects numerous false peaks in a spectrum estimate, knowing the expected rate of false peaks helps to decide whether the number observed is abnormal and hence determine the true nature of the process. An example using solar wind data from the Advanced Composition Explorer is given where spectra display pathological numbers of significant peaks, while temporally permuted versions of the data possess spectra with the number expected for a white, Gaussian process. The permutation test is a valuable diagnostic for processes suspected to contain many line components.

Loss of the skin barrier facilitates the colonization of underlying tissues with various bacteria, where they form biofilms that protect them from antibiotics and host responses. Such wounds then become chronically infected. Topical antimicrobials are a major component of chronic wound therapy, yet currently available topical antimicrobials vary in their effectiveness on biofilm-forming pathogens. In this study, we evaluated the efficacy of Next Science wound gel technology (NxtSc), a novel topical agent designed to kill planktonic bacteria, penetrate biofilms, and kill the bacteria within. In vitro quantitative analysis, using strains isolated from wounds, showed that NxtSc inhibited biofilm development by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae by inhibiting bacterial growth. The gel formulation NxtSc-G5, when applied to biofilms preformed by these pathogens, reduced the numbers of bacteria present by 7 to 8 log10 CFU/disc or CFU/g. In vivo, NxtSc-G5 prevented biofilm formation for 72 h when applied at the time of wounding and infection and eliminated biofilm infection when applied 24 h after wounding and infection. Storage of NxtSc-G5 at room temperature for 9 months did not diminish its efficacy. These results establish that NxtSc is efficacious in vitro and in vivo in preventing infection and biofilm development by different wound pathogens when applied immediately and in eliminating biofilm infection already established by these pathogens. This novel antimicrobial agent, which is nontoxic and has a usefully long shelf life, shows promise as an effective agent for the prevention and treatment of biofilm-related infections., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Mental health problems during pregnancy can influence fetal growth. However, studies examining the influence of maternal mental health across the normal range of birth outcomes are uncommon. This study examined the associations between symptoms of maternal depression and anxiety during pregnancy on birth size among term Asian infants., Methods: One thousand forty-eight Asian pregnant women from a cohort Growing Up in Singapore Towards Healthy Outcomes were recruited between 2009 to 2010 at two Singaporean maternity hospitals. At 26 weeks gestation, depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory II (BDI-II), and anxiety was measured with the Spielberger State-Trait Anxiety Inventory (STAI). Health personnel recorded birthweight, birthlength, gestational age, and head circumference at birth., Results: Nine hundred forty-six women who delivered term infants had complete data. For this sample, the mean birthweight was 3146.6 g [standard deviation (SD) 399.0], the mean birthlength was 48.9 cm (SD 2.0). After controlling for several potential confounders, there was a significant negative association between STAI and birthlength [β = -0.248, confidence interval (CI) [-0.382, -0.115], P < 0.001] and a small negative association between EPDS and birthlength (β = -0.169, CI [-0.305, -0.033], P = 0.02). No associations were found between scores on the EPDS, BDI-II, and STAI with birthweight or head circumference., Conclusions: Our preliminary data suggest that among term infants, anxiety and depressive symptoms are not associated with birthweight, while anxiety and depressive symptoms are associated with a shorter birthlength., (© 2013 John Wiley & Sons Ltd.)

In Pseudomonas aeruginosa, type IV pili (TFP)-dependent twitching motility is required for development of surface-attached biofilm (SABF), yet excessive twitching motility is detrimental once SABF is established. In this study, we show that mucin significantly enhanced twitching motility and decreased SABF formation in strain PAO1 and other P. aeruginosa strains in a concentration-dependent manner. Mucin also disrupted partially established SABF. Our analyses revealed that mucin increased the amount of surface pilin and enhanced transcription of the pilin structural gene pilA. Mucin failed to enhance twitching motility in P. aeruginosa mutants defective in genes within the pilin biogenesis operons pilGHI/pilJK-chpA-E. Furthermore, mucin did not enhance twitching motility nor reduce biofilm development by chelating iron. We also examined the role of the virulence factor regulator Vfr in the effect of mucin. In the presence or absence of mucin, PAOΔvfr produced a significantly reduced SABF. However, mucin partially complemented the twitching motility defect of PAOΔvfr. These results suggest that mucin interferes with SABF formation at specific concentrations by enhancing TFP synthesis and twitching motility, that this effect, which is iron-independent, requires functional Vfr, and only part of the Vfr-dependent effect of mucin on SABF development occurs through twitching motility.

The Pseudomonas aeruginosa fimbrial structures encoded by the cup gene clusters (cupB and cupC) contribute to its attachment to abiotic surfaces and biofilm formation. The P. aeruginosa pvcABCD gene cluster encodes enzymes that synthesize a novel isonitrile functionalized cumarin, paerucumarin. Paerucumarin has already been characterized chemically, but this is the first report elucidating its role in bacterial biology. We examined the relationship between the pvc operon and the cup gene clusters in the P. aeruginosa strain MPAO1. Mutations within the pvc genes compromised biofilm development and significantly reduced the expression of cupB1-6 and cupC1-3, as well as different genes of the cupB/cupC two-component regulatory systems, roc1/roc2. Adjacent to pvc is the transcriptional regulator ptxR. A ptxR mutation in MPAO1 significantly reduced the expression of the pvc genes, the cupB/cupC genes, and the roc1/roc2 genes. Overexpression of the intact chromosomally-encoded pvc operon by a ptxR plasmid significantly enhanced cupB2, cupC2, rocS1, and rocS2 expression and biofilm development. Exogenously added paerucumarin significantly increased the expression of cupB2, cupC2, rocS1 and rocS2 in the pvcA mutant. Our results suggest that pvc influences P. aeruginosa biofilm development through the cup gene clusters in a pathway that involves paerucumarin, PtxR, and different cup regulators.

Objective: Data on psychiatric morbidity in high-risk pregnant Singaporean women are limited. This study aimed to establish the prevalence of antenatal depression and anxiety in high-risk pregnancies, compare the prevalence of antenatal depression in high-risk pregnancies vs. pregnancies of unspecified obstetric risk and examine the Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory (STAI) as screening tools for these disorders., Method: Two hundred high-risk pregnant inpatients at a national public maternity hospital were included. Three psychometric assessment tools were used to evaluate all participants: the diagnostic Mini International Neuropsychiatric Interview and the screening EPDS and STAI., Results: Rates of major depression, minor depression, anxiety disorder (agoraphobia, generalized anxiety disorder, panic disorder), and comorbid depression and anxiety were 11%, 7%, 12.5% and 5%, respectively. Major depression was more prevalent in high-risk pregnancies than in the historical cohort of unspecified obstetric risk (11% versus 4.3%). EPDS (cutoff 8/9) screens well for depression and anxiety in high-risk pregnancies (area under the receiver operating characteristic curve=0.82-0.87)., Conclusion: Antenatal depression and anxiety are highly prevalent in a sample of high-risk pregnant Singaporean women. EPDS performs well in screening for depression and anxiety in high-risk pregnant women, with further psychiatric assessment recommended for women with score ≥ 9., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine the incidence, clinical and demographic correlates, and relationship to treatment outcome of self-reported premenstrual exacerbation of depressive symptoms in premenopausal women with major depressive disorder who are receiving antidepressant medication., Method: This post-hoc analysis used clinical trial data from treatment-seeking, premenopausal, adult female outpatients with major depression who were not using hormonal contraceptives. For this report, citalopram was used as the first treatment step. We also used data from the second step in which one of three new medications were used (bupropion-SR [sustained release], venlafaxine-XR [extended release], or sertraline). Treatment-blinded assessors obtained baseline treatment outcomes data. We hypothesized that those with reported premenstrual depressive symptom exacerbation would have more general medical conditions, longer index depressive episodes, lower response or remission rates, and shorter times-to-relapse with citalopram, and that they would have a better outcome with sertraline than with bupropion-SR., Results: At baseline, 66% (n=545/821) of women reported premenstrual exacerbation. They had more general medical conditions, more anxious features, longer index episodes, and shorter times-to-relapse (41.3 to 47.1 weeks, respectively). Response and remission rates to citalopram, however, were unrelated to reported premenstrual exacerbation. Reported premenstrual exacerbation was also unrelated to differential benefit with sertraline and bupropion-SR., Conclusions: Self-reported premenstrual exacerbation has moderate clinical utility in the management of depressed patients, although it is not predictive of overall treatment response. Factors that contribute to a more chronic or relapsing course may also play a role in premenstrual worsening of major depressive disorder (MDD).

Aims: Catheter ablation for paroxysmal atrial fibrillation (AF) is rapidly becoming a standard practice. There is literature to support that catheter ablation of persistent AF requires additional 'substrate modification'. In clinical practice, operators rely on automated fractionation maps created by three-dimensional anatomic mapping systems to rapidly assess complex 'fractionated' signals (CFAE). These systems use differing algorithms to automate the process. The agreement between operators and contemporary algorithms has not been examined. We sought to assess the agreement between operators and a novel method of quantification calculating percentage fractionation (PF)., Methods and Results: Expert opinion on 80 atrial electrogram 4 s signals of varying levels of activity were gathered and pooled for comparison. Twelve independent experts visually quantified the signal fractionation and offered a threshold level for ablation. We developed an algorithm to find sites with high continuous electrical activity, or high PF. Correlation between experts and PF was 0.78 [P < 0.01, 95% confidence interval (CI) (0.68-0.86)]. Receiver operating characteristics curve sensitivity and specificity for PF were 0.7727 and 0.8103 at the optimal cut-off point of 58.45 PF with area under curve 0.89 CI (0.80-0.99)., Conclusion: The PF statistic represents a more robust and intuitive measure to represent fractionated atrial activity; importantly it demonstrates excellent agreement with expert users and presents a new standard for algorithm assessment. Use of a PF statistic should be considered in automated mapping systems.

Background: The accumulation of thick stagnant mucus provides a suitable environment for the growth of Pseudomonas aeruginosa and Staphylococcus aureus within the lung alveoli of cystic fibrosis (CF) patients. These infections cause significant lung damage, leading to respiratory failure and death. In an artificial mucin containing medium ASM+, P. aeruginosa forms structures that resemble typical biofilms but are not attached to any surface. We refer to these structures as biofilm like structures (BLS). Using ASM+ in a static microtiter plate culture system, we examined the roles of mucin, extracellular DNA, environmental oxygen (EO2), and quorum sensing (QS) in the development of biofilm-like structures (BLS) by P. aeruginosa; and the effect of EO2 and P. aeruginosa on S. aureus BLS., Results: Under 20% EO2, P. aeruginosa strain PAO1 produced BLS that resemble typical biofilms but are confined to the ASM+ and not attached to the surface. Levels of mucin and extracellular DNA within the ASM+ were optimized to produce robust well developed BLS. At 10% EO2, PAO1 produced thicker, more developed BLS, while under 0% EO2, BLS production was diminished. In contrast, the S. aureus strain AH133 produced well-developed BLS only under 20% EO2. In PAO1, loss of the QS system genes rhlI and rhlR affected the formation of BLS in ASM+ in terms of both structure and architecture. Whether co-inoculated into ASM+ with AH133, or added to established AH133 BLS, PAO1 eliminated AH133 within 48-56 h., Conclusions: The thick, viscous ASM+, which contains mucin and extracellular DNA levels similar to those found in the CF lung, supports the formation of biofilm-like structures similar to the aggregates described within CF airways. Alterations in environmental conditions or in the QS genes of P. aeruginosa, as occurs naturally during the progression of CF lung infection, affect the architecture and quantitative structural features of these BLS. Thus, ASM+ provides an in vitro medium in which the effect of changing levels of substances produced by the host and the bacteria can be analyzed to determine the effect on such structures and on the susceptibility of the bacteria within the BLS to various treatments.

Objective: To compare sociodemographic and clinical features, acute and continuation treatment outcomes, and adverse events/side effect burden between outpatients with chronic (current episode > 2 years) versus nonchronic major depressive disorder (MDD) who were treated with combination antidepressant therapy or selective serotonin reuptake inhibitor (SSRI) monotherapy., Method: 663 outpatients with chronic (n = 368) or nonchronic (n = 295) moderate to severe DSM-IV-TR MDD (17-item Hamilton Depression Rating Scale score ≥ 16) were enrolled from March 2008 through September 2009 in a single-blind 7-month prospective randomized trial conducted at 6 primary and 9 psychiatric care sites across the United States. Participants were treated with escitalopram monotherapy plus placebo or 1 of 2 combination treatments (bupropion sustained-release [SR] + escitalopram or venlafaxine extended-release [XR] + mirtazapine). Analyses compared baseline sociodemographic and clinical characteristics, rates of remission (at least 1 of the last 2 consecutive scores on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR16] < 6, with the other < 8), and adverse events/side effect burden (Frequency, Intensity, and Burden of Side Effects Ratings) obtained at 12 and 28 weeks., Results: Participants with chronic MDD were at greater socioeconomic disadvantage and had greater medical and psychiatric disease burden. The chronic and nonchronic groups did not differ in rates of remission at 12 weeks (35.9% vs 42.0%, respectively; odds ratio [OR] = 0.778, P = .1500; adjusted OR [AOR] = 0.956, P = .8130) or at 28 weeks (41.0% vs 49.8%, respectively; OR = 0.706, P = .0416; AOR = 0.837, P = .3448). Participants with chronic MDD had higher final QIDS-SR(16) scores and smaller overall percent changes in QIDS-SR(16) from baseline to exit, but these differences did not remain after adjusting for covariates. There were no significant differences in adverse events or side effect burden. No significant interactions were found between chronicity and type of treatment at 12 or 28 weeks., Conclusion: Chronicity of illness does not appear to differentially impact acute or longer-term outcomes with SSRI monotherapy or combination antidepressant medication treatment in patients with moderate to severe nonpsychotic MDD., Trial Registration: ClinicalTrials.gov identifier: NCT00590863., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Background: Major depressive disorder (MDD) is commonly chronic and/or recurrent. We aimed to determine whether a chronic and/or recurrent course of MDD is associated with acute and longer-term MDD treatment outcomes., Method: This cohort study recruited out-patients aged 18-75 years with non-psychotic MDD from 18 primary and 23 psychiatric care clinics across the USA. Participants were grouped as: chronic (index episode >2 years) and recurrent (n = 398); chronic non-recurrent (n=257); non-chronic recurrent (n=1614); and non-chronic non-recurrent (n = 387). Acute treatment was up to 14 weeks of citalopram (≤ 60 mg/day) with up to 12 months of follow-up treatment. The primary outcomes for this report were remission [16-item Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR(16)) ≤ 5] or response (≥ 50% reduction from baseline in QIDS-SR(16)) and time to first relapse [first QIDS-SR16 by Interactive Voice Response (IVR) ≥ 11]., Results: Most participants (85%) had a chronic and/or recurrent course; 15% had both. Chronic index episode was associated with greater sociodemographic disadvantage. Recurrent course was associated with earlier age of onset and greater family histories of depression and substance abuse. Remission rates were lowest and slowest for those with chronic index episodes. For participants in remission entering follow-up, relapse was most likely for the chronic and recurrent group, and least likely for the non-chronic, non-recurrent group. For participants not in remission when entering follow-up, prior course was unrelated to relapse., Conclusions: Recurrent MDD is the norm for out-patients, of whom 15% also have a chronic index episode. Chronic and recurrent course of MDD may be useful in predicting acute and long-term MDD treatment outcomes.

Objective: The aim of this study was to present the reliability and validity of the Children's Depression Rating Scale-Revised (CDRS-R) in the adolescent age group., Method: Adolescents with symptoms of depression were assessed using the CDRS-R and global severity and functioning scales at screening, baseline, and after 12 weeks of fluoxetine treatment. Global improvement was also assessed at week 12 (or exit). Reliability and validity were analyzed using Classical Test Theory (item-total correlations and internal consistency) and correlations between the CDRS-R and other outcomes., Results: Adolescents (n = 145) were evaluated at screening; 113 (77.9%) met criteria for major depressive disorder, 8 (5.5%) had subthreshold depressive symptoms, and 24 (16.6%) had minimal depressive symptoms. Ninety-four adolescents had a baseline visit after 1 week, and 88 were treated with fluoxetine. Internal consistency for the CDRS-R was good at all three visits (screening: 0.79; baseline: 0.74; exit: 0.92), and total score was highly correlated with global severity (r = 0.87, 0.80, and 0.93; p < 0.01). Only exit CDRS-R score was significantly correlated with global functioning (Children's Global Assessment Scale; r = -0.77; p < 0.01). Reductions on the CDRS-R total score were highly correlated with improvement scores at exit (Clinical Global Impressions-Improvement; r = -0.83; p < 0.01)., Conclusions: The results demonstrate good reliability and validity in adolescents with depression.

Lipid-associated membrane proteins (LAMPs) from 14 Mycoplasma hominis isolates or strains share similar protein and antigenicity profiles. Of 31 human immunodeficiency virus-infected patients from whose samples M. hominis was cultured, 28 tested strongly positive for serum antibodies to M. hominis LAMPs. The remaining 3 serum samples showed low antibody titer to LAMPs from all of the 14 M. hominis isolates or strains, which was likely the result of the compromised immune systems of the patients. Thus, M. hominis LAMPs as a whole are homogenous in antigenicity within the species, despite having many different serotypes. Serological study involving 564 healthy blood donors and 211 patients attending sexually transmitted disease clinics by LAMPs showed that general populations were widely exposed to M. hominis. Women were infected with M. hominis at a younger age than were men. The prevalence of infection increased markedly among sexually active persons.

Prevalence of Mycoplasma genitalium in humans is still not clear. We have developed a sensitive and specific serological assay for M. genitalium using lipid-associated membrane proteins (LAMPs) as antigens. Antibodies to LAMPs from M. genitalium showed little cross-reactivity to LAMPs from antigenically similar M. pneumoniae. For validity testing, urines from 104 patients were tested by PCR for M. genitalium. All 15 PCR+ patients had M. genitalium-LAMPs antibodies. Moreover, none of 64 antibody-negative patients were PCR+. Serological study of 1800 patients of various diseased groups and healthy blood donors showed M. genitalium was primarily a sexually transmitted microbe that infected patients with AIDS (44.0%), intravenous drugs users with or without HIV infection (42.5%), and also HIV- patients attending STD clinics (42.6%). Only 5.5% HIV- healthy blood donors and 1.3% HIV+ hemophiliacs tested positive. M. genitalium has been associated with acute non-gonococcal urethritis in male patients. However, many sexually active men and women appear to be chronically infected or colonized by the microbe without apparent clinical symptoms and may continue to transmit the organism through sexual contacts.

A prostate carcinoma-associated antigen recognized by MAb TURP-27 was characterized immunohistochemically and biochemically. TURP-27 antigen was found localized in the cell membrane and cytoplasm of the ductal epithelial cells of normal (10%), benign (75-100%) and malignant (20-100%) prostate cells. Fetal prostate tissues were also found to express the TURP-27 antigen, suggesting expression early in development. This antigen was not expressed by non-prostate tumors examined, but significant cross-reactivity was observed in myelinated nerves while minor cross-reactivity was seen in certain lymphocyte subsets, cells in the adrenal medulla and chief cells of stomach. Immunoblotting and biochemical data demonstrated that the TURP-27 antigen is a sialic-acid-containing glycoprotein complex with major molecular species in prostate tissues of 310-250, 180, 140, 115, 95-90, 69, and 40- to 35-kDa. Immunoblotting patterns similar to those observed for prostate tissues were also seen in CNS extracts with the exception of the 69 and 40- to 35-kDa proteins. This prostate carcinoma-associated sialoglycoprotein complex (PAC) recognized by MAb TURP-27 is likely to represent a novel tumor antigen expressed by prostate tumors.

A monoclonal antibody (MAb) designated PD41 (IgG1k) was generated by hyperimmunizing BALB/c mice with a membrane preparation prepared from a moderately to poorly differentiated prostate carcinoma surgical specimen. The immunohistochemical reactivity of MAb PD41 was shown to be highly restricted to the ductal epithelia and secretions of prostate adenocarcinoma tissues. Sixty-five % of the prostate tumor specimens were stained with MAb PD41, whereas no staining of the fetal or benign prostate specimens was observed. PD41 reacted minimally with normal prostate tissues, with less than 1% of the epithelial cells staining. This MAb did not react with nonprostate carcinomas or to a variety of normal human tissues. Using both radioimmunoassay and immunofluorescent procedures, several cultured human tumor cell lines, human blood cells, and purified antigens to prostate-specific antigen and prostatic acid phosphatase also were found not to express the PD41 antigen. MAb PD41 also was shown to bind to the target antigen present in seminal plasma obtained from prostate carcinoma patients but not to seminal plasma from normal donors. Immunoblots of gel-separated components of prostate carcinoma tissue extracts indicate that the molecular weight of the proteins carrying the PD41 antigenic determinant can differ among individual tumors, ranging from Mr 90,000 to greater than 400,000. However, in seminal plasma from prostate cancer patients, the predominant component recognized by PD41 is the diffuse Mr greater than 400,000 band. It appears that this monoclonal antibody may recognize a prostate carcinoma-associated mucin-like antigen, which is preferentially expressed on prostate carcinomas, and therefore, may be a useful marker to distinguish benign prostate hyperplasia from prostate carcinoma.

The biotin-avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma-associated markers in formalin-fixed paraffin-embedded tissue sections of three human prostate nude mouse heterotransplant lines PC-82, PC-EW, and PC-EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP-27, Leu-7, 7E11-C5, PSP-19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC-82 and PC-EW lines were the most efficient in terms of expression of multiple prostate carcinoma-associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP-27, PSP-19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti-prostate carcinoma monoclonal antibodies.