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Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bürger, von Schoenfeld, Scheiner, Seidel, Wasserscheid, Gad, Kittel-Schneider, Romanos and Reiter.)

A single-cycle light source in the near infrared is demonstrated enabling sensitive applications of ultrafast optical field control of electronic transport. The compact Er:fiber system generates passively phase-locked pulses with broadband spectra covering 150 THz to 350 THz at a duration of 4.2 fs and 40 MHz repetition rate. A second output arm is equipped with an electro-optic modulator (EOM) that switches the arrival time of the pulses by 700 ps at arbitrary frequencies up to 20 MHz, enabling timing modulation of the pump pulse without changing the average intensity. As a benchmark demonstration, we investigate the carrier relaxation dynamics in low-temperature-grown InGaAs (LT-InGaAs) using quantum interference currents (QuICs).

Background: Non-suicidal self-injury (NSSI) has become a substantial public health problem. NSSI is a high-risk marker for the development and persistence of mental health problems, shows high rates of morbidity and mortality, and causes substantial health care costs. Thus, there is an urgent need for action to develop universal prevention programs for NSSI before adolescents begin to show this dangerous behavior. Currently, however, universal prevention programs are lacking., Methods: The main objective of the present study is to evaluate a newly developed universal prevention program ("DUDE - Du und deine Emotionen / You and your emotions"), based on a skills-based approach in schools, in 3200 young adolescents (age 11-14 years). The effectiveness of DUDE will be investigated in a cluster-randomized controlled trial (RCT) in schools (N = 16). All groups will receive a minimal intervention called "Stress-free through the school day" as a mental health literacy program to prevent burnout in school. The treatment group (N = 1600; 8 schools) will additionally undergo the universal prevention program DUDE and will be divided into treatment group 1 (DUDE conducted by trained clinical psychologists; N = 800; 4 schools) and treatment group 2 (DUDE conducted by trained teachers; N = 800; 4 schools). The active control group (N = 1600; 8 schools) will only receive the mental health literacy prevention. Besides baseline assessment (T0), measurements will occur at the end of the treatment (T1) and at 6- (T2) and 12-month (T3) follow-up evaluations. The main outcome is the occurrence of NSSI within the last 6 months assessed by a short version of the Deliberate Self-Harm Inventory (DSHI-9) at the 1-year follow-up (primary endpoint; T3). Secondary outcomes are emotion regulation, suicidality, health-related quality of life, self-esteem, and comorbid psychopathology and willingness to change., Discussion: DUDE is tailored to diminish the incidence of NSSI and to prevent its possible long-term consequences (e.g., suicidality) in adolescents. It is easy to access in the school environment. Furthermore, DUDE is a comprehensive approach to improve mental health via improved emotion regulation., Trial Registration: German Clinical Trials Register (DRKS) DRKS00018945. Registered on 01 April 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018945., (© 2021. The Author(s).)

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA., Competing Interests: The authors have declared that no competing interests exist.

Background: The translation of phase-resolved functional lung (PREFUL)-MRI to routine practice in monitoring chronic thromboembolic pulmonary hypertension (CTEPH) still requires clinical corresponding imaging biomarkers of pulmonary vascular disease., Purpose: To evaluate successful pulmonary endarterectomy (PEA) via PREFUL-MRI with pulmonary pulse wave transit time (pPTT)., Study Type: Retrospective., Population: Thirty CTEPH patients and 12 healthy controls were included., Field Strength/sequence: For PREFUL-MRI a 2D spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence were performed on 1.5T., Assessment: Eight coronal slices of PREFUL-MRI were obtained on consecutive 13 days before and 14 days after PEA. PREFUL quantitative lung perfusion (PREFUL Q ) phases over the whole cardiac cycle were calculated to quantify pPTT, the time the pulmonary pulse wave travels from the central pulmonary arteries to the pulmonary capillaries. Also, perfusion defect percentage based on pPTT (QDP pPTT ), PREFUL Q (QDP PREFUL ), and V/Q match were calculated. For DCE-MRI, pulmonary blood flow (PBF) and QDP PBF were computed as reference. For clinical correlation, mean pulmonary arterial pressure (mPAP) and 6-minute walking distance were evaluated preoperatively and after PEA., Statistical Tests: The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Dice coefficient, and Spearman's correlation coefficient (ρ) were applied., Results: Median pPTT was significantly lower post PEA (139 msec) compared to pre PEA (193 msec), P = 0.0002. Median pPTT correlated significantly with the mPAP post PEA (r = 0.52, P < 0.008). Median pPTT was distributed more homogeneously after PEA: IQR pPTT decreased from 336 to 281 msec (P < 0.004). Median PREFUL Q (P < 0.0002), QDP pPTT (P < 0.0478), QDP PREFUL (P < 0.0001) and V/Q match (P < 0.0001) improved significantly after PEA. Percentage change of PREFUL Q correlated significantly with percentage change of 6-minute walking distance (ρ = 0.61; P = 0.0031) 5 months post PEA., Data Conclusion: Perioperative perfusion changes in CTEPH can be detected and quantified by PREFUL-MRI. Normalization of pPTT reflects surgical success and improvement of PREFUL Q predicts 6-minute walking distance changes., Level of Evidence: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:610-619., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with balloon pulmonary angioplasty (BPA) in inoperable patients. Sensitive non-invasive imaging methods are missing to detect treatment response after a single BPA treatment session. Therefore, the aim of this study was to measure treatment response after a single BPA session using cardio-pulmonary MRI., Materials and Methods: Overall, 29 patients with CTEPH were examined with cardio-pulmonary MRI before and 62 days after their initial BPA session. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Multiple linear regression analysis was implemented to estimate the relationship of PBF change in the treated lobe with treatment change of full width at half maximum (FWHM), cardiac output (CO), ventricular mass index (VMI), pulmonary transit time (PTT) and PBF change in the non-treated lobes. Paired Wilcoxon rank sum test and Spearman rho correlation were used., Results: After BPA regional PBF increased in the treated lobe (p < 0.0001) as well as in non-treated lobes (p = 0.015). PBF treatment changes in the treated lobe were significantly larger compared with the non-treated lobes (p = 0.0049). Change in NT proBNP, MRI-derived mean pulmonary artery pressure (mPAP), PTT, FWHM, right ventricular (RV) ejection fraction, RV stroke volume, CO, VMI and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05). PBF changes in the treated lobe were independently predicted by PTT as well as PBF change in the non-treated lobes., Conclusion: Cardio-pulmonary MRI detects and quantifies treatment response after a single BPA treatment session., Key Points: • Two months after BPA regional parenchymal pulmonary perfusion (PBF) increased in the total lung parenchyma (p = 0.005), the treated lobes (p < 0.0001) and non-treated lobes (p = 0.015). • The PBF treatment changes in the treated lobe were significantly larger than in the non-treated lobes (p = 0.0049). • Change in NT proBNP, MRI-derived mean pulmonary artery pressure, pulmonary transit time, full width at half maximum, right ventricular (RV) ejection fraction, RV stroke volume, cardiac output, ventricular mass index and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05).

Background: Decision making with advanced cancer patients is often associated with decisional conflict regarding treatment outcomes. This longitudinal multicenter study investigated German physicians' course of decisional conflict during the decision-making process for a Simulated advanced-stage cancer Patient (SP). Results were compared to a matched sample of Belgian physicians., Methods: German physicians' (n = 30) decisional conflict was assessed with the Decisional Conflict Scale (DCS) at baseline (t1) and after the four steps of a decision-making process: after reviewing the SP chart (t2), after viewing an assessment video interview with the SP (t3), after reviewing the team recommendations (t4), and after conducting the patient-physician decision-making interview (t5). The results were compared to those of a Belgian matched sample (n = 30)., Results: Decisional conflict of German physicians decreased during the Decision-Making process (M = 53.5, SD = 11.6 at t2 to M = 37.8, SD = 9.6 at t5, p < 0.001). This was similar to the pattern in the Belgian sample (M = 53.5, SD = 12.5 at t2 to M = 34.1, SD = 10.9 at t5, p < 0.001). There was no significant difference between the two groups for Decisional conflict end scores (p = 0.171). At the end of the Decision-making process, in both groups, still 43.3% of the physicians among each group (n = 13) reported a high Decisional Conflict (DCS > 37.5)., Conclusions: Physicians' decisional conflict decreases during the decision-making process for an advanced cancer SP, though it remains at a high level. Culture, language and different health care systems have no influence on this process. The results emphasize the influence of psychosocial factors. We conclude that this issue should be considered more intensively in future research and in clinical care.

Purpose: To test quantitative functional lung MRI techniques in young adults with cystic fibrosis (CF) compared to healthy volunteers and to monitor immediate treatment effects of a single inhalation of hypertonic saline in comparison to clinical routine pulmonary function tests., Materials and Methods: Sixteen clinically stable CF patients and 12 healthy volunteers prospectively underwent two functional lung MRI scans and pulmonary function tests before and 2h after a single treatment of inhaled hypertonic saline or without any treatment. MRI-derived oxygen enhanced T1 relaxation measurements, fractional ventilation, first-pass perfusion parameters and a morpho-functional CF-MRI score were acquired., Results: Compared to healthy controls functional lung MRI detected and quantified significantly increased ventilation heterogeneity in CF patients. Regional functional lung MRI measures of ventilation and perfusion as well as the CF-MRI score and pulmonary function tests could not detect a significant treatment effect two hours after a single treatment with hypertonic saline in young adults with CF (p>0.05)., Conclusion: This study shows the feasibility of functional lung MRI as a non-invasive, radiation-free tool for monitoring patients with CF.

Purpose To evaluate surgical success after pulmonary endarterectomy (PEA) by means of cardiopulmonary magnetic resonance (MR) imaging. Materials and Methods In this institutional review board-approved study, 20 patients with chronic thromboembolic pulmonary hypertension were examined at 1.5 T with a dynamic contrast material-enhanced three-dimensional fast low-angle shot sequence before and 12 days after PEA (25th-75th percentile range, 11-16 days). Lung segments were evaluated visually before PEA for parenchymal hypoperfused segments. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Mean pulmonary artery pressure (mPAP) and 6-minute walking distance were measured before and after PEA. The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Spearman ρ correlation, and multiple linear regression analysis were performed. Results Two weeks after PEA, regional PBF increased 66% in the total lung from 32.7 to 54.2 mL/min/100 mL (P = .0002). However, after adjustment for cardiac output, this change was not evident anymore (increase of 7% from 7.03 to 7.54 mL/min/100 mL/L/min, P = .1). Only in the lower lobes, a significant increase in PBF after cardiac output adjustment remained: a 16% increase in the right lower lobe from 7.53 to 8.71 mL/min/100 mL (P = .01) and a 14% increase in the left lower lobe from 7.42 to 8.47 mL/min/100 mL/L/min (P < .05). Right ventricular mass and function also improved. mPAP decreased from 46 to 24 mm Hg (P < .0001). Six-minute walking distance increased from 390 to 467 m (P = .02) 5 months after PEA. Percentage change of mPAP and PBF in the lower lobe tended to be significant predictors of percentage change in 6-minute walking distance (β = -1.79 [P = .054] and β = 0.45 [P = .076], respectively) in multiple linear regression analysis. Conclusion Improvement of PBF after PEA was observed predominantly in the lower lungs, and the magnitude of improvement of PBF in the lower lobes correlated with the improvement in exercise capacity, reflecting surgical success. (©) RSNA, 2016.

Rationale: There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS) following lung transplantation (LTx)., Objectives: The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx., Methods: Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1-3) and one without BOS (BOS 0/0p)., Measurements and Main Results: Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1-3 compared to the BOS 0/0p group (p < 0.05). In a stepwise logistic regression analysis global cardiac mass (p = 0.046) and days after LTx (p = 0.0001) remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005) and physical fitness (p = 0.01) remained independent predictors for BOS., Conclusion: The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function.

The genetic diagnosis in inherited optic neuropathies often remains challenging, and the emergence of complex neurological phenotypes that involve optic neuropathy is puzzling. Here we unravel two novel principles of genetic mechanisms in optic neuropathies: deep intronic OPA1 mutations, which explain the disease in several so far unsolved cases; and an intralocus OPA1 modifier, which explains the emergence of syndromic 'optic atrophy plus' phenotypes in several families. First, we unravelled a deep intronic mutation 364 base pairs 3' of exon 4b in OPA1 by in-depth investigation of a family with severe optic atrophy plus syndrome in which conventional OPA1 diagnostics including gene dosage analyses were normal. The mutation creates a new splice acceptor site resulting in aberrant OPA1 transcripts with retained intronic sequence and subsequent translational frameshift as shown by complementary DNA analysis. In patient fibroblasts we demonstrate nonsense mediated messenger RNA decay, reduced levels of OPA1 protein, and impairment of mitochondrial dynamics. Subsequent site-specific screening of >360 subjects with unexplained inherited optic neuropathy revealed three additional families carrying this deep intronic mutation and a base exchange four nucleotides upstream, respectively, thus confirming the clinical significance of this mutational mechanism. Second, in all severely affected patients of the index family, the deep intronic mutation occurred in compound heterozygous state with an exonic OPA1 missense variant (p.I382M; NM&#95;015560.2). The variant alone did not cause a phenotype, even in homozygous state indicating that this long debated OPA1 variant is not pathogenic per se, but acts as a phenotypic modifier if it encounters in trans with an OPA1 mutation. Subsequent screening of whole exomes from >600 index patients identified a second family with severe optic atrophy plus syndrome due to compound heterozygous p.I382M, thus confirming this mechanism. In summary, we provide genetic and functional evidence that deep intronic mutations in OPA1 can cause optic atrophy and explain disease in a substantial share of families with unsolved inherited optic neuropathies. Moreover, we show that an OPA1 modifier variant explains the emergence of optic atrophy plus phenotypes if combined in trans with another OPA1 mutation. Both mutational mechanisms identified in this study-deep intronic mutations and intragenic modifiers-might represent more generalizable mechanisms that could be found also in a wide range of other neurodegenerative and optic neuropathy diseases., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The aim of this study was to investigate the effects of age on outcome in a large cohort of surgical intensive care unit (ICU) patients., Methods: In this retrospective analysis of prospectively collected data, all 11537 adult patients admitted directly from the operating room to our 50-bed surgical ICU between January 1, 2004, and January 31, 2009, were included. Patients were classified into 5 subgroups according to age (18-50 [reference category], 51-65, 66-75, 76-85, >85 years)., Results: Severity scores and the incidence of comorbid conditions on ICU admission increased steadily with age. Intensive care unit and hospital mortality rates were 4.4% and 8.7%, respectively, and increased with age to reach 12.4% and 28.2%, respectively, in patients older than 85 years. In multivariate logistic regression analysis, age was an independent risk factor for in-hospital death (odds ratio, 1.04; 95% confidence interval, 1.03-1.04, per year; P < .001). Gastrointestinal surgery was independently associated with a higher risk of in-hospital mortality in patients older than 50 years, whereas neurosurgery was associated with a higher risk of in-hospital death only in patients older than 65 years., Conclusions: Mortality rates increase with age, with an exponential increase in patients older than 65 years. Age is an independent risk factor for in-hospital death, irrespective of the type of surgical intervention., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO)., Materials and Methods: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined., Results: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements., Conclusion: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.

The transcriptional responses of Pasteurella multocida to eight antibiotics with known mode of actions (MoAs) and one novel antibiotic compound with an unknown MoA were collected to create a compendium of transcriptional profiles for MoA studies. At minimal inhibitory concentration the three bactericidal compounds enrofloxacin, cefquinome and the novel compound had a minor impact on gene regulation with approximately 1% of the P. multocida genome affected, whilst the bacteriostatic compounds florfenicol, tilmicosin, rifampin, trimethoprim and brodimoprim regulated 20% of the genome. Novobiocin was special in that it regulated 40% of all P. multocida genes. Regulation of target genes was observed for novobiocin, rifampin, florfenicol and tilmicosin and signature genes were identified for most antibiotics. The transcriptional profile induced by the novel compound was unrelated to the compendium profiles suggesting a new MoA. The transcription of many P. multocida virulence factors, particularly genes involved in capsule synthesis and export, LPS synthesis, competence, adherence and iron transport were altered in the presence of antibiotics. Virulence gene transcription was mainly negatively affected, however the opposite effect was also observed in the case of rifampin where the up-regulation of the tad locus involved in tight adherence was seen. Novobiocin and trimethoprim caused a marked reduction in the transcription of capsule genes, which correlated with a concomitant reduction of the capsular layer on the surface of P. multocida. The broad negative impact on virulence gene transcription supports the notion that the therapeutic effect of some antibiotics could be a combination of growth and virulence inhibition.

We evaluated the effects of dihydroxyacetone (DHA) on Trypanosoma brucei bloodstream forms. DHA is considered an energy source for many different cell types. T. brucei takes up DHA readily due to the presence of aquaglyceroporins. However, the parasite is unable to use it as a carbon source because of the absence of DHA kinase (DHAK). We could not find a homolog of the relevant gene in the genomic database of T. brucei and have been unable to detect DHAK activity in cell lysates of the parasite, and the parasite died quickly if DHA was the sole energy source in the medium. In addition, during trypanosome cultivation, DHA induced growth inhibition with a 50% inhibitory concentration of about 1 mM, a concentration that is completely innocuous to mammals. DHA caused cell cycle arrest in the G(2)/M phase of up to 70% at a concentration of 2 mM. Also, DHA-treated parasites showed profound ultrastructural alterations, including an increase of vesicular structures within the cytosol and the presence of multivesicular bodies, myelin-like structures, and autophagy-like vacuoles, as well as a marked disorder of the characteristic mitochondrion structure. Based on the toxicity of DHA for trypanosomes compared with mammals, we consider DHA a starting point for a rational design of new trypanocidal drugs.

Dihydroxyacetone (DHA) was examined to explore its trypanocidal activity. The compound is easily taken up by trypanosomes via its aquaglyceroporins but is not converted to a glycolytic intermediate due to the lack of a respective kinase. Investigating the DHA-induced cell death it became evident that parasites die by autophagy rather than by necrosis or apoptosis. Since autophagy is not well studied in African trypanosomes our work offers a way to investigate the importance of autophagy for trypanosomes not only for stress coping but also for organelle reconstruction during differentiation.

Recently, we reported the induction of a programmed cell death (PCD) in bloodstream forms of Trypanosoma brucei by prostaglandin D(2) (PGD(2)). As this prostanoid is readily metabolized in the presence of albumin, we were prompted to investigate if PGD(2) metabolites rather than PGD(2) itself are responsible for the observed PCD. In fact, J series metabolites, especially PGJ(2) and Delta(12)PGJ(2), were able to induce PCD more efficiently than PGD(2). However, the stable PGD(2) analog 17phenyl-trinor-PGD(2) led to the same phenotype as the natural PGD(2), indicating that the latter induces PCD as well. Interestingly, the intracellular reactive oxygen species (ROS) level increased significantly under J series metabolites treatment and, incubation with N-acetyl-L-cysteine or glutathione reduced ROS production and cell death significantly. We conclude that PGJ(2) and Delta(12)PGJ(2) formation within the serum represents a mechanism to amplify PGD(2)-induced PCD in trypanosomes via ROS production.

Objective: To determine the diagnoses and outcomes of geriatric patients with abdominal pain, and to identify variables associated with adverse outcomes., Methods: Geriatric emergency patients (aged 65 years and older) with a complaint of abdominal pain were participants in this longitudinal case series. Eligible patients were followed by telephone contact and chart review, to determine outcomes and final diagnoses., Results: Of 380 eligible patients, follow-up information was available for 375 (97%), for the two months following the ED visit. Final diagnoses included infection (19.2%), mechanical-obstructive disorders (15.7%), ulcers/hypersecretory states (7.7%), urinary tract disease (7.7%), malignancy (7.2%), and others. Although 5.3% of the patients died (related to presenting condition), most (61.3%) patients ultimately recovered. Surgical intervention was required for 22.1% of the patients. Variables associated with adverse outcomes (death, and need for surgical intervention) included hypotension, abnormalities on abdominal radiography, leukocytosis, abnormal bowel sounds, and advanced age. Most physical examination findings were not helpful in identifying patients with adverse outcomes. This study demonstrated a higher incidence of malignancy (7.2%) and a lower incidence of disease necessitating surgical intervention (22.1%) than previously reported., Conclusions: The majority of geriatric emergency patients with abdominal pain have significant disease necessitating hospital admission. Morbidity and mortality among these patients are high, and specific variables are strongly associated with death and the need for surgical intervention. Absence of these variables does not preclude significant disease. Physical examination findings cannot reliably predict or exclude significant disease. These patients should be strongly considered for hospital admission, particularly when fever, hypotension, leukocytosis, or abnormal bowel sounds are present.

A 33-year-old white man injected approximately 4 cc of charcoal lighter fluid (99.4% naptha/0.6% inert ingredients) subcutaneously into his left antecubital fossa. The injection resulted in the toxic necrosis of his volar forearm skin extending proximally to mid-humerus and distally to the metacarpophalangeal joints of the left hand dorsally over a 6-day period. The patient ultimately required extensive surgical debridement, secondary operative closure, and approximately 150 cm2 of split-thickness skin grafting. This case demonstrates the potential for widespread, delayed toxic necrosis of the skin resulting from subcutaneous injection of naptha. This patient's case appears to represent the most severe and widespread case of toxic necrosis of the skin resulting from the subcutaneous injection of hydrocarbons reported in the literature. This case also demonstrates extensive toxic thrombophlebitis not reported in prior cases involving subcutaneous injection of hydrocarbons.

There is evidence suggesting reciprocal trophic interactions between photoreceptors and the retinal pigmented epithelium (RPE), but the factors involved have not been identified. In this study, we investigated the hypothesis that one or more known neurotrophic factors act upon the RPE. Cultured human and freshly isolated bovine RPE cells demonstrated saturable specific binding for [125I]labeled BDNF, NT-4/5 and NT-3 with little specific binding for CNTF and none for NGF. Cross-competition experiments showed that BDNF is the preferred ligand and cross-linking of [125I]BDNF resulted in a doublet at 160 kd that was increased in RPE cells incubated in all-trans retinoic acid. There was basal phosphorylation of a 145 kd protein recognized by an anti-trk antibody that was increased in RPE cells pulsed with BDNF. RT-PCR with primers spanning the transmembrane domain demonstrated that RPE cells express trkB mRNA lacking a region homologous to exon 9 of chicken trkB, a splice variant that has been demonstrated to preferentially interact with BDNF. Northern blots demonstrated that cultured RPE cells also express mRNA for BDNF. BDNF did not stimulate proliferation or increase survival of RPE cells in serum-free medium, but promoted a differentiated morphology and increased the expression of cellular retinaldehyde binding protein, a marker of the differentiated state in RPE cells. An RPE cell line that spontaneously shows differentiated features showed a high level of BDNF mRNA. These data demonstrate that RPE cells express a short splice variant of trkB whose activation correlates with expression of differentiated characteristics and the cells themselves are capable of producing a ligand for the receptors. Signaling through trkB could play a role in differentiation of RPE cells during development and maintenance of the differentiated state in adult RPE., (Copyright 1998 Elsevier Science B.V.)

Aims/background: Epiretinal membranes (ERMs) arise from a variety of causes or, in some cases, for unknown reasons. Once established, ERMs tend to progress, becoming more extensive and exerting increasing traction along the inner surface of the retina. One possible cause for their progression is the production of growth factors by cells within ERMs that may provide autocrine or paracrine stimulation. Platelet derived growth factor (PDGF) and its receptors have been localised to cells of ERMs and may play such a role. In this study, comparative data were sought for several other growth factors that have been implicated in ERM formation., Methods: Immunohistochemical staining of ERMs was done for PDGF-A, PDGF-B, basic fibroblast growth factor (bFGF), three isoforms of transforming growth factor beta (TGF-beta), and vascular endothelial growth factor (VEGF) and its receptors, flt-1 and flk-1/KDR. Expression of flt-1 and flk-1/KDR was examined in cultured retinal pigmented epithelial (RPE) cells and retinal glia from postmortem eyes by immunohistochemistry and by reverse transcription coupled to polymerase chain reaction (RT-PCR)., Results: Staining was most intense and most frequently observed for VEGF and PDGF-A, both in vascular and avascular ERMs. The majority of cells stained for VEGF in nine of 11 (81.8%) diabetic ERMs and in 14 of 24 (58.3%) proliferative vitreoretinopathy ERMs. The receptors for VEGF, flt-1, and flk-1/KDR were also identified on cells in ERMs and on cultured RPE cells. By RT-PCR, mRNA for flt-1 was identified in RPE cells and retinal glia, and mRNA for flk-1/KDR was identified in RPE cells., Conclusions: These data show that VEGF and its receptors are localised to both vascular and avascular ERMs and suggest that VEGF, like PDGF-A, may be an autocrine and paracrine stimulator that may contribute to progression of vascular and avascular ERMs.

Objective: To determine current practice and attitudes among emergency physicians (EPs) regarding the initiation and termination of CPR., Methods: An anonymous survey was mailed to randomly selected EPs. Main outcome measures included respondents' answers to questions regarding outcome of resuscitation, and current practice regarding initiation, continuation, and termination of resuscitation for victims of cardiopulmonary arrest., Results: The 1,252 respondents were from all 50 states, a variety of practice settings, and varying board certification. Most (78%) respondents honor legal advance directives regarding resuscitation. Few (7%) follow unofficial documents, or verbal reports of advance directives (6%). Many (62%) make decisions regarding resuscitation because of fear of litigation or criticism. A majority (55%) have recently attempted numerous resuscitations despite expectations that such efforts would be futile. Most respondents indicated that ideally, legal concerns should not influence physician practice regarding resuscitation (78%), but that in the current environment, legal concerns do influence practice (94%)., Conclusions: Most EPs attempt to resuscitate patients in cardiopulmonary arrest, regardless of futility, except in cases where a legal advance directive is available. Many EPs' decisions regarding resuscitation are based on concerns of litigation and criticism, rather than their professional judgment of medical benefit or futility. Compliance with patients' wishes regarding resuscitation is low unless a legal advance directive is present. Possible solutions to these problems may include standardized guidelines for the initiation and termination of CPR, tort reform, and additional public education regarding resuscitation and advance directives.

Basic fibroblast growth factor (bFGF) and FGF receptors have been localized to photoreceptors and retinal pigmented epithelium (RPE), but the function of bFGF in adult retina and RPE is unknown. Exogenous bFGF has a neuroprotective effect in retina and brain and its expression is increased in some neurons in response to cytokines or stress. In this study, we investigated the effect of light, other types of stress, neurotrophic factors, and cytokines on bFGF levels in cultured human RPE. Some agents that protect photoreceptors from the damaging effects of constant light, including brainderived neurotrophic factor (BDNF), ciliary neurotrophic factor, and interleukin-1 beta, increase bFGF mRNA levels in RPE cells. Intense light and exposure to oxidizing agents also increase bFGF mRNA levels in RPE cells and cycloheximide blocks the increase. An increase in bFGF protein levels was demonstrated by ELISA in RPE cell supernatants after incubation with BDNF or exposure to intense light or oxidizing agents. These data indicate that bFGF is modulated in RPE cells by stress and by agents that provide protection from stress and support the hypothesis that bFGF functions as a survival factor in the outer retina.

Vascular endothelial growth factor (VEGF) is induced by hypoxia and it has been implicated in the development of iris and retinal neovascularization (NV) in ischemic retinopathies in which it has been suggested that Muller cells are responsible for increased VEGF production. VEGF, however, is also known to be a potent mediator of vascular permeability in other tissues and may perform this function in retina. Immunohistochemical staining for VEGF was performed on a variety of human and experimental ischemic and non-ischemic ocular disorders in which blood retinal barrier (BRB) breakdown is known to occur to determine if there is an upregulation of VEGF in these conditions. We found increased VEGF immunoreactivity in ganglion cells of rats with oxygen-induced ischemic retinopathy and in ganglion cells, the inner plexiform layer, and some cells in the inner nuclear layer of rats with experimental autoimmune uveoretinitis (EAU), in which there was no identifiable ischemia or NV. In rats with EAU, VEGF staining intensity increased from 8 to 11 days after immunization, coincident with BRB failure. These results were confirmed using two distinct anti-VEGF antibodies and by immunoblot and the immunohistochemical staining was eliminated by pre-incubating the antibodies with VEGF peptide. VEGF staining was also increased in the retina and iris of patients with ischemic retinopathies, such as diabetic retinopathy and retinal vascular occlusive disease, and in patients with disorders in which retinal ischemia does not play a major role, such as aphakic/ pseudophakic cystoid macular edema, retinoblastoma, ocular inflammatory disease or infection, and choroidal melanoma. VEGF was primarily localized within retinal neurons and retinal pigmented epithelial cells in these cases. In addition or in association with its role of inducing NV, VEGF may contribute to BRB breakdown in a variety of ocular disorders and blockage of VEGF signaling may help to reduce some types of macular edema.

Background: Retinal pigment epithelial (RPE) cells that enter the vitreous in pathologic conditions, such as retinal detachment, may proliferate and contribute to the formation of epiretinal membranes., Objective: To study whether hyalocytes, endogenous vitreous cells, play a role in modulating the proliferation of RPE cells., Methods: Cell proliferation was measured by tritiated thymidine incorporation in density-arrested human RPE cells after incubation with media that had been conditioned by cultured bovine hyalocytes. Preliminary characterization of inhibitory activity in hyalocyte-conditioned medium was performed, including blocking experiments with a neutralizing antibody to transforming growth factor-beta 2 (TGF-beta) and proliferation assays that used MV-1-Lu mink lung epithelial cells. Northern blots were done to asses hyalocyte expression of TGF-beta messenger RNA., Results: Hyalocyte-conditioned medium inhibited tritiated thymidine incorporation in RPE cells and MV-1-Lu mink lung epithelial cells in the presence or absence of serum or protease inhibitors. A portion of the inhibitory activity was neutralized by an antibody directed against TGF-beta. Northern blots of hyalocyte RNA demonstrated the presence of messenger RNA for TGF-beta 2. These data suggest that TGF-beta is responsible for a portion of the inhibitory activity secreted by hyalocytes. Additional inhibitory activity is attributable to one or more low-molecular-weight molecules distinct from TGF-beta., Conclusions: Hyalocyte-conditioned medium inhibits RPE cell proliferation in vitro through TGF-beta and at least one other molecule. Production of these factors by hyalocytes in vivo could provide a deterrent for epiretinal membrane formation that may be perturbed under pathologic conditions.

Study Objective: To determine the clinical significance of fever in geriatric emergency department patients., Design: Case series with follow-up., Setting: Urban, university-affiliated community hospital., Participants: Consecutive patients over the age of 65 years who presented to the ED during a 12-month period with an oral temperature of 100.0 degrees F (37.8 degrees C) or higher., Results: We considered the following features indicators of serious illness: positive blood culture(s), related death within 1 month of ED visit, need for surgery or other invasive procedure, hospitalization for 4 or more days, IV antibiotics for 3 or more days, and repeat ED visit within 72 hours for related condition. Four hundred eighty-nine patients were eligible for study. Of the 470 patients with complete follow-up data, 357 (76.0%) had indicators of serious illness. Clinical features found to be independently associated with serious illness included oral temperature of 103 degrees F (39.4 degrees C) or more, respiration rate of 30 or more, leukocytosis of 11.0 x 10(9)/L or more, presence of an infiltrate, and pulse of 120 or more. At least one indicator of serious illness was present in 63 of 128 patients (49.6%) with none of these independently predictive clinical features. The most common final diagnoses were pneumonia (24.0%), urinary-tract infection (21.7%), and sepsis (12.8%)., Conclusion: Fever among geriatric ED patients frequently marks the presence of serious illness. All such patients should be strongly considered for hospital admission, particularly when certain clinical features are present. The absence of abnormal findings does not reliably rule out the possibility of serious illness.

To define ranges of plasma specific gravity useful for identifying volume depletion in older adults, plasma specific gravity was measured in 170 young adults (mean age 28 years) and 100 retirees (mean age 81 years), and ranges of values likely to be associated with volume depletion were defined. Subsequently, measurements of plasma specific gravity were made in 68 older emergency room (ER) patients (mean age 74 years), a few of whom had obvious reasons for being hypovolaemic, e.g. dehydrating diarrhoea, and these results were compared to those for the control groups. Ranges for plasma specific gravity useful for identifying volume depletion were designated as possible hypovolaemia (1.0265-1.0279), probable hypovolaemia (1.0280-1.0294), and hypovolaemia (> or = 1.0295). Using these definitions, there were more older ER patients compared to both young and old control group subjects, respectively, with probable hypovolaemia (21% vs. 5% and 8%; p < 0.03) and hypovolaemia (16% vs. 0% and 0%; p < 0.03). This study establishes ranges for plasma specific gravity for young and old adults likely to be associated with hypovolaemia, and shows that based upon measurement of plasma specific gravity, older ER patients may often be hypovolemic even in the absence of obvious fluid-wasting illnesses. Future studies are needed to identify the risk factors for hypovolaemia in ER patients, and more vigorously substantiate the findings of this study.

This study evaluated the performance of seven rapid radiographic processing products. A conventional automatic processing solution was evaluated as a standard of comparison. The products were analyzed with respect to image quality and speed. The results indicate that rapid manual processing generally involves some compromise of image quality as well as slower speeds with an accompanying increase in patient radiation exposure. Accordingly, there seems to be little motivation for the use of rapid manual processing solutions unless there is a compelling rationale in terms of time or convenience.

The temperature of freshly voided urine has been shown to be a reliable predictor of body temperature. This relationship was confirmed for the measurement of BBT. A method was described for patients to obtain their BBT in a way that they may find more convenient than obtaining either oral or rectal temperature. The BBT graph patterns generated from the temperature of freshly voided urine closely paralleled those generated by oral temperature.

Rabbit anti-relaxin antisera, but not normal rabbit sera, causes a rapid decline of motility of washed human sperm. Preincubation of the antisera with relaxin eliminates this effect. This sperm immobilization effect can serve as a basis of a rapid screening test for anti-relaxin antisera and as a novel adjuvant to barrier contraceptive methods.

Relaxin and prostaglandin E2 (PGE2) are present in human semen and have been shown to affect sperm motility. The authors further examined the effects of porcine relaxin and PGE2 on the motility of human spermatozoa. A dose-response study revealed that PGE2 at a concentration of 25 micrograms/ml is most effective in improving the motility of washed human sperm. Relaxin (100 ng/ml), PGE2 (25 micrograms/ml), or the two combined have no effect on the motility of spermatozoa in fresh, normal semen, suggesting that the constituents of fresh semen are optimal for motility. Relaxin and PGE2 individually improve the motility of washed spermatozoa. However, relaxin, but not PGE2, improves the motility of sperm in semen incubated at 37 degrees C for 5 hours (aged). In contrast to the individual substances, a combination of relaxin + PGE2 has no effect on the motility of washed spermatozoa or aged spermatozoa, suggesting that these two substances antagonize each other's actions on sperm motility. The presence of both relaxin and PGE2 in seminal plasma with normal motility spermatozoa suggests that other factors in seminal plasma regulate the effects of these substances on sperm motility.

The interaction between tooth and amalgam during in vitro corrosion of dental amalgams has been studied in this investigation. Extracted teeth have been restored with five commercial amalgams, one of which was gamma 2 -free and the others contained the gamma 2-phase. The restored teeth were immersed in a 1% NaC1 solution for 9 months. Post corrosion restorations have been examined by optical microscopy, scanning electron microscopy, and X-ray microanalysis. The results are: (1) gamma 2-containing amalgam surfaces were covered with Ca-Sn-P-rich corrosion products of various morphology which occasionally contained relatively low concentrations of C1 and/or Zn; (2) the corrosion products on the gamma 2-free amalgam surface indicated relatively high concentrations of Hg in addition to Ca, p, Sn, Cu, and Zn. These results agree with the past observations that corrosion of amalgam restorations is not an isolated process. Rather it may involve reactions of the restoration and the surrounding oral environment including tooth and oral fluids in which interactions of Sn, Zn, Hg, Ca and P take place.

Caffeine (1, 3, 7-trimethyl-2, 6-dioxypurine), a cyclic nucleotide phosphodiesterase inhibitor, increased the motility of ejaculated human spermatozoa. Both the percent motility and the grade of forward progression were significantly increased (P smaller than 0.001) and maintained in the presence of 6 mM of caffeine for up to five hours at 37 C. Increases in percent motility greater than two-fold occurred among the groups having low initial motility. Increases in samples with a high initial percent motility (greater than 60%) were not as dramatic, but they were still significant. In addition, the grade of motility or forward progression was increased in all groups up to one full unit. The longevity of the spermatozoa, judged by activity, was also increased for up to five hours.

The release of monomer from methylmethacrylate bone cements was studied during immersion in an aqueous environment intended to simulate in vivo polymerization of the material. Monomer release from disk-shaped specimens into an aqueous environment was assayed by gas chromatography. The simulated intracorporal polymerization was carried out under a variety of conditions intended to encompass possible clinical variables. The majority of monomer release occurred within the first 15 min of immersion. Under conditions generally recommended for commercial cements the release into aqueous media was always less than 3% of the total monomer weight. Clinically feasible options of delaying the time from onset of mixing of the cement to insertion into the host resulted in only a 0.7 wt % difference in the amount of released monomer. Measurements for a variety of monomer/powder ratios demonstrated a minimum in the amount of released monomer at a ratio of about 0.4 ml/g. In terms of unit area covered, thin specimens released less monomer than thick specimens.

Relaxin has recently been identified in human seminal plasma (SP). This investigation was undertaken to determine the effect of relaxin on sperm motility. Washed ejaculated human sperm were incubated with or without porcine relaxin. In a series of 37 normal specimens (motility greater than or equal to 60%) relaxin attenuated the decline in grade of forward progression and percentage of motile sperm. Relaxin had a similar effect on a series of 47 subfertile specimens (motility 30% to 40%). Endogenous relaxin may play a role in delaying declines of motility and grade of forward progress in ejaculated sperm.

Human seminal plasma contains approximately 50 ng/ml of relaxin (specific activity = 1.3 ng/mg protein). During preliminary purification, semen plasma was delipidated, rehydrated, and loaded onto small octadecyl silica columns that were eluted with a TEAF/acetonitrile gradient system. Results were monitored by radioimmunoassay. The resultant partially purified human relaxin demonstrated biologic activity in the rat uterine segment bioassay. Nine liters of semen plasma was delipidated, rehydrated in TEAF, and subjected to high-performance liquid chromatography by a step gradient followed by a linear gradient. The active eluate was further purified by ion exchange chromatography. Pooled recovery fractions provided a total of 45.8 micrograms of relaxin. An aliquot flash evaporated and desalted by gel filtration chromatography provided 1.85 micrograms of relaxin in 25.2 mg protein, specific activity 73.4. This material is being used as immunogen in the production of antihuman relaxin antibodies by monoclonal technique. Our procedure represents the first and only successful partial purification of human relaxin to yield sufficient quantity and purity for antibody production.

Inhibition of sperm motility by anti-relaxin antiserum has been previously reported. This effect may be secondary to a nonspecific effect of immunoglobulins binding to sperm or to a specific inhibition of relaxin activity at the sperm surface. The current investigation demonstrates that an anti-insulin antiserum does not inhibit sperm motility in the same system in which an anti-relaxin antiserum results in inhibition. This supports the hypothesis that the anti-relaxin antiserum effect is specific.

Radiographic images of teeth and restorations were used to evaluate the radiopacity of 11 light-cured posterior composite resins. The radiopacity of these composite resins provided enough variation on radiographs so that clinicians distinguished the images of the restoration from adjacent tooth structure.

Polyzoospermia is a rare cause of male infertility. In our clinical practice, patients with exceedingly high sperm counts (ranging from 650 million/ml to 1.75 billion/ml) have invariably been found to have associated poor sperm motility and poor sperm migration in postcoital tests, although the sperm appear morphologically normal. Cases of two infertile couples are presented in which each husband had sperm counts greater than 1 billion/ml. Two methods are reported for the successful management of their infertility problems: (1) precoital dilutional douching and (2) in vitro seminal fluid dilution with 5% dextrose-Ringer's lactate solution and artificial insemination homologous. Each method resulted in improved sperm motility, postcoital tests, and pregnancy.

A new Silastic seminal fluid collection device has been tested and compared in vitro with glass jars, latex condoms, and the Milex polyethylene sheath. In a series of tests utilizing 50 different semen samples and observing the effects on motility over a period of 4 hours, the Silastic seminal fluid collection device demonstrated sperm survival slightly better than that with glass jars, superior to that with the polyethylene Milex sheath, and far greater survival (by several hours) than with the latex condom. The Silastic collection device was found to be more comfortable and more pleasurable to the patients than was the Milex sheath. The accuracy of seminal volume measurements was also found to be better in the Silastic collection device.