Chronic Timeframe Research Articles

Characterizing practice-dependent motor learning after a stroke.

After stroke, patients must learn to use residual motor function correctly. Consistently, motor learning is crucial in stroke motor recovery. We assessed motor performance, practice-dependent on-line motor learning, and factors potentially affecting them in stroke patients. This is a cross-sectional observational study. Twenty-six patients with first brain stroke leading to upper limb motor deficit in the subacute or chronic timeframe were enrolled. They performed a Finger Tapping Task (FTT) with both the affected and unaffected limbs. We assessed how patients learn to perform motor tasks despite the motor deficit and the differences in performance between the unaffected and affected limbs. Furthermore, by randomizing the order, we evaluated the possible inter-limb transfer of motor learning (i.e. transfer of a motor skill learned in one limb to the opposite one). Moreover, sleep, attention, anxiety, and depression were assessed through specific tests and questionnaires. Improved FTT accuracy and completed sequences for the affected limb were observed, even if lower than for the unaffected one. Furthermore, when patients initially performed the FTT with the unaffected limb, they showed higher accuracy in subsequent task completion with the affected limb than subjects who started with the affected limb. Only anxiety and attentional abilities showed significant correlations with motor performance. This work provides relevant insights into motor learning in stroke. Practice-dependent on-line motor learning is preserved in stroke survivors, and an inter-limb transfer effect can be observed. Attentional abilities and anxiety can affect learning after stroke, even if the effect of other factors cannot be excluded.

The neurocognitive correlates of DTI indicators of white matter disorganization in pediatric moderate-to-severe traumatic brain injury.

Neuroimaging has expanded our understanding of pediatric brain disorders in which white matter organization and connectivity are crucial to functioning. Paralleling the known pathobiology of many neurodevelopmental disorders, traumatic brain injury (TBI) in childhood can alter trajectories of brain development. Specifically, diffusion tensor imaging (DTI) studies in TBI have demonstrated white matter (WM) abnormalities that suggest microstructural disruptions that may underlie atypical neurodevelopment. The neurocognitive correlates of these previous findings will be explored in this study. Indicators of WM organization were collected in 44 pediatric patients with moderate/severe TBI and 76 controls over two post-injury time points: T1 (8-20 weeks) and T2 (54-96 weeks). Our previous work identified two TBI subgroups based on information processing differences: one with slower interhemispheric transfer times (IHTT) of visual information than controls and another with comparable IHTT. We extend this prior work by evaluating neurocognitive trajectories associated with divergent WM structure post-injury in slow and normal IHTT TBI subgroups. At T1, both TBI subgroups performed significantly worse than controls on a norm-referenced working memory index (WMI), but only the Normal IHTT TBI subgroup significantly improved over the 12-month follow-up period (p = 0.014) to match controls (p = 0.119). In contrast, the Slow IHTT TBI subgroup did not show any recovery in working memory performance over time and performed more poorly than the control group (p < 0.001) at T2. Improvement in one of the two WMI subtests was associated with DTI indicators of WM disorganization in CC tracts to the precentral, postcentral, frontal, and parietal cortices. IHTT and WM mean diffusivity predicted 79% of the variance in cognitive recovery from T1 to T2 when also accounting for other known predictors of TBI recovery. In the year following TBI, some pediatric patients experienced persisting working memory disturbance while others exhibited recovery; stratification was based on an event-related potential marker. More or less improvement in neurocognition was also associated with the degree of WM disorganization. IHTT, measured post-acutely after TBI, and progression of WM disorganization over time predicted neurocognitive trajectories at the chronic timeframe - potentially representing a prognostic biomarker.

Diagnosis of methamphetamine-induced psychotic disorder: Findings of an expert consensus panel.

We define criteria for methamphetamine-induced psychotic disorder (MIPD) to aid in accurate and reliable diagnosis. An expert panel was recruited and engaged in an iterative consensus process. A literature search supported this work. The a priori level for consensus was considered ≥80% of voting panellists. The final expert panel included 22 physicians from different backgrounds and practice environments. The panel produced two consensus diagnoses: (1) acute MIPD and (2) persisting MIPD, which is further separated into subacute and chronic timeframes. Although certain characteristics differentiate methamphetamine-induced psychosis shortly after use, identification of persisting MIPD depends largely on a history of symptom onset. All respondents voted in the final round, and both criteria were fully endorsed by 91% (20/22) of respondents. Panellists further recommended next steps in validation and research on this topic. These diagnostic criteria aid clinicians in differentiating methamphetamine-induced psychotic symptoms from psychosis because of other psychiatric disorders and can guide future studies. Future research might examine these criteria's prognostic significance, interrater reliability and acceptability including among persons in recovery. This work is a necessary and vital step in advancing the science of methamphetamine addiction treatment.

Boldine Alters Serum Lipidomic Signatures after Acute Spinal Cord Transection in Male Mice.

Traumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction in the acute and chronic time frames after the injury. Chronic SCI has well-described secondary medical consequences while acute SCI has unique metabolic challenges as a result of physical trauma, in-patient recovery and other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe the circulating lipidomic and metabolomic signatures using blood serum from mice 7 d after a complete SCI. Additionally, we probed whether the aporphine alkaloid, boldine, was able to prevent SCI-induced changes observed using these 'omics platforms'. We found that SCI resulted in large-scale changes to the circulating lipidome but minimal changes in the metabolome, with boldine able to reverse or attenuate SCI-induced changes in the abundance of 50 lipids. Multiomic integration using xMWAS demonstrated unique network structures and community memberships across the groups.

Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.

Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats. MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization. PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (P=0.007). PF4618433 improved stroke volume (P=0.031) and cardiac output (P=0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (P=0.002) and fractional shortening (P=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (P=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI. Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.

Integrated multi-biomarker responses in Mozambique tilapia, Oreochromis mossambicus under acute and chronic Diazinon® exposures

ABSTRACT The pesticide ecosystem impacts are very diverse, and depending on their persistence could exert their intrinsic toxicity within an acute to a chronic timeframe. This study examined the toxic effects of Diazinon on haematological and biochemical endpoints in Oreochromis mossambicus after chronic exposure. After a prior range fining test, fishes were exposed to predetermined diazinon concentrations (T1-0.906 mg/L) and (T2-1.812 mg/L) and sampled after 28 days for toxicity endpoints. In Diazinon-exposed fish, haemoglobin content, Total Red Blood Cells, Total White Blood Cells, and MCH levels were substantially lower (p < 0.05) than in the control fish group. The total blood glucose concentrations in treated fish were substantially greater (p < 0.05) than in the control group, whereas serum protein concentrations were significantly lower (p < 0.05). Observation for most biomarkers revealed patterns of decreasing values with increasing toxicant concentration and exposure duration. The integrated indices (IBR and BRI) indexes were used to provide visual and understandable depictions of toxicity effects and emphasised the relativity of biomarkers in terms of sensitivity and magnitude or severity of responses under graded toxicant exposures. In acute and chronic diazinon exposure circumstances, the analysed metrics show significant impairment to Oreochromis mossambicus.

The meningeal transcriptional response to traumatic brain injury and aging.

Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.

Modeling acute and chronic vascular responses to a major arterial occlusion.

To incorporate chronic vascular adaptations into a mathematical model of the rat hindlimb to simulate flow restoration following total occlusion of the femoral artery. A vascular wall mechanics model is used to simulate acute and chronic vascular adaptations in the collateral arteries and collateral-dependent arterioles of the rat hindlimb. On an acute timeframe, the vascular tone of collateral arteries and distal arterioles is determined by responses to pressure, shear stress, and metabolic demand. On a chronic timeframe, sustained dilation of arteries and arterioles induces outward vessel remodeling represented by increased passive vessel diameter (arteriogenesis), and low venous oxygen saturation levels induce the growth of new capillaries represented by increased capillary number (angiogenesis). The model predicts that flow compensation to an occlusion is enhanced primarily by arteriogenesis of the collateral arteries on a chronic time frame. Blood flow autoregulation is predicted to be disrupted and to occur for higher pressure values following femoral arterial occlusion. Structural adaptation of the vasculature allows for increased blood flow to the collateral-dependent region after occlusion. Although flow is still below pre-occlusion levels, model predictions indicate that interventions which enhance collateral arteriogenesis would have the greatest potential for restoring flow.

Seizures and status epilepticus may be risk factor for cardiac arrhythmia or cardiac arrest across multiple time frames

ObjectiveTo determine if Emergency Department (ED) or inpatient encounters for epilepsy or status epilepticus are associated with increased odds of cardiac arrhythmia or cardiac arrest over successively longer time frames. MethodsThe State Inpatient and ED Databases (from New York, Florida, and California) are statewide datasets containing data on 97% of hospitalizations and ED encounters from these states. In this retrospective, case-crossover study, we used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index cardiac arrhythmia encounters. Exposures were inpatient or ED encounters for epilepsy or status epilepticus. The case-crossover analysis tested whether an epilepsy or status epilepticus encounter within various case periods (1, 3, 7, 30, 60, 90, and 180 days prior to index encounter) was associated with subsequent ED or inpatient encounter for cardiac arrhythmia, as compared to control periods of equal length one year prior. ResultsThe odds ratio (OR) for cardiac arrhythmia after an epilepsy encounter was significant at all time intervals (OR range 2.37–3.36), and highest at 1 day after epilepsy encounter (OR 3.63, 95% confidence interval [CI] 1.66–7.93, p = 0.0013). The OR after status epilepticus was significant at 7- to 180-day intervals (OR range 2.25–2.74), and highest at 60 days (OR 2.74, CI 2.09–3.61, p < 0.0001). SignificanceEpilepsy and status epilepticus events are associated with increased odds of subsequent cardiac arrhythmia or cardiac arrest over multiple chronic timeframes. Increased cardiac surveillance may be warranted to minimize morbidity and mortality in patients with epilepsy.

Perinatal Stroke: A Practical Approach to Diagnosis and Management.

Perinatal stroke is a focal vascular brain injury that occurs from the fetal period to 28 days of postnatal age. With an overall incidence of up to 1 in 1,000 live births, the most focused lifetime risk for stroke occurs near birth. Perinatal stroke can be classified by the timing of diagnosis, vessel involvement, and type of injury. Timing of diagnosis may be in the acute neonatal period or retrospectively after a period of normal development, followed by abnormal neurologic findings, with the injury presumed to have occurred around the time of birth. Strokes may be arterial or venous, ischemic, and/or hemorrhagic. Within these classifications, 6 perinatal stroke diseases are recognizable, based on clinical and radiographic features. Morbidity is high in perinatal stroke, because it accounts for most cases of hemiparetic cerebral palsy, with disability lasting a lifetime. Additional complications include disorders of sensation and vision, language delays, cognitive and learning deficits, epilepsy, and mental health consequences that affect the entire family. Advances in neonatal neurocritical care may afford opportunity to minimize brain injury and improve outcomes. In the chronic timeframe, progress made in neuroimaging and brain mapping is revealing the developmental plasticity that occurs, informing new avenues for neurorehabilitation. This review will summarize the diagnosis and management of each perinatal stroke disease, highlighting their similarities and distinctions and emphasizing a patient- and family-centered approach to management.

Psychological Factors Are Associated with Pain at All Time Frames After Breast Cancer Surgery: A Systematic Review with Meta-Analyses.

This systematic review aimed to 1) assess associations between psychological factors and pain after breast cancer (BC) treatment and 2) determine which preoperative psychological factors predicted pain in the acute, subacute, and chronic time frames after BC surgery. A systematic review with meta-analysis. Women with early-stage BC. The Medline, EMBASE, CINAHL, and Web of Science databases were searched between 1990 and January 2019. Studies that evaluated psychological factors and pain after surgery for early-stage BC were included. Associations between psychological factors and pain, from early after surgery to >12 months after surgery, were extracted. Effect size correlations (r equivalents) were calculated and pooled by using random-effects meta-analysis models. Of 4,137 studies, 47 were included (n = 15,987 participants; 26 studies ≤12 months after surgery and 22 studies >12 months after surgery). The majority of the studies had low to moderate risk of bias. Higher preoperative anxiety and depression were weak but significant predictors of pain at all time points up to 12 months (r equivalent: 0.15-0.22). Higher preoperative pain catastrophizing and distress were also weak but significant predictors of pain during the acute (0-7 days) and chronic (3-12 months) periods (r equivalent: 0.10-0.20). For the period >12 months after surgery, weak but significant cross-sectional associations with pain were identified for anxiety, depression, pain catastrophizing, and distress (r equivalents: 0.15, 0.17, 0.25, 0.14, respectively). Significant pooled effect size correlations between psychological factors and pain were identified across all time frames. Though weak, these associations should encourage assessment of key psychological factors during preoperative screening and pain assessments at all postoperative time frames.

Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators.

Common data elements collected among universities for sport-related concussion studies

BackgroundUniversities are increasingly implementing programs to effectively respond to and manage sport-related concussions (SRCs). One such effort is to develop common data elements (CDEs) and standardize data collection methods. The objectives of this study were to describe CDEs currently collected by Big Ten and Ivy League universities for SRC studies, and to compare the data collected with the core CDEs recommended by the National Institute of Neurological Disorders and Stroke (NINDS).MethodsWe conducted an anonymous cross-sectional online survey among medical staff at the 14 Big Ten and 8 Ivy League universities (one per university) between September and October 2015. The survey instrument, including 9 questions corresponding to the concussion data collected before, during, and after a concussion, was developed and pilot-tested before field use. We analyzed patterns of the concussion CDEs being collected, including when, what, and how the data were collected and stored, and compared them with the NINDS' recommended core CDEs.ResultsA total of 19 out of 22 universities were included, with 13 from Big Ten and 6 from Ivy-League universities. All 19 participating universities currently collected concussion data with athletes before, during, and after a concussion. Great similarities in data collection were observed at baseline and acutely post-concussion across participating universities. All 19 universities collected at least one of the ten recommended acute symptoms checklists, and 18 universities collected one of the four recommended core neuropsychological function cognitive measures. However, CDEs in the sub-acute and chronic timeframes were limited, with only 9 (47%) universities collecting post-concussion short to long term outcome data. While over 60% of universities collected and stored concussion data electronically, only 17% to 42% of data collected were readily available for research.ConclusionsSignificant inter-institutional similarities in acute concussion CDEs were found. Further efforts should focus on collecting sub-acute and chronic timeframe core CDEs and creating data access protocols to facilitate evidence-based concussion prevention and treatment for all collegiate athletes.

Identifying high risk loading conditions for in-season injury in elite Australian football players.

To examine different timeframes for calculating acute to chronic workload ratio (ACWR) and whether this variable is associated with intrinsic injury risk in elite Australian football players. Prospective cohort study. Internal (session rating of perceived exertion: sRPE) and external (GPS distance and sprint distance) workload and injury data were collected from 70 players from one AFL club over 4 seasons. Various acute (1-2 weeks) and chronic (3-8 weeks) timeframes were used to calculate ACWRs: these and chronic load categories were then analysed to determine the injury risk in the subsequent month. Poisson regression with robust errors within a generalised estimating equation were utilised to determine incidence rate ratios (IRR). Altering acute and/or chronic timeframes did not improve the ability to detect high injury risk conditions above the commonly used 1:4 week ACWR. Twenty-seven ACWR/chronic load combinations were found to be "high risk conditions" (IRR>1, p<0.05) for injury within 7 days. Most (93%) of these conditions occurred when chronic load was low or very low and ACWR was either low (<0.6) or high (>1.5). Once a high injury risk condition was entered, the elevated risk persisted for up to 28 days. Injury risk was greatest when chronic load was low and ACWR was either low or high. This heightened risk remained for up to 4 weeks. There was no improvement in the ability to identify high injury risk situations by altering acute or chronic time periods from 1:4 weeks.

Health Hazard Assessment for Native Americans Exposed to the Herbicide Fluridone via the Ingestion of Tules at Clear Lake, California, USA

ABSTRACT This study addresses concerns expressed by Native Americans regarding exposure via the consumption of aquatic vegetation to the herbicide fluridone (active ingredient) used by the California Department of Food and Agriculture (CDFA) Hydrilla Eradication Program in Clear Lake, California. In 2005, the Department monitored lakeshore vegetation, water, and sediment at four locations, before and after seasonal applications of fluridone. Subchronic and chronic exposures were evaluated, and hazard quotients calculated for a worst-case exposure (WCE) scenario. Ingestion rates and other exposure factors were developed in public meetings with tribal members. Environmental sampling found fluridone present at extremely low levels in tule vegetation, water, and sediment. Exposures were four times greater in subchronic timeframes than chronic timeframes; however, hazards were less due to the 25-fold larger reference dose (RfD) used for subchronic calculations: RfD(subchronic) = 2.0 mg/kg-day, RfD(chronic) = 0.08 mg/kg-day. Conservative, child, total daily ingestion (TDI) doses were calculated to be 8.3 × 10−5 mg/kg-day (subchronic) and 2.1 × 10−5 mg/kg-day (chronic). Hazard quotients (HQ) for subchronic and chronic exposures were on the order of 10−5 and 10−4, respectively, indicating that at current application regimes, there is little to no hazard of adverse effects from fluridone exposure via ingesting Clear Lake tules.

Adverse Effects Associated with the Use of Porcine Cross-Linked Collagen Implants in an Experimental Model of Incisional Hernia Repair

Porcine cross-linked collagen (PermaCol, PCL; TSL, Aldershot, United Kingdom) has been proposed as permanent biomaterial in incisional hernia repair. We evaluated the biocompatibility of PCL in an established animal model. In 10 Sprague Dawley rats, two hernias per animal were created in the abdominal wall left and right of the linea alba (1.5 cm in diameter), and the peritoneum was spared. The lesions were left untreated for 10 days, until incisional hernias developed. These defects were covered with non-perforated (out-of-the-box, n = 12) or perforated (modified; n = 8) PCL (2 x 2 cm). In a first step, 12 non-perforated implants were tested in a short-term observation period of 17 days. Eight of these non-perforated implants were fibrin sealed (0.3 mL, Tissucol; Baxter, Vienna, Austria), whereas four non-perforated implants were sutured with non-resorbable material. In a second step, perforations were added as modification to PCL to facilitate drainage of fluids, cell ingrowth, and transgression of fibrin sealant. All perforated implants were fibrin sealed and included in a long-term observation period of 3 months. The observation periods allowed the evaluation of the complete degradation of the fibrin sealant fixation after 2 weeks and of the implant integration in a chronic timeframe. Implant sites were analyzed macroscopically and histologically. All PCL samples elicited strong local inflammation with signs of foreign body reaction. Integration of perforated PCL appeared limited after 3 months. Three animals had to be euthanized prior to intended time points because of transcutaneous migration of implants. In an experimental model of incisional hernia repair, PCL does not integrate well in the abdominal wall and shows poor biocompatibility.

Transvaginal Radio Frequency Treatment of the Endopelvic Fascia: A Prospective Evaluation for the Treatment of Genuine Stress Urinary Incontinence

We evaluate the safety and efficacy of a new treatment modality for genuine stress urinary incontinence which was a transvaginal radio frequency applicator to deliver radio frequency energy to the endopelvic fascia. The purported mechanism of effect for this therapy is shrinkage of the collagenated tissue which composes the endopelvic fascia that supports the bladder neck and proximal urethra, thus stabilizing the proximal urethra and bladder neck. In prior animal trials and early pilot studies this therapy was shown to cause a reproducible thermal effect manifested by fascial shrinkage. Preliminary human trials indicated a therapeutic benefit of this therapy for women with genuine stress urinary incontinence. To our knowledge this is the first multicenter study of a transvaginal approach for radio frequency of the endopelvic fascia for treatment of genuine stress incontinence. Between June 1999 and June 2000, 120 consecutive women (mean age 49.9 years) at 10 sites underwent transvaginal radio frequency treatment in a prospective trial to evaluate the overall efficacy and safety profile of this therapy. All patients had preoperative urethral hypermobility (average cotton swab change 38 degrees). Detrusor instability was excluded by cystometry. In all procedures precisely controlled radio frequency energy was applied to the endopelvic fascia to heat and shrink the tissue. The patients were evaluated postoperatively at 1 week and at 1, 3, 6 and 12 months using objective and subjective measures. Primary end points consisted of physician assessment of continence, patient reported pad use and the number of patient reported episodes. Safety was determined for acute (immediate postoperative) and chronic time frames. Of the 120 patients 96 completed 1-year evaluation. Average operative time was less than 30 minutes, and all patients were treated as outpatients. Preoperatively 101 patients (84%) averaged 1 or more episodes of urinary incontinence per day. At 3, 6 and 12 months 57%, 66% and 59% of patients, respectively, averaged 1 or no daily episodes of urinary incontinence. At 12-month followup 79 of 109 patients (73%) reported being continent or improved. Preoperatively, 43% of patients reported using 1 or no pads daily. At 3, 6 and 12 months 69%, 70% and 72% of patients, respectively, required 1 or no pads daily. On urodynamic evaluation at 12-month followup 76.0% of the patients did not leak with a Valsalva maneuver. A total of 30 cases were classified as failures and 11 women were lost to followup. There were no intraoperative complications, 3 (4%) minor postoperative complications which resolved, and no device related complications. The transvaginal radio frequency applicator demonstrated good efficacy and excellent safety at 1-year followup. Ongoing analysis of the data has indicated opportunities for improvement of this new surgical technique that could result in higher efficacy rates without compromising safety. Further long-term evaluation is being conducted to assess chronic durability of the procedure.

Interacting Effects of pH Acclimation, pH, and Heavy Metals on Acute and Chronic Toxicity to Ceriodaphnia dubia (Cladocera)

Understanding the factors that modify the sensitivity of the zooplankton Ceriodaphnia dubia to toxicants is important to the interpretation of chronic toxicity data generated for granting industrial permits. Early reports of high sensitivity of Ceriodaphnia to brief pH excursions led toxicologists to question the use of C. dubia as a test organism. Acute and chronic toxicity of pH and heavy metals, pH acclimation to acidic and alkaline conditions and the role of pH in modifying heavy metal (copper and zinc) toxicities were investigated. Ceriodaphnia dubia acclimated near neutral pH had acute (48-hr) lethal concentrations of 4.6 and 10.3 SU. Reproduction and mortality were not impaired between pH 6.14-8.99 regardless of pH acclimation history. Reproduction was significantly impaired beyond these extremes. Acute exposures to both heavy metals at pH 6, 8 and 9 and in water hardness of 180, 110 and 100 mg/L showed C dubia was consistently most sensitive in low pH and low hardness waters. Reproduction and mortality were not so affected by pH in chronic exposures. Similar concentrations of metals at all pH levels resulted in equivalent reductions in offspring per female. The results strongly suggest that effluent guidelines for pH at 6-9 are sound, and that toxicantmore » activity in chronic time frames is directed primarily by concentration and water hardness, not by pH. 34 refs., 2 figs., 8 tabs.« less

Plasma urea and electrolytes: the clinical need

Over the past decade, science has greatly advanced our understanding of interdependent feedback mechanisms involving the heart, lung, and kidney. Organ injury is the consequence of maladaptive neurohormonal activation, oxidative stress, abnormal immune cell signaling, and a host of other mechanisms that precipitate adverse functional and structural changes. The presentation of interorgan crosstalk may include an acute, chronic, or acute on chronic timeframe. We review the current, state-of-the-art understanding of cardio-pulmonary-renal interactions and their related pathophysiology, perpetuating nature, and cycles of increased susceptibility and reciprocal progression. To this end, we present a multidisciplinary approach to frame the diverse spectrum of published observations on the topic. Assessment of organ functional reserve and use of biomarkers are valuable clinical strategies to screen and detect disease, assist in diagnosis, assess prognosis, and predict recovery or progression to chronic disease.

Long-term consequences of exposure to ozone: I. Lung collagen content

Lung collagen content of rats and monkeys ( Macaca fascicularis) exposed to ozone for 1 to 13 weeks and for 1 year, respectively, was quantified by measurement of 4-hydroxyproline in hydrolysates of whole lungs. In addition, ratios of type I to type III collagen in the lungs of the same monkeys were also evaluated by cyanogen bromide peptide mapping techniques. We observed elevated levels of collagen in lungs of both species of animals exposed to ozone. We conclude that elevations in collagen synthesis rates in lungs of rats and monkeys acutely exposed to high levels of ozone are reflected by corresponding increases in lung collagen content over subchronic and chronic time frames. Preliminary results on young rats also suggest that removal of rats from atmospheres containing ozone does not cause reversal of such increases in lung collagen content. To the contrary, recovery periods of up to 6 weeks seem to exacerbate the observed increases in lung collagen content.