Far from urban areas: plastic uptake in fish populations of subtropical headwater streams.

This study investigated the occurrence of plastic particles in the digestive tracts of fish from headwater streams in a human-thinly populated region of the subtropical Sinos River basin in southern Brazil. In total, 258 individuals from 17 species were collected using electric fishing. Thirty-eight percent (38%) of the specimens contained plastic particles. All of them were fibers, with a maximum count of 43 per individual. Plastic fibers were the fourth most abundant food category. Results showed that the uptake of these plastic particles was proportional to the number of ingested food items. Fiber counts in the guts correlated with the uptake of Trichoptera, which are invertebrates using plastic particles to construct their protective cases. No significant difference in plastic uptake was detected between benthic and water column fish. No evidence of bioaccumulation of plastic particles was found in the intestines. The distance from urban areas was not related to the number of ingested plastic particles, concluding that plastics are ubiquitous and available to biota, even in remote locations. The most probable source of these particles is residences close to the streams which discharge the sewage of washing machines without any treatment.

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial.

Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6-3.79) for all evaluable patients and 8.4 months (95% CI: 0-18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08-9.31) and 9.4 months (95% CI: 4.82-13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24-15.35) versus 2.7 months (95% CI: 1.03-4.36; P = 0.002), and 9.8 months (95% CI: 3.23-16.37) versus 4.4 months (95% CI: 3.14-5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of < 5 cm. The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control. Biomodulatory therapy in advanced HCC may be a low toxic, efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC.

Adherence of Heart Transplant Recipients to Prescribed Medication and Recommended Lifestyle Habits.

INTRODUCTION: Nonadherence may cause severe health problems in heart transplant (HTx) recipients. RESEARCH QUESTIONS: The present study aimed to investigate adherence to prescribed medication and recommended lifestyle habits in post-HTx patients and to assess associations between adherence, quality of life (QOL), and psychological well-being. DESIGN: A questionnaire package was sent to all HTx patients from our clinic (n = 858) to answer questions anonymously on medication adherence, dietary recommendations (avoidance of raw animal products and ice cream), pet keeping (risk of zoonosis), anxiety and depression, QOL, and posttraumatic stress disorders. RESULTS: Of the contacted patients, 524 (61%) responded and 505 fulfilled the inclusion criteria (age ≥18 years and ability to understand German). Of the study participants, 72.4% reported taking their medications very correctly, 72.2% stated consuming alcohol less often than once a week, 58.3% performed physical exercise at least once a week, one-third reported eating nonrecommended foods, 22.1% stated pet keeping, and 4.3% reported smoking. Adherence to prescribed medication was positively associated with age ( P < .001) and mental QOL ( P = .015) but was unrelated to eating nonrecommended foods ( P > .05). Depressiveness correlated inversely with physical QOL ( r = -0.232; P < .01) and mental QOL ( r = -0.411; P < .01). Stress disorders and minor stressful events were reported by 7.8% and 46.6%, respectively. Stress disorders correlated inversely with mental QOL ( r = -0.282; P < .01) and physical QOL ( r = -0.422; P < .01). DISCUSSION: Many HTx patients adhere to prescribed medications and health advice. Nevertheless, nonadherence is a problem, especially in younger HTx patients, indicating the need for a nonadherence crisis intervention program for long-term HTx patients.

Synthesis, chemical behavior, structure elucidation and iNOS inhibitory activity of 1-substituted 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines.

Novel slim and shapely sp3-rich nitrogen containing heterocyclic ring systems are sought-after platforms for the expansion of molecular diversity in lead discovery. The present work describes the synthesis and characterization of a series of derivatives of hitherto unknown 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines 2. This approach was guided by a computational study, aiming at an optimization of previously reported [1,2,4]triazolo[1,2-a]pyridazine-1-thiones 1 known to inhibit the inducible nitric oxide synthase (iNOS). The title compounds are accessible by methylation of compounds 1 under mild conditions. The products were biologically evaluated by the same cell-based assay as applied for previous products of type 1 using RINm5F cells, which were stimulated to produce NO on the influence of proinflammatory cytokines IL-1ß and IFN-γ. Compounds 2 did not display the anticipated improved iNOS inhibitory activity in the selected assay but contribute to SAR in the field. In addition, an unprecedented formation of side-products 3 via oxidation has been investigated. The novel scaffolds represent attractive starting points for the construction of diverse molecules which differ considerably from known compounds based on flat and lipophilic aromatic scaffolds.

Aspects of fish conservation in the upper Patos Lagoon basin.

The Patos Lagoon basin is a large (201 626 km(2) ) and complex drainage system in southern Brazil. The lagoon is 250 km long and 60 km wide, covering an area of 10 360 km(2) . The exchange of water with the Atlantic Ocean occurs through a 0·8 km wide and 15 m deep inlet, fixed by 4 km long jetties, at the southernmost part of the Patos Lagoon. The estuarine area is restricted to its southern portion (10%), although the upper limit of saline waters migrates seasonally and year to year, influenced by the wind regime and river discharge. The known number of recorded limnetic fish species is 200, but this number is expected to increase. A higher endemism is observed in fish species occurring in upper tributaries. The basin suffers from the direct impact of almost 7 million inhabitants, concentrated in small to large cities, most with untreated domestic effluents. There are at least 16 non-native species recorded in natural habitats of the Patos Lagoon basin, about half of these being from other South American river basins. Concerning the fishery, although sport and commercial fisheries are widespread throughout the Patos Lagoon basin, the lagoon itself and the estuarine area are the main fishing areas. Landing statistics are not available on a regular basis or for the whole basin. The fishery in the northern Patos Lagoon captures 31 different species, nine of which are responsible for most of the commercial catches, but only three species are actually sustaining the artisanal fishery: the viola Loricariichthys anus: 455 kg per 10 000 m(2) gillnet per day, the mullet Mugil liza: 123 kg per 10 000 m(2) gillnet per day and the marine catfish Genidens barbus: 50 kg per 10 000 m(2) gillnet per day. A decline of the fish stocks can be attributed to inadequate fishery surveillance, which leads to overfishing and mortality of juveniles, or to decreasing water quality because of urban and industrial activities and power production. Global climatic changes also represent a major threat to the Patos system by changing the frequency of El Niño-La Niña-Southern Oscillation (ENSO).

Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation.

BACKGROUND: In solid organ transplantation, sensitive real-time biomarkers to assess the graft health are desirable to enable early intervention, for example, to avoid full-blown rejections. During rejection, high amounts of graft-derived cell-free DNA (GcfDNA) are shed into the blood stream. The quantification of this GcfDNA in allotransplantation is considered to fulfill this need, because it can be measured with great precision and at reasonable cost. PATIENTS AND METHODS: Patients from 2 ongoing studies in kidney (KTx) and heart (HTx) transplantation were monitored blinded on a scheduled basis, by means of a published universal droplet digital polymerase chain reaction to quantify the GcfDNA. RESULTS: Immediately after engraftment, GcfDNA reaches high values (>5% of total cfDNA), with a rapid decrease to values of <0.5% within 1 week. Living-related KTx recipients show lower initial values, reflecting the absence of preservation injury. Episodes of rejection in KTx and HTx are accompanied by a significant increase of GcfDNA (>5-fold) above values in patients without complications, occurring earlier than clinical or biochemical hints to rejection. One case of rejection, which became clinically suspect after 1 year and was proven with biopsy, showed a significant 10-fold increase 3 months earlier. CONCLUSIONS: The quantification of GcfDNA has the potential to detect rejection episodes at early stages, when other means of diagnosis are not effective. The method's noninvasiveness enables the monitoring recipients at intervals that are desired to catch rejections at early actionable stages to prevent full-blown rejection. This biomarker will be particularly valuable in regimens to minimize immunosuppression.

The effects of press and pulse disturbance by long and short-term pollution on the fish community in the Sinos River, RS, Brazil.

The fish fauna of the Sinos River has been subjected to severe pollution since the 1970´s. Continuous discharges of industrial and municipal sewage cause hypoxia and often even fish kills. The objectives of the present study are to assess long-term effects of pollution on the fish community over a time scale of approximately ten years and to investigate recuperation of the fish fauna after a massive fish kill in 2006. To assess the long-term impacts, seasonal sampling was conducted from September 2007 to March 2009 in four sites which were investigated in 1998/99 with the same methodology. The effects of the fish kill were investigated by comparing the present fauna in the affected river stretch with the fauna of an unaffected adjacent river stretch. The collective community properties richness and Shannon diversity changed during the ten year interval in a consistent pattern. Richness and Shannon diversity increased significantly in all sites, abundance values, however, did not. Analysis of species constancy and cluster analysis showed that the differences between the 1998/99 and 2007/09 studies were relatively small. The comparison of the reaches affected by the 2006 fish kills showed a rapid recovery within one year. Probably the Sinos fish fauna suffered the most severe impacts in the 70s of the last century, which could not be documented by this study. After an initial decline, the community displays relatively stable patterns with a tendency of recovery. After a severe fish kill, faunal recovery was rapid, probably favoured by the proximity of unpolluted source areas and physical habitat integrity of the Sinos River.

High prevalence of peripheral arterial disease in patients with obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) merits increasing attention as cardiovascular risk factor. Whereas carotid and coronary artery disease have been associated with OSA, occurrence of peripheral arterial disease (PAD) in OSA remains undefined. METHODS: We screened 100 patients with suspected OSA for PAD. After polysomnography, each patient underwent standardized angiological testing including ankle-brachial index (ABI), central pulse wave velocity, pulse wave index and duplex sonography. RESULTS: Among total study population, PAD prevalence accounted for 88%, of those 68% had asymptomatic plaques and 20% were symptomatic Fontaine ≥ IIa. In confirmed OSA, prevalence raised up to 98%. Except for smoking habits, distribution of established risk factors did not differ between OSA groups (patients without, mild, intermediate and severe OSA). Presence of plaque, Fontaine PAD stages and intermittent claudication exhibited significant gain with increasing AHI. A logistic regression model revealed that age (OR = 1.199, 95% CI [1.066; 1.348]) and the logarithmically transformed AHI (OR = 5.426, 95% CI [1.068; 27.567]) had the strongest influence on plaque presence. Central pulse wave velocity as marker of arterial stiffness was positively correlated with AHI. CONCLUSION: OSA is associated with a high prevalence of PAD. This implies substantial diseasés under-recognition and a presumable atherogenic role of OSA in the pathogenesis of PAD. However, vasoprotective impact of OSA treatment remains to be determined.

Delayed recovery from Cheyne-Stokes respiration in heart failure after successful cardiac transplantation: a case report.

BACKGROUND: Sleep-disordered breathing (SDB), especially central sleep apnea with Cheyne-Stokes respiration (CSA-CSR), is highly prevalent in patients with severe heart failure (HF). SDB, and predominantly CSR, may improve after recovery of cardiac function, but available data are limited and inconclusive, particularly in patients who have undergone heart transplantation (HTX). CASE REPORT: The case of a 59-year-old man with dilated cardiomyopathy and advanced chronic HF, plus CSA-CSR, is reported. The patient showed normalization of cardiac function after successful HTX, with delayed but gradual stepwise improvements in CSA-CSR over time. CONCLUSIONS: Although there is a close relationship between cardiac function and manifestations of SDB and CSA-CSR, stabilization of nocturnal respiration after improvement in cardiac function may be delayed rather than immediate.

Otolith atlas of fish of the Sinos River.

Otoliths are calcium carbonate structures located in the inner ear of fish; they are responsible for hearing and balance. The inner ear has three pairs of otoliths: the lapilli, the sagittae and the asterisci. The sagittae otoliths are the largest and their format is species-specific. Because of their composition, otoliths can resist to the digestive tract of ichthyophagous species, and they can be used as an important tool for identifying species of fish found in stomach contents. The purpose of this work is to provide a photographic guide of the sagittae otoliths of the main fish species from the Sinos River. This atlas consists of photographs of the sagittae otoliths of 36 species belonging to 15 families distributed in five orders.

[Pulmonary capillary blood volume and membrane components of pulmonary diffusion capacity in patients with chronic obstructive bronchitis (COPD)]. / Pulmonales kapilläres Blutvolumen und Membrankomponente der pulmonalen Diffusionskapazität bei Patienten mit chronisch obstruktiver Bronchitis (COPD).

Reduced pulmonary diffusion capacity is a hallmark of COPD, although the relative contribution of the subcomponents of pulmonary diffusion--membranous component (Dm) and capillary volume (Vc)--is unknown. These components can be measured with the method of NO single-breath diffusion (DLNO). In a prospective study, pulmonary function tests including spirometry, body plethysmography and single-breath measurements of diffusion capacity with CO and NO were performed in 183 patients with COPD of varying severity. There was a severity-dependent decrease in DLCO. Furthermore, Dm as well as Vc was positively correlated with the severity of COPD measured by FEV1. In all stages of COPD, reduction of Vc was more pronounced than constriction of Dm. In patients with most severe COPD, the preponderance of the reduction of Vc was significantly more marked than in milder stages.We conclude that Dm as well as Vc contributes to the reduction of DLCO in COPD, with a predominance of Vc at all stages of COPD. This confirms the idea that the loss of pulmonary capillaries in COPD is functionally relevant.

[Heart and combined heart-lung transplantation. Indications, chances and risks]. / Herz- und Herz-Lungen-Transplantation. Indikationen, Chancen, Risiken.

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.

Value of digital radiography in expiration in detection of pneumothorax.

PURPOSE: The purpose of this study was to find out whether pneumothorax detection and exclusion is superior in expiratory digital chest radiography. MATERIALS AND METHODS: 131 patients with pneumothorax with paired inspiratory and expiratory chest radiographs were analyzed regarding localization and size of pneumothorax. Sensitivity, specificity, negative (npv) and positive predictive value (ppv) as well as the positive (LR+) and negative likelihood ratio (LR-) were determined in a blinded randomized interobserver study with 116 patients. The evaluation was performed by three board-certified radiologists. RESULTS: In 131 patients, there were 139 pneumothoraces, 135 (97.1 %) were located apical, 88 (63.3 %) lateral and 33 (23.7 %) basal. Sensitivity was 99 % for inspiratory and 97 % for expiratory radiographs. The interobserver study yielded a mean sensitivity of 86.1 %/86.1 %, specificity of 97.3 %/93.4 %, npv of 88.7 %/88.5 % and ppv of 96.7 %/92.1 % for inspiration/expiration. For inspiratory radiographs the LR+/LR- were 40.2/0.14 and for expiration 13.9 and 0.15. McNemar-Test showed no significant difference for the detection of pneumothoraces in in-/exspiration. CONCLUSION: Inspiratory and expiratory digital radiographs are equally suitable for pneumothorax detection. Inspiratory radiographs are recommended as the initial examination of choice for pneumothorax detection, an additional expiratory radiograph is only recommended in doubtful cases. KEY POINTS: • Basal pneumothoraces during inspiration demonstrate a greater width than during expiration. • There is statistically no difference between inspiration/expiration for the diagnosis of pneumothorax. • An image taken during inspiration is recommended to confirm or rule out a pneumothorax.

Synthesis and structure elucidation of 2,3,5,6,7,8-hexahydro-1 H-[1,2,4]triazolo[1,2-a]pyridazine-1-thione, 3,3-disubstituted and 2-substituted derivatives and evaluation of their inhibitory activity against inducible nitric oxide synthase.

The 3-monosubstituted 2,3,5,6,7,8-hexahydro-1 H-[1,2,4]triazolo[1,2-a]pyridazine-1-thiones 3 (R1, R3 = H) were recently reported to possess inhibitory activity against inducible nitric oxide synthase in a cell based assay (Schulz et al. 2013). The 3,3-disubstituted 2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thiones 3 and 4 (R2,R3 ≠ H) were synthesized by cyclocondensation of the hexahydropyridazine-1-carbothioamides 1 with ketones. In order to access the 3,3-unsubstituted 2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thiones, the unsubstituted parent system of these compounds, several synthetic routes were studied. By these methods the desired heterocyclic system 2a as well as new a-anellated and N-substutited hexahydropyridazines were obtained. The biological evaluation of the title compounds confirmed the previously made finding that an aromatic moiety in position 3 of the substance is important for an inducible nitric oxide synthase (iNOS) inhibitory activity.

Clinical outcome in cardiac transplant recipients receiving tacrolimus retard.

Tacrolimus (TAC) retard is a new oral formulation of TAC that is given once instead of twice daily. We investigated the efficacy and safety of TAC retard in heart transplant recipients during a 36-month follow-up period. We included 11 patients receiving TAC retard (once-daily [OD] group) and 11 age- and sex-matched patients receiving TAC (twice-daily [TD] group). The primary endpoint was a composite of death, graft loss, and drug discontinuation (treatment failure). Secondary endpoints were biopsy-proven rejection, malignancy, infection, and safety parameters determined on the basis of laboratory evaluations. In the OD and TD groups, the primary endpoint was reached by 18.2% and 45.54% of patients, respectively (P = .277). In detail, 3-year survivals were 90.0% and 70.0% (P = .291) and freedom from drug discontinuation 90.9% and 77.9% (P = .533), respectively. Freedom from biopsy-proven rejection, malignancy, and infection were similar between the groups. Moreover, biochemical parameters of kidney and liver function, hematologic parameters, and C-reactive protein levels were similar. Despite a remarkably higher prescribed dose, blood trough levels of TAC were below the lower target value in several patients of the OD group at the end of the follow-up period, but in none of the patients in the TD group. In conclusion, this small 3-year follow-up study suggests efficacy and safety in patients receiving TAC retard similar to those in patients receiving TAC. Nevertheless, the required dose of TAC retard for achieving acceptable blood trough levels should be investigated in more detail.

Hemodynamic alterations in vertebrobasilar large artery disease assessed by arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease. MATERIALS AND METHODS: ASL was performed on a 3T MR imaging scanner in 41 participants. Twenty-one patients had a history of ischemic events in the VB circulation (14 men, 7 women, age 66 ± 11 years). Clinical data and CE-MRA were used to classify VB disease severity. Twenty age-matched adults were controls. Group and within-VB analyses were performed. Mean CBF and ATT values in the ROIs were adjusted by excluding voxels that did not produce a reliable ASL estimate. RESULTS: CBF was reduced (P < .003) in patients compared with controls, which was significant after excluding voxels with a poor fit. Differences in ATT between patients and controls were not significant after voxel correction. There was a strong correlation between CBF and ATT among patients. Finally, ATT was significantly correlated with VB disease severity (P = .026). CONCLUSIONS: Multiple inflow ASL distinguished patients with VB disease from age matched-controls. VB disease rating was associated with prolonged ATT downstream. ASL may have diagnostic potential among patients in whom risk of intervention is high.

Bosentan effects on hemodynamics and clinical outcome in heart failure patients with pulmonary hypertension awaiting cardiac transplantation.

BACKGROUND: In heart failure (HF) patients, pulmonary hypertension (PH) is associated with a poor prognosis. We assessed whether low dose treatment with the dual endothelin-1 receptor antagonist bosentan is associated with improved hemodynamics and clinical outcome in these patients. METHODS: We performed a retrospective data analysis in 82 end-stage heart failure patients on the waiting list for cardiac transplantation since January 2006. All patients had pulmonary arterial pressure >35 mmHg, pulmonary vascular resistance >240 dyn × s × cm-5, and/or a transpulmonary gradient (TPG) >15 mmHg. Fifty-four patients received a median dose of 125 mg bid bosentan (BOS group), and 28 patients received standard medical treatment (CON group). Data were assessed until June 2009. RESULTS: Hemodynamic parameters improved significantly in the BOS group but remained unchanged in the CON group. The percentage of patients who fell below the thresholds of PAP, PVR, and TPG for cardiac transplantation increased significantly by 20.3%, 34.5%, and 20.8%, respectively (p = 0.007-0.013) in the BOS group, but did not change significantly in the CON group. One-year survival on the waiting list was approximately 20% higher in the BOS group than in the CON group (p = 0.020). Bosentan treatment remained an independent predictor of reduced mortality risk on the waiting list after propensity score adjustment (relative risk = 0.107; 95% CI: 0.013-0.869; p = 0.036). CONCLUSION: Treatment with the endothelin-1 antagonist bosentan is associated with improvements in hemodynamics and clinical outcome in end-stage heart failure patients with PH. If these results can be confirmed by randomized controlled trials, bosentan may represent a treatment option in these patients.