Mitochondrial DNA (mtDNA) A 3243G mutation associated with an annular perimacular retinal atrophy

BACKGROUND: A point mutation at the locus 3243 of the mitonchondrial DNA (mtDNA) is associated with either the MIDD syndrome (maternally inherited diabetes, deafness), the MELAS syndrome (myopathy, encephalitis, lactic acidosis, stroke) or cardiac, digestive, endocrine or exocrine dysfunctions. We report a peculiar maculopathy in two patients with an mtDNA 3243 mutation. HISTORY AND SIGNS: Case 1: A visually asymptomatic 40-year-old woman was examined for screening of diabetic retinopathy. Visual acuity was 10 / 10 in both eyes. Case 2: A 54-year-old woman with deafness and diabetes complained of visual loss. Visual acuity was 6 / 10 for the right eye and 0.5 / 10 for the left eye. Both patients exhibited a chorioretinal areolar atrophy. Case 1 was followed over 15 years and exhibited a slow progression of the maculopathy with moderate loss of visual acuity to 6 / 10 in both eyes, but marked handicap from the annular scotoma. THERAPY AND OUTCOME: None. CONCLUSION: Both patients presented a perimacular annular retinal atrophy. Patients harbouring mtDNA 3243 mutation should be examined for the presence of a maculopathy, even if they are asymptomatic. Conversely, the finding of such a geographic maculopathy should suggest the possibility of a point mutation at the locus 3243 of the mitochondrial DNA, especially in the presences of diabetes mellitus and/or deafness

Transcatheter aortic "valve-in-valve" for degenerated bioprostheses: Choosing the right TAVI valve.

Bioprosthetic aortic valve replacement is the treatment of choice for patients over 65 years of age suffering from aortic valve disease, and for younger patients with contraindications to long-lasting anticoagulation. Despite several technical improvements to reduce the risk of structural valve degeneration (SVD), the risk of SVD still exists, in particular for hemodialysis patients and patients under 60 years of age at surgery. Redo open heart surgery is the treatment of choice in case of valve degeneration, but caries a higher surgical risk when elderly patients with comorbidities are concerned. In the last 5 years, transcatheter aortic "valve-in-valve" procedures represent a valid alternative to standard redo surgery in selected patients. Valve-in-valve procedures represent a less invasive approach in high-risk patients and the published results are very encouraging. Technical success rates of 100% have been reported, as have the absence of paravalvular leaks, acceptable trans-valvular gradients (depending on the size of the original bioprosthesis), and low complication rates. The current article focuses on choosing the correct transcutaneous valve to match the patient's existing bioprosthesis for valve-in-valve procedures.

Long-term cognitive profile and incidence of dementia after STN-DBS in Parkinson's disease

An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition has been suspected but long-term observations are lacking. The aim of this study was to evaluate the long-term cognitive profile and the incidence of dementia in a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive patients were prospectively assessed by the mean of a neuropsychological battery over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded. 24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000 per year). This group of patients cognitively continuously worsened over 3 years up to fulfilling dementia criteria (PDD). The rest of the cohort remained cognitively stable (PD) over the whole follow-up. Preoperative differences between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years), presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/- 4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one reported in medically treated patients. The PDD presented preoperative risk factors of developing dementia similar to those described in medically treated patients. These observations suggest dementia being secondary to the natural evolution of PD rather than a direct effect of STN-DBS.

Clinical Experience with Immune Monitoring for Cytomegalovirus in Solid-Organ Transplant Recipients.

Novel strategies are needed to further reduce the burden of cytomegalovirus (CMV) disease in solid-organ transplant (SOT) recipients. Measurement of the specific cell-mediated immunity against CMV can identify the actual risk for the development of CMV disease in a given patient. Thus, immune monitoring is an attractive strategy for individualizing the management of CMV after transplantation. A growing number of observational studies on immune monitoring for CMV have been published over recent years, although there is a lack of data coming from interventional trials. In high-risk patients, measurement of CMV-specific T-cell responses appropriately stratifies the risk of CMV disease after discontinuation of antiviral prophylaxis. Immune monitoring may also help to identify patients followed by the preemptive approach at low risk for progression to CMV disease. Pretransplant assessment of cell-mediated immunity in seropositive patients may predict the development of posttransplant CMV infection. Overall, these studies indicate that the use of cell-mediated immunity assays has the potential to improve the management of CMV disease in SOT recipients.

Electronic journals, scholarly communication and libraries

The recent surge in scientific electronic journals began when libraries began having access to the WWW in the mid-1990s. The shift from paper to digital has affected the traditional alignment and role of the primary "stakeholders" -mainly authors, publishers, universities and libraries. The author offers a brief review of the history of the scholarly journal followed by the evolution of e-journals in during the past two decades. The article then focuses on the implications that these have had on traditional library processes and services such as selection, acquisitions, cataloguing, storage, preservation and user services. In the conclusion the author speculates on the long term effect of Web-based publishing on the format of the traditional scholarly journal as it has existed for over 300 years.

Lessons From the Swiss Medical Board Recommendation Against Mammography Screening Programs

When the US Preventive Services Task Force (USPSTF) in 2009 recommended against universal breast cancer screening with mammography in women aged 40 to 49 years, some scientists, radiologists, politicians, and patients strongly objected. The controversy has been called the "mammography wars." The latest chapter in these wars comes from the Swiss Medical Board, which is mandated by the Conference of Health Ministers of the Swiss Cantons, the Swiss Medical Association, and the Swiss Academy of Medical Sciences to conduct health technology assessments. In a February 2014 report, the Swiss Medical Board stated that new systematic mammography screening programs should not be introduced, irrespective of the age of the women, and that existing programs should be discontinued. The board's main argument was that the absolute reduction in breast cancer mortality was low and that the adverse consequences of the screening were substantial. The absolute risk reduction in breast cancer mortality has been estimated by the board at 0.16% for women screened during 6.2 years and followed-up over 13 years, based on the results of a recent Cochrane Review. The adverse consequences include falsepositive test results, overdiagnosis and overtreatment of patients, and high costs, including the expense of follow-up testing and procedures.

Acute pulmonary embolectomy.

Acute pulmonary embolism (PE) is a common condition frequently associated with a high mortality worldwide. It can be classified into non-massive, sub-massive and massive, based on the degree of haemodynamic compromise. Surgical pulmonary embolectomy, despite having been in existence for over 100 years, is generally regarded as an option of last resort, with expectedly high mortality rates. Recent advances in diagnosis and recognition of key qualitative predictors of mortality, such as right ventricular stress on echocardiography, have enabled the re-exploration of surgical pulmonary embolectomy for use in patients prior to the development of significant circulatory collapse, with promising results. We aim to review the literature and discuss the indications, perioperative workup and outcomes of surgical pulmonary embolectomy in the management of acute PE.

Low birthweight, preterm, and small for gestational age babies in Scotland, 1981-1984.

The aim was to examine the effect of maternal age, gravidity, marital status, previous perinatal deaths, and parental social class on babies born low birthweight, preterm, and small for gestational age. DESIGN--The study used data on discharge summaries from all maternity hospitals in Scotland. SETTING--The study was based on all singleton deliveries in Scotland. PARTICIPANTS--The analysis involved information on 259,462 singleton babies born during the four years 1981-84 in Scotland. MEASUREMENTS AND MAIN RESULTS--Previous perinatal death was found to be the strongest predictor for both preterm and low birthweight. Single mothers were at particularly high risk of having a small for gestational age baby and those who were previously married of having a preterm baby. Women aged less than 20 years old, those over 34 years old, nulligravidae, and those of parity 3 or more were also at increased risk of adverse pregnancy outcome. Mothers and fathers in manual social classes and those who could not be assigned a social class on the basis of their occupation were at increased risk for all three adverse outcomes studied. The babies of parents who were in manual occupations were twice as likely as those of parents in non-manual occupations to be small for gestational age and almost twice as likely to be low birthweight. CONCLUSIONS--Mother's social class is a risk factor for adverse pregnancy outcome independent of maternal age, parity, and adverse reproductive history, and also independent of father's social class. Information on both parents' occupations should be collected in maternity discharge systems.

Spatial variability of soil chemical properties after coffee tree removal

Assessing the spatial variability of soil chemical properties has become an important aspect of soil management strategies with a view to higher crop yields with minimal environmental degradation. This study was carried out at the Centro Experimental of the Instituto Agronomico, in Campinas, São Paulo, Brazil. The aim was to characterize the spatial variability of chemical properties of a Rhodic Hapludox on a recently bulldozer-cleaned area after over 30 years of coffee cultivation. Soil samples were collected in a 20 x 20 m grid with 36 sampling points across a 1 ha area in the layers 0.0-0.2 and 0.2-0.4 m to measure the following chemical properties: pH, organic matter, K+, P, Ca2+, Mg2+, potential acidity, NH4-N, and NO3-N. Descriptive statistics were applied to assess the central tendency and dispersion moments. Geostatistical methods were applied to evaluate and to model the spatial variability of variables by calculating semivariograms and kriging interpolation. Spatial dependence patterns defined by spherical model adjusted semivariograms were made for all cited soil properties. Moderate to strong degrees of spatial dependence were found between 31 and 60 m. It was still possible to map soil spatial variability properties in the layers 0-20 cm and 20-40 cm after plant removal with bulldozers.

Characterization of soil structure and porosity under long-term conventional tillage and no-tillage systems

Different management systems tend to modify soil structure and porosity over the years. The aim of this study was to study modifications in the morphostructure and porosity of dystroferric Red Latosol (Oxisol) under conventional tillage and no-tillage over a 31- year period. The study began with the description of soil profiles based on the cropping profile method, to identify the most compact structures, define sample collection points for physical and chemical analysis, and determine the water retention curve. A forest soil profile was described and used as reference. The results showed that, under conventional tillage, the microaggregate structure of the Oxisol was fragmented between 0 and 0.20 m, and compact (bulk density = 1.52 Mg m-3) in the sub-surface layer between 0.20 and 0.50 m. Under no-tillage, the structure became compacted (bulk density = 1.40 Mg m-3) between 0 and 0.60 m, but contained fissures and biopores. The volume of the class with a pore diameter of > 100 µm under no-tillage was limited, but practically non-existent in the conventional management system. On the other hand, the classes with a pore diameter of < 100 µm were not affected by the type of soil management system.

Nutrient supply by mass flow and diffusion to maize plants in response to soil aggregate size and water potential

Nutrients are basically transported to the roots by mass flow and diffusion. The aim of this study was to quantify the contribution of these two mechanisms to the acquisition of macronutrients (N, P, K, Ca, Mg, and S) and cationic micronutrients (Fe, Mn, Zn, and Cu) by maize plants as well as xylem exudate volume and composition in response to soil aggregate size and water availability. The experiment was conducted in a greenhouse with samples of an Oxisol, from under two management systems: a region of natural savanna-like vegetation (Cerradão, CER) and continuous maize under conventional management for over 30 years (CCM). The treatments were arranged in a factorial [2 x (1 + 2) x 2] design, with two management systems (CER and CCM), (1 + 2) soil sifted through a 4 mm sieve and two aggregate classes (< 0.5 mm and 0.5 - 4.0 mm) and two soil matric potentials (-40 and -10 kPa). These were evaluated in a randomized block design with four replications. The experiment was conducted for 70 days after sowing. The influence of soil aggregate size and water potential on the nutrient transport mechanisms was highest in soil samples with higher nutrient concentrations in solution, in the CER system; diffusion became more relevant when water availability was higher and in aggregates < 0.5 mm. The volume of xylem exudate collected from maize plants increased with the decrease in aggregate size and the increased availability of soil water in the CER system. The highest Ca and Mg concentrations in the xylem exudate of plants grown on samples from the CER system were related to the high concentrations of these nutrients in the soil solution of this management system.

FOXC2 and NFATc1 control formation and maturation of collecting lymphatic vessels

The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. These data provide novel insights into the molecular program of lymphatic vascular specification and suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

Pediatric tracheotomy: a 30-year experience.

BACKGROUND/PURPOSE: The aim of this study was to investigate changes of pediatric tracheotomy practice over time. METHODS: A retrospective analysis of all tracheotomies at the University Children's Hospital Zurich from January 1990 to December 2009 was performed. Data analyzed included the indication for tracheotomy, patient comorbidities, age, duration of cannulation, and complications. The second part of the study consisted of comparing our results with data from an earlier study done at the same institution by Simma et al. (Eur J Pediatr 1994;153:291-296) reviewing the patients with tracheotomies treated from 1979 to 1989. RESULTS: Between 1990 and 2009, 119 patients were included. The indication for tracheotomy was airway obstruction in 70% and prolonged ventilation in 30%. 70% of the patients were operated on before 1 year of age. Serious postoperative complications occurred in 25 patients (23%). There was one death related to tracheotomy. Successful decannulation was achieved in 60%, on average 28 months after tracheotomy. The decannulation rate in patients with airway obstruction was 74% compared to 52% for the patients in prolonged ventilation group; a statistically significant difference was observed (p < 0.05). The longitudinal analysis showed an increase of indications for prolonged ventilation and a trend toward decreased tracheotomy complications. CONCLUSION: Over 30 years, a shift in the indications of pediatric tracheotomy, with an increasing number of procedures performed for prolonged ventilation, was found. The tracheotomy-related mortality was under 1%. Tracheotomy remains a valid and safe option for pediatric patients. Level of evidence 2c.

Phosphorus accumulation and pollution potential in a hapludult fertilized with pig manure

Successive applications of pig litter to the soil surface can increase the phosphorus (P) content and alter its adsorption, promoting P transfer to surface or subsurface waters. The purpose of this study was to evaluate P accumulation and the pollution potential of a soil after application of pig litter. In March 2010, eight years after the installation of an experiment in Braço do Norte, Santa Catarina, SC, Brazil, on a Typic Hapludult, soil was sampled (layers 0-2.5, 2.5-5, 5-10, 10-15, 15-20 and 20-30 cm) after the following fertilization treatments: no pig litter fertilization, pig slurry application and pig manure application. In this period, 694 and 1,890 kg P2O5 ha-1 were applied in the treatments with pig slurry and pig manure, respectively. The P content was determined, based on Mehlich-1, anion exchange resin (AER), 0.01 mol L-1 CaCl2 and total P in the samples. The adsorption isotherm parameters were also determined by the Langmuir and Koski-Vähälä & Hartikainem models in the layers 0-2.5 and 20-30 cm. The application of 1,890 kg P2O5 ha-1 in the form of pig manure led to P accumulation, as evidenced by Mehlich-1, down to a depth of 15 cm, by AER and 0.01 mol L-1 CaCl2 down to 20 cm and by total P to 30 cm. After application of 1,890 kg P2O5 ha-1 in the form of pig manure, the values of maximum P adsorption capacity were lowest in the deepest layer (20-30 cm), indicating the occupation of part of the adsorption sites of the particles. The application of swine manure to the soil over eight years increased the P quantity in the soil solution of the surface layer, indicating environmental contamination risk for surface and subsurface waters.