Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions

This study was designed to examine whether anxious personality, i.e. trait anxiety, influences the autonomic nervous functions in humans without manipulation of experimental stressors. The degrees of state and trait anxiety, blood pressure, heart rate, pupillary light reflex (PLR), and body temperature were measured at the same hour on four different days in 14 healthy college students. A multiple regression analysis showed that trait anxiety predominantly influenced state anxiety and the PLR parameters. A single regression analysis showed that trait anxiety positively correlated to the initial pupillary diameter and the constricted diameter of PLR and negatively to the amplitude of PLR. It was concluded that trait anxiety predicts state anxiety and a smaller amplitude of PLR in humans at rest.     

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large,multi-centre study

Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.     

What’s important when caring for a loved one? Population-based preference weights for the Adult Social Care Outcomes Toolkit for informal carers (ASCOT-Carer) for Austria

Quality of Life Research - The Adult Social Care Outcomes Toolkit for informal carers (ASCOT-Carer) can be used to assess long-term care-related quality of life (LTC-QoL) of adult informal carers...     

Translation,cultural adaptation and construct validity of the German version of the Adult Social Care Outcomes Toolkit for informal Carers (German ASCOT-Carer)

Quality of Life Research - The Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer), developed in England, measures the effects of long-term care (LTC) services and carer support on informal...     

Influence of HRT on prognostic factors for breast cancer: a systematic review after the Women's Health Initiative trial

INTRODUCTION: Mortality due to breast cancer has been reported to be the same or even lower in HRT users than in non-users. This has been attributed to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease in HRT users was reported recently by the Women's Health Initiative (WHI) study. The objective of this study was to assess, using a systematic review of current literature, whether the data of the WHI study are in contradiction to observational data. METHODS: We selected 25 studies, for which we evaluated the methodology, the characteristics of the studied populations, confounding breast cancer risk factors and prognostic indicators. RESULTS: The WHI study, showing a worsening of some prognostic parameters, is in contradiction to most published observational studies. Most observational studies are retrospective, not well matched and did not consider most confounding factors. Their methodology and selection criteria varied considerably and the number of patients was often small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some of the observational studies. Other parameters (S phase, protein Neu, Bcl-2 gene, protein p53 and E-cadherin, cathepsin D) were not reported in the WHI trial. CONCLUSIONS: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed while using HRT are of better prognosis.     

Ablation of the cornea by using a low-energy excimer laser

We describe a new multipurpose method for corneal refractive surgery by using a focused excimer laser beam, which allows the application of a small, compact low-energy excimer laser. It is possible to ablate any area desired in the cornea without masking by scanning the focused beam. The ablation depths in freshly enucleated swine eyes were measured in relation to the number of laser pulses (at fixed fluence) and the pulse fluence at wavelengths = 248 nm and =193 nm. The irradiation conditions were investigated to obtain smooth ablation of the corneal material over an area of about 1 cm². The experiments show that smooth ablation is obtained when the ratio of the excimer laser beam spot diameter on the corneal surface and the displacement for one scanning step is given by a whole number. A simple model based on rectangular beam profiles is presented to exemplify this.     

Analysis of Drug/Plasma Protein Interactions by Means of Asymmetrical Flow Field-Flow Fractionation

Purpose. The applicability of Asymmetrical Flow Field-Flow Fractionation (Asymmetrical Flow FFF) as an alternative tool to examine the distribution of a lipophilic drug (N-Benzoyl-staurosporine) within human plasma protein fractions was investigated with respect to high separation speed and loss of material on surfaces due to adsorption. Methods. Field-Flow Fractionation is defined as a group of pseudo-chromatographic separation methods, where compounds are separated under the influence of an externally applied force based on differences in their physicochemical properties. This method was used to separate human plasma in its protein fractions. The drug distribution in the fractions was investigated by monitoring the fractionated eluate for drug content by fluorescence spectroscopy. Results. Human plasma was separated into human serum albumin (HSA), high density lipoprotein (HDL), ₂-macroglobulin and low density lipoprotein (LDL) fractions in less than ten minutes. Calibration of the system and identification of the individual fractions was performed using commercially available protein reference standards. The influence of membrane type and carrier solution composition on the absolute recovery of N-Benzoyl-staurosporine and fluorescein-isothio-cyanate-albumin (FITC-albumin) was found to be quite significant. Both factors were optimized during the course of the investigations. N-Benzoyl-staurosporine was found to be enriched in the fraction containing HSA. Conclusions. If experimental conditions are thoroughly selected and controlled to suppress drug and plasma protein adsorption at the separation membrane, Asymmetrical Flow FFF shows high recoveries and fast separation of human plasma proteins, and can be a reliable tool to characterize drug / plasma protein interactions. For analytical purposes it has the potential to rival established technologies like ultracentrifugation in terms of ease-of-use, precision, and separation time.     

Two Types of Health Care Systems and Their Influence on the Introduction of Perinatal Care: An Epidemiological Twin Model in Berlin from 1950 to 1990

Objectives: When perinatal medicine emerged as a new medical discipline in the 1960s, Berlin was as one of the world's leading centers. During that time, the city was separated into two parts, each fostering its own health care system. After the destruction of the Berlin Wall, it was possible to speak with the citizens of East Berlin and to access their database systems. This created the singular opportunity to objectively compare the development of perinatal care in both parts of Berlin. Methods: Rates of maternal, perinatal, and infant mortality as well as the rate of preterm deliveries were evaluated over time and between East and West Berlin. The timing of introduction of 20 specific perinatal interventions was evaluated across 18 hospitals with more than 500 deliveries (11 in West Berlin and 7 in East Berlin). Interviews were conducted with 100 gynecologists, 100 midwives, and 100 women who had recently delivered their first child from each side of the city regarding their opinions of the importance of these interventions for the quality of perinatal medicine and how they would distribute a budget to improve maternity care. Results: Maternal, perinatal, and infant mortality decreased in both parts of Berlin until 1990 (p<0.0001), without significant differences between East and West Berlin, though the preterm delivery rate was slightly lower in East Berlin compared with West Berlin (p<0.06). Some new clinical techniques and treatments—such as cardiotocography, ultrasound, tocolytic therapy, and peridural anesthesia—were introduced earlier in West Berlin. In contrast, certain public health measures—such as maternal transport, screening programs for diabetes, and support of breastfeeding—were introduced much earlier in East Berlin. There were significant differences between the beliefs of gynecologists, midwives, and mothers in East and West Berlin. In general, citizens of East Berlin were more enthusiastic about technological medical advances, whereas citizens of West Berlin were more supportive of public health and alternative methods. In addition, there were significant differences between female and male physicians in their beliefs about how to improve health care, regardless of whether they resided in East or West Berlin. Conclusions: The results of this study may serve as a basis for reflection on how different social circumstances and health care policies can influence the improvement of maternal and child health care.     

Echovirus 9 strain barty non-structural protein 2C has NTPase activity

Non-structural protein 2C is known to play a fundamental role in the replication of picornaviruses. Sequence analyses revealed that 2C belongs to a rapidly expanding group of proteins containing a consensus sequence for nucleotide binding (NTB). We report that echovirus 9 polypeptide 2C displays NTPase activity in vitro. In our experiments, several P2 genes were expressed in Escherichia coli as fusion proteins linked to glutathione S-transferase (GST) prior to purification close to homogeneity. In contrast to GST-2B, both GST-2C and GST-2BC showed ATPase as well as GTPase activity indicating that the site for NTB binding and splitting is located in 2C.