Into the Blue: First in Man Data on Diving Physiology in Fontan Patients.

Swimming and diving are popular recreational activities. As congenital heart disease, especially patients with univentricular hearts after Fontan palliation are thought to have reduced physiologic capacities for compensation of submersion-associated physiologic demands, current guidelines put restraints on this group of patients. Although these restrictions on doctoral advice place a significant burden on affected patients, it is especially interesting that these guideline recommendations are merely based on physiologic assumptions, i.e., expert consensus. A recent study by Paech et al. presented the first in vivo data on the effects of immersion in Fontan patients, stating no major adverse events in their study group as well as comparable physiologic adaption as reported in the literature for healthy people. Yet, submersion was not reflected in this study, and the current study therefore aimed to conduct a first study for the evaluation of the effects of submersion and apnea diving in Fontan patients. A control group of healthy adults as well as patients recruited from the Heart Center Leipzig, Department of pediatric cardiology underwent a standardized diving protocol including a static as well as dynamic apnea phase. Physiologic data were recorded. This study presents the first structured data on diving physiology in Fontan patients compared to healthy probands. There were no adverse events. The physiologic response to diving seems to be comparable between healthy probands and Fontan patients. Although, healthy probands did reach a much better performance, the basic mechanisms of physiologic adaption seem comparable.

Daily iTBS worsens hand motor training--a combined TMS, fMRI and mirror training study.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is used to increase regional excitability to improve motor function in combination with training after neurological diseases or events such as stroke. We investigated whether a daily application of intermittent theta burst stimulation (iTBS; a short-duration rTMS that increases regional excitability) improves the training effect compared with sham stimulation in association with a four-day hand training program using a mirror (mirror training, MT). The right dorsal premotor cortex (dPMC right) was chosen as the target region for iTBS because this region has recently been emphasized as a node within a network related to MT. METHODS: Healthy subjects were randomized into the iTBS group or sham group (control group CG). In the iTBS group, iTBS was applied daily over dPMC right, which was functionally determined in an initial fMRI session prior to starting MT. MT involved 20 min of hand training daily in a mirror over four days. The hand tests, the intracortical excitability and fMRI were evaluated prior to and at the end of MT. RESULTS: The results of the hand training tests of the iTBS group were surprisingly significantly poorer compared with those from the CG group. Both groups showed a different course of excitability in both M1 and a different course of fMRI activation within the supplementary motor area and M1 left. CONCLUSION: We suggest the inter-regional functional balance was affected by daily iTBS over dPMC right. Maybe an inter-regional connectivity within a network is differentially balanced. An excitability increase within an inhibitory-balanced network would therefore disturb the underlying network.

Maintaining integrity of germline DNA: individuals age, species do not.

All life forms are under constant assault, resulting in an accumulation of damage within each individual, in both somatic and germline cells. The obvious causes are: (1) mutations from radiation, chemical reactions like peroxidation and errors in replicating genetic material; (2) injury due to environmental insults, such as chemical alteration of proteins by reactive oxygen species; (3) epigenetic errors, such as failure of appropriate maintenance methylation of cytosines of DNA; and (4) numerous other problems, including retroviral invasions, inflammation and unhealthy microbiomes. Collectively, these phenomena constitute aging and/or certain disease states. Nature has developed numerous mechanisms to counteract these problems, such as proofreading enzymes, ubiquitous antioxidants and apoptotic death of unfit cells. However, none of these is completely effective. Although individuals accumulate damage, species usually do not become increasingly damaged; however, this could be one of the mechanisms for eventual extinction or evolution to a different species, the apparent fate of essentially all species. Nevertheless, germline DNA appears to remain sufficiently pristine to maintain fairly stable phenotypes over many generations. How do species avoid accumulating damage when composed of individuals that do? One broad answer seems to be reproductive redundancy followed by elimination of defects through the death of gametes, embryos, fetuses, neonates and postpubertal individuals, with the culling pressure increasing as potential parents age. Another major force appears to be evolutionary pressure; individuals that best fit the environment out-reproduce those that fit less well. What is impressive is that older and older parents continue to have offspring that are nearly as pristine as those of younger parents, even though their germline cells have continued to age. Although the offspring of old parents are not as fit, on average, as those of young parents, differences are small and, in some species, compensated for by superior parenting with accumulated experience. To conclude, it appears that species do not age, even though they are composed of individuals whose somatic and germline cells have aged.

[Are German information materials on colorectal cancer screening understandable or do they fail? Rating of health information by users with different educational backgrounds]. / Sind Informationsmaterialien zur Darmkrebsfrüherkennung in Deutschland verständlich oder verfehlen sie ihre Wirkung? : Bewertung von Gesundheitsinformationen durch Nutzerinnen und Nutzer mit unterschiedlichem Bildungshintergrund.

Evidence-based patient information is an essential part of decision making in health issues. A qualitative study was conducted to examine whether consumers consider the health information on colorectal cancer screening in Germany helpful in supporting their decision making. In this study, eight texts from different German authors about colorectal cancer screening were evaluated with a criteria-based selection. The texts were tested for understandability, structure, design, and effect on readers. Thirteen semi-structured focus groups were formed including 59 higher-educated and 15 lower-educated testers, 46 % of them being male with a mean age of 62.9 years. The transcripts were analyzed by content-analytic assessment. The testers provided detailed comments on the content and design of the texts. They revealed inaccuracies and suggested improvements of the texts. The testers differed from each other in terms of the intensity of their participation in the discussions and comprehension of the material. The reception of the flyers and brochures varied according to the educational level of the testers. Lower-educated testers often skipped passages of texts about risks as well as passages containing numbers and graphics. The texts had different effects on the testers, regardless of the level of education. If adverse effects were presented, some testers became scared while others were reassured because they felt informed. Most of the testers appreciated a call for participation as a central message of the text. Sometimes, if there was no clear appeal to attend the screening, the testers even asked for it. The recently introduced political strategy of promoting an informed choice is applied to an unprepared population who was used to getting a clear yes-or-no recommendation. Thus, at first, the population has to learn how to make an informed choice. This topic must be addressed and taken into account in the process of developing health information. Since this is not always the case, we conclude that current materials are limited in their contribution toward the decision of attending CRC screening.

[Leaflets and websites on colorectal cancer screening and their quality assessment from experts' views]. / Printmedien- und Internetangebote mit Informationen zur Darmkrebsfrüherkennung und ihre kriteriengestützte Bewertung aus Expertensicht.

In Germany, individuals who have statutory health insurance have free access to colorectal cancer (CRC) screening tests, and can choose between a fecal occult blood test and a screening colonoscopy. Evidence-based health information may support informed choices regarding whether or not to undergo CRC screening. The aim of this study was to assess whether the available German information materials on CRC screening meet evidence-based health information standards. A systematic search was made for print media and websites on CRC screening addressed to German people with average CRC risk (search period for print media August 2010, for websites January-March 2012). The identified information was assessed with a newly developed comprehensive list of criteria. In all, 41 print media, including 28 flyers and 13 brochures, and 36 websites were identified and assessed. These materials reported more often the benefits than the risks of CRC screening, and quantified presentations of benefits and risks were less frequently given. Most of the materials called for participation and did not indicate the option to decide whether or not to attend CRC screening. This bias in favor of screening was increased by fear-provoking or downplayed wording. Most materials included false and misleading information. The requirements for evidence-based patient information were currently not met by most of the leaflets and websites in Germany. Feedback was given to the producers of the leaflets including a discussion of the findings. The results may be used to revise existing leaflets or to develop new health information on CRC screening.

[Secondary prophylaxis of stroke from a neurological perspective]. / Sekundärprophylaxe des Schlaganfalls aus neurologischer Perspektive.

Patients who have suffered ischemic stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke, myocardial infarction or vascular death. Early pathophysiological based diagnostics and resulting secondary prevention are critical for reduction of stroke risk. Optimization of lifestyle factors, treatment of hypertension, cholesterol reduction with statins and use of antiplatelet agents in non-cardiogenic or anticoagulation in cardiogenic ischemia as well as internal carotid revascularization, in cases of more than 50% diameter stenosis of the internal carotid artery, are proven strategies for reduction of ischemic stroke risk.

Optical illusion alters M1 excitability after mirror therapy: a TMS study.

The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training (P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1(left). IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the "contralesional" left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.

Applications and world-wide use of sexed semen in cattle.

Successful sorting of sperm based on presence of the X- or Y-chromosome was first reported in the early 1980's with the first live births reported in rabbits in 1988. Subsequent development of technological efficiencies resulted in commercialization of sex-sorted semen to cattle producers in 2003-2005. At product launch, low throughput dictated that reasonable prices to the producer could only be accomplished with extremely low sperm number dosages (2 × 106). Furthermore, conception rates were 70%-75% of those achieved by conventional unsorted product. Refinements in sorting equipment have enhanced the number of sperm that can be sorted from a semen sample and (or) aliquot of time, which translates into reduced production costs, while modifications to other aspects of sperm processing and freezing have facilitated maintenance of a conception potential more similar to that of conventional semen. More recently, strategic use of sex-sorted semen coupled with genomic technologies to identify superior females to satisfy replacement female needs has, by default, led to identification of a population of dairy cows from which replacements are not desired, leading to a tremendous increase in use of beef semen in dairy herds. Though exact numbers are unavailable, estimates indicate sex-sorted semen is rapidly approaching 30% of the total AI market share in North America. Though the primary application of sex-sorted semen is to accelerate genetic progress while enhancing biosecurity through in-house production of replacement animals, numerous other potential applications are evolving or are under consideration.

In vitro fertilization using non-sexed and sexed bovine sperm: sperm concentration, sorter pressure, and bull effects.

The objective of these experiments was to study bovine in vitro fertilization (IVF) conditions for blastocyst production using non-sexed sperm (Experiment 1) and sexed sperm (Experiment 2). For Experiment 1, in vitro-matured oocytes (N=707) were allocated to a 2 × 3 × 4 factorial design: time of co-incubation of gametes for fertilization (4 and 18 h), sperm dose (1, 0.33, and 0.11 × 10(6) frozen-thawed sperm/ml, and sperm source (four bulls). Pronuclear status was evaluated for a subset. Experiment 2 (N=2155 oocytes) was a 2 × 3 × 2 × 6 factorial design: sex of sperm (X and Y), sperm dose (1, 0.33, and 0.11 × 10(6) frozen-thawed sperm/ml), and sperm-sorting pressures (40 and 50 psi), replicated with sperm of six bulls. Presumptive zygotes were cultured 60 h in chemically defined medium-1 (CDM-1), and for 114 h in CDM-2. For Experiment 1, pronuclear formation, cleavage and blastocysts rates were greater for 1, and 0.33 × 10(6) than 0.11 × 10(6) sperm/ml (72 and 62 vs 42%; 89 and 81 vs 58%; and 21 and 17 vs 9%, respectively; all p<0.01); polyspermy was greater for 1, than 0.33 and 0.11 × 10(6) sperm concentrations (24 vs 2 and 0%; p<0.01). There were greater main effects (p<0.01) of pronuclear formation (69 vs 48%), polyspermy (13 vs 4%), and cleavage (63 vs 54%), at 18 than at 4 h of co-incubation of gametes (all p<0.01). For Experiment 2, cleavage and blastocyst rates were greater for 1 × 10(6) sperm/ml vs 0.33 and 0.11 (69%, 47%, and 30% cleavage and 30%, 14%, and 8% blastocysts) and 40 vs 50 psi (54% and 44% cleavage and 18% and 15% blastocysts) (p<0.01). A marked bull by fertilization sperm dose interaction was found for cleavage (p<0.05). The main conclusion was that the optimal sperm concentration for cleavage and producing blastocysts via IVF with sexed sperm was considerably higher and more variable among bulls than for unsexed sperm.

[Pseudo-Conn's syndrome with hypokalemic paralysis due to diuretics and licorice abuse]. / Pseudo-Conn-Syndrom mit hypokaliämischer Lähmung bei Lakritzabusus und Diuretikatherapie.

Dyskalemic paralyses are characterised by single or periodic episodes with muscle weakness that affect mostly the proximal skeletal muscles. Symptoms may last for a few hours or persist for several days, spontaneous recovery is common. Familial cases can be distinguished from secondary, non-familial forms which are based on other diseases, for example, of the thyroid gland, kidneys or gastrointestinal tract. Familial cases are mostly inherited in an autosomal-dominant pattern and belong to the channelopathies. Both groups are characterised by changed potassium levels in the blood during an episode. A detailed and accurate medical history (plus family history, use of medication and eating habits) often easily leads to the diagnosis. Provoking tests or instrumental and histological investigations can help to solve difficult cases. Treatment focuses on relieving acute symptoms and attacks can be managed by correcting the blood potassium to a normal level. Changing eating and/or exercise habits and also permanent medical treatment helps to prevent further attacks.

[Isolated metamorphopsia and visual pseudohallucinations in a patient with anti-NMDA receptor encephalitis]. / Isolierte Metamorphopsien und visuelle Pseudohalluzinationen bei einem Patienten mit Anti-NMDA-Rezeptor-Enzephalitis.

This article reports the case of a 40-year-old male patient with isolated metamorphopsia and visual pseudohallucinations lasting for 2 weeks. As the ophthalmological findings were not pathological, a further neurological examination was performed. After diagnosis of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, which can be manifested in various psychiatric, neurological and ophthalmological ways, the oligosymptomatic patient received high-dose corticosteroid treatment with intravenous immunoglobulins, which stopped the symptoms.

Pre-synchronization of ovulation timing and delayed fixed-time artificial insemination increases pregnancy rates when sex-sorted semen is used for insemination of heifers.

This study was conducted to determine effects of pre-synchronization of ovulation timing among heifers and delayed fixed-time artificial insemination (TAI) with sex-sorted semen on proportion of heifers pregnant after TAI (PR/AI). Heifers were assigned to one of eight treatments: 1 and 2), 7-d CO-Synch + CIDR treatment regimen with administration of gonadotropin-releasing hormone and a CIDR insert on Day 0, prostaglandin F2α (PGF) at CIDR removal on Day 7, and TAI occurring 54 h later with conventionally processed (CTRL54-CNV) or sex-sorted semen (CTRL54-SEX); 3 and 4), same as CTRL54 but TAI delayed to 72 h with conventionally processed (CTRL72-CNV) or sex-sorted semen (CTRL72-SEX); 5 and 6), same as CTRL54 but additional administration of PGF on Day -7 and TAI with conventionally processed (PRE54-CNV) or sex-sorted semen (PRE54-SEX); 7 and 8), same as PRE54 treatments but TAI delayed to 72 h with conventionally processed (PRE72-CNV) or sex-sorted semen (PRE72-SEX). Proportion of heifers pregnant after TAI was greater (P ≤  0.02) with conventionally processed semen compared with sex-sorted semen, yet PR/AI did not differ (P =  0.14) between heifers in PRE72-CNV and PRE72-SEX groups. There were greater PR/AI in the PRE72-SEX (P =  0.03) than CTRL54-SEX group (46.1 % and 36.9 %) and there was no difference (P =  0.31) in PR/AI between CTRL54-CNV and PRE72-SEX groups (50.4 % and 46.1 %). In conclusion, pre-synchronization of ovulation timing among heifers combined with delayed TAI resulted in increased PR/AI with sex-sorted semen compared with the 7-d CO-Synch+CIDR treatment regimen.

Brief introduction to whole-genome selection in cattle using single nucleotide polymorphisms.

Genomic selection using single nucleotide polymorphisms (SNPs) is a powerful new tool for genetic selection. In cattle, SNP profiles for individual animals are generated using a small plastic chip that is diagnostic for up to 50 000 SNPs spaced throughout the genome. Phenotypes, usually averaged over offspring of bulls, are matched with SNP profiles of bulls mathematically so that animals can be ranked for siring desirable phenotypes via their SNP profiles. For many traits in dairy cattle, the rate of genetic improvement can be nearly doubled when SNP information is used in addition to current methods of genetic evaluation. Separate SNP analyses need to be developed for different populations (e.g. the system for Holsteins is not useful for Jerseys). In addition, the value of these systems is very dependent on the number of accurate phenotypes matched with SNP profiles; for example, increasing the number of North American Holstein bulls evaluated from 1151 to 3576 quadrupled the additional genetic gain in net merit from this approach. Thus, the available information will be insufficient to exploit this technology fully for most populations. However, once a valid SNP evaluation system is developed, any animal in that population, including embryos, can be evaluated with similar accuracy. Biopsying embryos and screening them via SNP analysis will greatly enhance the value of this technology by minimising generation intervals.

Effect of different combinations of cryoprotectants on in vitro maturation of immature buffalo (Bubalus bubalis) oocytes vitrified by straw and open-pulled straw methods.

This study was designed to evaluate effects of different combinations of cryoprotectants on the ability of vitrified immature buffalo oocytes to undergo in vitro maturation. Straw and open-pulled straw (OPS) methods for vitrification of oocytes at the germinal vesicle stage also were compared. The immature oocytes were harvested from ovaries of slaughtered animals and were divided into three groups: (i) untreated (control); (ii) exposed to cryoprotectant agents (CPAs); or (iii) cryopreserved by straw and OPS vitrification methods. The vitrification solution (VS) consisted of 6 m ethylene glycol (EG) as the standard, control vitrification treatment, and this was compared with 3 m EG + 3 m dimethyl sulfoxide (DMSO), 3 m EG + 3 m glycerol, and 3 m DMSO + 3 m glycerol. Cryoprotectants were added in two steps, with the first step concentration half that of the second (and final) step concentration. After warming, oocyte samples were matured by standard methods and then fixed and stained for nuclear evaluation. Rates of MII oocytes exposed to CPAs without vitrification were lower (54.3 +/- 1.9% in EG, 47.5 +/- 3.4% in EG + DMSO, 36.8 +/- 1.2% in EG + glycerol and 29.9 +/- 1.0% in DMSO + glycerol; p < 0.05) than for the control group (79.8 +/- 1.3%). For all treatments in each vitrification experiment, results were nearly identical for straws and OPS, so all results presented are the average of these two containers. The percentages of oocytes reaching telophase-I or metaphase-II stages were lower in oocytes cryopreserved using all treatments when compared with control. However, among the vitrified oocytes, the highest maturation rate was seen in oocytes vitrified in EG + DMSO (41.5 +/- 0.6%). Oocytes cryopreserved in all groups with glycerol had an overall low maturation rate 19.0 +/- 0.6% for EG + glycerol and 17.0 +/- 1.1% for DMSO + glycerol. We conclude that the function of oocytes was severely affected by both vitrification and exposure to cryoprotectants without vitrification; the best combination of cryoprotectants was EG + DMSO for vitrification of immature buffalo oocytes using either straw or OPS methods.

[Sonography of the parenchyma in Parkinson's disease]. / Parenchym-Ultraschall bei Parkinson-Syndromen.

Transcranial sonography (TCS) of the brain parenchyma is a non-invasive and easily applicable neuroimaging technique which is used as a diagnostic tool in Parkinson's disease. Up to 90% of patients with idiopathic Parkinson's disease but only 10-15% of the healthy population show an abnormal echogenicity (hyperechogenicity) of the substantia nigra (SN). TCS has been demonstrated to be a useful tool in the differential diagnosis of patients with essential tremor or atypical parkinsonian syndromes, including the parkinsonian variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) where hyperechogenicity of the SN is less frequent. Abnormal echogenicity of the SN has been found in almost all investigated monogenic types of parkinsonism and even in asymptomatic mutation carriers. The nature of the pathological substrate leading to the abnormal echogenicity of the SN remains elusive. Longitudinal studies of asymptomatic subjects with abnormal echogenicity of the SN are still ongoing to evaluate the risk for developing Parkinson's disease in the future in these subjects.

Superovulation and embryo transfer in cattle.

About 17,000 bovine pregnancies were produced by superovulation and embryo transfer in North America in 1979. The major use of these techniques is to increase the reproductive rate of valuable cows. Other applications include circumventing infertility, exporting embryos, and testing potential carriers for Mendelian recessive alleles. Cryopreservation of embryos is beginning to be used commercially, and sexing embryos before transfer may soon become routine.

Effect of dehydration prior to cryopreservation of large equine embryos.

Cryopreservation of equine embryos>300microm in diameter results in low survival rates using protocols that work well for smaller equine embryos. These experiments tested the potential benefit of incorporating a dehydration step prior to standard cryopreservation procedures. Forty-six, day 7-8, grade 1, equine embryos 300-1350microm in diameter were subjected to one of the following treatments: (A) 2 min in 0.6M galactose, 10min in 1.5M glycerol, slow freeze (n=21); (B) 10min in 1.5M glycerol, slow freeze (n=15); (C) 2min in 0.6M galactose, 10min in 1.5M glycerol, followed by exposure to thaw solutions, then culture medium (n=5); (D) transferred directly to culture medium (n=5). Frozen embryos were thawed and subjected to a three-step cryoprotectant removal. Five embryos from each treatment were evaluated morphologically after 24 and 48h culture (1=excellent, 5=degenerate/dead). All treatments had at least 4/5 embryos with a quality score >or=3 at these time points except treatment B (2/5 at 24h, 1/5 at 48h). Subsequent embryos from treatment A (n=16) or B (n=10) were matched in sets of two for size and treatment, thawed, and immediately transferred in pairs to 13 recipients. Only two recipient mares were pregnant; one received two 400microm embryos from treatment A, and the other one 400 and one 415microm embryo from treatment B. There was no advantage of incorporating a 2min dehydration step into the cryopreservation protocol for large equine embryos.