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.

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.

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.

[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.

Two split-time artificial insemination programs in suckled beef cows.

Our objective was to determine which of 2 split-time AI programs applied to suckled beef cows would result in greater pregnancy risk. Suckled beef cows (n = 1,062) at 12 locations in 4 states (CO, KS, MY, and WA) were enrolled. Cows were treated on d -7 with a progesterone insert concurrent with 100 µg GnRH and on d 0 with 25 mg PGF plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. The study was designed as a completely randomized experiment of 2 treatment combinations. Within location and balanced for parity (primiparous vs. multiparous), cows were assigned randomly to 2 treatment times (55 vs. 65 h after CIDR insert removal) at which time estrus-detection patches were assessed. Estrus was defined to have occurred when an estrus-detection patch was > 50% colored (activated). Cows determined to be in estrus were inseminated at either 55 or 65 h, whereas the residual nonestrous cows in both treatment times received GnRH at 55 or 65 h but were inseminated 20 h later at 75 or 85 h, respectively. Pregnancy outcomes were determined at 36 d after AI and at the end of the breeding season. Thus, pregnancy outcomes of interest were compared between the 55 + 75-h treatment combination and that of the 65+85-h combination. Expression of estrus was greater ( = 0.001) by 65 h after PGF than by 55 h (62.0% vs. 41.9%), respectively, and this proportion was influenced by parity (time x parity interaction; = 0.006). As a result, proportionally more ( < 0.001) cows received the timed AI at 75 than 85 h (59.4% vs. 40.6%). Similar proportions of cows not in estrus by 55 or 65 h were detected in estrus by 75 or 85 h (40.1% vs. 39.3%), respectively. The cumulative proportion of cows in estrus by 75 h was less ( < 0.001) than that by 85 h (66.7% vs. 76.7%), respectively. Pregnancy risks at 36 d differed among treatments, with cows detected in estrus and inseminated at 55 or 65 h having greater pregnancy risks than their time-inseminated herd mates at 75 or 85 h (62.3% vs.49.7%), respectively. Overall pregnancy risk for cows in the 65+85-h treatment combination was greater at 36 d than for cows in the 55 + 75-h treatment combination (61.0% vs. 51.4%), respectively. We conclude that the 65 + 85-h treatment combination produced more pregnancies than the 55 + 75-h combination, but its implementation may be somewhat less convenient in terms of cow handling times.

Gonadotropin-releasing hormone increased pregnancy risk in suckled beef cows not detected in estrus and subjected to a split-time artificial insemination program.

We hypothesized that GnRH would increase pregnancy risk (PR) in a split-time AI program for cows in which estrus was not detected. A total of 1,236 suckled beef cows at 12 locations in 3 states (Colorado, Kansas, and North Dakota) were enrolled. Before applying the fixed-time AI program, BCS was assessed. Cows were treated on d -7 with a progesterone insert concurrent with 100 µg GnRH and on d 0 with 25 mg PGF plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. Estrus was defined to have occurred when an estrus-detection patch was >50% colored (activated). Cows in estrus by 65 h ( = 758; 61.3% of all cows) were randomly allocated to 2 treatments: 1) 100 µg GnRH and early + GnRH (E+G; = 373) or 2) AI only at 65 h (early - no GnRH [E-G]; = 385). The remaining cows were randomly allocated to 2 treatments: 1) 5(L+G; = 252) or 2) AI only at 84 h (late no GnRH [L-G]; = 226). Pregnancy was determined 35 d after AI via transrectal ultrasound. Pregnancy risk did not differ ( = 0.68) between E+G and E-G cows (61.9 vs. 60.4%, respectively). Conversely, for cows inseminated at 84 h, PR was greater ( = 0.01) in cows that received GnRH (L+G) compared with their herd mates not receiving GnRH (L- G; 41.7 vs. 30.8%, respectively). Of those cows not detected in estrus by 65 h, 42.1% were detected by 84 h, for a total expression of estrus by all cows of 77.6%. Administration of GnRH increased ( < 0.01) PR in cows not detected in estrus by 84 h (+GnRH = 33.4% [ = 146] vs. no GnRH = 15.0% [ = 128]) but had no effect in cows expressing estrus by 84 h (+GnRH = 65.3% [ = 103] vs. no GnRH = 61.7% [ = 97]). Neither estrus expression by 65 or 84 h nor PR was influenced by BCS, parity, or days postpartum at AI. Cows had greater PR when they had been detected in estrus before AI, and PR was improved by administration of GnRH at 65 h after insert removal in cows that were not detected in estrus and inseminated at 84 h.

Removing seminal plasma improves bovine sperm sex-sorting.

Bull ejaculates with sperm concentrations of less than 1 billion sperm sort poorly for sex chromosomes, but whether this is because of the sperm concentration or the concomitant seminal plasma content has not been elucidated. Experiments were conducted to determine why ejaculates with lower sperm concentrations sort poorly and develop a protocol to increase sorting efficiency. In Experiment I, spermatozoa at 160 or 240 × 106 sperm/mL were stained at 49, 65 or 81 µm Hoechst 33342 with 0 or 10% seminal plasma and then sex-sorted. In Experiment II, seminal plasma was adjusted to create samples with sperm concentrations of 0.7, 1.4 and 2.1 × 109 sperm/mL, prior to sex-sorting. In Experiment III, spermatozoa were diluted to 0.7, 1.4 and 2.1 × 109 sperm/mL using TALP containing 0 or 10% seminal plasma prior to sex-sorting and cryopreservation. In Experiment I, the optimal staining combination was 160 × 106 sperm/mL stained with 65 µm Hoechst 33342 and no seminal plasma. In Experiment II, the percentages of membrane-impaired sperm were lower for sample concentrations of 2.1 × 109 sperm/mL (15%) than for samples at 1.4 × 109 (17%) or 0.7 × 109 sperm/mL (18%; p < 0.01). The X sort rate was slower for samples stored at 0.7 × 109 sperm/mL (3.45 × 103 sperm/sec) than for samples stored at 1.4 × 109 and 2.1 × 109 sperm/mL (3.85 and 3.94 × 103 sperm/sec, respectively; p < 0.05). In Experiment III, samples containing 0% seminal plasma had higher percentages of live-oriented cells (54 vs. 50%; p < 0.05), fewer dead sperm (19 vs. 22%; p < 0.01) and higher post-thaw motility (41 vs. 35%; p < 0.05) than samples containing 10% seminal plasma. Ejaculates with high sperm concentrations result in superior sorting because these samples have less seminal plasma during staining than ejaculates with lower initial sperm concentrations as all samples are diluted to 160 × 106 sperm/mL for staining. Therefore, sorting efficiency appears to be affected by seminal plasma concentration, not by the original sperm concentration.

An apparatus for studying electrical breakdown in liquid helium at 0.4 K and testing electrode materials for the neutron electric dipole moment experiment at the Spallation Neutron Source.

We have constructed an apparatus to study DC electrical breakdown in liquid helium at temperatures as low as 0.4 K and at pressures between the saturated vapor pressure and ∼600 Torr. The apparatus can house a set of electrodes that are 12 cm in diameter with a gap of 1-2 cm between them, and a potential up to ±50 kV can be applied to each electrode. Initial results demonstrated that it is possible to apply fields exceeding 100 kV/cm in a 1 cm gap between two electropolished stainless steel electrodes 12 cm in diameter for a wide range of pressures at 0.4 K. We also measured the current between two electrodes. Our initial results, I < 1 pA at 45 kV, correspond to a lower bound on the effective volume resistivity of liquid helium of ρV > 5 × 10(18) Ω cm. This lower bound is 5 times larger than the bound previously measured. We report the design, construction, and operational experience of the apparatus, as well as initial results.

BEEF SPECIES SYMPOSIUM: Beef production without mature cows.

Nutrients in animal feed get partitioned to growth, lactation, pregnancy, fat accretion, and/or maintenance. For mature beef cows, >80% of nutrients consumed annually go to unproductive maintenance. Integrated over the entire U.S. beef cattle production system, nearly one-half of the nutrients consumed go to maintenance of cow herds. This accounts for much of the inefficiency of beef production and can be minimized by the single-calf heifer system, in which heifers are fattened and slaughtered after having their first calf. We propose a modification, use of sexed semen, so that most heifers replace themselves with a heifer calf. This greatly decreases the size of the inherently inefficient cow herd required for beef production and greatly increases efficiency of beef production in terms of nutrients consumed and waste produced, such as methane, by increasing the ratio of nutrients used for growth to those used for maintenance. Additional management is required including AI, early weaning, and the attention required when calving 2-yr-old heifers. Low conception rates with sexed semen and less efficient growth of females than males also must be considered. However, these issues seem greatly outweighed by the benefits of increased efficiency from decreasing cow herd size while eliminating the need for breeding back lactating first-calf heifers, the need for castration, and health problems inherent in older cows such as mastitis and lameness. Moreover, the decreased generation interval can greatly accelerate genetic progress.

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.

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.

Update on sexed semen technology in cattle.

The technology in current use for sexing sperm represents remarkable feats of engineering. These flow cytometer/cell sorters can make over 30 000 consecutive evaluations of individual sperm each second for each nozzle and sort the sperm into three containers: X-sperm, Y-sperm and unsexable plus dead sperm. Even at these speeds it is not economical to package sperm at standard numbers per inseminate. However, with excellent management, pregnancy rates in cattle with 2 million sexed sperm per insemination dose are about 80% of those with conventional semen at normal sperm doses. This lowered fertility, in part due to damage to sperm during sorting, plus the extra cost of sexed semen limits the applications that are economically feasible. Even so, on the order of 2 million doses of bovine semen are sexed annually in the United States. The main application is for dairy heifers to have heifer calves, either for herd expansion or for sale as replacements, often for eventual export. Breeders of purebred cattle often use sexed semen for specific matings; thawing and then sexing frozen semen and immediately using the few resulting sexed sperm for in vitro fertilization is done with increasing frequency. Beef cattle producers are starting to use sexed semen to produce crossbred female replacements. Proprietary improvements in sperm sexing procedures, implemented in 2013, are claimed to improve fertility between 4 and 6 percentage points, or about 10%.

[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.

[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.

Neuroimaging correlates of everyday action in dementia.

The everyday, functional impairments associated with dementia remain poorly understood from a neuropsychological perspective. This study investigated relations between brain structure volumes and two measures of everyday action-caregiver questionnaire and direct assessment-in 57 participants with dementia. Results showed that caregiver ratings reflecting more functional impairment were strongly associated with smaller volumes of deep white matter. Direct assessment of everyday task performance in a subsample revealed relations between unique neurological substrates and discrete everyday action error types. Findings emphasize differences in functional assessment methods and highlight the role of white matter in functional deficits in dementia.

[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.