A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects.

BACKGROUND: Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. METHODS: In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. RESULTS: Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago. CONCLUSION: Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course.

Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.

Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34(+) human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K transgene, transplanted into immunodeficient NOD/SCID IL2Rγ(null) mice, and selected in vivo for gene-modified cells. The retroviral insertion site profile of repopulating clones was examined using modified genomic sequencing PCR. We observed polyclonal repopulation with no evidence of clonal dominance even with the use of a strong internal spleen focus forming virus promoter known to be genotoxic. Our data supports the use of FV vectors with MGMTP140K for HSC gene therapy but also suggests additional safety features should be developed and evaluated.

In ovo inoculation of chicken embryos with probiotic bacteria and its effect on posthatch Salmonella susceptibility.

The feasibility of establishing probiotic bacteria in the intestine of broiler chickens by in ovo inoculation was investigated, followed by verifying possible subsequent protection against Salmonella Enteriditis infection. In a first study, 7 commercially available probiotics were screened for compatibility with in ovo inoculation. Two of these probiotics, one being a Enterococcus faecium and the other a Bacillus subtilis, were selected for colonizing the chick gut without compromising hatchability. In a second study, these 2 products were administered in ovo and in the feed to chicks reared until 18 d in comparison with noninoculated chicks and with chicks fed an antibiotic. All chicks were orally challenged with Salmonella Enteritidis at 4 d of age. Results showed reduced performance of Salmonella Enteritidis challenged chicks fed no additives compared with challenged chicks fed antibiotic, but no significant differences in mortality was observed. Probiotics offered in ovo or through the diet could only partially recover performance compared with antibiotic-fed chicks. A significant reduction in the number of Salmonella Enteritidis positive chicks was observed when chicks were in ovo inoculated with E. faecium and continued receiving it in the diet. This work establishes standards for future in ovo colonization research and emphasizes its value as a promising method to deliver individual precise dose of probiotics to poultry in mass scale at the earliest possible age based on the competitive exclusion concept. In ovo colonization with probiotic can therefore become an important ally in combination with other approaches to combat Salmonella and other intestinal bacterial infections in poultry.

Effects of moment of hatch and feed access on chicken development.

The current study evaluated effects of hatch moment and immediate feed and water access within a 24-h hatch window on chicken growth and development. Five hundred four male chickens obtained from a 49-wk-old Ross 308 breeder flock were assigned to 72 cages based on hatching moment (early, midterm, or late; selected during periods of 475 to 481, 483 to 487, and 489 to 493 h after onset of incubation). At the end of each hatching period, chickens were moved to the grow-out facility and one-half of the chickens received feed and water ad libitum immediately. Remaining chickens received feed and water from 504 h after onset of incubation (d 0). Body weight gain and feed intake for each cage were recorded at d 0, 1, 4, 7, 11, and 18. Chickens were sampled at d 4 and 18 for organ and carcass development. Early hatchers had lower BW at placement compared with midterm and late hatchers but compensated for this afterward, resulting in a higher BW at d 4 (112.8, 107.1, and 103.3 g, respectively). From d 0 to 18, early hatchers tended to have higher BW gain than both other groups. Relative breast meat yield at d 18, expressed as percentage of carcass weight, was higher for early (30.4%) than midterm (28.5%) and late hatchers (27.8%). Up to d 7, direct feed access resulted in higher BW gain (6.1%) and feed intake (4.2%) compared with delayed feed access. No effect of moment of feed access on feed efficiency or organ weights was found. Direct feed access resulted in a higher weight:length ratio of the jejunum (12.5%) and ileum (7.5%) at d 4 compared with delayed feed access. These results suggest that early hatchers have a different developmental and growth pattern than midterm or late hatchers within a 24-h hatch window. A mild delay in feed access after hatch affects growth and development during the first week after hatch.

Effect of different magnesium sources on digesta and excreta moisture content and production performance in broiler chickens.

Reducing litter moisture is an effective measure to reduce the incidence of footpad dermatitis. Dietary mineral levels affect intestinal conditions with regard to osmolarity and water reabsorption. Magnesium is often used as a laxative, preventing reabsorption of water from the digesta, and as a consequence, more moisture in the excreta. The objective of the current experiment was to evaluate Mg in broiler diets as a model for reduced intestinal water reabsorption. Effects of magnesium source (magnesium sulfate, magnesium oxide, and magnesium chloride), each at 3 levels (0.255, 1.02, and 2.04 g·kg(-1) diet), were studied. Measured effects were digesta moisture levels throughout the gastrointestinal tract and the moisture level of the excreta. The 10 treatments were randomly assigned to cages within 6 blocks, resulting in 6 replicates per treatments with 18 birds per replicate. Adding magnesium to the diet of broilers linearly increased the excreta moisture content, following the pattern MgCl > MgSO(4) = MgO. This rejects the hypothesis that MgO and MgCl are less laxative sources compared with MgSO(4). The magnesium sources most likely changed the water reabsorption in the distal gastrointestinal tract, as confirmed by the increased digesta moisture percentage in the ceca and colon. Increasing dietary MgSO(4) linearly reduced BW gain and feed intake, though absolute differences were minor. The results of this experiment show that Mg addition in the diet may be used as a model to study wet litter caused by reduced intestinal water reabsorption.

Effects of maternal dietary nitrate supplementation on farrowing and placental characteristics, level of asphyxiation at birth and piglet vitality.

We investigated whether maternal dietary nitrate supplementation, leading to nitric oxide (NO) formation, would affect duration of farrowing, levels of asphyxiation, vitality of piglets at birth and/or loss of potential viable piglets in the form of stillbirth and pre-weaning mortality. Data were collected from 190 crossbred (Yorkshire x Dutch Landrace) sows, which were allocated, balanced for parity, to six dietary nitrate levels (0, 0.03, 0.06, 0.09, 0.12 or 0.15% of nitrate). Sow received the lactational diet containing nitrate from approximately 7 days before farrowing until 5 days after farrowing. Blood acid-base parameters (pH, pO2, pCO2, BEecf, HCO3, sO2 and lactate) and nitrate concentration were determined in umbilical cord blood. The farrowing process was video recorded and later analysed for total duration of farrowing, piglet birth interval, piglet vitality was scored and piglet latency to stand right after birth. Placentas were collected after expulsion during and after farrowing. Placenta length and width were measured and placental color scores were assessed based on redness of the placenta. The probability of a higher vitality score of piglets (being more vital) linearly increased with increasing levels of maternal dietary nitrate. This higher vitality score however, was not reflected by changes in the blood acid-base parameters in umbilical cord blood, except for a tendency for a higher pO2 with increasing levels of nitrate, which could have been caused by a quicker onset of respiration or an increased blood flow to the piglets during birth. Placenta width increased with increasing levels of maternal dietary nitrate, but no effect on placenta length and redness was found. Neither duration of farrowing nor birth interval were affected by maternal dietary nitrate level. In conclusion, maternal nitrate supplementation may affect piglet vitality via vasodilatation (placental characteristics) rather than an increase in exercise efficiency (duration of farrowing).

GAFFE: a gaze-attentive fixation finding engine.

The ability to automatically detect visually interesting regions in images has many practical applications, especially in the design of active machine vision and automatic visual surveillance systems. Analysis of the statistics of image features at observers' gaze can provide insights into the mechanisms of fixation selection in humans. Using a foveated analysis framework, we studied the statistics of four low-level local image features: luminance, contrast, and bandpass outputs of both luminance and contrast, and discovered that image patches around human fixations had, on average, higher values of each of these features than image patches selected at random. Contrast-bandpass showed the greatest difference between human and random fixations, followed by luminance-bandpass, RMS contrast, and luminance. Using these measurements, we present a new algorithm that selects image regions as likely candidates for fixation. These regions are shown to correlate well with fixations recorded from human observers.

Effects of feed access after hatch and inclusion of fish oil and medium chain fatty acids in a pre-starter diet on broiler chicken growth performance and humoral immunity.

Delayed feed and water access is known to impair growth performance of day old broiler chickens. Although effects of feed access on growth performance and immune function of broilers have been examined before, effects of dietary composition and its potential interaction with feed access are hardly investigated. This experiment aimed to determine whether moment of first feed and water access after hatch and pre-starter composition (0 to 7 days) affect growth rate and humoral immune function in broiler chickens. Direct fed chickens received feed and water directly after placement in the grow-out facility, whilst delayed fed chickens only after 48 h. Direct and delayed fed chickens received a control pre-starter diet, or a diet containing medium chain fatty acids (MCFA) or fish oil. At 21 days, chickens were immunized by injection of sheep red blood cells. The mortality rate depended on an interaction between feed access and pre-starter composition (P=0.014). Chickens with direct feed access fed the control pre-starter diet had a higher risk for mortality than chickens with delayed feed access fed the control pre-starter diet (16.4% v. 4.2%) whereas the other treatment groups were in-between. BW gain and feed intake till 25 days in direct fed chickens were higher compared with delayed fed chickens, whilst gain to feed ratio was lower. Within the direct fed chickens, the control pre-starter diet resulted in the highest BW at 28 days and the MCFA pre-starter diet the lowest (Δ=2.4%), whereas this was opposite for delayed fed chickens (Δ=3.0%; P=0.033). Provision of MCFA resulted in a 4.6% higher BW gain and a higher gain to feed ratio compared with other pre-starter diets, but only during the period it was provided (2 to 7 days). Minor treatment effects were found for humoral immune response by measuring immunoglobulins, agglutination titers, interferon gamma (IFN- γ ), and complement activity. Concluding, current inclusion levels of fish oil (5 g/kg) and MCFA (30 g/kg) in the pre-starter diet appear to have limited (carryover) effects on growth and development, as well as on humoral immune function.

Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction.

In order to develop a suitable model for studying the role of granulocytes and monocytes in resistance against pathogenic microorganisms, we investigated the effect of irradiation and cytostatic treatment (cyclophosphamide and VP-16) on the number of both peripheral blood and peritoneal leukocytes in male Swiss mice. Irradiation and cyclophosphamide treatment severely decreased the number of both granulocytes and monocytes in peripheral blood, whereas VP-16 only lowered the number of blood monocytes to a significant degree and had little effect on the number of blood granulocytes or lymphocytes. When normal mice were injected intraperitoneally with newborn calf serum (NBCS) the number of peritoneal granulocytes rose about 100-fold within 6 h. In irradiated and cyclophosphamide-treated mice, this influx of granulocytes into the peritoneal cavity was virtually eliminated, as was the concomitant increase in the number of blood granulocytes; in VP-16-treated mice, on the other hand, the number of peripheral blood and peritoneal granulocytes increased to the same degree as in normal mice. An increase in the number of peripheral blood monocytes and peritoneal macrophages occurred 24-48 h after injection of NBCS in normal mice. This increase was significantly impaired by irradiation as well as by treatment with cyclophosphamide or VP-16.

DGGG Guidelines Programme: Status Quo - Quo Vadis!

The Guidelines programme of the German Society of Gynaecology and Obstetrics (DGGG) is an executive part of the DGGG Guidelines Commission. It includes in-house planning and organisation of all guidelines as well as representation outside of the DGGG. This article does not concern the development of the guidelines as much as it concerns the planning, organisation, registration, editing and publication of the guidelines in context of the DGGG Guidelines programme. It targets interested parties, especially authors and coordinators of guidelines.

Moisture content in broiler excreta is influenced by excreta nutrient contents.

High litter moisture content, often referred to as wet litter, is a major problem in poultry production. Wet litter is often related to poor management, diseases, and digestive problems. In this experiment, the objective was to study the relationship between nutrient content and the moisture content of the excreta of broilers. A dataset containing 351 observations was built and contained the nutrient contents data including moisture content of excreta samples collected in 8 different broiler feeding trials. A biological based model approach was used to create a model with 10 and another one with 14 variables that may explain the excreta moisture level response. Subsequently, these models were compared with a statistical model that was built automatically and adjusted only if this improved the biological model. The R(2) of the 10 variable model was 0.54, in which Zn content and the interaction of NDF × K and Ca × P content were negatively associated with excreta moisture. Sodium, P, and Ca content and the interaction between content of NDF × Na were positively associated with excreta moisture. The R(2) of the 14 variable model was 0.58, in which Zn and K content and the interaction of NDF × protein and Ca × P content were negatively associated with excreta moisture, and Na, protein, P, and Ca content and the interactions in contents of NDF × Na, NDF × Zn, and K × Cu were positively associated with excreta moisture content. In conclusion, the models confirmed the effect of Na, protein, P, and Ca on excreta moisture content. Furthermore, hitherto unknown nutrient interactions that contribute to excreta moisture level were identified. As excreta levels of most nutrients can be manipulated by adjusting dietary nutrient levels, dietary formulation can be adjusted with the findings of this analysis to change levels of excreted nutrients and, consequently, also moisture output.

Eye movements selective for spatial frequency and orientation during active visual search.

Visual search can simply be defined as the task of looking for objects of interest in cluttered visual environments. Typically, the human visual system succeeds at this by making a series of rapid eye movements called saccades, interleaved by discrete fixations. However, very little is known on how the brain programs saccades and selects fixation loci in such naturalistic tasks. In the current study, we use a technique developed in our laboratory based on reverse-correlation(1) and stimuli that emulate the natural visual environment to examine observers' strategies when seeking low-contrast targets of various spatial frequency and orientation characteristics. We present four major findings. First, we provide strong evidence of visual guidance in saccadic targeting characterized by saccadic selectivity for spatial frequencies and orientations close to that of the search target. Second, we show that observers exhibit inaccuracies and biases in their estimates of target features. Third, a complementarity effect is generally observed: the absence of certain frequency components in distracters affects whether they are fixated or mistakenly selected as the target. Finally, an unusual phenomenon is observed whereby distracters containing close-to-vertical structures are fixated in searches for nonvertically oriented targets. Our results provide evidence for the involvement of band-pass mechanisms along feature dimensions (spatial frequency and orientation) during visual search.

[Current application of osteoporosis guidelines--expert recommendations of the German Society of Orthopaedic Surgery and Traumatology]. / Umsetzung der Osteoporoseleitlinien in Orthopädie und Unfallchirurgie--Ergebnisse eines Expertenworkshops der DGOU.

AIM: As an increasing number of patients suffer from osteoporosis-related disorders worldwide, the medical as well as the socioeconomic impact of this problem is significant. Although evidence-based guidelines for diagnosis and treatment are available, their application in daily practice is insufficient. The aim of our initiative was to develop a strategy for supporting this transfer. METHODS: An expert group of the German Society of Orthopaedics and Traumatology (DGOU) has analysed the current scientific as well as health-care data bases regarding diagnosis and treatment of osteoporosis. Then a set of recommendations has been developed in order to improve this situation. RESULTS: The identified support strategy will focus on better identification of patients with osteoporosis and frailty, enhanced interdisciplinary approaches and increased activity to disseminate available guidelines. Additionally, more research activities are necessary in order to highlight the socioeconomic burden of the disease and to continuously improve surgical treatment strategies in the future. CONCLUSION: To ensure a successful application of the recommendations, continuous support of involved health professionals as well as political institutions, national health insurance systems, scientific societies and patient organisations is necessary.

Report and policy brief from the 4th Africa Conference on Social Aspects of HIV/AIDS Research: innovations in access to prevention, treatment and care in HIV/AIDS, Kisumu, Kenya, 29 April - 3 May 2007.

About 520 delegates from all over Africa and 21 countries attended the conference. This report and policy brief summarises the key findings and suggested policy options that emerged from rapporteur reports of conference proceedings including the following themes: (1) Orphans and vulnerable children, (2) Treatment, (3) Prevention, (4) Gender and male involvement, (5) Male circumcision, (6) People living with HIV/AIDS, (7) Food and nutrition, (8) Socioeconomics, and (9) Politics/policy. Two (11.8%) of the 17 OVC projects from the three countries were classified as best practice interventions. Of the 83 abstracts that were accepted at the conference, only 7 (8.4%) were dealing with antiretroviral therapy (ART). There has been tremendous effort by various organisations to provide information about prevention of HIV/AIDS. Information received by adolescents has been effective in increasing their knowledge, but without positive sexual behaviour change. The conference noted the contribution of gender discrimination and violence to the HIV epidemic and the different risks that men and women face in relation to the epidemic. Social scientists need to study the deep cultural meanings attached to male circumcision among different ethnic groups to be able to guide the debate on the latest biomedical findings on the protective effect of circumcision against HIV. Palliative care and support is crucial for coping among people living with HIV/AIDS (PLWHA) in order to deal with medical and psychological issues. Results from several countries have helped researchers to explore alternative ways of examining poverty in the context of HIV and AIDS. Policy frameworks which are likely to succeed in combating HIV/AIDS need to be updated to cover issues of access, testing, disclosure and stigma. In general, the conference was successful in identifying innovations in access to prevention, treatment and care in HIV/AIDS.

[Acute isovolemic hemodilution during intracranial interventions with normo- and hypothermia]. / Akute isovolämische Hämodilution bei intrakraniellen Eingriffen in Normo- und Hypothermie.

In 50 neurosurgical patients (39 cerebral tumours and 11 aneurysms) isovloaemic haemodilution (HD) was carried out immediately before the operation. Of these, 37 were subsequently operated on with pharmacological-physical decrease in metabolism (30 to 32 degrees C) partly with arterial hypotension while 13 patients were operated on in normothermia without hypotension. A control group was formed of 50 patients with cerebral tumours who were operated on without HD in normothermia. 76 per cent of the operations could be carried out without transfusion of foreign blood. The mean values of the amounts of foreign blood were 120.0 ml in the HD-group as against 1344.0 ml in the control group. In the HD-group, dehydration measures could be completely renounced. Complications did not occur. Isovolaemic haemodilution, especially combined with pharmacological decrease in metabolism and controlled hypotension, can be recommended for all intracranial interventions involving greater risks.

[Knee endoprosthesis: anesthesiological considerations]. / Knieendoprothetik--Anästhesiologische Besonderheiten.

The anesthetic care of patients undergoing total knee arthroplasty (TKA) is described based on experience with reports of the recent literature. The problems and complications of cooperation between different personnel and speciality groups treating the patient are of a more organizational nature during the preoperative phase, and are aimed primarily at determining the appropriate scheduling of the operation. At the forefront intraoperatively is the appropriate monitoring of the patient, and the adjustment of anesthetic regimes to the individual needs and requirements of the patient. The obligation for intensive monitoring as well as an appropriate pain therapy are indispensable in the postoperative phase.

[The indication to neuro-surgical intervention in higher age (author's transl)]. / Die Indikation zum neurochirurgischen Eingriff im höheren Lebensalter.

Higher life expectancy has entailed the necessity of treating syndromes in the age group over 60 more frequently. Therapy also includes surgical intervention in general and neurosurgery in particular. References in literature and cases from our own hospital showed that the necessity of performing surgery was extended to include persons of advanced age. Growing life expectancy during the last few decades was accompanied by an improvement in surgical techniques, in the substitution therapy of age-dependent dysfunctions, and the development of careful up-to-date anaesthesia. Good interdisciplinary cooperation resulted in a decisive reduction of the intra- and post-operative mortality rate, even if patients of higher age groups who underwent the selected major neuro-surgical interventions yet have twice the mortality rate (24 per cent) of patients under 60 (11.4 per cent). Early diagnosis is the weakest link in this chain. Cerebral and spinal symptoms in older people are often attributed to age-dependent factors of the vascular system. The space--occupying process is often recognized too late. Once the function of the CNS has failed, even risky interventions cannot bring about a favourable change in the disease.