Functional Variants Associated With CMPK2 and in ASB16 Influence Bovine Digital Dermatitis.

Bovine digital dermatitis (BDD) is an infectious disease of the hoof in cattle with multifactorial etiology and a polygenic influence on susceptibility. With our study, we identified genomic regions with the impact on occurrence and development of BDD. We used 5,040 genotyped animals with phenotype information based on the M-stage system for genome-wide association. Significant associations for single-nucleotide polymorphisms were found near genes CMPK2 (chromosome 11) and ASB16 (chromosome 19) both being implicated in immunological processes. A sequence analysis of the chromosomal regions revealed rs208894039 and rs109521151 polymorphisms as having significant influence on susceptibility to the disease. Specific genotypes were significantly more likely to be affected by BDD and developed chronic lesions. Our study provides an insight into the genomic background for a genetic predisposition related to the pathogenesis of BDD. Results might be implemented in cattle-breeding programs and could pave the way for the establishment of a BDD prescreening test.

Behavioural phenomena in persons with an intellectual developmental disorder according to the level of emotional development.

BACKGROUND: Challenging behaviours in people with an intellectual developmental disorder (IDD) are complex and often difficult to understand. The developmental perspective may provide additional insights into the specific behavioural patterns and underlying motives in different emotional reference ages. METHODS: The behaviours of 185 adults with IDD who were admitted to psychiatry were systematically assessed with the Aberrant Behaviour Checklist (ABC) and the Modified Overt Aggression Scale (MOAS). The association of the different behaviours with various emotional reference age groups as assessed with the Scale of Emotional Development - Short (SED-S) was analysed to deduce behavioural patterns typical for a certain level of functioning. RESULTS: Overall, the severity of challenging behaviours decreases in higher emotional reference age groups. Physical aggression was most prevalent in persons in the second phase of emotional development (7-18 months reference age). In SED-S-1 (reference age 0-6 months), the persons appeared to be searching for physical comfort and showed high scores in social withdrawal, stereotypies and aggression towards the self. Persons functioning in SED-S-2 (reference age 7-18 months) scored highest in irritability and physical aggression (searching for security), while those in SED-S-3 (19-36 months) exhibited the searching for autonomy type characterised by defiant and socially inappropriate behaviours. Persons with an emotional reference age of 4-7 years (SED-S-4) showed inappropriate speech, verbal self-regulation and depressive-like behavioural aspects (searching for identity). CONCLUSIONS: The behavioural phenomena exhibited in a certain emotional reference age may support the clinician to differentiate behavioural problems from psychopathological symptoms to yield the proper diagnosis.

Travelling with heart failure: risk assessment and practical recommendations.

Patients with heart failure are at a higher risk of cardiovascular events compared with the general population, particularly during domestic or international travel. Patients with heart failure should adhere to specific recommendations during travel to lower their risk of developing heart failure symptoms. In this Review, we aim to provide clinicians with a set of guidelines for patients with heart failure embarking on national or international travel. Considerations when choosing a travel destination include travel distance and time, the season upon arrival, air pollution levels, jet lag and altitude level because all these factors can increase the risk of symptom development in patients with heart failure. In particular, volume depletion is of major concern while travelling given that it can contribute to worsening heart failure symptoms. Pre-travel risk assessment should be performed by a clinician 4-6 weeks before departure, and patients should receive advice on potential travel-related illness and on strategies to prevent volume depletion. Oxygen supplementation might be useful for patients who are very symptomatic. Upon arrival at the destination, potential drug-induced photosensitivity (particularly in tropical destinations) and risks associated with the local cuisine require consideration. Special recommendations are needed for patients with cardiac implantable electronic devices or left ventricular assist devices as well as for those who have undergone major cardiac surgery.

Behavioral Observation Procedures and Tests to Characterize the Suitability of Sows for Loose-Housed Farrowing Systems.

The objective of the study was to evaluate behavioral observation procedures and tests to characterize sows' behavior for their suitability for free farrowing systems. Nest building activity (NB), lying-down behavior (LDB), and position after lying down (PLD) were assessed. Four tests were designed to characterize the reaction of sows to a novel object and an unexpected situation (Towel Test, TT), behavior towards humans (Dummy Arm Test, DAT; Trough Cleaning Test, TCT), and behavior towards piglets (Reunion Test, RT). The study was performed on a nucleus farm in 37 batches including 771 purebred landrace sows housed in farrowing pens with short-term fixation. The assessment of NB started 2 days before the expected date of the farrowing. In 56.2% of the observations, the sows showed increased chewing activity on gunnysacks. The LDB and PLD were assessed on days 3 and 19 post partum (p.p.). In 49.1% of the observations, sows showed careful lying-down behavior. In 50.1% of cases, sows preferred the stomach-teats-position when lying down. With the DAT on day 4 p.p., in 89.3% of observations, no or only slight reactions of the sow were documented. The TT and TCT were performed on days 3 and 10 p.p. Strong defensive reactions of animals towards humans were recorded in 4.5% of the observations in the TT, and in 4.0% of the observations in the TCT. In the RT on day 3 p.p., in 61.8%, a joyful response of the sows to the reunion with their piglets was observed. This study showed that the behavioral observation procedures and designed tests are suitable to characterize sows' behavior towards humans and piglets with regard to traits that are particularly important in systems without fixation.

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I).

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention.

A study of ultrasound-guided perineural injection of the caudal cervical spinal nerve roots in equine cadavers.

OBJECTIVES: To develop an ultrasound-guided cervical perineural injection technique for horses and to evaluate and compare the distribution of contrast agent among perineural, intra-articular and periarticular injections. STUDY DESIGN: Prospective, experimental cadaveric study. ANIMALS: A total of 14 equine cadaveric necks. METHODS: Bilateral ultrasound-guided perineural injection technique for the caudal cervical spinal nerve roots (CSNRs 5-7) was developed. Paramagnetic or iodinated contrast was injected and the distribution of contrast was evaluated using magnetic resonance (MR) or computed tomography (CT) imaging, respectively. The presence of contrast in the CSNR region was determined by an observer unaware of the technique used for each injection performed. The ability of the perineural injection technique to distribute contrast agent to the CSNR region was compared with intra-articular and periarticular injection techniques. RESULTS: Perineural injection delivered contrast agent to the CSNR region 100% of the time and was significantly different when compared with intra-articular injection (p = 0.008). There was no difference in ability to deliver contrast agent to the CSNR region between the perineural and periarticular injection techniques or between the intra-articular and periarticular injection techniques. CONCLUSION AND CLINICAL RELEVANCE: The ultrasound-guided perineural injection technique developed in this study accurately delivered contrast agent to the CSNR region in equine cadavers. This technique could potentially be used for the diagnosis and treatment of cervical pain in horses, particularly in cases where intra-articular cervical articular process joint injections have not been beneficial. Further studies are necessary to assess the effectiveness of the ultrasound-guided perineural injection technique in live horses.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain, Pulmonary Function, and Respiratory Muscle Strength After Posterolateral Thoracotomy: A Randomized Controlled Trial.

PURPOSE: To evaluate the effects of transcutaneous electrical nerve stimulation (TENS) compared to placebo TENS and a control group on pain, pulmonary function, respiratory muscle strength, and analgesic medications in the postoperative period of thoracotomy in an Intensive care unit (ICU). METHODS: Patients who had undergone posterolateral thoracotomy were randomly allocated to receive TENS during ICU stay, or placebo TENS, or into the control group. All groups received conventional physiotherapy. We analysed the intensity of pain, pulmonary function, respiratory muscle strength, and use of analgesia medications. Outcomes were evaluated before surgery, immediately after, 24 and 48 h after ICU admission. RESULTS: Forty-five patients were included. Regarding pain perception, there was no difference between groups (p = 0.172), but there was a significant reduction in pain intensity for patients receiving TENS after first physiotherapy session compared to baseline (4.7 ± 3.2 vs 3.3 ± 2.6; p < 0.05). All groups had a decrease in forced vital capacity (FVC) after surgery (p < 0.001). There was no difference between the groups regarding the use of analgesic medications, but a higher intake of morphine and acetaminophen were observed for the control (p = 0.037) and placebo group (p = 0.035), respectively. CONCLUSION: The use of TENS provides a little benefit of pain (in the first 12 h) but failed to demonstrate any improvement in the recovery of ICU patients after 48 h of posterolateral thoracotomy. TRIAL REGISTRATION: NCT02438241.

Interdigital Hyperplasia in Holstein Cattle Is Associated With a Missense Mutation in the Signal Peptide Region of the Tyrosine-Protein Kinase Transmembrane Receptor Gene.

Bovine interdigital hyperplasia (IH) is a typical disease of the foot with varying prevalence depending on age, breed, and environmental factors resulting in different degrees of lameness. In studies based on assessments of claw health status at time of hoof trimming and applying genetic-statistical models to analyze this data, IH consistently exhibits high estimates of heritability in the range of 0.30-0.40. Although some studies have identified chromosomal regions that could possibly harbor causative genes, a clear identification of molecular causes for IH is lacking. While analyzing the large database of claw health status as documented at time of hoof trimming, we identified one herd with extreme prevalence of IH of > 50% of affected Holstein dairy cows. This herd subsequently was chosen as the object of a detailed study. A total of n = 91 cows was assessed and revealed a prevalence of 59.3% and 38.5% for IH cases, documented as "one-sided" or "two-sided", respectively. Cows were genotyped using the BovineSNP50 BeadChip. A genome wide association study revealed two significantly associated chromosomal positions (-log10P = 5.57) on bovine chromosome 8 (BTA8) located in intron 5 and downstream of the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. As ROR2 plays a key role in ossification of the distal limbs and is associated with brachydactylies in humans, it was a reasonable candidate for IH. A comparative sequencing of the ROR2 gene between cases and controls revealed two missense variants in exon 1 (NC_037335.1:g.85,905,534T > A, ARS-UCD1.2) and exon 9 (NC_037335.1:g.86,140,379A > G, ARS-UCD1.2), respectively. Genotyping of both variants in the cohort of 91 cattle showed that the exon 1 variant (rs377953295) remained significantly associated with IH (p < 0.0001) as a risk factor of the disease. This variant resulted in an amino acid exchange (ENSBTAP00000053765.2:p.Trp9Arg) in the N-terminal region of the ROR2 signal peptide which is necessary for proper topology of the polypeptide during translocation. Quantification of ROR2 mRNA and ROR2 protein showed that the variant resulted in a significant suppression of ROR2 expression in homozygous affected compared to wild type and carrier cows.

[Syncope and fitness to drive]. / Fahreignung bei Synkope.

Although medical students are rarely instructed in traffic medicine in Germany, they are obliged to inform their patients about their fitness to drive after having become a medical doctor. This article gives an overview on the fitness to drive for patients with syncope by referring to the driving license regulation and the current guidelines released by the department of traffic. The driving license regulation distinguishes between group 1 and group 2 drivers. Group 1 drivers drive vehicles with a total weight less than 3.5 t, whereas group 2 drivers drive vehicles with a total weight above 3.5 t or provide commercial passenger transport. Since patients with syncope may suffer from different serious illnesses, the first approach is to clarify the cause of syncope. If no treatable cause of syncope (e. g., pacemaker, aortic valve replacement) is found, drivers of group 1 are not fit to drive for 6 months after a second unexplained syncope, whereas in this situation, drivers of group 2 are not fit to drive permanently. If, however, syncopes occur in conditions which cannot be expected to occur while driving (e. g. venipuncture, defecation, micturition) fitness to drive will persist. Syncope due to ventricular tachycardia in ischemic heart disease and reduced left ventricular ejection fraction are in general treated with an implantable cardioverter-defibrillator (ICD). Group 2 drivers with an ICD are normally unfit to drive. Group 1 drivers with an ICD are fit to drive when no syncope or adequate shock occurred within the last three months.

Fitness to Drive in Cardiovascular Disease.

BACKGROUND: Medical students are taught little or nothing about the medical considerations related to the driving of motor vehicles. Physicians treating patients with cardiovascular disease need to acquire competence in traffic medicine in order to be able to advise them about their fitness to drive. METHODS: We present the current governmental regulations and recommendations concerning fitness to drive in patients with cardiovascular disease. We also review pertinent publications that were retrieved by a selective search in PubMed with the search terms "cardiovascular disease and traffic accidents" and "cardiovascular disease and traffic deaths" for the decade 2007-2016, as well as further publications collected by us individually. RESULTS: Cardiovascular disease can make a driver lose control of a vehicle without warning and thereby lead to an accident. The main pathophysiological mechanisms of sudden loss of control are disturbances of brain perfusion (e.g., syncope with or without cardiac arrhythmia, sudden cardiac death due to ventricular fibrillation or asystole, stroke, aneurysm rupture) and marked general weakness (e.g., after major surgery or in cardiac insufficiency). CONCLUSION: Patients with cardiovascular disease should be advised by their physicians about their fitness to drive, and the discussion should be documented in writing. Because of the German law on the confidentiality of medical data, only the affected patient should receive this information, with very few exceptions.

Recent experimental results of effects of perfluoroalkyl substances in laboratory animals - Relation to current regulations and guidance values.

The detection of perfluoroalkyl substances (PFAS) in surface and drinking water from various countries raised the attention to the presence of these chemicals in environmental probes and led to several regulatory actions to limit exposure in human beings. There was particular concern about perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), due to their former wide-spread use. Recently, several institutions published revisions of former regulatory or recommended maximum concentrations in drinking water and food, which are markedly lower than the former values. The present short overview describes the current regulations for PFAS and compares them with the outcome of several experimental studies in laboratory animals at low-level exposure to PFOA and PFOS. In addition, regulations for short-chain PFAS are presented which, due to lack of toxicological information, are evaluated according to the concepts of Threshold of Toxicological Concern (TTC) or the Health-related Indication Values (HRIV).

[When to terminate resuscitation in adults?]. / Reanimation bei Erwachsenen: Wann kann eine Wiederbelebung beendet werden?

Resuscitation in cardiac arrest rarely results in survival with a good neurologic outcome. It is therefore a common problem to decide when resuscitation should not be initiated or an ongoing attempt has to be terminated. Resuscitation attempts should be withheld or terminated if there is a do not resuscitate order (DNR), if resuscitation is not in accordance with the presumptive will of the patient or does not have a chance to allow the patient to continue an independent living. As long as ventricular fibrillation or pulseless ventricular tachycardia are present, however, resuscitation should be continued. Also in pulmonary embolism prolonged resuscitation measures may be necessary. In out-of-hospital cardiac arrest resuscitation may be stopped when the three criteria are met: not witnessed arrest, no ventricular fibrillation or pulseless tachycardia, and no return of spontaneous circulation before arrival at the hospital. According to current guidelines in-hospital resuscitation can be terminated if the patient is in asystole for at least 20 minutes. In any case termination of a resuscitation attempt is an individual decision where all possible information on circumstances and on the patient should be taken into account.

[New guidelines on resuscitation in adults: What has changed?]. / Neue Reanimationsleitlinie bei Erwachsenen: Was hat sich geändert?

In October 2015, new guidelines for cardiopulmonary resuscitation (CPR) were published, which represent a revision of the guidelines 2010. The new recommendations are based on an update of knowledge on resuscitation, which was evaluated for the first time by GRADE (Grading of Recommendations Assessment, Development and Evaluation). The key messages of the guidelines 2010 were retained in 2015. Adult basic life support consists of a sequence of 30 chest compressions at a rate of 100-120/min with a depth of 5 to maximally 6 cm and 2 ventilations. As soon as possible, an automated external defibrillator (AED) should be applied. Interruptions of chest compressions should be minimized. To improve bystander CPR emergency medical dispatchers should diagnose cardiac arrest when informed about unconscious persons not breathing normally. In this case, emergency medical staff should inform bystanders to resuscitate with compression only CPR until the arrival of an emergency team. In postresuscitation care, mild hypothermia (body temperature 32-34 °C) has been replaced by targeted temperature management in unconscious patients. Now, the guidelines recommend a constant body temperature between 32-36 °C for at least 24 h. Fever should be prevented or treated.

Application of acid-activated Bauxsol for wastewater treatment with high phosphate concentration: Characterization, adsorption optimization, and desorption behaviors.

Acid-activated Bauxsol was applied to treat wastewater with high phosphate concentration in a batch adsorption system in this paper. The effect of acid activation on the change of Bauxsol structure was systematically investigated. The mineralogical inhomogeneity and intensity of Bauxsol decreased after acid activation, and FeCl3·2H2O and Al(OH)3 became the dominant phases of acid-activated Bauxsol adsorption. Moreover, the BET surface area and total pore volume of Bauxsol increased after acid activation. Interaction of initial solution pH and adsorption temperature on phosphate adsorption onto acid-activated Bauxsol was investigated by using response surface methodology with central composite design. The maximum phosphate adsorption capacity of 192.94 mg g(-1) was achieved with an initial solution pH of 4.19 and an adsorption temperature of 52.18 °C, which increased by 7.61 times compared with that of Bauxsol (22.40 mg g(-1)), and was higher than other adsorbents. Furthermore, the desorption studies demonstrated that the acid-activated Bauxsol was successfully regenerated with 0.5 mol L(-1) HCl solution. The adsorption capacity and desorption efficiency of acid-activated Bauxsol maintained at 80.48% and 93.02% in the fifth adsorption-desorption cycle, respectively, suggesting that the acid-activated Bauxsol could be repeatedly used in wastewater treatment with high phosphate concentration.

Cardioversion in Non-Valvular Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia and is associated with elevated rates of stroke, heart failure, hospital admission, and death. Its prevalence in the overall population is 1.5% to 2%. To convert atrial fibrillation to sinus rhythm, cardioversion is needed. METHODS: This review is based on pertinent articles published from 2004 to December 2014 that were retrieved by a selective PubMed search employing the terms "atrial fibrillation" and "cardioversion." RESULTS: In electrical cardioversion, a defibrillator is used to pass a pulse of current between two electrodes. In pharmacological cardioversion, antiarrhythmic drugs are given intravenously or orally. Electrical cardioversion results in sinus rhythm in more than 85% of patients; pharmacological cardioversion results in sinus rhythm in about 70% of patients with recent-onset atrial fibrillation. As a rule, cardioversion should be carried out only under effective therapeutic anticoagulation with heparin, a vitamin K antagonist, or a new oral anticoagulant drug. If atrial fibrillation has been present for more than 48 hours, cardioversion must be preceded by transesophageal echocardiography to rule out blood clot in the left atrium, or else the patient is pretreated with an anticoagulant drug for at least 3 weeks. As cardioversion can transiently impair left atrial pumping function, anticoagulation is usually maintained for 4 weeks after the procedure. The decision whether to continue anticoagulation beyond this point is based on the risk of stroke, as assessed with the CHA2DS2-VASc score. CONCLUSION: The main risks of cardioversion-thrombo--embolism and clinically significant hemorrhage--occur in 1% of cases or less (in the first 30 days after treatment) if the procedure is carried out as recommended in therapeutic guidelines. Serious complications still occur, but they are rare.

The ex-vivo intestinal absorption rate of uranium is a two-phase function of supply.

The concentration-dependent absorption behaviour of uranium was investigated with surviving intestinal segments of rat jejunums, using an ex-vivo model. The results showed a monotonic slightly nonlinear increase in absorption as uranium concentrations increased. This trend was observed over the entire concentration range tested. In the lower concentration range a slower linear ascent was observed while a steeper linear ascent was found for the higher concentration range. Statistical fit was only slightly poorer for an exponential function in the range of lower values and a logarithmic function in the range of higher values. The proportion of uranium absorbed expressed as percent of uranium concentrations in the perfusion solutions followed a monotonically increasing trend from 20 to around 200 µg/l uranium in the perfusion solutions, which thereafter appears to reach a plateau, as further increase towards concentrations around 400 µg/l is not substantial. The uranium concentration administered had no effect on the vitality and consequently the functionality of the intestinal segments, measured in terms of active glucose transport. The results imply that uranium concentrations of more than 20 µg/l in drinking water, for example, could lead to elevated absorption rates and thus to higher internal exposures to consider when setting of Guideline values in this concentration range.