Comparison of two breeding systems for timing of whelpings in farmed silver foxes

Selostus: Vertaileva tutkimus kahden paritusjärjestelmän vaikutuksista tarhattujen hopeakettujen penikoimisten ajoittumiseen

SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients.

Caspase cleaved amyloid precursor protein (APPcc) and SET are increased and mislocalized in the neuronal cytoplasm in Alzheimer Disease (AD) brains. Translocated SET to the cytoplasm can induce tau hyperphosphorylation. To elucidate the putative relationships between mislocalized APPcc and SET, we studied their level and distribution in the hippocampus of 5 controls, 3 Down syndrome and 10 Alzheimer patients. In Down syndrome and Alzheimer patients, APPcc and SET levels were increased in CA1 and the frequency of both localizations in the neuronal cytoplasm was high in CA1, and low in CA4. As the increase of APPcc is already present at early stages of AD, we overexpressed APPcc in CA1 and the dentate gyrus neurons of adult mice with a lentiviral construct. APPcc overexpression in CA1 and not in the dentate gyrus induced endogenous SET translocation and tau hyperphosphorylation. These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation.

Prevalence of Joint Hypermobility and Joint Hypermobility Syndrome in a Swiss population with Chronic Low Back Pain

Objective¦Joint hypermobility (JH) and Joint Hypermobility Syndrome (JHS) are often underdiagnosed¦and were never specifically assessed in a selected population of chronic low back pain¦(LBP). This study aimed to assess JH and JHS among a population with chronic LBP using the¦Beighton and the Brigthon criteria.¦Methods¦We conducted a retrospective cross-sectional study based on a prospective data base¦among 143 patients with non-specific chronic LBP. Patients were seen by the same rheumatologist,¦who looked for JH and JHS and took their medical history. Data were analysed using logistic¦regression.¦Results¦We found a JH prevalence of 33,3% (CI 95% 22.0-44.6) among women and 21,4% (11.7-¦31.2) among men, and for JHS, of 37,9% (26.0-49.8) among women and 30,9% (19.7-42.0) among¦men. JH was less frequent among people older than fifty (P < 0.02). JHS was more prevalent among¦Swiss individuals (P < 0.01) and among individuals having a non-manual job (P<0.03) compared to¦there opposites. Patients having an important limitation for daily living activities were four times¦more likely to have JHS. Degenerative spinal disorders were negatively associated with JH (OR¦0.31 (0.13-0.73) and JHS (OR 0.31 (0.14-0.68).¦Conclusion¦A high prevalence of joint hypermobility was found in our population. JHS should be¦part of differential diagnosis in individuals with chronic non-specific LBP.

Discriminating Irritable Bowel Syndrome fromInflammatory Bowel Disease: what is the Role of Biomarkers in Daily Practice?

Background a nd A ims: D iscriminating irritable bowelsyndrome (IBS) from inflammatory bowel disease (IBD) can bea clinical c hallenge as s ymptoms c an overlap. We a nd othershave recently shown that fecal c alprotectin ( FC) is moreaccurate for d iscriminating IBS f rom IBD compared to C -reactive p rotein ( CRP) and b lood leukocytes. We a imed toassess which b iomarkers are used by g astroenterologists intheir daily practice for discriminating IBS from IBD.Methods: A q uestionnaire was sent to all board certifiedgastroenterologists in Switzerland in July 2010.Results: Response rate was 57% (153/270). Mean physician'sage was 50±9years, mean duration o f gastroenterologicpractice 1 4±8years, 52% of them were working in p rivatepractice a nd 48% in h ospitals. T he following biomarkers weredetermined for discriminating IBS from IBD: CRP 100%, FC79%, hematogram (red blood cells and leukocytes) 70%, ironstatus ( ferritin, t ransferrin s aturation) 59%, e rythrocytesedimentation rate 2.7%, protein electrophoresis 0.7%, andalpha-1 antitrypsin clearance 0.7%. There was a trend for usingFC more often in p rivate practice t han in h ospital ( P = 0.08).Eighty-nine percent of gastroenterologists considered FC to besuperior to CRP for discriminating IBS from IBD, 8 7% thoughtthat patient's compliance for fecal sampling is high, and 51%judged the fee of USD 60 for a FC test as appropriate.Conclusions: F C is widely used in c linical practice t odiscriminate IBS from IBD. In accordance with the scientificevidence, the majority of gastroenterologists consider FC to bemore accurate than CRP for discriminating IBS from IBD.

Prioritizing genetic testing in patients with kallmann syndrome using clinical phenotypes.

Context: The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. Objective: The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Subjects: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Main Outcome Measures: Reproductive and nonreproductive phenotypes within each genetic group were measured. Results: Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Conclusions: Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening.

Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

Diagnostic and ethical challenges in disorders of consciousness and locked-in syndrome: a survey of German neurologists.

Diagnosis and decisions on life-sustaining treatment (LST) in disorders of consciousness, such as the vegetative state (VS) and the minimally conscious state (MCS), are challenging for neurologists. The locked-in syndrome (LiS) is sometimes confounded with these disorders by less experienced physicians. We aimed to investigate (1) the application of diagnostic knowledge, (2) attitudes concerning limitations of LST, and (3) further challenging aspects in the care of patients. A vignette-based online survey with a randomized presentation of a VS, MCS, or LiS case scenario was conducted among members of the German Society for Neurology. A sample of 503 neurologists participated (response rate 16.4%). An accurate diagnosis was given by 86% of the participants. The LiS case was diagnosed more accurately (94%) than the VS case (79%) and the MCS case (87%, p < 0.001). Limiting LST for the patient was considered by 92, 91, and 84% of the participants who accurately diagnosed the VS, LiS, and MCS case (p = 0.09). Overall, most participants agreed with limiting cardiopulmonary resuscitation; a minority considered limiting artificial nutrition and hydration. Neurologists regarded the estimation of the prognosis and determination of the patients' wishes as most challenging. The majority of German neurologists accurately applied the diagnostic categories VS, MCS, and LiS to case vignettes. Their attitudes were mostly in favor of limiting life-sustaining treatment and slightly differed for MCS as compared to VS and LiS. Attitudes toward LST strongly differed according to circumstances (e.g., patient's will opposed treatment) and treatment measures.

Holt Oram syndrome: a registry-based study in Europe.

BACKGROUND: Holt-Oram syndrome (HOS) is an autosomal dominant disorder characterised by upper limb anomalies and congenital heart defects. We present epidemiological and clinical aspects of HOS patients using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. METHODS: The study was based on data collected during 1990-2011 by 34 registries. The registries are population-based and use multiple sources of information to collect data on all types of birth using standardized definitions, methodology and coding. Diagnostic criteria for inclusion in the study were the presence of radial ray abnormalities and congenital heart disease (CHD), or the presence of either radial ray anomaly or CHD, with family history of HOS. RESULTS: A total of 73 cases of HOS were identified, including 11 (15.1%) TOPFA and 62 (84.9%) LB. Out of 73 HOS cases, 30.8% (20/65) were suspected prenatally, 55.4% (36/65) at birth, 10.7% (7/65) in the first week of life, and 3.1% (2/65) in the first year of life. The prenatal detection rate was 39.2% (20/51), with no significant change over the study period. In 55% (11/20) of prenatally detected cases, parents decided to terminate pregnancy. Thumb anomalies were reported in all cases. Agenesis/hypoplasia of radius was present in 49.2% (30/61), ulnar aplasia/hypoplasia in 24.6% (15/61) and humerus hypoplasia/phocomelia in 42.6% (26/61) of patients. Congenital heart defects (CHD) were recorded in 78.7% (48/61) of patients. Isolated septal defects were present in 54.2 (26/48), while 25% (12/48) of patients had complex/severe CHD. The mean prevalence of HOS diagnosed prenatally or in the early years of life in European registries was 0.7 per 100,000 births or 1:135,615 births. CONCLUSIONS: HOS is a rare genetic condition showing regional variation in its prevalence. It is often missed prenatally, in spite of the existence of major structural anomalies. When discovered, parents in 45% (9/20) of cases opt for the continuation of pregnancy. Although a quarter of patients have severe CHD, the overall first week survival is very good, which is important information for counselling purposes.

Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report.

INTRODUCTION: Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. CASE PRESENTATION: We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. CONCLUSIONS: Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity-dependent spine dynamics are affected in Fmr knockout (Fmr1-KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1-KO mice, but markedly enhanced by activity. Additionally, activity-mediated spine stabilization was lost in Fmr1-KO mice. Application of the metabotropic glutamate receptor antagonist α-Methyl-4-carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity-mediated spine stabilization. In contrast, enhancing phosphoinositide-3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity-mediated spine stabilization. It also restored defective long-term potentiation mechanisms in slices and improved reversal learning in Fmr1-KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.

Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes.

Genomic imbalance is a common cause of phenotypic abnormalities. We measured the relative expression level of genes that map within the microdeletion that causes Williams-Beuren syndrome and within its flanking regions. We found, unexpectedly, that not only hemizygous genes but also normal-copy neighboring genes show decreased relative levels of expression. Our results suggest that not only the aneuploid genes but also the flanking genes that map several megabases away from a genomic rearrangement should be considered possible contributors to the phenotypic variation in genomic disorders.