Metabolic syndrome and the phenotype of multiple sclerosis.

BACKGROUND: Comorbidities, particularly vascular comorbidities, have been shown to exacerbate the progression of disability in multiple sclerosis (MS). Metabolic syndrome (MetS) is a cluster of conditions including abdominal obesity, insulin resistance, atherogenic dyslipidemia, and vascular dysfunction, which contribute to vascular morbidity and chronic inflammation. OBJECTIVE: To describe the characteristics of MetS in a cohort of MS patients and evaluate its relationship with the MS phenotype. METHODS: A monocentric cohort study was conducted on MS patients, collecting demographic, clinical, radiological, and therapeutic data, as well as metabolic data including waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. RESULTS: Among the 84 patients included in the study, 27% were diagnosed with MetS. MetS was found to be associated with secondary progressive MS (SPMS). Patients with SPMS had a higher prevalence of MetS compared to those with relapsing-remitting MS (RRMS), even after adjusting for disease duration. While MetS was associated with Expanded Disability Status Scale (EDSS) progression in the 3-year period according to univariate analysis, it did not show a significant association with disease activity. CONCLUSION: This study provides evidence supporting the connection between MetS and the progression of disability in MS, independent of disease relapse activity.

The A1/A2 ß-casein genotype of cows, but not their horn status, influences peptide generation during simulated digestion of milk.

The effect of the horn status of cows on their milk composition and quality is a controversial research topic. In this study, 128 milk samples from 64 horned and 64 disbudded Brown Swiss and Original Braunvieh cows were collected from alpine farms where both horned and disbudded cows were grazing on mountain pastures. The samples were analyzed for their detailed composition and protein digestion in a simulated in vitro digestion (INFOGEST). To exclude probable influences on digestion, the ß-casein genotype with its variants A1 and A2 was also included in the study. The effects of horn status and ß-casein genotype were investigated in linear mixed models, which included additional influencing random factors such as Original Braunvieh blood proportion, stage of lactation, and farm. Horn status did not have any effect on milk composition or digestion. In contrast, milk from A1A1 cows showed a different protein digestion than milk of A1A2 and A2A2 cows in the gastric phase, including smaller amounts of ß-casomorphin(BCM)21-associated peptides and larger amounts of BCM11-associated peptides. Abundances of BCM7 did not differ between ß-casein genotypes. At the end of the intestinal phase, the digested milk of A1A1 and A2A2 b-casein genotypes did not differ.

Influence of dietary fiber content and horn status on thermoregulatory responses of Brown Swiss dairy cows under thermoneutral and short-term heat stress conditions.

In the present experiment, 10 horned and 10 disbudded mid-lactating Brown Swiss cows were included in a crossover feeding trial with a hay or hay and concentrate diet. The effects of dietary neutral detergent fiber (NDF) content and horn status on thermoregulatory responses under thermoneutral and short-term heat stress conditions were studied, as both are considered to ease the cow's thermoregulation under an environmental heat load. Cows received either ad libitum hay and alfalfa pellets (85:15, C-, NDF content: 41.0%) or restricted amounts of hay and concentrate (70:30, C+, NDF content: 34.5%). The level of restriction applied with the C+ diet was determined from pre-experimental ad libitum intakes, ensuring that both diets provided the same intake of net energy for lactation (NEL). For data collection, cows were housed in respiration chambers for 5 d. The climatic conditions were 10°C and 60% relative humidity (RH), considered thermoneutral (TN) conditions (temperature-humidity index (THI): 52) for d 1 and 2, and 25°C and 70% RH, considered heat stress (HS) conditions (THI: 74), for d 4 and 5. On d 3, the temperature and RH were increased gradually. Compared with TN, HS conditions increased the water intake, skin temperature, respiration and heart rates, and endogenous heat production. They did not affect body temperature, feed intake, or milk production. Lowering dietary fiber content via concentrate supplementation lowered methane and increased carbon dioxide production. It did not mitigate physiological responses to HS. Although the responses of horned and disbudded cows were generally similar, the slower respiration rates of horned cows under HS conditions indicate a possible, albeit minor, role of the horn in thermoregulation. In conclusion, future investigations on nutritional strategies must be conducted to mitigate mild heat stress.

Breeding options for nematode resistance in Lacaune dairy sheep.

Due to progressing anthelmintic resistance of gastrointestinal nematodes (GIN), supportive measures are needed to control these parasites. In sheep, it has been shown that selection towards an increased nematode resistance is feasible and that faecal egg count (FEC) is the generally acknowledged trait for selection. However, a selection based on FEC would come with certain costs, therefore auxiliary, cheaper resistance traits would be most welcome. FAMACHA©, a colour classification of the eyelid, usually used to determine the manifestation of an infection with Haemonchus contortus, could serve as such. Therefore, we collected FAMACHA©, packed cell volume (PVC) and FEC phenotypes of approx. 1150 naturally infected Lacaune ewes on 15 commercial farms in Switzerland. The Haemonchus-proportion was determined on farm level. Phenotypic correlations of FEC and FAMACHA© as well as FAMACHA© and PCV were 0.25 (SE 0.03) and -0.35 (SE 0.08), respectively, and correspond well with the results of other studies. A multi-trait animal model was applied to estimate genetic parameters with FEC, FAMACHA©, PVC and milk yield as dependent variables. The heritabilities of FEC, FAMACHA©, PCV and milk yield were estimated to be moderate with values of 0.33 (SE 0.08), 0.30 (SE 0.08), 0.36 (SE 0.08) and 0.34 (SE 0.08), respectively. The genetic correlations between FEC and FAMACHA© and between FEC and PCV were estimated to be close to zero with values of 0.03 (SE 0.22) and 0.01 (SE 0.21), respectively. The average Haemonchus-proportion compared to other GIN was found to be 43%. The FAMACHA© classification of the Lacaune ewes seems to indicate a rather high worm challenge, with 38, 14 and 2% of observations classified to scores 3, 4 and 5, respectively. However, the worm challenge according to FEC was moderate. It has been suggested that the genetic correlation between FAMACHA© and FEC is more pronounced when FEC was high. It could therefore be that the lack of genetic correlation was due to an insufficient worm challenge, even though the Lacaune were grazing at least 70 days before phenotyping. The genetic correlation between FEC and milk yield was estimated to be 0.07 (SE 0.22, slightly unfavourable). We conclude that if FEC is used as trait, the Lacaune could be selected for lower susceptibility towards nematode infection. The use of FAMACHA© as an auxiliary trait for FEC is not feasible, due to an inexistent genetic correlation between these two traits.

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Accuracy of methane emissions predicted from milk mid-infrared spectra and measured by laser methane detectors in Brown Swiss dairy cows.

Since heritability of CH4 emissions in ruminants was demonstrated, various attempts to generate large individual animal CH4 data sets have been initiated. Predicting individual CH4 emissions based on equations using milk mid-infrared (MIR) spectra is currently considered promising as a low-cost proxy. However, the CH4 emission predicted by MIR in individuals still has to be confirmed by measurements. In addition, it remains unclear how low CH4 emitting cows differ in intake, digestion, and efficiency from high CH4 emitters. In the current study, putatively low and putatively high CH4 emitting Brown Swiss cows were selected from the entire Swiss herdbook population (176,611 cows), using an MIR-based prediction equation. Eventually, 15 low and 15 high CH4 emitters from 29 different farms were chosen for a respiration chamber (RC) experiment in which all cows were fed the same forage-based diet. Several traits related to intake, digestion, and efficiency were quantified over 8 d, and CH4 emission was measured in 4 open circuit RC. Daily CH4 emissions were also estimated using data from 2 laser CH4 detectors (LMD). The MIR-predicted CH4 production (g/d) was quite constant in low and high emission categories, in individuals across sites (home farm, experimental station), and within equations (first available and refined versions). The variation of the MIR-predicted values was substantially lower using the refined equation. However, the predicted low and high emitting cows (n = 28) did not differ on average in daily CH4 emissions measured either with RC or estimated using LMD, and no correlation was found between CH4 predictions (MIR) and CH4 emissions measured in RC. When individuals were recategorized based on CH4 yield measured in RC, differences between categories of 10 low and 10 high CH4 emitters were about 20%. Low CH4 emitting cows had a higher feed intake, milk yield, and residual feed intake, but they differed only weakly in eating pattern and digesta mean retention times. Low CH4 emitters were characterized by lower acetate and higher propionate proportions of total ruminal volatile fatty acids. We concluded that the current MIR-based CH4 predictions are not accurate enough to be implemented in breeding programs for cows fed forage-based diets. In addition, low CH4 emitting cows have to be characterized in more detail using mechanistic studies to clarify in more detail the properties that explain the functional differences found in comparison with other cows.

Impact of US Brown Swiss genetics on milk quality from low-input herds in Switzerland: interactions with grazing intake and pasture type.

This study investigated the effect of, and interactions between, contrasting crossbreed genetics (US Brown Swiss [BS] × Improved Braunvieh [BV] × Original Braunvieh [OB]) and feeding regimes (especially grazing intake and pasture type) on milk fatty acid (FA) profiles. Concentrations of total polyunsaturated FAs, total omega-3 FAs and trans palmitoleic, vaccenic, α-linolenic, eicosapentaenoic and docosapentaenoic acids were higher in cows with a low proportion of BS genetics. Highest concentrations of the nutritionally desirable FAs, trans palmitoleic, vaccenic and eicosapentaenoic acids were found for cows with a low proportion of BS genetics (0-24% and/or 25-49%) on high grazing intake (75-100% of dry matter intake) diets. Multivariate analysis indicated that the proportion of OB genetics is a positive driver for nutritionally desirable monounsaturated and polyunsaturated FAs while BS genetics proportion was positive driver for total and undesirable individual saturated FAs. Significant genetics × feeding regime interactions were also detected for a range of FAs.

Accuracy of direct genomic values for functional traits in Brown Swiss cattle.

In this study, direct genomic values for the functional traits general temperament, milking temperament, aggressiveness, rank order in herd, milking speed, udder depth, position of labia, and days to first heat in Brown Swiss dairy cattle were estimated based on ~777,000 (777 K) single nucleotide polymorphism (SNP) information from 1,126 animals. Accuracy of direct genomic values was assessed by a 5-fold cross-validation with 10 replicates. Correlations between deregressed proofs and direct genomic values were 0.63 for general temperament, 0.73 for milking temperament, 0.69 for aggressiveness, 0.65 for rank order in herd, 0.69 for milking speed, 0.71 for udder depth, 0.66 for position of labia, and 0.74 for days to first heat. Using the information of ~54,000 (54K) SNP led to only marginal deviations in the observed accuracy. Trying to predict the 20% youngest bulls led to correlations of 0.55, 0.77, 0.73, 0.55, 0.64, 0.59, 0.67, and 0.77, respectively, for the traits listed above. Using a novel method to estimate the accuracy of a direct genomic value (defined as correlation between direct genomic value and true breeding value and accounting for the correlation between direct genomic values and conventional breeding values) revealed accuracies of 0.37, 0.20, 0.19, 0.27, 0.48, 0.45, 0.36, and 0.12, respectively, for the traits listed above. These values are much smaller but probably also more realistic than accuracies based on correlations, given the heritabilities and samples sizes in this study. Annotation of the largest estimated SNP effects revealed 2 candidate genes affecting the traits general temperament and days to first heat.

Estimation of genetic parameters for individual udder quarter milk content traits in Brown Swiss cattle.

The aim of this study was to estimate genetic parameters and accuracies of breeding values for milk content traits of individual udder quarters in Brown Swiss cattle. Data of 1,799 phenotyped cows from 40 Swiss dairy herds were analyzed, taking the complete pedigree into account. Fat, protein, lactose, and urea contents, somatic cell score (SCS), and information about hyperkeratosis were available for each udder quarter. The milk of rear udder quarters was found to have significantly higher lactose content and significantly lower fat content than milk of the front udder quarters. The same trend found for fat content was observed for protein content, whereas no differences between the udder quarters were observed for urea content, SCS, or hyperkeratosis. Heritabilities for each udder quarter were in the following ranges: fat content 0.09±0.06 to 0.14±0.06, protein content 0.20±0.09 to 0.33±0.07, lactose content 0.04±0.03 to 0.16±0.07, urea content 0.13±0.07 to 0.22±0.08, SCS 0.18±0.06 to 0.32±0.07, and hyperkeratosis 0.12±0.04 to 0.26±0.05. In our study, hyperkeratosis, protein content, and SCS showed higher heritabilities in the front udder quarters, fat content had higher heritabilities in the rear udder quarters, and no systematic pattern in heritability was observed for lactose content or urea content. Additive genetic correlations between all udder quarters were >0.90 for protein and urea contents, whereas they were remarkably low (<0.60) for SCS. For fat and lactose contents, the genetic correlations between the 2 front or between the 2 rear quarters, respectively, were notably higher than correlations between 1 front and 1 rear quarter, suggesting that the front and the rear udders could be considered as partly genetically different organs. The variability within the udder as such was found to be of low heritability (<0.10) in general, but repeatability was moderate to high for some traits (lactose content: 0.33±0.05, protein content: 0.53±0.05). Some of these findings can be explained by differences in the physiological background of the traits.

Estimation of genetic parameters for novel functional traits in Brown Swiss cattle.

The aim of this study was to estimate genetic parameters and accuracies of breeding values for a set of functional, behavior, and conformation traits in Brown Swiss cattle. These traits were milking speed, udder depth, position of labia, rank order in herd, general temperament, aggressiveness, milking temperament, and days to first heat. Data of 1,799 phenotyped Brown Swiss cows from 40 Swiss dairy herds were analyzed taking the complete pedigree into account. Estimated heritabilities were within the ranges reported in literature, with results at the high end of the reported values for some traits (e.g., milking speed: 0.42±0.06, udder depth: 0.42±0.06), whereas other traits were of low heritability and heritability estimates were of low accuracy (e.g., milking temperament: 0.04±0.04, days to first heat: 0.02±0.04). For most behavior traits, we found relatively high heritabilities (general temperament: 0.38±0.07, aggressiveness: 0.12±0.08, and rank order in herd: 0.16±0.06). Position of labia, arguably an indicator trait for pathological urovagina, was genetically analyzed in this study for the first time, and a moderate heritability (0.28±0.06) was estimated.

Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep.

Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirusbattus, Nematodirusfilicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95<100%) efficacy of monepantel when administered orally to sheep at 2.5mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (> or =90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed.

Efficacy of a single application of a 12.5% pyriprole topical solution against laboratory infestations with ticks (Ixodes ricinus, Dermacentor reticulatus, and Rhipicephalus sanguineus) on dogs.

In three separate studies, the efficacy of a single treatment with a 12.5% pyriprole spot-on solution was investigated against induced infestation with Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus on dogs (both sexes; Beagles in Studies 1 and 2, mixed-breed in Study 3). For each tick species, one group of 8 dogs left untreated (Studies 1 and 2) or treated with a placebo solution (Study 3) was compared with another group treated once with the spot-on solution at a dose rate of at least 12.5mg/kg. The dogs were infested with 50 unfed adult ticks of the respective species at various time-points before and after treatment and the surviving attached and unattached ticks were recorded 48 h after re-infestation. For each tick species, efficacy was assessed for each time-point and cumulatively for the whole evaluation period. The dogs were submitted to general health observations and clinical assessments during the study. Efficacy against I. ricinus and R. sanguineus was 100% during the whole evaluation period of 30 days. For D. reticulatus cumulative efficacy for the 30 days after treatment was 98.9%. The product was well tolerated by all the animals.

The effect of water and shampooing on the efficacy of a pyriprole 12.5% topical solution against brown dog tick (Rhipicephalus sanguineus) and cat flea (Ctenocephalides felis) infestations on dogs.

The efficacy of a single treatment with a 12.5% pyriprole spot-on formulation against induced infestations with R. sanguineus ticks and cat fleas (C. felis) as well as its persistence after repeated washing and shampooing was investigated in four separate studies. In a first study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.3%. No engorged ticks, alive or dead, were found in the treated animals. Shampooing 2 days after treatment and weekly washings did not affect the efficacy. In a second study on R. sanguineus involving 32 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation ranged from 100% to 96.8%. Single washing 8h after treatment and single shampooing 24 h after treatment had no negative impact on the efficacy of the product. In a third study on C. felis involving 28 beagle dogs, the efficacy at various time-points during the 30 days that followed treatment assessed 48 h after re-infestation was always 100% and weekly washings did not diminish the efficacy. In a last study on C. felis involving 24 beagle dogs, the efficacy at various time-points during the 5 weeks that followed treatment assessed 48 h after re-infestation ranged from 100% to 99.8%, and shampooing 24 h after treatment did not reduce the efficacy. The product was well tolerated by the dogs.