Evaluation of plant commercial feed additives for equine cyathostomin control.

The increasing emergence of anthelmintic-resistant parasitic isolates prompts us to reassess the management of intestinal strongylosis in horses. Additionally, societal demand is shifting toward reducing the use of chemical treatments, aligning with environmentally-friendly practices and the exploration of natural alternatives. In this context, we provide an initial view of the antiparasitic activity and the effect on immune circulating blood cells of three commercialized plant-based feed additives in ponies. Three treatments, based either on mugwort (Artemisia vulgaris), echinacea (Echinacea purpurea) or curcumin (Curcuma longa) were administrated to 18 (six per treatment) Welsh female ponies naturally infected with cyathostomins to mimic their practical use in farming conditions. Another group of six untreated ponies was used as a control. Fecal egg count (FEC), the larval development percentage and the number of red blood cells, lymphocytes, monocytes, neutrophils, eosinophils and basophils were measured the first and the last day of each treatment, and compared with those characterizing the control group. None of the three treatments showed a significant effect on the studied parameters. Moreover, the efficacy of treatments, measured from the FEC reduction compared to the control group, was weak (≤ 38.6 %). Therefore, these results do not support the practical use of these additives in equine farming, even if the determination of Cohen's d values associated with the three treatments revealed some incidences on FEC and blood immune cell counts, as well as on larval development for mugwort.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

PFAS levels and determinants of variability in exposure in European teenagers - Results from the HBM4EU aligned studies (2014-2021).

BACKGROUND: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma concentrations in this specific age group. METHODS: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post-harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately. RESULTS: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 µg/L (1.63-2.78)], PFOA ([0.97 µg/L (0.75-1.26)]), PFNA [0.30 µg/L (0.19-0.45)] and PFHxS [0.41 µg/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently. CONCLUSION: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food.

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data.

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.

Severe pulmonary arterial hypertension and massive ascites in a patient with systemic lupus erythematosus and secondary Sjogren's syndrome.

BACKGROUND: Pulmonary arterial hypertension (PAH), is a rare manifestation of systemic lupus erythematosus (SLE), characterized by pulmonary arterial remodeling leading to right ventricular failure and death. To date, optimal management of SLE-associated PAH should be clarified, especially regarding the respective places of immunosuppressants and PAH vasodilator treatments. CASE REPORT: We report the case of a 48-year-old woman with SLE and secondary Sjogren syndrome, associated with severe PAH and lupus peritonitis with massive ascites, who showed a remarkable response, both for SLE flare and PAH, to a treatment combining immunosuppressants and pulmonary arterial vasodilator treatment. CONCLUSION: This observation highlights the interest of combining immunosuppressive therapy in SLE-PAH, whose modalities in association with PAH treatments should be clarified.

Clinical characteristics of and outcomes for patients with COVID-19 and comorbid lung diseases primarily hospitalized in a conventional pulmonology unit: A retrospective study.

BACKGROUND: Scant data are currently available about a potential link between comorbid chronic lung diseases (CLD) and the risk and severity of the coronavirus disease 2019 (COVID-19) infection. METHODS: To describe the clinical characteristics of and outcomes for patients with COVID-19 infection, including patients with comorbid respiratory diseases, who have been primarily hospitalized in the pulmonology department of Strasbourg University Hospital, France. In this retrospective, single-center study, we included all confirmed cases of COVID-19 from March 3 to April 15, 2020. We then compared the symptoms, biological and radiological findings, and outcomes for patients with and without CLD. RESULTS: Of the 124 patients that were enrolled, the median age was 62 years, and 75 patients (60%) were male. Overall, 40% of patients (n=50) had preexisting CLD, including chronic obstructive pulmonary disease (COPD) (n=15, 12%) and asthma (n=19, 15%). Twenty-eight patients were transferred to the intensive care unit (ICU), and six patients died in our unit. CLD were not predictive of ICU hospitalization, but a significantly higher total mortality was observed (17.6% vs. 5.5%, P<0.05) in these patients. CONCLUSIONS: Our results suggest the lack of an over-representation of CLD in COVID-19, representing 40% of patients in this cohort and even within a pulmonology department. CLD were not a risk factor for ICU management. However, a tendency to higher global mortality was observed in COVID-19 patients with CLD. Further studies are warranted to determine the risk of COVID-19 for patients with comorbid CLD.

Acute Cardiac Failure Due to Takotsubo Cardiomyopathy Secondary to a Phone Call for Lung Transplantation: A Case Report.

Lung transplantation is a therapeutic option for certain end-stage lung diseases. The phone call for lung transplantation is a major event in the life of these patients; as a result, it can generate significant stress. We herein present the case of a 58-year-old female patient with end-stage chronic obstructive pulmonary disease (COPD) who, while on the lung transplantation waiting list, received such a call. Complete transplant work-up, including cardiac tests undertaken shortly before, had revealed no contraindication to lung transplantation. She was admitted with severe acute respiratory failure, and her extensive work-up was compatible with pulmonary edema due to takotsubo cardiomyopathy. The lung transplantation was thus cancelled, owing to the patient's health condition and the poor quality of the graft as well. The patient stayed in the intensive care unit for several days, requiring noninvasive ventilation. The left ventricular function recovered completely within 10 days postdiagnosis, and the patient was discharged 13 days after her admission. The patient was transplanted 1 month thereafter, without any particular problems; she is currently, 8 months post-transplantation, in good condition. In the given case, the call for lung transplantation could have generated emotional stress severe enough to lead to takotsubo cardiomyopathy.

Temporal pattern recognition with delayed feedback spin-torque nano-oscillators.

The recent demonstration of neuromorphic computing with spin-torque nano-oscillators has opened a path to energy efficient data processing. The success of this demonstration hinged on the intrinsic short-term memory of the oscillators. In this study, we extend the memory of the spin-torque nano-oscillators through time-delayed feedback. We leverage this extrinsic memory to increase the efficiency of solving pattern recognition tasks that require memory to discriminate different inputs. The large tunability of these non-linear oscillators allows us to control and optimize the delayed feedback memory using different operating conditions of applied current and magnetic field.

[Liver diseases and pulmonary vascular disorders]. / Hépatopathies et maladies vasculaires pulmonaires.

About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]>3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP<35mmHg without severe right ventricular dysfunction and PVR<4 WU).

Neuromorphic Computing through Time-Multiplexing with a Spin-Torque Nano-Oscillator.

Fabricating powerful neuromorphic chips the size of a thumb requires miniaturizing their basic units: synapses and neurons. The challenge for neurons is to scale them down to submicrometer diameters while maintaining the properties that allow for reliable information processing: high signal to noise ratio, endurance, stability, reproducibility. In this work, we show that compact spin-torque nano-oscillators can naturally implement such neurons, and quantify their ability to realize an actual cognitive task. In particular, we show that they can naturally implement reservoir computing with high performance and detail the recipes for this capability.

Schmallenberg virus: experimental infection in goats and bucks.

BACKGROUND: Schmallenberg virus (SBV) is an emerging Orthobunyavirus of ruminant livestock species currently circulating in Europe. SBV causes a subclinical or mild disease in adult animals but vertical transmission to pregnant dams may lead to severe malformations in the offspring. Data on the onset of clinical signs, viremia and seroconversion in experimentally infected adult animals are available for cattle and sheep but are still lacking for goats. For a better understanding of the pathogenesis of SBV infection in adult ruminants, we carried out experimental infections in adult goats. Our specific objectives were: (i) to record clinical signs, viremia and seroconversion; (ii) to monitor viral excretion in the semen of infected bucks; (iii) to determine in which tissues SBV replication took place and virus-induced lesions developed. RESULTS: Four goats and two bucks were inoculated with SBV. Virus inoculation was followed by a short viremic phase lasting 3 to 4 days and a seroconversion occurring between days 7 and 14 pi in all animals. The inoculated goats did not display any clinical signs, gross lesions or histological lesions. Viral genomic RNA was found in one ovary but could not be detected in other organs. SBV RNA was not found in the semen samples collected from two inoculated bucks. CONCLUSIONS: In the four goats and two bucks, the kinetics of viremia and seroconversion appeared similar to those previously described for sheep and cattle. Our limited set of data provides no evidence of viral excretion in buck semen.

Light physical activity is a better determinant of lower adiposity during the menopausal transition.

OBJECTIVE: To investigate the relationship between time spent performing physical activity (PA) and adiposity across the menopausal transition. METHODS: Body weight and body composition were analyzed in 65 women (47-54 years old; body mass index 23.2 ± 2.4 kg/m(2)) in a 5-year prospective study. Time spent in PA of varying intensities (sedentary, light, moderate and vigorous) was determined from 7-day accelerometer measurement and energy intake with a 7-day food diary. RESULTS: Significant negative correlations were observed between the time spent in light-intensity PA and fat mass (FM) (r = -0.38, p < 0.005), central FM (r = -0.36, p < 0.005), peripheral FM (r = -0.33, p < 0.01), and percent body fat (r = -0.42, p < 0.001) at year 1, respectively. No significant correlations were noted between measures of adiposity and time spent performing either moderate or vigorous PA. Analyses using tertiles of time spent in light PA at year 1 showed that FM (20.7 ± 4.0 vs. 20.3 ± 6.6 vs. 16.6 ± 4.6 kg, p < 0.05), central FM (10.1 ± 2.6 vs. 10.0 ± 3.8 vs. 7.8 ± 2.4 kg; p < 0.05) and percent body fat (34.5 ± 5.1 vs. 32.2 ± 7.7 vs. 28.1 ± 6.2%, p < 0.01) were all significantly lower in women in the highest tertile. These differences remained significant after covariate analyses using time spent in moderate- and high-intensity PA and total energy intake. Finally, lower levels of FM, percent body fat, central and peripheral FM persisted in women who spent more time in light PA (highest tertiles) over the 5-year follow-up. CONCLUSION: Our results suggest that the time spent performing light PA may have a greater impact on adiposity than moderate and/or vigorous PA, an observation independent of the menopausal status.

Relationship of mid-thigh adiposity to the metabolic syndrome in postmenopausal women.

BACKGROUND: In postmenopausal women, a population at risk for the metabolic syndrome, the relative contribution of central fat versus peripheral muscle fat to the metabolic risk profile is unknown. This study explored the relationship between muscle fat infiltration derived from computed tomography (CT) scans and metabolic syndrome. METHODS: Mid-thigh CT scans measured the surface of muscle with low attenuation (LAMS) [0-34 Hounsfield units (HU)], which represented the specific component of fat-rich muscle. Insulin sensitivity was evaluated by an euglycemic-hyperinsulinemic clamp. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria were used to determine the presence of the metabolic syndrome. RESULTS: A total of 103 postmenopausal women were studied. Metabolic syndrome was found in 43 women with significantly higher levels of abdominal adiposity, higher LAMS (27 +/- 8 vs. 23 +/- 7 cm(2)), and lower insulin sensitivity compared to those without the metabolic syndrome. Women with higher levels of LAMS presented higher metabolic risk features such as higher blood pressure, abdominal adiposity, inflammatory markers, and blood lipid levels. LAMS and visceral adipose tissue correlated significantly with the presence of metabolic syndrome, but these relationships were lost when LAMS was adjusted for visceral adipose tissue but not when visceral adipose tissue was adjusted for LAMS. CONCLUSIONS: These results suggest that postmenopausal women who present with metabolic syndrome had increased fat-rich mid-thigh muscle. Moreover, women with more fat-rich muscle had many features of the metabolic syndrome. These relations were weakened when visceral adipose tissue was taken into account suggesting that LAMS may play a relatively smaller role, compared to VAT, in the contribution to the metabolic syndrome.

[Biological therapy for psoriasis: practical experience at a French dermatology unit]. / Utilisation des biothérapies dans le psoriasis modéré à sévère : expérience du service de dermatologie du CHU de Besançon (2004-2008).

BACKGROUND: The course of biological therapy (BT) in clinical practice may differ markedly from treatment schedules in clinical trials. Treatment modifications and patient characteristics can affect treatment safety and efficacy. In addition, long-term results concerning the use of BT in clinical practice are lacking. OBJECTIVES: To report our experience of BT in terms of short- and long-term efficacy and safety. PATIENTS AND METHODS: The retrospectively analysed cohort consisted of psoriasis patients receiving BT between 2004 and 2008. Patients in clinical trials were excluded. Mean body surface area (BSA) and Dermatology Life Quality Index were recorded. RESULTS: Fifty-eight patients undergoing 86 courses of BT were enrolled. Thirty-three patients were treated with efalizumab, 21 with infliximab and 32 with etanercept. During the study period, 40% of patients were switched to another BT. The number of patients attaining BSA-75 at 3and 6months respectively was 38% and 75% for efalizumab, 62% and 61% for infliximab, and 36% and 61% for etanercept. After 24months of follow-up, only 33% of patients (34% of patients with efalizumab, 52% with infliximab and 22% with etanercept) were still following their initial BT, with treatment being discontinued in 52% of patients due to adverse events or treatment failure. DISCUSSION: Our study confirms the efficacy and feasibility of BT in clinical practice. However, the high frequency of BT discontinuation for adverse events or non-response led to sequential therapy using different biological treatments.

Validation of a simple index (SIisOGTT) of insulin sensitivity in a population of sedentary men.

AIM: The ongoing obesity epidemic is associated with numerous health problems related to altered metabolic function. Among these is type 2 diabetes, characterized by lowered insulin sensitivity (IS). Consequently, the development of simple indices to assess IS has research and clinical importance. The SI(is)OGTT, a new index of IS, was recently described by Bastard et al. (Diabetes & Metabolism 2007;33:261-8), and validated in sedentary, non-diabetic, overweight and obese postmenopausal women. The aim of the present study was to validate the index in men. METHODS: The data used in this project came from sedentary men (n=36), aged 34-53 years, all of whom underwent a hyperinsulinaemic-euglycaemic clamp and 2-hour oral glucose tolerance test (OGTT). Correlations with M/I (glucose infusion rate [GIR] divided by insulin concentration), GIR and GIR divided by fat-free mass (FFM) were obtained by four well-known indices (HOMA, QUICKI, Cederholm and Matsuda) as well as with the new SI(is)OGTT index. Pearson correlations and Bland-Altman analyses were obtained for every index versus clamp value. RESULTS: The best correlate of IS in the present study was the SI(is)OGTT (r=0.84, P<0.0001). The agreement of this method with the hyperinsulinaemic-euglycaemic clamp, as assessed by Bland-Altman plots, was similar to those of the other indices and to those previously described in postmenopausal women. CONCLUSION: The new index proposed by Bastard et al. is as good a predictor of IS in sedentary men as the other commonly used indices, and appears to be as reliable in this population as it was in the original study of postmenopausal women.

Flavonoids and related compounds in parasitic disease control.

Flavonoids are natural plant compounds increasingly used in therapeutic applications. Their large spectrum of activities depends on their structures and cellular targets. Most recent research shows they are promising drugs for controlling human and animal parasitic diseases. Their multiple effects make it difficult to understand their modes of action, but some of them have been elucidated. This review also deals with their toxicity in mammals.

[Antibody avidity: use for the diagnosis of HIV early infection]. / Avidité des anticorps: application au diagnostic d'infection récente à VIH1.

Determination of IgG avidity is useful to distinguish primary infection from reactivation or reinfection in viral, parasitic or bacterial infections. For diagnosis of HIV type 1 primary infection, the detection of IgM antibodies is often useless since they are also found in chronic infection. The usual serology (Elisa, western-blot, p24 antigen) may present no interest if done too late (more than 2 or 3 months after infection). Therefore, we have developed a test to determine the avidity of anti-HIV1 antibodies, using 1 M guanidine as denaturing agent. We have adapted the measurement of avidity to the Axsym automatic system for a routine use. Indeed, since requests for avidity determinations are sporadic, the use of microplates is not convenient. Using this assay, we found a low avidity (less than 50%) in immunocompetent and recent infected patients (less than 6 months), compared to old infected patients (more than 12 months) who had high avidity (80 to 100%). However, early treated patients (in the 6 months after contamination) had also low avidities but with a slower development of antibody maturation (8 to 27 months versus 2 to 8 months in non treated patients). To conclude, the determination of the anti-HIV1 avidity, according to the proper procedures explained here (notion of treatment and/or serious immunodepression), may help the physician to date the infection in each new infected patient who might benefit from an early treatment.

Hormonal variation in bitches after early or mid-pregnancy termination with aglepristone (RU534).

Seven bitches in early pregnancy (12.8 +/- 3.8 days after ovulation; group 1) and seven bitches in mid-pregnancy (32.0 +/- 1.53 days after ovulation; group 2) were used in this study. For each group, five bitches were treated with 0.10 mg aglepristone (Alizine) kg-1 and this dose was repeated 24 h later. Two control bitches received a placebo. Blood samples were collected at 6 h intervals to determine plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in the four control bitches. All bitches treated with aglepristone aborted. In group 1, embryonic death occurred; in group 2, fetal expulsion occurred 60-132 h after administration of aglepristone. After pregnancy termination, the interoestrous interval of aglepristone-treated bitches was significantly shorter than that before treatment. Treatment with aglepristone did not modify plasma concentrations of progesterone, prostaglandin, oxytocin or cortisol within 24 h after its administration, but it induced, in mid-pregnancy (group 2) a discharge of prolactin within 12 h after its administration. As an abortifacient, aglepristone acted on the uterus and, therefore, did not have direct or immediate luteolytic properties. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterized by an increase in the concentration of PGFM, but oxytocin and cortisol remained at basal concentrations.