Vaccination protocols in Québec dairy herds.

Information is needed on vaccination protocols used by veterinarians and dairy producers to prevent and control infections in dairy herds. This observational study described farm's vaccination standard operating procedures (SOP) developed by veterinarians in collaboration with dairy producers in Québec. Data pertaining to vaccination protocols and dairy producer practices were collected as part of the biosecurity component of the National Mandatory Quality Assurance Certification Program (proAction). Generalized statistical mixed-effects models were used to assess associations between dairy herd characteristics and the vaccination SOP, encompassing various vaccination types. These included any vaccination, core vaccines only (bovine respiratory syncytial virus, infectious bovine rhinotracheitis herpesvirus, parainfluenza virus type 3, bovine viral diarrhea virus type 1 and type 2) and vaccination against diarrhea, mastitis, or clostridial diseases. These models accounted for random variations related to clustering by veterinarians and veterinary clinics. Furthermore, the variance of the outcome was partitioned into producer, veterinarian, and veterinary clinic levels to explore the proportion of the total variance attributable to each group. A total of 3,759 standardized vaccination procedures completed between 2018 and 2021 were analyzed. At least one vaccination target was included in the vaccination SOP in 89% of the dairy herds. The most frequently included vaccine in the SOP was core vaccines, comprising 88%, followed by mastitis (22%), neonatal diarrhea (18%), and clostridial diseases (15%). The vaccination SOPs, particularly core, mastitis, and diarrhea vaccinations, mainly varied due to the veterinarian's characteristics, followed by the clinic's characteristics. In contrast, the decision to included clostridial vaccination primarily varied with the veterinary clinic (76%). Organic producers generally included fewer vaccinations in their SOPs, including core vaccines, than conventional producers. In addition, producers who were providing access to pasture had fewer vaccination SOP for vaccination against mastitis and neonatal diarrhea but more vaccination SOP for clostridial vaccination.

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study.

Objective: To determine whether a family history of spondyloarthritis (SpA) is associated with clinical presentation at the start of tumour necrosis factor inhibitor (TNFi) treatment, or predictive of TNFi drug survival and treatment response in patients with SpA.Method: Family history of SpA in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated SpA (uSpA) from the Swedish Rheumatology Quality register starting a TNFi as their first biologic in 2006-2018 was assessed through national registers. Clinical characteristics at treatment start were compared by family history status. We used Cox regression to estimate hazard ratios for drug discontinuation, and analysed treatment response at 3 and 12 months with linear regression. Multiple imputation was used to address missing data.Results: We included 9608 patients. Patients with family history had an earlier age at onset and longer disease duration at TNFi treatment start, but did not differ regarding disease activity and presence of SpA manifestations. Hazard ratios for drug discontinuation were 1.08 [95% confidence interval (CI) 0.89-1.31] for AS patients with a family history of AS, 1.02 (95% CI 0.89-1.18) for PsA patients with a family history of PsA, and 1.11 (95% CI 0.85-1.45) for uSpA patients with a family history of uSpA, after adjusting for demographic, socioeconomic, and SpA-related factors. Treatment response at 3 and 12 months was similar between groups.Conclusion: Family history of SpA was not found to be associated with clinical presentation at the start of TNFi treatment, nor was it associated with drug survival or treatment response in SpA patients starting a first TNFi.

Short communication: Diagnostic accuracy of the Petrifilm culture system for identifying colostrum with excessive bacterial contamination in Quebec dairy herds.

The objective of this study was to validate the diagnostic accuracy of the Petrifilm culture system (3M, St. Paul, MN) for identifying colostrum with excessive bacterial contamination. An observational cross-sectional study was conducted between October 2015 and February 2016. Two colostrum aliquots were collected during the first meal of 332 calves (33 commercial Holstein dairy farms) in Quebec, Canada. One aliquot per calf was used to quantify the total bacteria count and the total coliform count using standard bacteriological laboratory testing (reference test). These results were dichotomized to identify colostrum with excessive bacterial contamination [aerobic count plate (AC) >100,000 cfu/mL; coliform count plate (CC) >10,000 cfu/mL]. The Petrifilm system was used to quantify both aerobic and coliform contamination of the other colostrum aliquot from each calf. As such, AC and CC were used according to the manufacturer's recommendations. The area under the curve of the receiver operating characteristic curve of AC and CC compared with the laboratory were 0.83, and 0.95, respectively. Using the optimal threshold of >24,000 cfu/mL for AC results, the Petrifilm system had a sensitivity (Se) of 69%, specificity (Sp) of 86%, and a kappa value of 0.54. Using the optimal threshold of >4,000 cfu/mL for CC results, the Petrifilm system had a Se of 93%, Sp of 90%, and kappa value of 0.64. Overall, these results suggest that the Petrifilm system is an appropriate alternative for identifying colostrum with excessive bacterial contamination.

A calf-level study on colostrum management practices associated with adequate transfer of passive immunity in Québec dairy herds.

The objective of this study was to identify the calf-level colostrum management practices associated with an adequate transfer of passive immunity (TPI; defined as serum Brix refractance ≥8.4% in the first week of life) in small-sized herds. A total of 818 calves from 61 commercial Holstein dairy farms were included in this observational cross-sectional study. For each calf, sex, colostrum delivery method, colostrum volume fed at first meal, and time to first feeding (delay between birth and first colostrum meal) were noted. Blood and colostrum samples were collected to estimate the serum and colostrum quality using Brix refractometry. To quantify the level of bacterial contamination in colostrum samples, total bacteria count and total coliform count (TCC) were measured using the Petrifilm (3M, St. Paul, MN) culture system. In this study, 68% of calves had an adequate TPI (≥8.4%). For data distribution, the 25th, 50th, and 75th percentiles were 1.3, 2.8, and 3.3 L for the colostrum volume fed at the first meal; 20.9, 23.5, and 26.5% Brix; and 1.1, 3.1, and 6.5 h for the time to first feeding of colostrum, respectively. The odds of adequate TPI were 2.6 times higher in calves receiving ≥2.5 L colostrum at their first meal, 2.9 times higher in calves receiving colostrum with ≥24.5% Brix, and 1.6 times higher in calves receiving colostrum within 3 h after birth, than in calves not meeting these criteria. In the present study, median bacterial contamination distribution (interquartile range) in the first colostrum meal was 14,000 cfu/mL (3,000-83,000 cfu/mL) for total bacteria count, and 0 cfu/mL (0-1,000 cfu/mL) for TCC. Total bacteria count and TCC were not associated with the odds of adequate TPI in the final model. Overall, these results suggest that specific calf-level colostrum management practices are associated with adequate TPI in small- to medium-sized dairy herds.

A herd-level study on colostrum management factors associated with the prevalence of adequate transfer of passive immunity in Québec dairy herds.

The objective of this study was to identify herd-level colostrum management factors associated with the adequate transfer of passive immunity (TPI; defined as serum Brix refractance ≥8.4% in the first week of life). A total of 59 commercial Holstein dairy farms were included in this observational cross-sectional study. In every participating herd, a minimum of 14 Holstein calves were sampled to measure their TPI using a digital Brix refractometer. Colostrum samples fed to each of these calves were collected to estimate IgG concentration (colostrum quality) using a digital Brix refractometer and bacterial contamination using the Petrifilm (3M, St. Paul, MN) culture system. Dairy producers completed a questionnaire on colostrum management to assess on-farm practices. The study outcome was the prevalence of adequate TPI calculated based on the proportion of adequate TPI (defined with an individual threshold ≥8.4% Brix) on the total samples tested within each herd. According to the threshold determined in a previous study investigating the influencing colostrum management factors to achieve adequate TPI at the calf level, the prevalence of an adequate colostrum volume fed at first meal (≥2.5 L), the prevalence of adequate colostrum quality (≥24.5% Brix), the prevalence of an adequate time to first feeding (delay between birth and the first colostrum meal, ≤3 h), the prevalence of low aerobic bacterial contamination (≤20,000 cfu/mL), the prevalence of low coliform contamination (≤1,000 cfu/mL), and the prevalence of females were calculated. The herd-level prevalence of adequate TPI ranged from 24% to 100%, with a median of 68%. The median herd prevalences of an adequate colostrum volume fed at first meal, of adequate colostrum quality, of an adequate time to first feeding, of low aerobic bacterial contamination, of low coliform contamination, and of females, were 71, 42, 41, 64, 88, and 61%, respectively. In the final model, the prevalence of adequate TPI was associated with the prevalence of an adequate colostrum volume fed at first meal and the prevalence of an adequate time to first feeding. In summary, management practices varied greatly between farms and influenced the prevalence of adequate TPI.

Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model.

BACKGROUND: Titanium dioxide (TiO2) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO2-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO2-NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO2 particles. RESULTS: By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48 mg/kg of tissue) and in 50% of the meconium samples (0.02-1.50 mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO2-NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO2 particles recovered in the foetal exudate were nanosized. CONCLUSIONS: Altogether, these results show a materno-foetal transfer of TiO2 particles during pregnancy, with food-grade TiO2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO2-NPs during pregnancy.

Pelvic floor muscle training: mechanisms of action for the improvement of genitourinary syndrome of menopause.

Objective: This study aims to investigate the mechanism of action of pelvic floor muscle training (PFMT) for the improvement of the signs and symptoms of genitourinary syndrome of menopause (GSM) in postmenopausal women with GSM and urinary incontinence (UI).Methods: Twenty-nine women were included in the secondary analysis of a single-arm feasibility study. Using color Doppler ultrasound, the peak systolic velocity, time-averaged maximum velocity, and pulsatility index of the internal pudendal and dorsal clitoral arteries were measured at rest and after a pelvic floor muscle (PFM) contraction task. PFM function was assessed by dynamometry, and vulvovaginal tissue elasticity was measured using the Vaginal Atrophy Index.Results: PFMT significantly improved blood flow parameters in both arteries (p < 0.05) and significantly increased the speed of PFM relaxation after a contraction (p = 0.003). After the intervention, a marginally significant decrease in PFM tone was observed, as well as an increase in PFM strength (p = 0.060 and p = 0.051, respectively). Finally, improvements in skin elasticity and introitus width were observed as measured by the Vaginal Atrophy Index (p < 0.007).Conclusion: Our findings suggest that PFMT improves blood flow in vulvovaginal tissues, PFM relaxation capacity, and vulvovaginal tissue elasticity in postmenopausal women with GSM and UI.

Amplification and quantification of cold-associated microRNAs in the Colorado potato beetle (Leptinotarsa decemlineata) agricultural pest.

The Colorado potato beetle [Leptinotarsa decemlineata (Say)] is an important insect pest that can inflict considerable damage to potato plants. This insect can survive extended periods of cold exposure, and yet the molecular switches underlying this phenomenon have not been fully elucidated. A better characterization of this process would highlight novel vulnerabilities associated with L. decemlineata that could serve as targets for the management of this devastating pest. Using high-throughput sequencing, the current work reveals a cold-associated signature group of microRNAs (miRNAs) in control (15 °C) and -5 °C-exposed L. decemlineata. The results show 42 differentially expressed miRNAs following cold exposure including miR-9a-3p, miR-210-3p, miR-276-5p and miR-277-3p. Functional analysis of predicted targets associated with these cold-responsive miRNAs notably linked these changes with vital metabolic and cellular processes. Overall, this study highlights the miRNAs probably responsible for facilitating cold adaptation in L. decemlineata and implicates miRNAs as a key molecular target to consider in the development of novel pest management strategies against these insects.

Effect of microbial activity on penetrometer resistance and elastic modulus of soil at different temperatures.

We explore the effect of microbial activity stimulated by root exudates on the penetrometer resistance of soil and its elastic modulus. This is important because it is a measure of the mechanical strength of soil and it correlates closely with the rate of elongation of roots. A sandy soil was incubated with a synthetic root exudate at different temperatures, for different lengths of time and with selective suppression of either fungi or bacteria. The shape of the temperature response of penetrometer resistance in soil incubated with synthetic exudate was typical of a poikilothermic temperature response. Both penetrometer resistance and small strain shear modulus had maximum values between 25 and 30°C. At temperatures of 20°C and less, there was little effect of incubation with synthetic root exudate on the small strain shear modulus, although penetrometer resistance did increase with temperature over this range (4-20°C). This suggests that in this temperature range the increase in penetrometer resistance was related to a greater resistance to plastic deformation. At higher temperatures (> 25°C) penetrometer resistance decreased. Analysis of the DNA sequence data showed that at 25°C the number of Streptomyces (Gram-positive bacteria) increased, but selective suppression of either fungi or bacteria suggested that fungi have the greater role with respect to penetrometer resistance. HIGHLIGHTS: Effect of microbial activity stimulated by synthetic root exudates on the mechanical properties.We compared penetrometer measurements and estimates of elastic modulus with microbial community.Penetrometer resistance of soil showed a poikilothermic temperature response.Penetrometer resistance might be affected more by fungi than bacteria.

Characterization of miRNAs modulated by torpor in the hibernating ground squirrel Ictidomys tridecemlineatus liver by next-generation sequencing.

BACKGROUND: Mammalian hibernation is a fascinating phenomenon that involves multiple molecular and biochemical changes to proceed. While the molecular picture associated with torpor has become clearer in recent years, the function of non-coding RNAs, and especially of microRNAs, solicited during this process is not well understood. OBJECTIVE: To better characterize a signature of cold torpor-associated miRNAs in the hibernating thirteen-lined ground squirrel Ictidomys tridecemlineatus. MATERIALS AND METHODS: Next-generation sequencing and qRT-PCR approaches were conducted in euthermic and hibernating ground squirrel liver tissues. RESULTS: This high-throughput approach notably revealed modulation during hibernation of various miRNAs previously associated with lipid metabolism, glucose metabolism and antioxidant responses such as miR-145a-3p, miR-22-3p and miR-25-3p, respectively. CONCLUSION: Overall, these results present a group of miRNAs differentially expressed in hibernating ground squirrel liver and provide additional knowledge on the underlying functions of these small non-coding molecules during cold torpor.

Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.

BACKGROUND AND OBJECTIVE: Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. MATERIAL AND METHODS: A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. RESULTS: Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 µg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. CONCLUSION: Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy.

Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain.

We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signaling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and temporomandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest.

Exploring high-throughput synchrotron X-Ray powder diffraction for the structural analysis of pharmaceuticals.

Synchrotron radiation offers a host of advanced properties, surpassing conventional laboratory sources with its high brightness, tunable phonon energy, photon beam coherence for advanced X-ray imaging, and a structured time profile, ideal for capturing dynamic atomic and molecular processes. However, these benefits come at the cost of operational complexity and expenses. Three decades ago, synchrotron radiation facilities, while technically open to all scientists, primarily served a limited community. Despite substantial accessibility improvements over the past two decades, synchrotron measurements still do not qualify as routine analyses. The intrinsic complexity of synchrotron science means experiments are pursued only when no alternatives suffice. In recent years, strides have been made in technology transfer offices, intermediate synchrotron-based analytical service companies, and the development of high-throughput synchrotron systems at various facilities, reshaping the perception of synchrotron science. This article investigates the practical application of synchrotron X-Ray Powder Diffraction (s-XRPD) techniques in pharmaceutical analysis. By utilizing concrete examples, we demonstrate how high-throughput systems have the potential to revolutionize s-XRPD applications in the pharmaceutical industry, rapidly generating XRPD patterns of comparable or superior quality to those obtained in state-of-the-art laboratory XRPD, all in less than 5 s. Additional cases featuring well-established pharmaceutical active ingredients (API) and excipients substantiate the concept of high throughput in pharmaceuticals, affirming data quality through structural refinements aligned with literature-derived unit cell parameters. Synchrotron data need not always be state-of-the-art to compete with lab-XRPD data. The key lies in ensuring user-friendliness, reproducibility, accessibility, cost-effectiveness, and the streamlined efforts associated with synchrotron instrumentation to remain highly competitive with their laboratory counterparts.

Association between neuroimaging findings and neurological sequelae in patients with congenital cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of disability. There is little evidence on the prognostic value of lesions identified in neuroimaging studies. AIM: The study aimed to assess the severity of lesions detected with brain MRI and transfontanellar ultrasound and their relationship with long-term neurological deficits. PATIENTS AND METHODS: We performed a retrospective, analytical, observational study of 36 patients with congenital CMV infection. Neuroimaging studies were reviewed and classified according to the modified Noyola' scale. Imaging findings were compared with neurological alterations in the patients' most recent follow-up evaluation at the paediatric neurology department. RESULTS: Thirty-six patients were studied (transfontanellar ultrasound: 30; brain MRI: 29). Twenty of 30 patients showed ultrasound abnormalities; of these, 11 showed alterations on brain MR images (P = .04) and 10 had neurological impairment (P = .008). Transfontanellar ultrasound had a sensitivity of 83.3%, 90% CI: 58-100 and a specificity of 44.4%, 90% CI: 18.7-70.2 for predicting neurological sequelae. Brain MRI displayed abnormalities in 20 of 29 patients, of whom 16 had neurological impairment (P < .001). MRI had a sensitivity of 94%, 95% CI: 80-100 and a specificity of 66.6%, 95% CI: 36-97.5 for predicting neurological sequelae. Modified Noyola' scale values > 2 were correlated with psychomotor retardation (P < .001). CONCLUSIONS: Our findings validate previous studies reporting a statistical significant correlation between the extension of neuroimaging lesions and severity of neurological deficits.

A pathway for entry of reoviruses into the host through M cells of the respiratory tract.

Many microorganisms gain access to the systemic circulation after entering the respiratory tract. The precise pathways used to cross the mucosal barriers of the lungs have not been clearly described. We have used the mammalian reoviruses in order to determine the pathway that a systemic virus uses to penetrate the mucosal barrier and enter the systemic circulation after entering the airways of the lungs. Reoviruses enter through pulmonary M cells, which overlie bronchus-associated lymphoid tissue, and subsequently spread to regional lymph nodes. Thus, the pathway through M cells represents a strategy by which viruses and probably other microorganisms can penetrate the mucosal surface of the respiratory tract and thereby enter the systemic circulation.

Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO.

BACKGROUND: Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. RESULTS: We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4') or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial destruction of NPA cell line by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of anti-TPO aAbs shows that B4' induced an anti-proliferative effect and a better ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody-dependent cell-mediated cytotoxicity was increased when human peripheral blood mononuclear cells were used as effector cells, suggesting that FcgammaRs, CD64, CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4 and B4', exhibited CDC activity. CONCLUSIONS: These data indicate that anti-TPO aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG glycosylation appears to be important for cytotoxic activity and ADCC efficiency depends on FcgammaR-bearing cells. Finally, recombinant human anti-TPO aAbs cannot yet be considered as an optimal tool for the development of a novel therapeutic approach for thyroid cancer.

Pharmacological rescue of mutant p53 conformation and function.

Compounds that stabilize the DNA binding domain of p53 in the active conformation were identified. These small synthetic molecules not only promoted the stability of wild-type p53 but also allowed mutant p53 to maintain an active conformation. A prototype compound caused the accumulation of conformationally active p53 in cells with mutant p53, enabling it to activate transcription and to slow tumor growth in mice. With further work aimed at improving potency, this class of compounds may be developed into anticancer drugs of broad utility.

Subjective interpretation of inconclusive BRCA1/2 cancer genetic test results and transmission of information to the relatives.

OBJECTIVE: BRCA1/2 gene mutations are not frequently identified in breast or ovarian cancer patients who are the first members of their family to be tested. Little is known about how probands interpret and cope with these results, which are generally referred to as 'inconclusive'. The aim of this study was to describe subjective understanding by women with cancer in response to an inconclusive BRCA1/2 test, describing the difficulties or non-difficulties they encountered about the transmission of information to their family. METHODS: A cohort of 30 women with breast/ovarian cancer were followed for a period of up to 2 years after delivery of their inconclusive genetic test results. Self-administered questionnaires with closed and open questions were distributed. A qualitative analysis of open-ended questions is presented here. RESULTS: These women's reactions to inconclusive results were of three kinds. The majority (n=14) were still uncertain about their carrier status, which is an adequate medical interpretation of the results, while others (n=9) took their inconclusive results to mean that they were definitely not carriers, and the women in the last group (n=7) were convinced that they were actually carriers. There was some overlap between these perceptions and actual genetic risk. CONCLUSIONS: The transmission of information to the family was found to differ qualitatively across the three groups and more difficulties in this respect were expressed by those who were uncertain about their carrier status.

Association between neuroimaging findings and neurological sequelae in patients with congenital cytomegalovirus infection. / Asociación entre neuroimagen y secuelas neurológicas en pacientes con infección congénita por citomegalovirus.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is an important cause of disability. There is little evidence on the prognostic value of lesions identified in neuroimaging studies. AIM: The study aimed to assess the severity of lesions detected with brain MRI and transfontanellar ultrasound and their relationship with long-term neurological deficits. PATIENTS AND METHODS: We performed a retrospective, analytical, observational study of 36 patients with congenital CMV infection. Neuroimaging studies were reviewed and classified according to the modified Noyola' scale. Imaging findings were compared with neurological alterations in the patients' most recent follow-up evaluation at the paediatric neurology department. RESULTS: Thirty-six patients were studied (transfontanellar ultrasound: 30; brain MRI: 29). Twenty of 30 patients showed ultrasound abnormalities; of these, 11 showed alterations on brain MR images (P=.04) and 10 had neurological impairment (P=.008). Transfontanellar ultrasound had a sensitivity of 83.3%, 90% CI: 58-100 and a specificity of 44.4%, 90% CI: 18.7-70.2 for predicting neurological sequelae. Brain MRI displayed abnormalities in 20 of 29 patients, of whom 16 had neurological impairment (P<.001). MRI had a sensitivity of 94%, 95% CI: 80-100 and a specificity of 66.6%, 95% CI: 36-97.5 for predicting neurological sequelae. Modified Noyola' scale values >2 were correlated with psychomotor retardation (P<.001). CONCLUSIONS: Our findings validate previous studies reporting a statistical significant correlation between the extension of neuroimaging lesions and severity of neurological deficits.

[Targeted screening for pre-eclampsia in the first trimester of pregnancy at Toulouse University Hospital]. / Le dépistage ciblé de la pré-éclampsie au premier trimestre de la grossesse au CHU de Toulouse.

GOALS: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality. Early treatment by aspirin has been shown to significantly reduce PE risk before 37weeks supporting the implementation of first-trimester screening. SUBJECTS AND METHODS: A targeted screening was recently implemented at Toulouse University Hospital for women in their first pregnancy or those with personal or familial history of PE. It uses Fetal Medicine Foundation (FMF) algorithm that combines maternal characteristics, clinical, biophysical and biochemical (PAPP-A, Pregnancy Associated Plasma Protein-A, and PlGF, Placental Growth Factor) data. We describe this first population of pregnant women and compare our results with those of a mini-test that excludes PlGF and biophysical data. RESULTS: Between October 2016 and September 2017, 500women have benefited from this screening. In such targeted population, we identified 3,6 % (n=18) of women at high risk to develop PE before 34weeks and 9,6 % (n=48) of women at high risk to develop PE between 34 and 37weeks. When we recalculated the risk using the mini-test, only 10women (56 %) were identified at high risk of early PE. CONCLUSION: For the first time in France, we report the result of a targeted screening of PE during the first trimester using the FMF algorithm. We describe the screened population and show that it is more efficient than the mini-test.