Evaluation of early single dose vaccination on swine influenza A virus transmission in piglets: From experimental data to mechanistic modelling.

Swine influenza A virus (swIAV) is a major pathogen affecting pigs with a huge economic impact and potentially zoonotic. Epidemiological studies in endemically infected farms permitted to identify critical factors favoring on-farm persistence, among which maternally-derived antibodies (MDAs). Vaccination is commonly practiced in breeding herds and might be used for immunization of growing pigs at weaning. Althoughinterference between MDAs and vaccination was reported in young piglets, its impact on swIAV transmission was not yet quantified. To this aim, this study reports on a transmission experiment in piglets with or without MDAs, vaccinated with a single dose injection at four weeks of age, and challenged 17 days post-vaccination. To transpose small-scale experiments to real-life situation, estimated parameters were used in a simulation tool to assess their influence at the herd level. Based on a thorough follow-up of the infection chain during the experiment, the transmission of the swIAV challenge strain was highly dependent on the MDA status of the pigs when vaccinated. MDA-positive vaccinated animals showed a direct transmission rate 3.6-fold higher than the one obtained in vaccinated animals without MDAs, estimated to 1.2. Vaccination nevertheless reduced significantly the contribution of airborne transmission when compared with previous estimates obtained in unvaccinated animals. The integration of parameter estimates in a large-scale simulation model, representing a typical farrow-to-finish pig herd, evidenced an extended persistence of viral spread when vaccination of sows and single dose vaccination of piglets was hypothesized. When extinction was quasi-systematic at year 5 post-introduction in the absence of sow vaccination but with single dose early vaccination of piglets, the extinction probability fell down to 33% when batch-to-batch vaccination was implemented both in breeding herd and weaned piglets. These results shed light on a potential adverse effect of single dose vaccination in MDA-positive piglets, which might lead to longer persistence of the SwIAV at the herd level.

Chronotype, Longitudinal Volumetric Brain Variations Throughout Adolescence, and Depressive Symptom Development.

OBJECTIVE: Adolescence is a critical period for circadian rhythm, with a strong shift toward eveningness around age 14. Also, eveningness in adolescence has been found to predict later onset of depressive symptoms. However, no previous study has investigated structural variations associated with chronotype in early adolescence and how this adds to the development of depressive symptoms. METHOD: Assessment of 128 community-based adolescents (51% girls) at age 14 and 19 years was performed. Using whole-brain voxel-based morphometry, baseline (at age 14) regional gray matter volumes (GMVs), follow-up (at age 19) regional GMVs, and longitudinal changes (between 14 and 19) associated with Morningness/Eveningness Scale in Children score and sleep habits at baseline were measured. The association of GMV with depressive symptoms at 19 years was studied, and the role of potential clinical and genetic factors as mediators and moderators was assessed. RESULTS: Higher eveningness was associated with larger GMV in the right medial prefrontal cortex at ages 14 and 19 in the whole sample. GMV in this region related to depressive symptoms at age 19 in catechol-O-methyltransferase (COMT) Val/Val, but not in Met COMT, carriers. Larger GMV also was observed in the right fusiform gyrus at age 14, which was explained by later wake-up time during weekends. CONCLUSION: In adolescence, eveningness and its related sleep habits correlated with distinct developmental patterns. Eveningness was specifically associated with GMV changes in the medial prefrontal cortex; this could serve as a brain vulnerability factor for later self-reported depressive symptoms in COMT Val/Val carriers.

Normal aging modulates prefrontoparietal networks underlying multiple memory processes.

A functional decline of brain regions underlying memory processing represents a hallmark of cognitive aging. Although a rich literature documents age-related differences in several memory domains, the effect of aging on networks that underlie multiple memory processes has been relatively unexplored. Here we used functional magnetic resonance imaging during working memory and incidental episodic encoding memory to investigate patterns of age-related differences in activity and functional covariance patterns common across multiple memory domains. Relative to younger subjects, older subjects showed increased activation in left dorso-lateral prefrontal cortex along with decreased deactivation in the posterior cingulate. Older subjects showed greater functional covariance during both memory tasks in a set of regions that included a positive prefronto-parietal-occipital network as well as a negative network that spanned the default mode regions. These findings suggest that the memory process-invariant recruitment of brain regions within prefronto-parietal-occipital network increases with aging. Our results are in line with the dedifferentiation hypothesis of neurocognitive aging, thereby suggesting a decreased specialization of the brain networks supporting different memory networks.

Yield and impact of emergency capsule enteroscopy in severe obscure-overt gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Patients with obscure-overt gastrointestinal bleeding (OOGIB) are defined by overt hemorrhage and negative upper and lower endoscopy findings. At present, the place of emergency capsule enteroscopy in patients with severe OOGIB is unknown. The aim of this study was to assess the diagnostic yield and the impact of emergency capsule enteroscopy on further management in patients with severe OOGIB. PATIENTS AND METHODS: Between 2003 and 2010, we retrospectively included all patients with severe OOGIB who underwent emergency capsule enteroscopy in the 24-48 h following negative urgent upper and lower endoscopy. Severe OOGIB was defined by ongoing bleeding with hemodynamic instability and/or the need for significant red blood cell transfusion. RESULTS: Out of 5744 patients hospitalized in our Gastrointestinal Bleeding Unit, 55 (1%) presented with severe OOGIB and underwent emergency capsule enteroscopy. Capsule enteroscopy showed blood in 41 patients (75%) and lesions in 37 patients (67%). Findings included small bowel angiodysplasia in 19 patients (35%), ulcers in 7 (13%), tumors in 5 (9%), small-bowel varices in 2 (3%), cecum angiodysplasia in 4 (7%), fresh blood in small bowel without identified lesion in 12 (22%). Specific diagnostic and therapeutic procedures were undertaken in 78 % of patients. Further management included endoscopy (54%), surgery (22%), and radiology (2%). CONCLUSIONS: Emergency capsule enteroscopy identified bleeding lesions in 67 % of patients with severe OOGIB. Emergency capsule enteroscopy seems to be a promising diagnostic tool with a subsequent impact on clinical management in patients with severe OOGIB.

Correction: Effect of the orientation and fluid flow on the accumulation of organotin compounds to Chemcatcher passive samplers.

Correction for 'Effect of the orientation and fluid flow on the accumulation of organotin compounds to Chemcatcher passive samplers' by H. Ahkola et al., Environ. Sci.: Processes Impacts, 2015, 17, 813-824, https://doi.org/10.1039/C4EM00585F.

Repositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis.

African animal trypanosomiasis or nagana, caused principally by infection of the protozoan parasites Trypanosoma congolense and Trypanosoma vivax, is a major problem in cattle and other livestocks in sub-Saharan Africa. Current treatments are threatened by the emergence of drug resistance and there is an urgent need for new, effective drugs. Here, we report the repositioning of a compound series initially developed for the treatment of human African trypanosomiasis. A medicinal chemistry program, focused on deriving more soluble analogues, led to development of a lead compound capable of curing cattle infected with both T. congolense and T. vivax via intravenous dosing. Further optimization has the potential to yield a single-dose intramuscular treatment for this disease. Comprehensive mode of action studies revealed that the molecular target of this promising compound and related analogues is the cyclin-dependent kinase CRK12.

Translocation of an intra-uterine contraceptive device with sigmoid penetration through an endometriosic nodule.

The intra-uterine device (IUD) is the most common existing reversible contraception. Uterine perforation occurs in 0.6 to 3.4 per 1000 insertions. We describe the first report of IUD translocation and subsequent penetration of the sigmoid through an endometriosic nodule. A 44-year-old gravida 2 para 2 woman consulted for rectal bleeding and melena. Rectosigmoidoscopy revealed ischemic colitis secondary to the use of NSAIDs, which explained the bleeding, but also sigmoid perforation from part of an intra-uterine device. This was discovered by chance. Perforation had occurred though an endometriosic nodule.

Development of 100 Mo -containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search.

This paper reports on the development of a technology involving 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼ 1 kg ), high optical quality, radiopure 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100 Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8 σ . Less than 10 µ Bq/kg activity of 232 Th ( 228 Th ) and 226 Ra in the crystals is ensured by boule recrystallization. The potential of 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10 kg × d exposure: the two neutrino double-beta decay half-life of 100 Mo has been measured with the up-to-date highest accuracy as T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100 Mo .

Effect of the orientation and fluid flow on the accumulation of organotin compounds to Chemcatcher passive samplers.

Monitoring of harmful substances in an aquatic environment is based on spot sampling which is the only sampling technique accepted by environmental authorities in the European Union. Still the implementation of the European Union Water Framework Directive (WFD) requires novel sampling tools for monitoring priority pollutants since their concentrations in natural waters can often remain below the limit of detection when using the conventional spot sampling method. However, this does not necessarily mean that the pollutant is not present in the aquatic environment. Many chemicals that are considered to be harmful are bioaccumulative and can affect, e.g., reproduction of aquatic organisms even at very low concentration levels. Also the timing is crucial since with spot sampling the pulse of harmful substances can easily be missed. Passive samplers collect the compounds for a certain amount of time which allows the concentrations in the sampler to rise to the measurable level where they are easy to detect. Organotin compounds (OTCs) have been widely used as plastic stabilizers and antifouling agents in ship paints and in many industrial processes. Among the OTCs, tributyltin is listed as a WFD priority substance. In this study a small-scale flow simulation around the Chemcatcher passive sampler was performed to visualize the flow streamlines in the vicinity of the sampler and to study the pressure experienced by the receiving phase in different sampler positions. With laboratory experiments the sampling rates for each OTC were determined and the effect of the flow velocity and sampler orientation on the accumulation of OTCs is discussed. The pressure changes were observed on the surface of the receiving phase in simulations with varying sampler orientations. Despite that, the laboratory experiments discovered no difference in the accumulation of compounds when varying the sampler orientation. The concentrations of OTCs in the surrounding water calculated from the passive sampling results were equivalent to the spot sampling ones. Hence, the Chemcatcher passive sampler provides a practical tool for the implementation of WFD.

Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation.

The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty-four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high-amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 +/- 11.6 vs 1 +/- 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food-induced colonic motor response and significantly lower colonic activity in transverse colon (374 +/- 1220 vs 3249 +/- 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 +/- 6364 vs 88780 +/- 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.

Does the supplementation of the formula with fibre increase the risk of gastro-oesophageal reflux during enteral nutrition? A human study.

BACKGROUND & AIMS: Fibre-supplements in enteral feeding could increase the risk of gastro-oesophageal reflux (GOR). The aim of this study was to assess in humans the physiological effects of the supplementation of the enteral diet with different types of dietary fibre on gastro-oesophageal reflux episodes, gastric acidity and gastric emptying. METHODS: pH profiles were compared in 12 healthy volunteers between three different formula (500 kcal, 250 mL x h-1) delivered in a random order and containing either no fibre, either soy polysaccharide fibre only or mixed fibre from pea and inuline. Enteral diets were instilled through a nasogastric tube. Oesophageal and gastric pH recordings were combined with the ultrasound measurement of gastric antral area during the infusion. RESULTS: More GOR were observed with a fibre-free diet (median 4, range 1-10) than with a mixed (median 1.5, range 0-5) (P=0.04) or soy polysaccharide fibre (median 1.5, range 0-5) (P=0.04) diet. The median duration of GOR was longer with the mixed fibre (median 3.6, range 1.8-7.2) than with the fibre-free diet (mean 1.8 min, range 1-3.6) (P<0.05). The number of GOR episodes lasting more than 5 min, the duration of the longest GOR and the percent of time under pH 4 were not significantly different with the three diets. The intragastric pH profile and the ultrasound antral area were not different with all three diets. CONCLUSIONS: Addition of fibre to the enteral formula had limited effects on the onset of GOR episodes. It decreased the number of GOR but increased their duration. These effect were more pronounced with the formula containing soluble fibre. At variance, the addition of fibre had no significant effect on gastric emptying and gastric acid secretion.

Argon plasma coagulation in the treatment of hemorrhagic radiation proctitis is efficient but requires a perfect colonic cleansing to be safe.

AIMS: We evaluate prospectively effectiveness, tolerance, predictive factors of failure and complications of argon plasma coagulation (APC) in the treatment of hemorrhagic radiation proctitis (HRP). PATIENTS AND METHODS: Twenty-seven patients were treated by APC for HRP. Eight patients needed blood transfusion before APC. Six patients were anti-coagulated and one had severe thrombocytopenia. APC was performed without sedation in 25/27 patients. Before APC treatment, bowel preparation was performed by enema (n = 19 sessions), polyethylene glycol or sodium phosphate (n = 53 sessions). APC treatment was performed every 5 weeks. Effectiveness of APC was based on clinical and endoscopic score and biological status before and after APC treatment. RESULTS: The mean follow-up was 13.6 months (range, 3-31 months). After one to seven sessions of APC (average, 2.66 sessions), twenty-five patients (92%) had no recurrence of bleeding. The bleeding score decreased from 3.03 to 0.42 (P < 0.001) and the endoscopic score from 3.08 to 0.73 (P < 0.001). Out of the eight patients requiring blood transfusion prior to APC sessions, only one required blood transfusion after APC (P < 0.05). One late relapse was observed and successfully re-treated by APC. Side effects were anal or rectal pain (n = 3) and vagal symptoms (n = 2). Three colonic explosions occurred, with perforation leading to surgery in one case. The incidence of bowel explosion was higher after local preparation (3/19 sessions) compared with oral preparation (0/53 sessions) (P < 0.05). No stricture due to APC appeared, even if telangiectasias coagulated during a session were circumferential. CONCLUSION: Coagulation by APC is an effective and safe treatment of HRP if a complete cleansing preparation is performed to avoid explosion.

Effects of polyethylene glycol 4000 on 24-h manometric recordings of left colonic motor activity.

BACKGROUND: It has been shown that low doses of polyethylene glycol (PEG) 4000 are effective in the treatment of chronic constipation. The aim of this study was to describe the effects on colonic motility of oral PEG 4000 treatment and intraluminal instillation of PEG 4000. METHODS: Left colonic and rectosigmoid manometric recordings were performed for 27 h in six constipated patients and in six healthy volunteers. At the end of the recording, bisacodyl and PEG 4000 were instilled into the lumen of the colon. To assess the effects of oral administration of PEG 4000 on colonic motility, manometric recordings were also performed in constipated patients after 4 weeks of treatment with PEG 4000. RESULTS: All patients had significantly more stools during than before PEG treatment. There was no significant difference between the number and the characteristics of high-amplitude propagating contractions (HAPC) or the area under the curve (AUC) before or during treatment with PEG 4000. Intraluminal instillation of PEG induced HAPC in only one patient and in no controls. CONCLUSION: This study shows that PEG 4000 has no effect on left colonic and rectosigmoid motor activity during oral treatment, despite its clinical effectiveness, or after local instillation.

Low levels of gastric mucosal glutathione during upper gastric bleeding associated with the use of nonsteroidal anti-inflammatory drugs.

OBJECTIVES: To investigate the glutathione concentrations in gastric mucosa from patients with acute gastric bleeding related to nonsteroidal anti-inflammatory drugs (NSAIDs), and to test the influence of nutritional status on mucosal glutathione. Glutathione protects the gastrointestinal mucosa against reactive oxygen species, and glutathione content in various tissues may be depleted during malnutrition. METHODS: Endoscopic biopsies were obtained from 39 patients. Eighteen of these (9 well-nourished, 9 malnourished) presented with gastric bleeding ulcers related to NSAIDs. Twenty-one other patients (12 well-nourished, 9 malnourished) underwent normal routine diagnostic endoscopy and served as controls. Malnutrition was defined as a loss of over 10% of normal body weight and/or plasma albumin levels below 30 g/l. Gastric biopsies were taken from the fundus and antrum (controls) and from the region of the ulcer (patients with acute bleeding) and frozen quickly until glutathione analysis by high-performance liquid chromatography (HPLC) coulometric detection. Results were expressed as nmol/mg wet tissue. RESULTS: Gastric mucosal glutathione levels were significantly (P < 0.05) lower in both the antrum (0.81 +/- 0.34 v. 1.41 +/- 0.88 nmol/mg tissue) and the fundus (1.04 +/- 0.54 v. 1.43 +/- 0.92 nmol/mg tissue, P < 0.05) in malnourished than in well-nourished control patients. Glutathione mucosal concentrations were decreased significantly in patients with NSAID-induced gastric bleeding compared with control patients (0.38 +/- 0.36 v. 1.12 +/- 0.56 nmol/mg tissue, P < 0.001), and the lowest glutathione levels were observed in malnourished patients (0.28 +/- 0.20 v. 0.48 +/- 0.15 nmol/mg tissue in well-nourished patients, not significant). CONCLUSION: Malnutrition is associated with low levels of gastric glutathione. This may contribute to the severity and the onset of haemorrhage in NSAID-induced gastric ulcers.

Chronic hepatitis C with normal or abnormal aminotransferase levels: is it the same entity?

OBJECTIVE: The features of hepatitis C virus (HCV) infection with persistently normal serum alanine aminotransferase (ALT) activity levels are not well defined. This study evaluated the characteristics of HCV infection according to the presence or absence of elevated ALT. METHODS: Demographic data, liver histology and HCV genotype were studied in a group of 80 HCV-RNA-positive subjects with persistently normal ALT (PNALT) (group 1), and compared with a second group of 455 HCV-RNA-positive patients with elevated ALT (group 2). The annual progression of liver fibrosis was also calculated. RESULTS: A higher proportion of women was found in group 1:64% vs 42% in group 2 (P< 0.0002). The HCV genotype 1 was less frequent in group 1:49% vs 60% in group 2 and genotype 2 was more frequent: 16% in group 1 vs 4% in group 2 (P< 0.002). Cirrhosis was less frequent in group 1 (4% vs 13% in group 2 (P< 0.0001)). Normal liver was more frequent in group 1:9% vs 1% in group 2 (P< 0.0001). The Knodell score was significantly different between the two groups: 3.2 +/- 0.27 vs 7.15 +/- 0.22 (P< 0.0001). The progression of liver fibrosis was lower in group 1: 0.053 +/- 0.14 units/year vs 0.13 +/- 0.24 in group 2 (P < 0.007). CONCLUSION: HCV infection with PNALT is associated with less severe histological liver disease and a lower fibrosis progression rate. This suggests that the natural history of HCV infection in these patients is different from that in patients with abnormal ALT.

Circulating endotoxin and antiendotoxin antibodies during severe sepsis and septic shock.

The presence of circulating endotoxin is common during sepsis but its prognostic value is poor. We hypothesized that this lack of correlation with outcome could be related in part to the presence of circulating antiendotoxin antibodies. In a 14-bed medical intensive care unit, in an 821-bed tertiary teaching hospital, we prospectively assessed endotoxin and antiendotoxin antibodies in patients with severe sepsis or septic shock. Blood samples for the determination of circulating endotoxin and antiendotoxin antibodies were drawn when severe sepsis or septic shock were diagnosed (day 0) and then on day 1, day 2, and day 4. Daily measurements of antiendotoxin antibodies did not discriminate survivors from nonsurvivors. No antibody depletion was observed. However, during follow-up, the antiendotoxin immunoglobulin (Ig)M antibody level increased among survivors but decreased among nonsurvivors (51.2 vs -44.8 MU/mL, P=007). Circulating endotoxin was detectable among 9 of 17 patients on inclusion but neither the basal value nor sequential measurements correlated with outcome. These results suggest that during severe sepsis and septic shock, circulating endotoxin is a poor prognostic marker whereas the detection of an increase in IgM antiendotoxin antibody levels could identify survivors. This increase in IgM antibody levels could be attributed to a reactivation of the immune system.

Management of sinonasal hemangiopericytomas.

The purpose of the present study is to report four cases of sinonasal hemangiopericytoma (HP) diagnosed and treated in our department between 1987 and 1998. The pretreatment findings and the treatment are described and discussed in the light of the literature. HP are unusual vascular tumors, featuring pericytes distributed around normal vascular channels. Two of these four cases were located in the nasal cavity and the other two were located in the maxillary sinus. Inside the nasal cavity, HP presented as a protruding reddish-gray mass with marked bleeding on contact. Electron microscopy and immunohistochemical techniques are essential for diagnosis and to distinguish HP from other sarcomatous tumors. Preoperative assessment included routine CT, MRI, arteriography and selective embolization. These tumors must be treated surgically with complete excision. An endonasal approach was performed in two cases of intranasal HP, while a combined external-endonasal approach was required for the other two cases of HP.

Endoscopic sinus surgery for sinonasal haemangiopericytomas.

Haemangiopericytomas are rare peri-vascular tumours with variable malignant potential. The nasal cavity and the paranasal sinuses are most often involved in the head and neck. Five cases of haemangiopericytomas treated by a strict endonasal endoscopic approach are presented. Bleeding and nasal obstruction are the most frequent symptoms. Computed tomography (CT) scan and magnetic resonance imaging (MRI) allowed pre-operative assessment. Angiography with embolization was needed in two of the five cases. None of our patients presented with malignant histology. Our five cases were operated on, and a total tumour excision was performed through the endoscopic endonasal approach. We had one recurrence with a mean follow-up of 4.5 years. We suggest that when the tumour is purely intranasal or strictly located in the ethmoid or sphenoid sinus, it can be removed via an endonasal approach under endoscopic guidance in experienced hands.

Acute laryngeal paralysis induced by the migration of a totally implantable venous access device's catheter tip.

The authors report a case of acute vagus nerve paralysis that appeared during a course of chemotherapy. The drugs had been administered through a totally implantable venous access device (TIVAD), whose catheter tip had migrated into the right internal jugular vein (IJV) and was surrounded by a complete venous thrombosis. The supposed aetiology of this paralysis was a leakage of the cytotoxic drug (5-fluorouracil) from the vessel wall into the surrounding carotid space, because of the stagnation of the chemotherapeutic agent above the thrombosis. Four months after cessation of chemotherapy, the laryngeal paralysis was still evident.

[Intrahepatic portocaval shunt: review of the literature, apropos of 1 case]. / Shunt porto-cave intra-hépatique. Revue de la littérature, à propos d'un cas.

We report a case of portal-hepatic shunt which was detected fortuitously by ultrasonography in a 66-year-old patient. This abnormality, mainly described in cirrhotic liver and rarely in healthy liver, is usually revealed by hepatic encephalopathy or glycoregulation disorders. We propose a diagnostic and therapeutic approach based on a review of the literature.