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.

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.

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.

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.

Detection of multiple drug-resistant Trypanosoma congolense populations in village cattle of south-east Mali.

BACKGROUND: Tsetse fly-transmitted African animal trypanosomosis causes annual losses that run into billions of dollars. The disease is assumed to cause hunger and poverty in most sub-Saharan countries since it represents a serious impediment to sustainable livestock production. Both a cross-sectional and a longitudinal study were carried out from November to December 2007 to evaluate trypanosomosis risk and susceptibility of trypanosomes to trypanocidal drug treatment in village cattle populations in south-east Mali. METHODS: Eight purposively selected villages participated in the study. In each village, eight traps deployed along drainage lines over 24 hour duration were used to catch tsetse. One hundred systematically selected cattle in the study villages were examined for trypanosomes. All trypanosome-positive cattle were randomly allocated into two treatment groups: a group treated with 0.5 mg/kg bw. isometamidium chloride (ISMM) and a group treated with 3.5 mg/kg bw. diminazene aceturate (DIM). The cattle were monitored for trypanosomes at day 14 and 28 post-treatment. RESULTS: Of the 796 cattle examined, 125 (15.7%) were trypanosome-positive. Village trypanosome prevalences ranged between 11% and 19%. There were no significant (p > 0.05) differences in the village trypanosome prevalences. Trypanosoma congolense was the dominant trypanosome species accounting for 73% (91/125) of the infections and T. vivax the remainder. Twenty (31.7%) of the 63 cattle on 0.5 mg/kg bw. ISMM treatment were still positive14 days post-treatment. Of the 43 aparasitaemic cattle monitored to day 28, 25.6% (11) became parasitaemic, resulting in a cumulative failure rate of 49.2% (31/63). Trypanosoma congolense accounted for 77.4% (24/31) of failed ISMM treatments. The 62 cattle treated with 3.5 mg/kg bw. DIM resulted in 30.6% (19/62) failed treatments. Although 42.2% (19/45) of T. congolense positive cattle did not respond to DIM treatment, all T. vivax positive cattle responded positively to DIM treatment. CONCLUSIONS: The overreliance on trypanocides in the control of trypanosomosis will ultimately lead to multiple drug-resistant trypanosome populations as detected in villages in south-east Mali rendering the use of drugs doubtful. Effective alternative methods for trypanosomosis control ought to substitute chemotherapy to ensure sustainable cattle production in these villages. Since there is no single strategy for containing trypanocidal drug resistance, promotion of an integrated approach combining proven trypanosomosis control approaches in high trypanosomosis risk areas is most desirous. The best-bet strategy this study recommended for areas with multiple drug resistance included area-wide community tsetse control, control of co-infections to exploit self-cure against resistant trypanosome populations and the rational use of trypanocidal drugs which should be urgently promoted at all levels as a way of containing or reversing resistance.

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.

Endoscopic band ligation could decrease recurrent bleeding in Mallory-Weiss syndrome as compared to haemostasis by hemoclips plus epinephrine.

BACKGROUND: Mallory-Weiss syndrome (MWS) with active bleeding at endoscopy may require endoscopic haemostasis the modalities of which are not well-defined. AIM: To compare the efficacy of endoscopic band ligation vs. hemoclip plus epinephrine (adrenaline) in bleeding MWS. METHODS: From 2001 to 2008, 218 consecutive patients with a MWS at endoscopy were hospitalized in our Gastrointestinal Bleeding Unit. In 56 patients (26%), an endoscopic haemostasis was required because of active bleeding. Band ligation was performed in 29 patients (Banding group), while hemoclip application plus epinephrine injection was performed in 27 patients (H&E group). Treatment efficacy and early recurrent bleeding were retrospectively compared between the two groups. RESULTS: Primary endoscopic haemostasis was achieved in all patients. Recurrent bleeding occurred in 0% in Banding group vs. 18% in H&E group (P = 0.02). The use of hemoclips plus epinephrine (OR = 3; 95% CI = 1.15-15.8) and active bleeding at endoscopy (OR = 1.9; 95% CI = 1.04-5.2) were independent predictive factors of early recurrent bleeding. CONCLUSIONS: Haemostasis by hemoclips plus epinephrine was an independent predictive factor of rebleeding. This result suggests that band ligation could be the first choice endoscopic treatment for bleeding MWS, but requires further prospective assessment.

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.

Irritable bowel syndrome is more frequent in patients hospitalized for ischaemic colitis: results of a case-control study.

It has been suspected that there is an epidemiological link between irritable bowel syndrome (IBS) and ischaemic colitis (IC). We performed a retrospective case-control study to compare the frequency of IBS in patients hospitalized for IC compared with that of patients with peptic ulcer bleeding. Cases were patients with a first episode of IC and controls were patients with a first episode of peptic ulcer bleeding, matched to cases for sex and 10-year age-class. Diagnosis of IBS was based on medical information extracted from hospital medical files and a standard self-questionnaire. The association between IBS and IC was tested using Mc Nemar's paired odds ratio (OR); confidence interval at 95% (CI 95%) was calculated; Mantel-Haenzel's Chi(2) was applied. A total of 113 cases and 113 matched controls were studied. There were 37 males and 76 females and the mean age was 69 +/- 15 years in each group. The prevalence of IBS in cases was 16.9%vs 1.8% in controls. The risk of IBS was 11.05 times higher among cases than in controls (P < 0.001); CI 95%: (2.45-49.74). A total of 87 pairs with complete data were used for OR calculation. The risk of IBS was 7.5 times higher in cases than in controls (P = 0.002); CI 95%: (1.72-32.80). This case-control study shows that IBS is more frequent in IC patients than in controls.

Evaluation of biodegradation of nonylphenol ethoxylate and lignin by combining toxicity assessment and chemical characterization.

The aerobic biodegradation of commercial nonylphenol ethoxylate (NPE) mixture and alkali lignin was studied using the OECD headspace test accompanied by the simultaneous measurement of ecotoxicity directly from the biodegradation liquors and by the follow-up of the chemical composition of the studied chemicals. NPE degradation was dependent on the inoculum source: approximately 40% of NPE was mineralized into CO(2) during the 4-week experiment when inoculum from Helsinki City wastewater treatment plant (WWTP) was used, and only 12% was mineralized when inoculum from Jyväskylä City WWTP was used. Chemical analyses revealed a shift in the ethoxylate chain length from longer to shorter soon after the beginning of the NPE biodegradation tests. At the same time also toxicity (reverse electron transport assay, RET) and estrogenic activity (human estrogen receptor yeast) measured directly from the biodegradation liquors decreased. In case of alkali lignin, approximately 11% was mineralized in the test and chemical analysis showed in maximum a 30% decrease in lignin concentration. Toxicity of lignin biodegradation liquors started to decrease in the beginning of the test, but became more toxic towards the end of the test again. Especially RET assay proved to be sensitive enough for measuring toxicity changes directly from biodegradation liquors, although a concentrating treatment of the liquors is recommended for a more detailed characterization and identification of toxic metabolites.

Watermelon stomach in systemic sclerosis: its incidence and management.

BACKGROUND: To date, there are no large endoscopic studies in systemic sclerosis (SSc), and both prevalence and characteristics of watermelon stomach in SSc have not been determined. AIMS: To determine the prevalence, clinical presentation, endoscopic appearance, therapy success and long-term outcome in SSc patients with watermelon stomach and make predictions about which SSc patients are at risk for watermelon stomach. Patients and methods From 1990 to 2008, 264 patients were seen for evaluation of SSc. Data were collected as regards patients' characteristics, time of watermelon stomach onset, features, therapy and outcome of watermelon stomach. RESULTS: Fifteen SSc patients (5.7%) exhibited watermelon stomach. SSc onset preceded watermelon stomach manifestations in 13 patients (86.7%). Most patients (86.7%) presented with iron-deficiency anaemia, two other patients experienced gastrointestinal haemorrhage. Gastroscopy disclosed typical 'watermelon stomach' characterized by prominent, erythematous stripes, radiating in a spoke-like fashion from the antrum to the pylorus. All patients received conservative therapy; because of deterioration of watermelon stomach, eight patients (53.3%) underwent endoscopic procedures. During follow-up, five patients (33.3%) exhibited recurrences of watermelon stomach. CONCLUSIONS: Our series indicates that watermelon stomach should be considered when unexplained iron-deficiency anaemia occurs in SSc patients. Moreover, because watermelon stomach may be the first manifestation of SSc, patients with unexplained watermelon stomach should systematically undergo physical examination and autoantibody testing to detect the underlying SSc.

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.

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.

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.

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.

Spontaneous passage of a dislocated esophageal metal stent: report of two cases.

Delayed transpyloric impaction is a very rare complication of esophageal metallic stent placement. Authors report different endoscopic removal techniques, but none of these has been validated yet because of their variable success, time-consuming nature, and risk of perforation and hemorrhage. We report that a "wait-and-see" approach is a safe and effective policy in patients with permeable transpyloric impacted esophageal stents.