Albendazole metabolites excretion in human saliva as a biomarker to assess treatment compliance in mass drug administration (MDA) anthelmintic programs.

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.

X-Ray induced desorption and photochemistry in CO ice.

We report an investigation of X-ray induced desorption of neutrals, cations and anions from CO ice. The desorption of neutral CO, by far the most abundant, is quantified and discussed within the context of its application to astrochemistry. The desorption of many different cations, including large cations up to the mass limit of the spectrometer, is observed. In contrast, the only desorbing anions detected are O- and C-. The desorption mechanisms of all these species are discussed with the aid of their photodesorption spectrum. The evolution of the X-ray absorption spectrum shows significant chemical modifications of the ice upon irradiation, which along with the desorption of large cations gives a new insight into X-ray induced photochemistry in CO ice.

Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers.

Soil-transmitted-helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting preschool- and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to (i) evaluate the effect of type of diet (a heavy or light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and (ii) evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulfoxide (ALBSO) metabolite was enhanced more than 2-fold after food ingestion (a heavy or light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulfone (NHALBSO2) derivative and ALBSO for up to 96 h suggests that it may be feasible to develop a noninvasive tool to evaluate compliance/adherence to ALB treatment.

Mechanism of Indirect Photon-Induced Desorption at the Water Ice Surface.

Electronic excitations near the surface of water ice lead to the desorption of adsorbed molecules, through a so far debated mechanism. A systematic study of photon-induced indirect desorption, revealed by the spectral dependence of the desorption (7-13 eV), is conducted for Ar, Kr, N_{2}, and CO adsorbed on H_{2}O or D_{2}O amorphous ices. The mass and isotopic dependence and the increase of intrinsic desorption efficiency with photon energy all point to a mechanism of desorption induced by collisions between adsorbates and energetic H/D atoms, produced by photodissociation of water. This constitutes a direct and unambiguous experimental demonstration of the mechanism of indirect desorption of weakly adsorbed species on water ice, and sheds new light on the possibility of this mechanism in other systems. It also has implications for the description of photon-induced desorption in astrochemical models.

Influence of individual or group housing of newborn calves on rotavirus and coronavirus infection during the first 2 months of life.

Bovine rotavirus A (RVA) and bovine coronavirus (CoV) are the two main viral enteropathogens associated with neonatal calf diarrhea. The aim of the present work was to study the impact of group and individual housing systems in the epidemiology of RVA and CoV infection. Eleven calves reared in individual housing (FA) and nine calves in group housing (FB) were monitored during the first 7 weeks of life. Stool and serum samples were screened for RVA and CoV antigens by ELISA. IgG1 antibodies (Ab) to both antigens were also measured. From the 160 fecal samples collected, the proportion of positive samples to RVA and CoV was significantly higher in FB (23.6%) than in FA (9%) (p = 0.03). The geometric mean of colostral IgG1 Ab titers to CoV and RVA in FA (IgG1 anti-CoV 1024 and anti-RVA 1782.9) was lower than in FB (IgG1 anti-CoV 10,321.2 and anti-RVA 4096) at birth. Calves less than 2 weeks of life from FB had a higher risk of being infected by RVA (OR = 4.9; p = 0.01) and CoV (OR = 17.15; p = 0.01) than calves from FA. The obtained results showed that there was higher RVA and CoV shedding in group-housed calves than in individual-housed animals.

A spectroscopic and molecular dynamics study on the aggregation process of a long-acting lipidated therapeutic peptide: the case of semaglutide.

The aggregation properties of semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for the treatment of type 2 diabetes, have been investigated by spectroscopic techniques (UV-Vis absorption, steady-state and time-resolved fluorescence, and electronic circular dichroism) and molecular dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 µM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by blue luminescence and a ß-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs.

First report of group A rotavirus and bovine coronavirus associated with neonatal calf diarrhea in the northwest of Argentina.

Group A rotavirus (RVA) and bovine coronavirus (BCoV) are the two main viral enteropathogens associated with neonatal calf diarrhea. The aim of the present survey was to investigate the epidemiology and the role of RVA and BCoV in the presentation of dairy and beef calf diarrhea in Lerma Valley of Salta province, within the Northwest region of Argentina. Stool samples of calves with or without diarrhea younger than 2 months of age were collected from 19 dairy farms and 20 beef farms between the years 2014 and 2016. Stool samples were screened for RVA and BCoV detection by ELISA. Heminested multiplex RT-PCR was used for RVA typing and RT-PCR to confirm BCoV. Positive samples were submitted to sequencing analysis. Bovine RVA and BCoV were circulating in 63% (12/19) and 10.52% (2/19) of the dairy farms, respectively, where 9.5% (46/484) of the calves were positives to RVA and 0.4% (2/484) to BCoV. In beef herds, RVA was detected in 40% (8/20) of the farms and in 6.75% (21/311) of the calves, without positives cases of BCoV. Molecular analysis showed that in dairy farms, G6P[11] and G10P[11] were the prevalent RVA strains, while in beef farms, G10P[11] was the prevalent. The main finding was the detection for the first time of a G15P[11] causing diarrhea in beef calves of Argentina that represents a new alert to be consider for future vaccine updates. Analysis of detected BCoV showed that it is related to the other circulating strains of Argentina.

Desorption of neutrals, cations, and anions from core-excited amorphous solid water.

Core-excitation of water ice releases many different molecules and ions in the gas phase. Studying these desorbed species and the underlying desorption mechanisms can provide useful information on the effects of x-ray irradiation in ice. We report a detailed study of the x-ray induced desorption of a number of neutral, cationic, and anionic species from amorphous solid water. We discuss the desorption mechanisms and the relative contributions of Auger and secondary electrons (x-ray induced electron stimulated desorption) and initial excitation (direct desorption) as well as the role of photochemistry. Anions are shown to desorb not just through processes linked with secondary electrons but also through direct dissociation of the core-excited molecule. The desorption spectra of oxygen ions (O+, OH+, H2O+, O-, and OH-) give a new perspective on their previously reported very low desorption yields for most types of irradiations of water, showing that they mostly originate from the dissociation of photoproducts such as H2O2.

Analysis of the reliability of the Italian version of the Oral Behaviours Checklist and the relationship between oral behaviours and trait anxiety in healthy individuals.

BACKGROUND: The Oral Behaviours Checklist (OBC) is a valid 21-item instrument quantifying the self-reported frequency of oral behaviours. An Italian version (OBC-It) has been released recently. Anxiety and oral behaviours are known to be associated in individuals with oro-facial pain due to temporomandibular disorders (TMD). However, information about this relationship in pain-free individuals is still limited. OBJECTIVES: The aim of this study was to test the reliability of the OBC-It and its reduced version (OBC-It 6), focusing on tooth clenching-related wake-time oral behaviours, and the effect of patient instructions on reliability. A second aim was to test the association between trait anxiety and oral behaviours in pain-free individuals. METHODS: Two hundred and eighty-two TMD-free students, divided into 2 groups (Group A, n = 139, mean age ± SD = 22.6 ± 5.4 years; Group B, n = 143, 23.7 ± 4.2 years), filled in the State-Trait Anxiety Inventory and the OBC-It. Group B received instructions about the OBC-It, while Group A did not. After 2 weeks, both groups filled in the OBC-It again. However, Group B was further divided into 2 subgroups, B1 and B2 . The first received the same instructions again, while B2 did not. RESULTS: The test-retest reliability of the OBC-It (A: ICC = .87; B1 : ICC = .94; B2 : ICC = .95) and OBC-It 6 (A: ICC = .85; B1 : ICC = .89; B2 : ICC = .93) was excellent in all groups. Trait anxiety was weakly associated with OBC-It only in women (R2  = .043, P = .021). CONCLUSIONS: The OBC-It is a reliable tool but further subjects' instructions might be needed. Trait anxiety has a limited effect on oral behaviours in TMD-free subjects.

The TcTASV proteins are novel promising antigens to detect active Trypanosoma cruzi infection in dogs.

In regions where Chagas disease is endemic, canine Trypanosoma cruzi infection is highly correlated with the risk of transmission of the parasite to humans. Herein we evaluated the novel TcTASV protein family (subfamilies A, B, C), differentially expressed in bloodstream trypomastigotes, for the detection of naturally infected dogs. A gene of each TcTASV subfamily was cloned and expressed. Indirect enzyme-linked immunosorbent assays (ELISA) were developed using recombinant antigens individually or mixed together. Our results showed that dogs with active T. cruzi infection differentially reacted against the TcTASV-C subfamily. The use of both TcTASV-C plus TcTASV-A proteins (Mix A+C-ELISA) enhanced the reactivity of sera from dogs with active infection, detecting 94% of the evaluated samples. These findings agree with our previous observations, where the infected animals exhibited a quick anti-TcTASV-C antibody response, coincident with the beginning of parasitaemia, in a murine model of the disease. Results obtained in the present work prove that the Mix A+C-ELISA is a specific, simple and cheap technique to be applied in endemic areas in screening studies. The Mix A+C-ELISA could help to differentially detect canine hosts with active infection and therefore with high impact in the risk of transmission to humans.

Potential Remedies for the High Synchrotron-Radiation-Induced Heat Load for Future Highest-Energy-Proton Circular Colliders.

We propose a new method for handling the high synchrotron radiation (SR) induced heat load of future circular hadron colliders (like FCC-hh). FCC-hh are dominated by the production of SR, which causes a significant heat load on the accelerator walls. Removal of such a heat load in the cold part of the machine, as done in the Large Hadron Collider, will require more than 100 MW of electrical power and a major cooling system. We studied a totally different approach, identifying an accelerator beam screen whose illuminated surface is able to forward reflect most of the photons impinging onto it. Such a reflecting beam screen will transport a significant part of this heat load outside the cold dipoles. Then, in room temperature sections, it could be more efficiently dissipated. Here we will analyze the proposed solution and address its full compatibility with all other aspects an accelerator beam screen must fulfill to keep under control beam instabilities as caused by electron cloud formation, impedance, dynamic vacuum issues, etc. If experimentally fully validated, a highly reflecting beam screen surface will provide a viable and solid solution to be eligible as a baseline design in FCC-hh projects to come, rendering them more cost effective and sustainable.

Evaluation of recombinant antigens of Trypanosoma cruzi to diagnose infection in naturally infected dogs from Chaco region, Argentina.

Dogs are considered the main mammal reservoir of Trypanosoma cruzi in domiciliary environments. Consequently, accurate detection of T. cruzi infection in canine populations is epidemiologically relevant. Here, we analysed the utility of the T. cruzi recombinant antigens FRA, SAPA, CP1, Ag1 and a SAPA/TSSA VI mixture, in an ELISA format. We used a positive control group of sera obtained from 38 dogs from the Chaco region in Argentina with positive homogenate-ELISA reaction, all of them also positive by xenodiagnosis and/or PCR. The negative group included 19 dogs from a nonendemic area. Sensitivity, specificity, area under the curve (AUC) of the receiver operating charactheristic (ROC) curve and Kappa index were obtained to compare the diagnostic efficiency of the tests. The SAPA/TSSA VI had the highest performance, with a sensitivity of 94.7% and an AUC ROC of 0.99 that indicates high accuracy. Among individual antigens, SAPA-ELISA yielded the highest sensitivity (86.8%) and AUC ROC (0.96), whereas FRA-ELISA was the least efficient test (sensitivity = 36.8%; AUC ROC = 0.53). Our results showed that the use of SAPA/TSSA VI in ELISAs could be a useful tool to study dogs naturally infected with T. cruzi in endemic areas.

Communication: Thermodynamic analysis of critical conditions of polymer adsorption.

Polymer adsorption to solid surfaces is a ubiquitous phenomenon, which has attracted long-lasting attention. Dependent on the competition between the polymer-solid adsorption and polymer-solvent solvation interactions, a chain may assume either 3d solvated conformation when adsorption is weak or 2d adsorbed conformation when adsorption is strong. The transition between these conformations occurring upon variation of adsorption strength is quite sharp, and in the limit of "infinite" chain length, can be treated as a critical phenomenon. We suggest a novel thermodynamic definition of the critical conditions of polymer adsorption from the equality of incremental chemical potentials of adsorbed and free chains. We show with the example of freely jointed Lennard-Jones chains tethered to an adsorbing surface that this new definition provides a link between thermodynamic and geometrical features of adsorbed chains and is in line with classical scaling relationships for the fraction of adsorbed monomers, chain radii of gyration, and free energy.

Benznidazole treatment in chronic children infected with Trypanosoma cruzi: serological and molecular follow-up of patients and identification of Discrete Typing Units.

A total of 221 children from two rural settlements in Northeast Argentina were examined for T. cruzi infection. Blood samples were taken for serology tests and PCR assays. In addition, T. cruzi Discrete Typing Units (DTUs) were determined by hybridization with specific DNA probes of the minicircle hypervariable regions (mHVR). Serological results indicated that 26% (57/215) were reactive against T. cruzi antigens. PCR analyses were performed on seropositive samples showing presence of parasite DNA in 31 out of 53 samples (58.5%). All seropositive children underwent specific chemotherapy with Benznidazole (5mg/kg/day) for a period of two months and were monitored two and five years after treatment. Overall the treatment was well tolerated and low side effects were observed. Serological conversion was observed at two years post -treatment in one child form Pampa Ávila and at five years in two children from Tres Estacas. However, at the end of the follow-up period, T. cruzi DNA could not be detected by PCR in samples from treated children, except in two cases. In addition, the results of hybridizations with specific DNA probes showed that DTU TcV was detected in 68% (21/31), TcVI in 7% (2/31) and TcV/VI in 3% (1/31) of the samples. Altogether, results of the follow-up of treated children showed a low rate of seroconversion; however trend toward seroconversion was evident at five years post-treatment. On the other hand, detection of T. cruzi DNA by PCR significantly decreased after Benznidazole treatment. The existence of data regarding serological and molecular follow-ups from controlled studies in the Chaco Region will be important for future treatment efforts against T. cruzi infection in this region. The results obtained in the present study represent a contribution in this regard.

Efficacy of the Sander bite-jumping appliance in growing patients with mandibular retrusion: a randomized controlled trial.

OBJECTIVES: The efficacy of functional appliances remains highly debated. This randomized controlled trial investigated the skeletal and dentoalveolar effects determined by the Sander bite-jumping appliance (BJA). The null hypothesis to be tested was that the appliance would not induce supplementary mandibular growth compared to untreated controls. SETTING AND SAMPLE POPULATION: This study was carried out at the Section of Orthodontics, University of Naples Federico II, Italy. Forty-six patients receiving a clinical diagnosis of skeletal and dental class II due to mandibular retrusion were either allocated to a treatment (23 patients;15 boys, 8 girls; mean age ± SD: 10.9 ± 1.3 years) or to an untreated control group (23 patients;11 boys, 12 girls; mean age ± SD: 10.5 ± 1.2 years), by using a balanced block randomization. METHODS: Lateral cephalograms were taken before and after treatment and used for comparisons. Measurements were analyzed by descriptive statistics, univariate and multivariate statistical tests. RESULTS: Treated individuals had a significant increase in mandibular length (6.4 ± 2.3 vs. 3.5 ± 2.5 mm; p < 0.001), overjet reduction (-5.0 ± 2.9 vs. 0.3 ± 1.2 mm; p < 0.001) and molar relationship improvement (-5.3 ± 2.4 vs. 0.1 ± 1.1 mm; p < 0.001) compared to controls. The use of the appliance did not significantly affect jaw divergence. Proclination of lower incisors was slightly greater (3.0°, p = 0.023) in treated patients than in controls. The increase in mandibular length was not significantly influenced by cervical stage (p = 0.40). CONCLUSION: The BJA can effectively correct class II malocclusions by a combination of dentoalveolar and skeletal effects. The long-term stability of the correction needs to be evaluated.

Nature of the decrease of the secondary-electron yield by electron bombardment and its energy dependence.

We performed a combined secondary electron yield (SEY) and x-ray photoelectron spectroscopy study as a function of the electron dose and energy on a Cu technical surface representative of the LHC accelerator walls. The electron bombardment is accompanied by a clear chemical modification, indicating an increased graphitization as the SEY decreases. The decrease in the SEY is also found to depend significantly on the kinetic energy of the primary electrons. When low-energy primary electrons are employed (E≤20 eV), the reduction of the SEY is slower and smaller in magnitude than when higher-energy electrons are used. Consequences of this observation are discussed mainly for their relevance on the commissioning scenario for the LHC in operation at CERN (Geneva), but are expected to be of interest for other research fields.

Immuno-enzymatic evaluation of the recombinant TSSA-II protein of Trypanosoma cruzi in dogs and human sera: a tool for epidemiological studies.

The rTSSA-II (recombinant Trypomastigote Small Surface II) antigen was evaluated by ELISA to detect anti-Trypanosoma cruzi antibodies in sera from naturally infected dogs and humans. For this evaluation ELISA-rTSSA-II was standardized and groups were classified according to the results obtained through xenodiagnosis, ELISA and PCR. Sensitivity (Se), Specificity (Sp), Kappa index (KI) and area under curve (AUC) were determined. The Se was determined by using 14 sera from dogs infected with T. cruzi VI (TcVI) whereas Sp was determined by using 95 non-chagasic sera by xenodiagnosis, ELISA-Homogenate and PCR. The performance of ELISA-rTSSA-II in dog sera was high (AUC=0·93 and KI=0·91). The Se was 92·85% (1 false negative) and Sp was 100%. Two sera from dogs infected with TcI and 1 with TcIII were negative. For patients infected with T. cruzi, reactivity was 87·8% (36/41), there was only 1 indeterminate, and Sp was 100%. Fifty-four sera from non-chagasic and 68 sera from patients with cutaneous leishmaniasis did not react with rTSS-II. ELISA-rTSSA-II showed a high performance when studying sera from naturally infected dogs and it also presented 100% Sp. This assay could be an important tool to carry out sero-epidemiological surveys on the prevalence of T. cruzi circulating lineages in the region.

Oromandibular dystonia and hormonal factors: twelve years follow-up of a case report.

Oromandibular dystonia (OMD) is a focal neurological movement disorder characterized by involuntary sustained and often painful muscle contraction, usually producing repetitive movements or abnormal positions of the mouth, jaw and/or tongue. We report on a 30-year-old woman affected with OMD with a 12-year follow-up. Focal dystonia involved an involuntary activity of the lateral pterygoid muscles causing forceful jaw displacement in the maximal protrusive position. These episodes initially occurred during jaw function and increased up to an open-lock with bilateral pre-auricular pain. Dystonic spasms were absent during sleep and were reduced temporarily by sensory tricks. Treatment with botulinum toxin type A (BTX) was performed during three different sessions over a 1-year period. Electromyographic-guided BTX injections into the lateral pterygoid muscles were given with cannula electrodes. Botox reduced the involuntary activity of the muscles. Recurrence and exacerbation of dystonic symptoms occurred during the two pregnancies and completely disappeared immediately after both deliveries with prolonged symptom-free periods. During the last 8 years, the patient had a slight relapse of symptoms during flu attacks, periods of stress and during menses. The temporal pattern of these symptoms indicates a possible relationship between OMD and hormonal factors.

Effects of orthognathic surgery for class III malocclusion on signs and symptoms of temporomandibular disorders and on pressure pain thresholds of the jaw muscles.

The aim of this longitudinal study was to determine the effects of orthognathic surgery on signs and symptoms of temporomandibular disorders (TMD) and on pressure pain thresholds (PPTs) of the jaw muscles. Fourteen consecutive class III patients undergoing pre-surgical orthodontic treatment were treated by combined Le Fort I osteotomy and bilateral sagittal ramus osteotomy. The clinical examination included the assessment of signs and symptoms of TMD and the assessment of PPTs of the masseter and temporalis muscles. Anamnestic, clinical and algometric data were collected during five sessions over a 1-year period. Seven out of 14 patients presented with disc displacement with reduction at baseline, whereas four patients (two of them were new cases) did so at the end of follow up (p>0.05). None of the patients were diagnosed with myofascial pain of the jaw muscles at the beginning or end of follow up. PPTs of the masseter and temporalis muscles did not change significantly from baseline values throughout the whole study period. The occurrence of signs and symptoms of TMD fluctuates with an unpredictable pattern after orthognathic surgery for class III malocclusions.

Experimental observation of optical rotation generated in vacuum by a magnetic field.

We report the experimental observation of a light polarization rotation in vacuum in the presence of a transverse magnetic field. Assuming that data distribution is Gaussian, the average measured rotation is (3.9 +/- 0.5) x 10(-12) rad/pass, at 5 T with 44 000 passes through a 1 m long magnet, with lambda = 1064 nm. The relevance of this result in terms of the existence of a light, neutral, spin-zero particle is discussed.