The anatomy of the pelvic plexus in female cadavers: implications for retroperitoneal nerve-sparing surgery.

Background: The inferior hypogastric plexus (IHP) is a crucial structure for female continence and sexual function. A nerve-sparing approach should be pursued to reduce the risk of pelvic plexus damage during retroperitoneal pelvic surgery. Objectives: To analyse the relationship between the female IHP and several pelvic anatomical landmarks. Materials and Methods: Standardised cadaveric dissection was performed on 5 nulliparous female cadavers. The relationships of the IHP and the mid-cervical plane (MCP), the mid-sagittal plane (MSP), and the uterosacral ligament (USL) were investigated. Main outcome measures: Distance between IHP and MCP, MSP, and USL. Results: Distances between the right IHP and the right MSP (mean distance: 16.3 mm; range: 10.0-22.5 mm) and the right USL (mean distance: 4.8 mm; range: 0-15.0 mm) were shorter than those between the left IHP and ipsilateral landmarks (left MSP distance: 23.5 mm; range 18.0-30.0 mm; left USL distance: 5.0 mm; range: 0-20.0 mm). Although the MCP was 3.3 mm (range: 2.5-4.0 mm) left and lateral to the midsagittal line, the right IHP was closer to the MCP (mean distance: 19.6 mm; range: 13.0-25.0 mm) than the left one (mean distance: 20.2 mm; range: 15.0-26.0 mm). Conclusions: Distances between the right IHP and the MSP, MCP, and ipsilateral USL, are shorter compared to these associated to the left IHP. What is new?: Right autonomic pelvic plexus is closer to the midline planes and the ipsilateral USL. These anatomical relationships may be greatly helpful for pelvic surgeon while facing retroperitoneal pelvic surgery and looking for a nerve-sparing approach.

Dosimetric feasibility study ("proof of concept") of refractory ventricular tachycardia radioablation using proton minibeams.

PURPOSE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. MATERIAL AND METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. CONCLUSION: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

An α-Gal antigenic surrogate as a biomarker of treatment evaluation in Trypanosoma cruzi-infected children. A retrospective cohort study.

BACKGROUND: Proper evaluation of therapeutic responses in Chagas disease is hampered by the prolonged persistence of antibodies to Trypanosoma cruzi measured by conventional serological tests and by the lack of sensitivity of parasitological tests. Previous studies indicated that tGPI-mucins, an α-Gal (α-d-Galp(1→3)-ß-d-Galp(1→4)-d-GlcNAc)-rich fraction obtained from T. cruzi trypomastigotes surface coat, elicit a strong and protective antibody response in infected individuals, which disappears soon after successful treatment. The cost and technical difficulties associated with tGPI-mucins preparation, however, preclude its routine implementation in clinical settings. METHODS/PRINCIPLE FINDINGS: We herein developed a neoglycoprotein consisting of a BSA scaffold decorated with several units of a synthetic α-Gal antigenic surrogate (α-d-Galp(1→3)-ß-d-Galp(1→4)-ß-d-Glcp). Serological responses to this reagent, termed NGP-Tri, were monitored by means of an in-house enzyme-linked immunosorbent assay (α-Gal-ELISA) in a cohort of 82 T. cruzi-infected and Benznidazole- or Nifurtimox-treated children (3 days to 16 years-old). This cohort was split into 3 groups based on the age of patients at the time of treatment initiation: Group 1 comprised 24 babies (3 days to 5 months-old; median = 26 days-old), Group 2 comprised 31 children (7 months to 3 years-old; median = 1.0-year-old) and Group 3 comprised 26 patients (3 to 16 years-old; median = 8.4 years-old). A second, control cohort (Group 4) included 39 non-infected infants (3 days to 5 months-old; median = 31 days-old) born to T. cruzi-infected mothers. Despite its suboptimal seroprevalence (58.4%), α-Gal-ELISA yielded shorter median time values of negativization (23 months [IC 95% 7 to 36 months] vs 60 months [IC 95% 15 to 83 months]; p = 0.0016) and higher rate of patient negative seroconversion (89.2% vs 43.2%, p < 0.005) as compared to conventional serological methods. The same effect was verified for every Group, when analyzed separately. Most remarkably, 14 out of 24 (58.3%) patients from Group 3 achieved negative seroconversion for α-Gal-ELISA while none of them were able to negativize for conventional serology. Detailed analysis of patients showing unconventional serological responses suggested that, in addition to providing a novel tool to shorten follow-up periods after chemotherapy, the α-Gal-ELISA may assist in other diagnostic needs in pediatric Chagas disease. CONCLUSIONS/SIGNIFICANCE: The tools evaluated here provide the cornerstone for the development of an efficacious, reliable, and straightforward post-therapeutic marker for pediatric Chagas disease.

RadioLab project: knowledge of radon gas in Italy.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.

Pudendal Neuralgia: Two case reports with laparoscopic nerve decompression.

Pudendal neuralgia (PN) is a rare and underestimated condition. The reported incidence by the International Pudendal Neuropathy Association is 1/100000. However, the actual rate may be significantly higher, with a propensity for women. It is most frequently caused by an entrapment of the nerve at the level of the sacrospinous and sacrotuberous ligament, also known as pudendal nerve entrapment syndrome. Due to the late diagnosis and inadequate management, pudendal nerve entrapment syndrome often leads to considerable reduction in the quality of life and high health care costs. The diagnosis is made using Nantes Criteria, in conjunction with the patient's clinical history and physical findings. Clinical examination with an accurate assessment of the territory of the neuropathic pain is mandatory to set the therapeutic strategy. The aim of the treatment is to control the symptoms and it usually starts with conservative approaches which include analgesics, anticonvulsants, and muscle relaxants. Surgical nerve decompression can be proposed after failure of conservative management. The laparoscopic approach is a feasible and appropriate technique to explore and decompress the pudendal nerve, and to rule out other pelvic conditions that can cause similar symptomatology. In this paper, the clinical history of two patients affected by compressive PN is reported. Both patients underwent laparoscopic pudendal neurolysis suggesting that the treatment for PN should be individualised and carried out by a multidisciplinary team. When conservative treatment fails, laparoscopic nerve exploration and decompression is an adequate option to propose and should be performed by a trained surgeon.

Fetal brain imaging provides valuable information in cCMV infected infants.

BACKGROUND: Congenital CMV infection (cCMV) is the most common congenital infection with 10-15% of cases developing symptomatic disease. Early antiviral treatment is of essence when symptomatic disease is suspected. Recently, the use of neonatal imaging has been implicated as a prognostic tool for long term sequalae among asymptomatic newborns at high risk. Even though neonatal MRI is commonly used in neonatal symptomatic cCMV disease, it is less often used in asymptomatic newborns, mainly due to cost, access and difficulty to perform. We have therefore developed an interest in assessing the use of fetal imaging as an alternative. Our primary aim was to compare the fetal and neonatal MRIs in a small cohort 10 asymptomatic neonates with congenital CMV infection. METHODS: We performed a single-center retrospective cohort study (case-series) on a convenience sample of children born from January 2014 to March 2021 with confirmed congenital CMV infection who had undergone both fetal and neonatal MRIs. We created a checklist of relevant cerebral abnormalities and asked 4 blinded radiologists to assess the MRIs (2 for each, namely fetal and neonatal) and then compared the findings between the fetal and neonatal imaging as well as the concordance in reporting of abnormalities within each category. FINDINGS: Overall concordance between prenatal and postnatal scans was high (70%). When comparing the two blinded reports for each MRI, we found high levels of concordance: 90% concordance for fetal MRIs and 100% for neonatal MRIs. The most common abnormalities identified in both fetal and neonatal scans were "abnormal white matter hyperintensity" and "subependymal cysts." INTERPRETATION: Even though this is a small descriptive study, it indicates that fetal MRI could potentially provide us with similar information as neonatal imaging. This study could form the basis for subsequent larger future studies.

A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

OBJECTIVE: To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. MATERIALS AND METHODS: In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. RESULTS: Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. CONCLUSIONS: Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Presence of inulin in sunflower (Helianthus annuus L.) grown under high irradiance.

Fructans are important polysaccharides synthesized from sucrose which are present in about 12-15% of angiosperms. Sunflower (Helianthus annuus L.) is considered a non-fructan bearing plant even though its close relative, Helianthus tuberosus, accumulates the inulin type of the polymer in large amounts. Previous work suggested that putative fructan-synthesizing enzymes may be expressed in sunflower, but only very limited amounts of the trisaccharide isokestose were found in stems of plants storing high levels of sucrose due to capitulum removal. The present work is aimed at investigating whether intact sunflower plants may indeed synthesize fructans in any of its parts when grown in conditions that favor sucrose availability. Plants were grown in the field at a low density, resulting in a high light availability and low competition for resources, in comparison with controls (usual crop planting density). Plants were harvested at anthesis. Thinned treatment led to an increase in carbohydrates level especially in the capitulum. Carbohydrates analysis of this tissue in thinned plants revealed, for the first time in this species, the presence of inulin-type fructans. The amount of each member of the series appeared to decline starting from isokestose, being DP = 15 the longest fructan detected. Results suggest that, in sunflower, fructans could be synthesized only when sucrose availability exceeds a high threshold, which may not be attained under usual growing conditions. Given the relationship between fructans and tolerance to abiotic stresses including drought, the present finding opens a new perspective for breeding and management of this crop.

Pharmacokinetics of ivermectin after oral and intravenous administration in Bilgorajska geese (Anser anser domesticus).

AIMS: To assess the pharmacokinetic profile of ivermectin in Bilgorajska geese (Anser anser domesticus) after single I/V or oral administration, in order to compare these routes of administration and assess oral bioavailability. METHODS: Ten healthy male geese were used in a single-dose, two-phase study with a 3-month washout period between phases. In the first phase, all geese were given 0.2 mg/kg I/V ivermectin, while in the second phase they were treated orally with the same dosage. Blood samples were collected at selected time points up to 480 hours after each administration. Samples were purified using protein precipitation and drug concentration was quantified using HPLC. The analytical method was validated on blank goose plasma and was characterised by an optimal linearity and a limit of quantification of 0.025 µg/mL. The pharmacokinetic analysis was carried out using a non-compartmental approach. RESULTS: The drug was quantifiable up to 240 hours after I/V administration, while after oral treatment it was quantifiable up to 144 hours in most of the geese. The elimination half-life of ivermectin was approximately 3.8 (95% CI = 1.98-7.92; p = 0.027) times higher after I/V administration compared to oral administration. Moreover, the area under the curve from zero to the last detectable timepoint was 6.4 (95% CI = 4.65-8.74; p < 0.001) hours greater after I/V than oral administration. This difference led to a bioavailability of 20.38 (SD 5.92) %. CONCLUSIONS: Following oral administration in geese, ivermectin has a bioavailability of approximately 20%. Further research on the action of ivermectin in the gastrointestinal tract is required along with assessment of tissue residues to allow calculation of withdrawal time to ensure consumer safety. ABBREVIATIONS: AUC: Area under the concentration-time curve; AUClast: Area under the curve from zero to the last detectable timepoint; AUMC: Area under the first moment curve; Cmax: Maximum concentration; Tmax: Time at maximum plasma concentration.

Polariton Bose-Einstein condensate from a bound state in the continuum.

Bound states in the continuum (BICs)1-3 are peculiar topological states that, when realized in a planar photonic crystal lattice, are symmetry-protected from radiating in the far field despite lying within the light cone4. These BICs possess an invariant topological charge given by the winding number of the polarization vectors5, similar to vortices in quantum fluids such as superfluid helium and atomic Bose-Einstein condensates. In spite of several reports of optical BICs in patterned dielectric slabs with evidence of lasing, their potential as topologically protected states with theoretically infinite lifetime has not yet been fully exploited. Here we show non-equilibrium Bose-Einstein condensation of polaritons-hybrid light-matter excitations-occurring in a BIC thanks to its peculiar non-radiative nature, which favours polariton accumulation. The combination of the ultralong BIC lifetime and the tight confinement of the waveguide geometry enables the achievement of an extremely low threshold density for condensation, which is reached not in the dispersion minimum but at a saddle point in reciprocal space. By bridging bosonic condensation and symmetry-protected radiation eigenmodes, we reveal ways of imparting topological properties onto macroscopic quantum states with unexplored dispersion features. Such an observation may open a route towards energy-efficient polariton condensation in cost-effective integrated devices, ultimately suited for the development of hybrid light-matter optical circuits.

Single and multiple oral amoxicillin treatment in geese: a pharmacokinetic evaluation.

1. Although amoxicillin has broad-spectrum antibiotic activity and is extensively used in poultry, its use has never been investigated in geese. This study aimed to evaluate the pharmacokinetics of amoxicillin after a single and multiple oral doses in geese.2. A total of 20 geese were enrolled in this study and randomly pooled in two groups (n = 10). In group I, animals were treated with a single oral 20 mg/kg dose of amoxicillin, while geese in group II were administered multiple doses (20 mg/kg/day for 4 d). Concentrations of amoxicillin in plasma were analysed using a validated HPLC-UV method and drug plasma concentrations were modelled for each subject using a non-compartmental approach.3. amoxicillin showed rapid absorption after a single-dose treatment, with an elimination half-life of approximately 1 h. Cmax, Tmax and AUC values differed statistically between groups I and II (after the first dose administered). A large variability was observed in the pharmacokinetic profiles and drug accumulation may occur after the multiple administration.4. No accumulation in plasma was predicted from an in-silico simulation performed using the same multiple dosage schedule. The in-silico simulation does not seem to accurately predict in-field conditions.

The proper orthogonal decomposition: A powerful tool for studying drop oscillations.

Liquid metal drops are released onto different wettable solid substrates. Their post-impact oscillations are recorded at 1000 images/s as soon as the triple line is at rest. The proper orthogonal decomposition (POD) is used to get and identify the frequencies involved. The POD is a technique widely used in the fluid dynamics community to study turbulent flows, but it is not used to determine droplet-free oscillation frequencies. The vertical and horizontal vibration frequencies of the sessile drop center of mass are successfully extracted from the images by POD. The first POD mode captures the vertical displacement frequency, and the second or third POD mode captures the horizontal displacement frequency of the drop center of mass. The spatial structure of the modes is the characteristic of the vertical and horizontal movement. Therefore, the POD can be used instead of the interface displacement tracking to determine the free oscillation frequencies of liquid metal drops and, more generally, of any vibrating sessile drops. As it is a standardized method, it can be used with confidence for routine measurements, especially for sensors.

Secondary neutron dose contribution from pencil beam scanning, scattered and spatially fractionated proton therapy.

The Orsay Proton therapy Center (ICPO) has a long history of intracranial radiotherapy using both double scattering (DS) and pencil beam scanning (PBS) techniques, and is actively investigating a promising modality of spatially fractionated radiotherapy using proton minibeams (pMBRT). This work provides a comprehensive comparison of the organ-specific secondary neutron dose due to each of these treatment modalities, assessed using Monte Carlo (MC) algorithms and measurements. A MC model of a universal nozzle was benchmarked by comparing the neutron ambient dose equivalent,H*(10), in the gantry room with measurements obtained using a WENDI-II counter. The secondary neutron dose was evaluated for clinically relevant intracranial treatments of patients of different ages, in which secondary neutron doses were scored in anthropomorphic phantoms merged with the patients' images. The MC calculatedH*(10) values showed a reasonable agreement with the measurements and followed the expected tendency, in which PBS yields the lowest dose, followed by pMBRT and DS. Our results for intracranial treatments show that pMBRT yielded a higher secondary neutron dose for organs closer to the target volume, while organs situated furthest from the target volume received a greater quantity of neutrons from the passive scattering beam line. To the best of our knowledge, this is the first study to compare MC secondary neutron dose estimates in clinical treatments between these various proton therapy modalities and to realistically quantify the secondary neutron dose contribution of clinical pMBRT treatments. The method established in this study will enable epidemiological studies of the long-term effects of intracranial treatments at ICPO, notably radiation-induced second malignancies.

[Recurrent respiratory papillomatoses despite vaccination]. / Larynxpapilloom ondanks vaccinatie.

BACKGROUND: Recurrent respiratory papillomatosis (RRP, also known as laryngeal papillomatosis) is a debilitating chronic disease induced by a human papilloma virus (HPV). Wart-like lesions develop in the airways. Patients suffer from dysphonia, coughing and ultimately dyspnea. There is no curative treatment. Recurrent surgical intervention is necessary to keep the airways free of disease. CASE REPORT: We describe a 25-year-old woman who developed RRP, despite having been vaccinated according to the national vaccination program. She underwent 11 surgeries in the past 5 years. CONCLUSION: RRP is an invalidating disease, necessitating repeated surgical interventions. Despite worldwide use and availability of adequate preventive HPV vaccines against this disease, the Dutch government choose to use a vaccine which does not prevent against this chronic disease.

Altered responsiveness to pups in virgin female mice of the BTBR strain: Insights from pattern of c-Fos expression in brain regions involved in maternal behavior.

BTBR is an inbred mouse strain that displays several behavioral alterations resembling the core symptoms of Autism Spectrum Disorder, including deficit in sociability. In the present study, we investigated whether the pup-induced maternal behavior in virgin female mice, a naturally rewarding behavior, is impaired in this strain similarly to social interaction with adult conspecifics. We firstly assessed the maternal responsiveness towards newly born pups expressed by either virgin female mice of the BTBR strain or of the normo-social B6 strain. Next, we examined in both strains the expression of c-Fos as a marker of neuronal activity in selected brain areas involved in the regulation of maternal behavior in rodents including the olfactory bulb, the medial preoptic area and the paraventricular nucleus (PVN). We also examined the effects of pup presentation on oxytocinergic neurons of the PVN, the major brain site of synthesis of oxytocin, which has a pivotal role in facilitation of maternal response and social responsiveness in general. As a final step, we assessed the c-Fos expression pattern comparing the effect of exposure to pups with that induced by exposure to another social stimulus, focusing on other areas implicated in maternal responsiveness as well as in the affective component of social behavior such as pyriform cortex and central and basolateral amygdala. Our data showed that BTBR virgin females are less responsive to presentation of pups in comparison to B6, in parallel with lower activation of brain areas implicated in the maternal and social responsiveness.

Enhancement of Parametric Effects in Polariton Waveguides Induced by Dipolar Interactions.

Exciton-polaritons are hybrid light-matter excitations arising from the nonperturbative coupling of a photonic mode and an excitonic resonance. Behaving as interacting photons, they show optical third-order nonlinearities providing effects such as optical parametric oscillation or amplification. It has been suggested that polariton-polariton interactions can be greatly enhanced by inducing aligned electric dipoles in their excitonic part. However, direct evidence of a true particle-particle interaction, such as superfluidity or parametric scattering, is still missing. In this Letter, we demonstrate that dipolar interactions can be used to enhance parametric effects such as self-phase modulation in waveguide polaritons. By quantifying these optical nonlinearities, we provide a reliable experimental measurement of the direct dipolar enhancement of polariton-polariton interactions.

Quantum dynamics of Mn2+ in dimethylammonium magnesium formate.

Dimethylammonium magnesium formate, [(CH3)2NH2][Mg(HCOO)3] or DMAMgF, is a model used to study high temperature hybrid perovskite-like dielectrics. This compound displays an order-disorder phase transition at about 260 K. Using multifrequency electron spin resonance in continuous wave and pulsed modes, we herein present the quantum dynamics of the Mn2+ ion probe in DMAMgF. In the high temperature paraelectric phase, we observe a large distribution of the zero field splitting that is attributed to the high local disorder and further supported by density functional theory computations. In the low temperature ferroelastic phase, a single structure phase is detected and shown to contain two magnetic structures. The complex electron paramagnetic resonance signals were identified by means of the Rabi oscillation method combined with the crystal field kernel density estimation.

Comparative pharmacokinetics of metronidazole in healthy and Trichomonas gallinae infected pigeons (Columba livia, var. domestica).

1. This study investigated the pharmacokinetics of metronidazole after intravenous (i.v.) and oral administration to healthy and experimentally Trichomonas gallinae-infected pigeons, and determined the in vitro antiprotozoal activity of metronidazole against T. gallinae.2. Twelve pigeons which were experimentally infected to T. gallinae and twelve healthy pigeons received metronidazole at the dose of 25 mg/kg by oral or i.v. administration. Serial blood sampling was used for pharmacokinetic analysis. The metronidazole minimum lethal concentration (MLC) and the concentration killing 50% of the trophozoites (LC50) in the culture media were determined.3. In vitro data showed that the 24 h LC50 and MLC of metronidazole were 0.31 and 25 µg/ml, respectively. In vivo results showed no statistical differences between pharmacokinetics in infected and non-infected pigeons for both routes of administration. The area under the curve was statistically higher after the i.v. administration in both infected and healthy pigeons. The mean oral bioavailability was similar in the infected (83.8%) and the healthy (81.5%) birds.4. In conclusion, the pharmacokinetics of metronidazole in pigeons was not affected by experimentally-induced trichomoniasis. Despite in vitro susceptibility testing, which showed probable resistance of the isolated T. gallinae to metronidazole, five-day oral treatment of infected pigeons with 25 mg/kg metronidazole twice a day resulted in total eradication of trophozoites recovered in crop lavage of infected birds.

Levofloxacin pharmacokinetics and tissue residue concentrations after oral administration in Bilgorajska geese.

1. The aim of this study was to assess the pharmacokinetics of levofloxacin, a third-generation fluoro-quinolone antimicrobial drug, in geese (n = 26) after either single intravenous or oral administration, and to evaluate the depletion profile in goose muscle, heart, liver, kidney and lung after a single oral dose.2. The pharmacokinetic study involved 16 geese which were randomly divided into two groups (n = 8/group), the first received levofloxacin (2 mg/kg) intravenously while the second was treated with orally (5 mg/kg). The tissue depletion study involved 10 geese which were dosed orally (5 mg/kg) and two animals were killed at different time-points in order to collect the selected tissues. Levofloxacin was quantified in all the matrices tested by a validated high-performance liquid chromatography (HPLC) method, using a spectrofluorimetric detector. The pharmacokinetics were analysed using a non-compartmental model.3. Plasma concentrations were quantified after up to 24 h in animals administered intravenously and up to 48 h after oral treatment. Levofloxacin was rapidly absorbed after oral administration (Tmax = 0.38 h) showing high bioavailability (95.57 ± 20.61%). The drug showed a moderate volume of distribution (1.40 ± 0.28 ml/g) and rapid clearance (0.28 ± 0.06 ml/g/h). No statistical differences in estimates were found between the two different administration methods (P > 0.05). Drug residues were highest at 6 h and decreased constantly up to 48 h in all the selected tissues. Liver and kidney had the highest levofloxacin concentrations.4. According to the pharmacokinetic/pharmacodynamic surrogate index (AUC/MIC) the levofloxacin dose regimen (after oral administration) used in the present study could be active against bacteria at a minimum inhibitory concentration (MIC) > 0.24  µg/ml in geese. In addition, drug accumulation in the liver might be controlled using an estimated preliminary withdrawal time of 90 h.

10th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals.

Therapeutic proteins and emerging gene and cell-based therapies are attractive therapeutic tools for addressing unmet medical needs or when earlier conventional treatment approaches failed. However, the development of an immune response directed against therapeutic agents is a significant concern as it occurs in a substantial number of cases across products and indications. The specific anti-drug antibodies that develop can lead to safety adverse events as well as inhibition of drug activity or accelerated clearance, both phenomena resulting in loss of treatment efficacy. The European Immunogenicity Platform (EIP) is a meeting place for experts and newcomers to the immunogenicity field, designed to stimulate discussion amongst scientists across industry and academia, encourage interactions with regulatory agencies and share knowledge and the state-of-the-art of immunogenicity sciences with the broader scientific community. Here we report on the main topics covered during the EIP 10th Open Symposium on Immunogenicity of Biopharmaceuticals held in Lisbon, 26-27 February 2019, and the 1-d training course on practical and regulatory aspects of immunogenicity held ahead of the conference. These main topics included immunogenicity testing, clinical relevance of immunogenicity, immunogenicity prediction, regulatory aspects, tolerance induction as a mean to mitigate immunogenicity and immunogenicity in the context of gene therapy.