[Possibilities of the personalized approach to solitary thyroid nodules based on molecular profiling]. / Möglichkeiten des personalisierten Vorgehens bei solitären Schilddrüsenknoten basierend auf molekularem Profiling.

BACKGROUND: Molecular profiling is currently not yet widespread in Germany and its potential for personalized treatment of solitary thyroid nodules is not exhausted. METHOD: Narrative assessment of the available options and their evidence based on the current international literature as well as discussion of the options in the German context from the perspective of a thyroid surgeon and a thyroid pathologist. RESULTS: The commercial tests available, especially in the USA, for molecular profiling of thyroid nodules offer good rule-in and somewhat poorer rule-out options, as many differentiated thyroid carcinomas do not display genetic alterations. The costs of these tests and molecular pathology for nodule assessment are still high and the individual mutations have not yet been clearly characterized. CONCLUSION: It can be assumed that molecular profiling will become more important in the coming years and find its way into the clinical routine. At this point in time, however, there is not yet sufficient evidence of the clinical significance of most mutations in thyroid carcinomas to derive therapeutic consequences from them.

Introduction of laparoscopic nephrectomy for autosomal dominant polycystic kidney disease as the standard procedure.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder and accounts for 5-10% of all cases of kidney failure. 50% of ADPKD patients reach kidney failure by the age of 58 years requiring dialysis or transplantation. Nephrectomy is performed in up to 20% of patients due to compressive symptoms, renal-related complications or in preparation for kidney transplantation. However, due to the large kidney size in ADPKD, nephrectomy can come with a considerable burden. Here we evaluate our institution's experience of laparoscopic nephrectomy (LN) as an alternative to open nephrectomy (ON) for ADPKD patients. MATERIALS AND METHODS: We report the results of the first 12 consecutive LN for ADPKD from August 2020 to August 2021 in our institution. These results were compared with the 12 most recent performed ON for ADPKD at the same institution (09/2017 to 07/2020). Intra- and postoperative parameters were collected and analyzed. Health related quality of life (HRQoL) was assessed using the SF36 questionnaire. RESULTS: Age, sex, and median preoperative kidney volumes were not significantly different between the two analyzed groups. Intraoperative estimated blood loss was significantly less in the laparoscopic group (33 ml (0-200 ml)) in comparison to the open group (186 ml (0-800 ml)) and postoperative need for blood transfusion was significantly reduced in the laparoscopic group (p = 0.0462). Operative time was significantly longer if LN was performed (158 min (85-227 min)) compared to the open procedure (107 min (56-174 min)) (p = 0.0079). In both groups one postoperative complication Clavien Dindo ≥ 3 occurred with the need of revision surgery. SF36 HRQol questionnaire revealed excellent postoperative quality of life after LN. CONCLUSION: LN in ADPKD patients is a safe and effective operative procedure independent of kidney size with excellent postoperative outcomes and benefits of minimally invasive surgery. Compared with the open procedure patients profit from significantly less need for transfusion with comparable postoperative complication rates. However significant longer operation times need to be taken in account.

Characterization of the O/ME-SA/Ind-2001d foot-and-mouth disease virus epidemic recorded in the Maghreb during 2014-2015.

The O/ME-SA/Ind-2001d has been the main foot-and-mouth disease virus (FMDV) lineage responsible for FMD epidemics outside the Indian subcontinent from 2013 to 2017. In 2014, outbreaks caused by this FMDV lineage were reported in Maghreb, where it was initially detected in Algeria and Tunisia and later in Morocco. This was the first incursion of an FMDV type O of exotic origin in the Maghreb region after 14 years of absence. In this study, we report analyses of both VP1 and whole-genome sequences (WGSs) generated from 22 isolates collected in Algeria and Tunisia between 2014 and 2015. All the WGSs analysed showed a minimum pairwise identity of 98.9% at the nucleotide level and 99% at the amino acid level (FMDV coding region). All Tunisian sequences shared a single putative common ancestor closely related to FMDV strains circulating in Libya during 2013. Whereas sequences from Algeria suggest the country experienced two virus introductions. The first introduction is represented by strains circulating in 2014 which are closely related to those from Tunisia, the second one, of which the origin is more uncertain, includes strains collected in Algeria in 2015 that gave origin to the 2015 outbreak reported in Morocco. Overall, our results demonstrated that a unique introduction of O/Ind-2001d FMDV occurred in Maghreb through Tunisia presumably in 2014, and from then the virus spread into Algeria and later into Morocco.

Salvage surgery for cervical radioiodine refractory 18F-FDG-PET positive recurrence of papillary thyroid cancer.

PURPOSE: Five percent of patients with differentiated thyroid cancer are diagnosed with radioiodine refractory relapse in the course of the disease. For isolated or oligometastatic cervical recurrence, resection or another local treatment is recommended. In this study, the impact of surgical treatment of cervical radioiodine refractory 18F-FDG-PET positive relapse of papillary thyroid cancer (PTC) was evaluated. METHODS: Patients receiving radioiodine therapy between 2005 and 2015 at the University Hospital of Cologne, Germany, for PTC were screened. The subgroup of patients undergoing surgery during the course of disease after recommendation by a multidisciplinary endocrine team for cervical radioiodine refractory 18F-FDG-PET positive recurrence was identified. Demographics, clinic-pathologic characteristics, oncologic treatment, and outcome were analyzed. RESULTS: Thirty (3%) of 969 patients with PTC treated with radioiodine therapy at our institution underwent surgery for radioiodine refractory 18F-FDG-PET positive cervical recurrence during the course of the disease. In eight (26.6%) patients, more than one operation was performed. Sixteen (53%) patients received external beam radiation therapy (EBRT) after surgery. Follow-up was on average, 79.2 ± 61.6 months after the last surgical treatment. Biochemical and radiological cure was seen in 12 (40%) patients. Remission was significantly more frequent in younger patients (P = 0.0001) with lymph node rather than soft tissue tumor recurrence (P = 0.004). CONCLUSIONS: Surgical treatment of radioiodine refractory 18F-FDG-PET positive cervical recurrence led to biochemical and radiological cure in about 40% of patients in this study. Further data are needed concerning risk stratification of potential subgroups benefitting of surgical approach and the possible role of EBRT after repetitive surgery.

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Genetic analysis of human and swine influenza A viruses isolated in Northern Italy during 2010-2015.

Influenza A virus (IAV) infection in swine plays an important role in the ecology of influenza viruses. The emergence of new IAVs comes through different mechanisms, with the genetic reassortment of genes between influenza viruses, also originating from different species, being common. We performed a genetic analysis on 179 IAV isolates from humans (n. 75) and pigs (n. 104) collected in Northern Italy between 2010 and 2015, to monitor the genetic exchange between human and swine IAVs. No cases of human infection with swine strains were noticed, but direct infections of swine with H1N1pdm09 strains were detected. Moreover, we pointed out a continuous circulation of H1N1pdm09 strains in swine populations evidenced by the introduction of internal genes of this subtype. These events contribute to generating new viral variants-possibly endowed with pandemic potential-and emphasize the importance of continuous surveillance at both animal and human level.

Incidental diagnosis of the tall-cell variant of the papillary microcarcinoma of the thyroid gland requires completion lymphadenectomy: case report.

Papillary thyroid carcinoma is the most common neoplasm of the thyroid gland which is usually associated with a very good prognosis. The aim of this case report is to present the disease course of a rare tumor of the thyroid gland, which is worthwhile due to its extraordinary appearance and specific management. A 46-year-old patient presented with a pronounced right-sided, but bilateral, multinodular goiter, with a volume of approximately 80 mL, as assessed on ultrasonography. Surgical removal was indicated as scintigraphy showed a 4-cm cold nodule that almost completely took up the right thyroid lobe. Because of the micronodular texture of the left thyroid lobe, complete thyroidectomy was performed according to well-established guidelines. Histopathological investigation of the specimen revealed a follicular adenoma without any malignancy in the right thyroid lobe and the tall-cell variant of the papillary thyroid microcarcinoma in the left lobe, with a capsular invasion and diameter of 0.6 cm. Because this rare tumor subtype is known for its aggressive behavior, and there was capsular invasion, low-grade differentiation, and an increased risk for lymphatic metastases, completion lymphadenectomy of the central compartments was performed after an interdisciplinary board decision. On histopathology, there were 30 tumor-free lymph nodes; final TNM classification was as follows: pT3 pN0 [0/30] L0 V0 Pn0 R0). The postoperative course was uneventful, and surgery was followed by radioiodine therapy. Six months after the surgery, clinical follow-up did revealed any sign of recurrence. The tall-cell variant is a rare and aggressive subtype of the papillary thyroid carcinoma, and it is characterized by poor 5-year survival and high recurrence rate. According to our understanding and based on current literature, this disease requires an aggressive surgical treatment and a close follow-up, as recommended by the current guidelines.

[Chances and Potential of a Modern Surgical Skills Lab as Substantial Practical Part of the Study of Human Medicine - "The Magdeburg Model"]. / Chancen und Potenziale eines modernen chirurgisch geprägten SkillsLabs im Rahmen des Humanmedizinstudiums ­ das Magdeburger Modell.

Introduction: Surgical education of medical students within "skills labs" have not been standardised throughout Germany as yet; there is a substantial impact of available aspects such as personal and space at the various medical schools. Aim: The aim of this contribution is to illustrate the concept of a surgical skills lab in detail, including curricular teaching and integrated facultative courses at the Medical School, University of Magdeburg ("The Magdeburg Model") in the context of a new and reconstructed area for the skills lab at the Magdeburg's apprenticeship center for medical basic abilities (MAMBA). Method: We present an overview on the spectrum of curricular and facultative teaching activities within the surgical part of the skills lab. Student evaluation of this teaching concept is implemented using the programme "EvaSys" and evaluation forms adapted to the single courses. Results: By establishing MAMBA, the options for a practice-related surgical education have been substantially improved. Student evaluations of former courses presented within the skills lab and the chance of moving the skills lab into a more generous and reconstructed area led to a reorganisation of seminars and courses. New additional facultative courses held by student tutors have been introduced and have shown to be of great effect, in particular, because of their interdisciplinary character. Conclusion: Practice-related surgical education within a skills lab may have the potential to effectively prepare medical students for their professional life. In addition, it allows one to present and teach the most important basic skills in surgery, which need to be pursued by every student. An enthusiastic engagement of the Office for Student Affairs can be considered the crucial and indispensable link between clinical work and curricular as well as facultative teaching with regard to organisation and student evaluation. The practice-related teaching parts and contents at the surgical section of a skills lab should be integrated into the National Competence-based Catalogue of Teaching Aims in Medicine ("NKLM").

["STeP" ("Students Teaching Patients"): Medical Students Following up on Informed Consent Discussions. Results of a Methodological Change and Further Considerations]. / "STeP" ("Students Teaching Patients"): Abfrage der ärztlichen Aufklärung durch Medizinstudierende. Ergebnisse einer methodischen Umstellung und weiterführende Überlegungen.

Background: Literature shows an increasing number of reports on the incompleteness of informed consent discussions held by residents. Residents feel insecure and not adequately prepared for this task. This project aimed to integrate supervised informed consent discussions into the medical curriculum, working with "real" patients instead of other students or actors. Method: "STeP" ("Students Teaching Patients") is a teaching format which has been recently introduced at the University of Magdeburg. Initially, a certified physician prepares medical students for taking informed consent. Using standard questionnaires, students interview patients who have given consent, following up on what patients recall from the informed consent discussion. Afterwards the results are reported to the physician, who then checks back with the patient that there are no new or unanswered questions. In this part of the project, the original process was changed in that a group of patients was interviewed twice to evaluate whether students were able to increase patients' knowledge. Results: Although all students taking part in this study had already completed the surgery course, they were not sufficiently aware of the most relevant complications of laparoscopic cholecystectomy. Also it was difficult for informed patients to render the consequences and complications resulting from such a procedure. Randomly chosen patients recalled only one possible complication on average, although they had signed the informed consent form. Most of them could not explain the effects of a lesion of the bile duct. Although those patients who had been interviewed twice recalled more complications than those who had been interviewed only once, patients generally did not like to be interviewed twice, which caused us to discontinue this part of the project. Conclusions: Based on the analysis of the limitations of this method of repeated interviews, we now plan to perform STeP as a "student consultation" before the physician takes informed consent, with students reflecting their own consultation. Increase in knowledge and patient satisfaction will be measured postoperatively by the students. The results of this project are pending.

Spontaneous omental bleeding in a 20-year old patient with hemophilia A. A rare cause for emergency laparotomy.

Spontaneous intraabdominal hemorrhage is a very rare event even in patients with bleeding disorders like hemophilia. Nevertheless this rare case must be considered in patients with coagulopathies presenting with abdominal pain. Prompt radiologic imaging and surgical consultation are of highest priority. Here we report on a 20-year-old patient with moderate hemophilia A, who underwent emergency laparotomy for a spontaneous idiopathic bleeding of the omentum majus. There are few cases in the literature on this sort of event in patients with hemophilia, who mostly suffer from spontaneous joint bleedings. These patients require an intensive, interdisciplinary perioperative care, involving haematologists, surgeons, radiologists and anesthesists. Finally we discuss, whether an optimized, individually adapted treatment with coagulation factors might possibly have prevented this bleeding event in this patient.

Brain structure, cognition and negative symptoms in schizophrenia are associated with serum levels of polysialic acid-modified NCAM.

The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell-cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.

[Teamwork in the operating theatre: the German Observational Teamwork Assessment for Surgery (OTAS-D) and its first application in Germany]. / Interdisziplinäre Teamarbeit im Operationssaal: Das Beobachtungsverfahren OTAS-D und erste Anwendungsergebnisse aus Deutschland.

BACKGROUND: The quality of surgical teamwork contributes to performance of the operating theatre team, service quality and patient safety in surgery. Observational tools are a feasible and reliable way to capture and evaluate teamwork in the operating theatre (OT). We introduce the German version of the Observational Teamwork Assessment for Surgery (OTAS-D) and present the first observational results from German OTs. METHODS: Quality of surgical teamwork was assessed with observational teamwork assessment for surgery (OTAS-D). It evaluates five dimensions of OT teamwork: communication, coordination, cooperation/backup behaviour, leadership, and team monitoring/situation awareness. Each dimension is evaluated for each profession (surgical, nursing, and anaesthesia team) as well for each phase of the procedure (pre-, intra-, and post-operative). We observed n = 63 procedures, mainly in abdominal/general and orthopaedic surgery. Additionally, all OT team members scored their individual evaluation of the intra-operative teamwork (standardised 1-item questions). RESULTS: The OTAS-D evaluations showed meaningful results and differences for the OT professions as well as across the different phases of the procedures. Overall, a medium to good level of the OT teamwork was observed. There were no differences in regard to type of surgery (minimally invasive vs. open) or surgical specialties. With an increased coordination of the surgical team we observed a significantly increased cooperation of the nursing team (r = 0.36, p = 0.004). Concerning the OT staffs self-reports, the surgical and nursing teams reported higher scores for quality of surgical teamwork during the procedure than their anaesthesia team members. No significant relationships between observed quality of OT teamwork and self-reports were found. CONCLUSIONS: The German version of OTAS-D is a psychometrically robust method to capture the quality of teamwork in operating theatres. It enables the analyses of teamwork between the surgical, nursing and anaesthesia professions in acute surgical care. Limitations of the first application results are considered. Finally, potential applications for surgical teaching, research and quality management are discussed.

[Structured teaching of surgery the LMU model in Munich]. / Strukturierte Lehre in der Chirurgie am Beispiel des Humanmedizinstudiums an der Ludwig-Maximilians-Universität München.

The medical curriculum (MeCuM) of the Ludwig Maximilian University (LMU) in Munich is a dynamic curriculum aimed to support the learning process of all students with their different learning styles. It is based on interactive, activating teaching methods in order to increase students' interest, and on repetitive evaluation of teaching units to modify the teaching in order to meet students' needs and wishes. In this context the teaching of surgery at our faculty takes place. Besides interdisciplinary lessons where diseases are taught in cooperation with our colleagues from internal medicine, indications for surgery, complications and consequences of surgery for the patients are analysed in PBL tutorials, online cases, bedside teachings and practical teaching on the ward. Surgical skills like suturing are demonstrated in videos, practiced on models or during practical teaching on the ward and they are tested in OSCEs. During the "praktisches Jahr", the students in the last year of their medical studies are supposed to apply their practical skills besides repeating theoretical knowledge in order to pass the final examination. For this purpose they are taught in a revision course called "LMU-StaR" (revision course for the Staatsexamen). In this paper we describe in detail the teaching of surgery at our faculty.

[Legal considerations regarding radiological examinations of bodypackers ordered by police officers]. / Röntgenuntersuchungen von Bodypackern auf Anordnung durch Polizeibeamte.

A 28-year-old woman was arrested for body packing. One pack was removed from her vagina by the forensic pathologist. She was referred by the police to an emergency surgical department to obtain a radiological examination of the abdomen in order to rule out the presence of further packs in the intestines. In the case of a negative result it would not be necessary to be kept under arrest. For this reason the woman agrees to the examination. The surgeon in the emergency department refused to perform an examination involving radiation exposure to a young woman without any medical indications according to the German X-Ray Ordinance § 23 subsection I. Generally a physician can refuse to perform examinations ordered by state authorities; however, the provision of expert testimony in legal proceedings by a judge, a state attorney or a high ranking police officer makes collaboration mandatory in accordance with § 75 of the German penal code of procedures. However, any relevant harm caused by the examination must be excluded with a very high degree of certainty.

The surgical treatment of Graves' disease in children and adolescents.

BACKGROUND: Surgery as definitive treatment of pediatric Graves' disease is recommended for children and adolescents experiencing adverse effects of thionamides or disease relapse after at least 2 years of medical treatment. In addition, it is indicated in patients with a large goiter or with suspicious nodules. Total or near-total thyroidectomy should be performed, since subtotal thyroidectomy is associated with a high risk of relapse in this group. Patients should be referred to surgeons experienced in thyroid surgery because studies show that children and adolescents have a higher complication rate than adults. METHODS: This is a retrospective matched case-control study. To analyze postoperative morbidity of children and adolescents (mean age = 15 ± 3 years) with Graves' disease who underwent total thyroidectomy between 2000 and 2010 in our department, a statistically identical group of adults (mean age = 46 ± 3) who also underwent total thyroidectomy for Graves' disease was matched as a control. End points were surgical complications like postoperative bleeding, transient and permanent recurrent laryngeal nerve palsy, and transient and permanent hypoparathyroidism. RESULTS: There was no significant difference in the mean operation time (137 ± 33 min), the rate of intraoperative parathyroid gland autotransplantation (9.5%), postoperative bleeding (4.8%), transient and permanent recurrent laryngeal nerve palsy (4.8 and 0%), and transient and permanent hypocalcemia (28.6 and 0%). CONCLUSION: Total thyroidectomy in children and adolescents with Graves' disease performed in a department that specializes in endocrine surgery is a safe procedure with no higher complication rates than total thyroidectomy in adults with Graves' disease.

Virological surveillance and preliminary antigenic characterization of influenza viruses in pigs in five European countries from 2006 to 2008.

This study presents the results of the virological surveillance for swine influenza viruses (SIVs) in Belgium, UK, Italy, France and Spain from 2006 to 2008. Our major aims were to clarify the occurrence of the three SIV subtypes - H1N1, H3N2 and H1N2 - at regional levels, to identify novel reassortant viruses and to antigenically compare SIVs with human H1N1 and H3N2 influenza viruses. Lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in pigs were investigated by virus isolation. The hemagglutinin (HA) and neuraminidase (NA) subtypes were determined using standard methods. Of the total 169 viruses, 81 were classified as 'avian-like' H1N1, 36 as human-like H3N2 and 47 as human-like H1N2. Only five novel reassortant viruses were identified: two H1N1 viruses had a human-like HA and three H1N2 viruses an avian-like HA. All three SIV subtypes were detected in Belgium, Italy and Spain, while only H1N1 and H1N2 viruses were found in UK and Northwestern France. Cross-hemagglutination inhibition (HI) tests with hyperimmune sera against selected older and recent human influenza viruses showed a strong antigenic relationship between human H1N1 and H3N2 viruses from the 1980s and H1N2 and H3N2 human-like SIVs, confirming their common origin. However, antisera against human viruses isolated during the last decade did not react with currently circulating H1 or H3 SIVs, suggesting that especially young people may be, to some degree, susceptible to SIV infections.

[Optical coherence tomography: preliminary results with a new noninvasive technique for evaluating uterine cervical tissue and vulvar epithelium]. / La tomografia a coerenza ottica, una nuova tecnica non invasiva per valutare il tessuto cervicale uterino e l'epitelio vulvare. Risultati preliminari.

AIM: Optical coherence tomography (OCT) is a noninvasive diagnostic imaging technique that captures high-definition real-time images at near-microscopic resolution (1-2 mm below the surface) of biological tissue morphology. The aim of this study was to define the characteristics of uterine cervical and vulvar pathologies by means of OCT and to compare OCT findings versus histopathological features. MATERIALS AND METHODS: This prospective single-center study was approved by the regional ethical committee. The OCT scans were performed in women with suspected cervical intraepithelial neoplasia (CIN) or vulvar intraepithelial neoplasia (VIN). The suspicious lesions were identified using colposcopy, visualized by OCT, and then biopsied. The OCT scans were evaluated by two independent examiners. The results were then compared with the histopathological findings. The sensitivity and specificity of OCT were calculated. RESULTS: Overall, 50 of the 54 CIN and 2 carcinomas confirmed on histology were correctly diagnosed with OCT, yielding a sensitivity of 93%; specificity was 33%, with 8 false positives and 4 true negatives. In 10 patients with suspected VIN, 19 OCT images were compared with the corresponding biopsies. Three states of tissue structure could be distinguished, with typical features of normal tissue and tissue altered by neoplastic transformation. CONCLUSION: OCT is a noninvasive, fast and simple technique to obtain real-time information on tissue microstructure. Further study is needed to assess its use in routine diagnostic imaging; however, these preliminary results indicate its high sensitivity.

Single layer transdermal film containing lidocaine: water and lidocaine mobility determined using neutron scattering.

The diffusivity of lidocaine through a polymer film developed for transdermal drug administration has been characterized by macroscopic permeation experiments and by neutron quasielastic spectroscopy that provides information on microscopic diffusivity parameters. It turns out that film hydration plays a key role on the performance and efficiency of the investigated system. Diffusion of lidocaine, at the microscopic level, is triggered by the presence of "mobile water." At hydration levels below 15% (weight water/weight hydrated film) neither lidocaine nor water show any appreciable long-range diffusion. At higher hydration levels, the onset of water long-range diffusion triggers diffusion of lidocaine through the film. The use of neutron quasielastic scattering makes it possible to measure lidocaine mobility within the film without the need of any additional physical barrier.

Characterization of low-pathogenic H5 subtype influenza viruses from Eurasia: implications for the origin of highly pathogenic H5N1 viruses.

Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many Asian countries, resulting in repeated outbreaks in poultry and increased cases of human infection. The immediate precursor of these HPAI viruses is believed to be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1 influenza viruses or genotypes have emerged in southern China. However, precursors of the Gs/GD-like viruses and their subsequent reassortants have not been fully determined. Here we characterize low-pathogenic avian influenza (LPAI) H5 subtype viruses isolated from poultry and migratory birds in southern China and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD-like virus was likely derived from an LPAI H5 virus in migratory birds. However, its variants arose from multiple reassortments between Gs/GD-like virus and viruses from migratory birds or with those Eurasian viruses isolated in the 1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses have not become established in aquatic or terrestrial poultry. Phylogenetic analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia with repeated transmissions between the eastern and western extremities of the continent. The data also show reassortment between influenza viruses from domestic and migratory birds in this region that has contributed to the expanded diversity of the influenza virus gene pool among poultry in Eurasia.