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Background: The objectives of this study were to evaluate the frequency of bony dehiscences in the optico-carotid recess (OCR) area and to measure the thickness of the bony lamellas bordering the OCR, according to our previously proposed OCR classification taking into account the extent of the recess. Methodology: A total of 100 human cadaver heads (n= 200 sphenoid sinuses) were investigated. Samples were divided into groups according to the presence and extent of OCR (no OCR, sub-optical OCR, latero-optical OCR). Bony dehiscences were visually identified and bone thickness was measured by using a high-resolution micrometer. Results: A bony dehiscence in the OCR area was observed in 20%. A significant difference in bony dehiscence occurrence rate between OCR types was found. The wall thickness of the bony carotid artery- and optic nerve canals bordering the OCR were 0.25 ± 0.16 mm and 0.27 ± 0.15 mm, respectively. Significant differences between OCR groups in bony wall thickness of the carotid artery canal and optic nerve canal were found. Samples with a latero-optical OCR had a significant thinner wall of the carotid artery and optic nerve canal than samples with a sub-optical OCR and no OCR. Conclusions: The current results indicate that the presence of an extended OCR, e.g. latero-optical, is highly associated with a greater risk of bony dehiscences and thinner bony lamellas in the OCR region.

Abstract The feasibility and surgical effort of a pre-lacrimal window approach (PLWA) depends on the width of the bony window anterior to the nasolacrimal duct. This study aimed to investigate gender-specific differences in feasibility of PLWA. A consecutive series of paranasal computed tomography scans from 50 females (n = 100) and 50 males (n = 100) were retrospectively analyzed. The primary outcome measure was the antero-posterior length of the bony pre-lacrimal window (BPLWA). The secondary outcome measure was the distribution of Simmen’s PLWA feasibility types (major, moderate and minor surgical effort). On average, males had a 1.5 mm (95% CI 0.8–2.2) significantly higher BPLW length in comparison to females [t(198) = 4.4, p

Chronic rhinosinusitis with nasal polyps (CRSwNP) significantly impacts quality of life and often presents therapeutic challenges, with biologics like dupilumab showing promise in managing severe, uncontrolled cases. The aim of this study was to assess the influence of overweight on the effectiveness of dupilumab in patients with uncontrolled CRSwNP. This retrospective study analyzed treatment outcomes of 75 CRSwNP patients receiving dupilumab, categorizing them into underweight/normal-weight (BMI ≤ 24.9 kg/m 2 ) and overweight/obese (BMI ≥ 25 kg/m 2 ) groups. Outcome measures included changes in nasal polyp score (NPS) and sinonasal outcome test (SNOT-22) scores. Results demonstrated that the underweight/normal-weight group experienced significantly greater improvements in NPS and a higher rate of total NPS improvement compared to the overweight/obese group. While SNOT-22 scores improved in both groups, no significant differences were observed. Among patients with comorbid asthma, the underweight/normal-weight subgroup also showed significantly better outcomes, including greater reductions in both NPS and SNOT-22 scores. Multiple regression analysis identified BMI as an independent prognostic factor for NPS outcomes. The findings suggest that overweight/obesity adversely affects the response to dupilumab in CRSwNP, emphasizing the need for personalized treatment strategies considering BMI.

Cerebrospinal fluid (CSF) leaks originating from defects within the anterior and middle cranial fossa typically manifest as unilateral clear watery rhinorrhea. Continuous CSF leakage mandates surgical repair due to the risk of meningitis and brain abscess. It can be categorized based on its underlying etiology into traumatic, iatrogenic and non-traumatic CSF leaks.

Retrograde clay mineral reactions (reverse weathering), including glauconite formation, are first-order controls on element sequestration in marine sediments. Here, we report substantial element sequestration by glauconite formation in shallow marine settings from the Triassic to the Holocene, averaging 3 ± 2 mmol·cm - ²·kyr -1 for K, Mg and Al, 16 ± 9 mmol·cm - ²·kyr -1 for Si and 6 ± 3 mmol·cm - ²·kyr -1 for Fe, which is ~2 orders of magnitude higher than estimates for deep-sea settings. Upscaling of glauconite abundances in shallow-water (0-200 m) environments predicts a present-day global uptake of ~≤ 0.1 Tmol·yr -1 of K, Mg and Al, and ~0.1-0.4 Tmol·yr -1 of Fe and Si, which is ~half of the estimated Mesozoic elemental flux. Clay mineral authigenesis had a large impact on the global marine element cycles throughout Earth's history, in particular during 'greenhouse' periods with sea level highstand, and is key for better understanding past and present geochemical cycling in marine sediments., (© 2022. The Author(s).)

Patients with scala tympani (ST) ossification present a distinct surgical challenge. Three-dimensional (3D) segmentation of the inner ear offers accurate identification of ossification and surgical planning of the cochleostomy to access the scala vestibuli. The scala vestibuli placement of cochlear implantation electrode is an alternate solution in these patients and is well supported by the literature.The present report describes a case of cochlear implantation in the scala vestibuli assisted by 3D segmentation of the cochlea for a patient with ossification in the ST and reviews the relevant literature. Clinical presentation of a 45-year-old Austrian female who was referred with a history of sudden sensorineural hearing loss 2 years ago in the right ear, confirmed by pure tone audiometry (PTA) and acoustically evoked auditory brainstem response (ABR). 3D segmentation of the inner ear identified the extent of ossification in the ST and assisted in the surgical planning of cochleostomy drilling anterior-superior to the round window to access the scala vestibuli for the electrode placement. Postoperative computed tomography (CT) to confirm the electrode placement in the scala vestibuli and PTA was performed to assess the hearing threshold following the cochlear implantation. Postoperative CT confirmed the full insertion of a flexible electrode. The hearing threshold measured by PTA was ≤ 40 dB across all frequencies tested. Review of the literature identified a total of 13 published reports on cochlear implantation electrode placement in scala vestibuli in cases with ossification in the ST., (© 2021. The Author(s).)

Purpose: We aimed to investigate the effect of interval length and total count of intratympanic steroid (ITS) injections in salvage treatment of patients with idiopathic sudden sensorineural hearing loss (ISSNHL)., Methods: This retrospective case-control study included 64 patients with ISSNHL, who were treated with ITS injections as salvage therapy at a tertiary referral centre. From September 2019 to December 2020, 32 patients received up to four injections every 2-4 days (revised-protocol group). These patients were 1:1 matched to patients, who received up to three injections at 1-week intervals between January 2014 and August 2019 (initial-protocol group). Hearing outcomes of the two groups were compared., Results: Both ITS salvage treatment protocols resulted in a statistically significant hearing improvement (p < 0.05). The initial-protocol declined hearing thresholds by 12 ± 11.7 dB (p < 0.001, d = 1, P = 99%). Mean hearing function was improved by 13.4 ± 19.1 dB in the revised-protocol group [p < 0.001, d = 0.7, P = 98%]. A clinically significant hearing improvement (> 10 dB) was seen in 18 patients (58.1%) in the initial-protocol group and in 14 patients (41.9%) in the revised-protocol group. A comparison of the hearing outcomes between protocol groups revealed no statistically significant differences (p > 0.05)., Conclusion: These results indicate that a shorter injection interval does not lead to better hearing outcomes in ITS salvage treatment for ISSNHL. Moreover, fewer ITS injections may reduce costs, physical/mental stress of the patients and lower the risk of persistent tympanic perforations., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Restless legs syndrome (RLS) is a common neurological disorder characterised by an irresistible urge to move the lower limbs, often accompanied by unpleasant sensations in the legs, typically occurring in the evening and at night and improving with movement. Restless arms syndrome (RAS) predominantly affects the arms, while the legs are rarely affected. RAS appears to be very rare, with very few cases described to date, but the diagnosis of RAS is probably made too infrequently, especially for milder and transient forms. The patient reported here even had severe symptoms for years that could have indicated RAS. He observed an immediate improvement in all RAS-related symptoms after administration of 100 mg L-dopa +25 mg benserazide, which continues to this day. Clinicians should always be alert for RLS-like symptoms in one or both arms that worsen at rest and improve with movement, thinking of possible RAS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Using data from a computer-based formative feedback system, we compare learning gains in the 8 weeks of school closures related to the COVID-19 pandemic in Switzerland with learning gains in the 8 weeks before these school closures. The school performance in mathematics and language of N = 28,685 pupils is modelled in second-order piecewise latent growth models with strict measurement invariance for the two periods under investigation. While secondary school pupils remain largely unaffected by the school closures in terms of learning gains, for primary school pupils learning slows down and at the same time interindividual variance in learning gains increases. Distance learning arrangements seem an effective means to substitute for in-person learning, at least in an emergency situation, but not all pupils benefit to the same degree., (© 2020 International Union of Psychological Science.)

Central pain after stroke due to brainstem infarction is very rare. Treatment is difficult and specific guidelines are lacking. This is the report of a 61-year-old female patient who, after a posterolateral left medulla oblongata insult with incomplete Wallenberg syndrome, subsequently developed a burning and tingling pain in the contralateral leg and a burning and shooting pain in the ipsilateral face in trigeminal branches 1 and 2. More than 3 years of therapy with amitriptyline, gabapentin, pregabalin and various grade II and III opioids was ineffective or showed intolerable side effects. The administration of tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio improved the pain situation and quality of life quickly and permanently. The encouraging results in the present case may suggest that treatment with medical cannabis should be considered in similar cases when standard therapies are insufficient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The feasibility and surgical effort of a pre-lacrimal window approach (PLWA) depends on the width of the bony window anterior to the nasolacrimal duct. This study aimed to investigate gender-specific differences in feasibility of PLWA. A consecutive series of paranasal computed tomography scans from 50 females (n = 100) and 50 males (n = 100) were retrospectively analyzed. The primary outcome measure was the antero-posterior length of the bony pre-lacrimal window (BPLWA). The secondary outcome measure was the distribution of Simmen's PLWA feasibility types (major, moderate and minor surgical effort). On average, males had a 1.5 mm (95% CI 0.8-2.2) significantly higher BPLW length in comparison to females [t(198) = 4.4, p < 0.0001]. The requirement of major surgical effort occurred 29% more frequently in females [χ 2 (1) = 17.7, p < 0.0001], whereas the necessity of moderate surgical effort was 21% more prevalent in males [χ 2 (1) = 8.8, p = 0.003]. The need of only minor surgical effort was twice as high in males compared to females [χ 2 (1) = 3, p = 0.081]. Our data indicates that females require more significant surgical effort during a PLWA to gain access to the maxillary sinus. These results are highly informative as a high amount of bone removal and nasolacrimal duct dislocation are associated with a higher likelihood of complications.

Introduction: Intratympanic steroid (ITS) injections represent an increasingly used salvage treatment option for patients with idiopathic sudden sensorineural hearing loss -(ISSHL) after systemic treatment. The most effective corticosteroid for this treatment modality still remains unclear. Triamcinolone acetonide has been used for ITS treatment in various clinical settings. However, there are limited clinical data of its usage in the therapeutic management of ISSHL. The aim of this study was to determine the efficacy of intratympanic triamcinolone acetonide injections as a salvage treatment for ISSHL., Methods: We conducted a retrospective chart review on patients affected by ISSHL with insufficient hearing recovery after primary systemic corticosteroid therapy and who were treated with intratympanic triamcinolone acetonide as a salvage therapy between January 2014 and August 2019. The patients were divided into groups according to their degree of hearing recovery, and we evaluated potential predictors of hearing recovery. Audiometric results were then compared to historic studies using dexamethasone or methylprednisolone., Results: One-hundred and fifty-two patients received up to 3 intratympanic injections with triamcinolone acetonide at 1-week intervals. The mean hearing improvement due to ITS salvage treatment was 15.9 ± 18.9 dB. Complete hearing recovery was noted in 15 patients (9.9%), while 73 patients (48%) obtained partial recovery, and 64 patients (42.1%) had no recovery. Primary systemic treatment delay, hearing improvement by primary systemic treatment, and severity of initial hearing loss were identified as significant predictors of hearing improvement. The first of the 3 injections resulted in the greatest hearing improvement., Conclusion: The use of triamcinolone acetonide in ITS salvage treatment resulted in similar hearing improvements as the use of the commonly used corticosteroids, namely, dexamethasone and methylprednisolone. Longer treatment delays, lower hearing improvement by primary systemic treatment, and higher initial hearing loss are associated with poorer prognoses of hearing recovery., (© 2021 S. Karger AG, Basel.)

The aims of this study were to determine the sphenoid sinus volume in an Austrian population, evaluate the relationship between volume and different types of pneumatization and investigate possible age-related sphenoid sinus volume degeneration in the elderly. A total of 50 human cadaver including 25 male and 25 female samples (=100 sphenoid sinuses, age range 65-100, mean age 84.52 ± 9.50) were selected to obtain volume and anatomical variants of pneumatization by using sphenoid sinus casts, made of quadrofunctional hydrophilic addition reaction silicone. The mean sphenoid sinus volume was 4.79 ± 2.39 cm. Males showed statistically significant larger sinus volumes than females (P = 0.048). The volume differed statistically significant for the different types of pneumatization (P < 0.001). The combined type of sphenoid sinus pneumatization presented the largest volume with 7.20 cm, followed by lateral, clival, sphenoid body, presellar, and conchal sinus type with 5.72, 5.63, 4.25, 2.08, and 0.5 cm, respectively. No significant correlation between age and sphenoid sinus volume was found (P = 0.707). This study highlights the close relationship between volume and morphology of sphenoid sinus and confirms ethnic variability. Moreover, our data shows no age-related volume degeneration.

Background: Generally, it is known that men are affected more frequently by nonmelanoma skin cancer (NMSC) than women. The aim of our study was to investigate the effect of sex on the characteristics of NMSCs of the pinna at the population that our center serves and to compare it with the international data., Methods: We analyzed retrospectively the data of 225 patients with NMSC of the pinna. Sex-specific differences were investigated for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) subgroups., Results: The ratio of BCC to cSCC was determined in male patients at 1:1.3, in contrast in females it was identified at 4:1 (P = .001)., Conclusion: In our study, a new aspect of the sex-dependent distribution of cSCC and BCC of the pinna was demonstrated. Women are affected four times more frequently by BCC than by cSCC, whereas in men this ratio is approximately equal., (© 2020 The Authors. Head & Neck published by Wiley Periodicals, Inc.)

Background: The outcome of patients with cancer of the head and neck is significantly improved by increased interdisciplinary cooperation. The main focus of this study was a comparison of epidemiologic factors (age, sex, origin, staging) of patients with head and neck cancer in Styria, with those for patients throughout Austria., Methods: A retrospective data analysis of collected archived tumor board protocols of the Comprehensive Cancer Center (CCC) Graz included the patient's age, sex, area of residence, TNM stage, reasons for inoperability, comorbidities and performance status by ECOG (Eastern Cooperative Oncology Group), was performed. This study focuses on 340 patients who presented with a head and neck malignancy for the first time., Results: In the period from January 2014 to December 2015 a total of 252 men (74.1%) and 88 women (25.9%) with malignant head and neck tumors, were presented in the tumor board for the first time. The mean age at diagnosis was 63.4 years. In 45.5% the patients already demonstrated advanced tumor stages (T4 = 27.9%, T3 = 17.6%). Most newly diagnosed neoplasms were cancers of the oropharynx (24.1%), larynx (19.4%) and oral cavity (18.8%) and 36.5% were considered to be inoperable. Curative and palliative treatments were initiated in 83.2% and 16.9%, respectively., Conclusion: The region of south Styria showed a higher incidence of T3 and T4 tumors of the oropharynx than the average Austrian population. Measures to increase awareness of this problem should be initiated to support general otorhinolaryngologists and general practitioners in detecting oropharyngeal cancers at an earlier stage.

Background: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay., Methods: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression., Findings: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 77 . 2-99 . 9%) for HPV16-driven HNSCC, and 90% (95% CI, 55 . 5-99 . 7%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 99 . 46% for men and 99 . 29% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue., Interpretation: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 0 . 96 indicates high sensitivity and specificity for early detection of HPV16-induced disease., Funding: The manufacturer provided assays free of charge., Competing Interests: Declaration of Competing Interest All participating authors hereby disclose any financial and personal relationships with other people or organisations that could have inappropriately influenced the current study., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

In magnetic resonance imaging, the use of array detection and the number of detector elements have seen a steady increase over the past two decades. As a result, per-channel analog connection via long coaxial cable, as commonly used, poses an increasing challenge in terms of handling, safety, and coupling among cables. This situation is exacerbated when complementary recording of radiofrequency transmission or NMR-based magnetic field sensing further add to channel counts. A generic way of addressing this trend is the transition to digital signal transmission, enabled by digitization and first-level digital processing close to detector coils and sensors in the magnet bore. The foremost challenge that comes with this approach is to achieve high dynamic range, linearity, and phase stability despite interference by strong static, audiofrequency, and radiofrequency fields. The present work reports implementation of a 16-channel in-bore receiver, performing signal digitization and processing with subsequent optical transmission over fiber. Along with descriptions of the system design and construction, performance evaluation is reported. The resulting device is fully MRI compatible providing practically equal performance and signal quality compared to state-of-the-art RF digitizers operating outside the magnet. Its use is demonstrated by examples of head imaging and magnetic field recording.

Thriving is a developmental process that is shaped by previous and current interactions within developmental contexts. We hypothesized that academic performance in the school context will positively predict thriving in young adulthood. Data of N = 2,043 students from Zurich were assessed with standardized tests in Grades 1, 3, 6, and 9. Results showed that a stronger increase in academic performance significantly predicted thriving at age 20, even after statistically controlling for various covariates. Further analyses showed that school bonding might represent a mediating link between the academic performance and thriving. We argue that although schools can be considered the most widespread and intensive "youth development program" of sorts, their role for thriving has been largely neglected in developmental science., (© 2018 Society for Research in Child Development.)

Formative assessments in schools have the potential to improve students' learning outcomes and self-regulation skills; they make learning visible and provide evidence-based guidelines for setting up and pursuing individual learning goals. With the recent introduction of the computer-based formative assessment systems for the educational contexts, there is much hope that such systems will provide teachers and students with valuable information to guide the learning process without taking much time from teaching and learning to spend on generating, evaluating and interpreting assessments. In this paper, we combine the theoretical and applied perspectives by addressing (a) the epistemological aspects of the formative assessment, with an emphasis on data collection, model building, and interpretation; (b) the methodological challenges of providing feedback in the context of instruction in the classroom; and (c) practical requirements for and related challenges of setting up and delivering the assessment system to a large number of students. In the epistemological section, we develop and explicate the interpretive argument of formative assessment and discuss the challenges of obtaining data with high validity. From the methodological perspective, we argue that computer-based formative assessment systems are generally superior to the traditional methods of providing feedback in the classroom, as they better allow supporting inferences of the interpretive argument. In the section on practical requirements, we first introduce an existing computer-based formative assessment system, as a case in point, for discussing related practical challenges. Topics covered in this section comprise the specifications of assessment content, the calibration and maintenance of the item bank, challenges concerning teachers' and students' assessment literacy, as well as ethical and data-protection requirements. We conclude with an outlook on possible future directions for computer-based formative assessment systems and the field in general.

Objectives: Reliable prognostic markers are lacking for tongue carcinoma. C-reactive protein (CRP) and a ratio from neutrophils/lymphocytes (NLR) are biomarkers, associated with prognosis in solid cancers. Aim of this work was to investigate the role of CRP and NLR in prognosis of patients with tongue carcinoma., Design: Retrospective cohort study., Setting: We retrospectively analysed data of patients treated for tongue carcinoma at our institution. Levels of CRP, Neutrophils and Lymphocytes were measured pretherapeutic., Participants: 197 patients treated for squamous cell carcinoma of the tongue between 2002 and 2015., Main Outcome Measures: Overall survival, disease-free survival., Results: Elevated CRP was significantly associated with shorter overall survival in our cohort in uni- and multivariate analysis. NLR was not associated with prognosis., Conclusion: In the present study we could confirm the role of CRP as an independent prognostic marker in patients with tongue carcinoma. Incorporating this marker in prognostication could represent a valuable and moreover inexpensive tool for improved decisions making concerning therapy in the future., (© 2018 John Wiley & Sons Ltd.)

Background: In Switzerland, the issue of young carers and young adult carers - young people under the age of 18 and 24 respectively, who take on significant or substantial caring tasks and levels of responsibility that would usually be associated with an adult - has not been researched before. The number of these younger carers is unknown, as is the extent and kind of their caring activities and the outcomes for their health, well-being, psycho-social development, education, transitions to adulthood, future employability and economic participation., Methods: The project is comprised of three stages: 1. A national Swiss-wide online survey to examine awareness of the issue of younger carers amongst professional populations in the education, health and social services sectors; 2. An online survey of 4800 Swiss pupils in schools using standardised instruments to identify the proportion and characteristics of pupils who are carers; and 3. Semi-structured interviews with 20 families comprising family members with care needs and younger carers, to consolidate and validate the other stages of the study; and to hear directly from care-dependent family members and younger carers about their experiences of the issues identified in the surveys and in previous published research., Discussion: The needs of younger carers and their ill and disabled family members in Switzerland have not been systematically investigated. This will be the first study in the country to investigate these issues and to develop evidence-based recommendations for policy and practice, drawing also on international research. The present study therefore fills an important national and international research gap. It will collect important data on the awareness, extent, kind and impact of caring amongst children and young people in Switzerland, and cross-link these findings with robust evidence from other countries. The study will reveal (a) the extent of awareness of the issue of young carers amongst medical, social, health, educational, and other groups in Switzerland; (b) the proportion and number of young carers amongst a normative child population, and what these young carers 'do' in terms of their caring roles; and, ((c) direct accounts by families of their care-giving and receiving experiences.)

The phonological awareness skills of 7- to 8-year-old children with intellectual disability (ID) were compared to those of 4- to 5-year-old typically developing children who were matched for early reading skills, vocabulary, and gender. Globally, children with ID displayed a marked weakness in phonological awareness. Syllable blending, syllable segmentation, and first phoneme detection appeared to be preserved. In contrast, children with ID showed a marked weakness in rhyme detection and a slight weakness in phoneme blending. Two school years later, these deficits no longer remained. Marked weaknesses appeared in phoneme segmentation and first/last phoneme detection. The findings suggest that children with ID display an atypical pattern in phonological awareness that changes with age. The implications for practice and research are discussed.

Congenital thumb hypoplasia is a radial deficiency occurring in the form of sole dysplasia or in combination with additional aberrations. Thumb hypoplasia can be categorised into 5 grades ranging from mild deformity to complete absence of the thumb. Thumb hypoplasia leads to a disturbance of grip function depending on its severity. The choice of treatment is based on the degree of thumb hypoplasia. For hypoplasia greater than grade 3B, restoration of the thumb using pollicization of the index finger is the treatment of choice. For this purpose the index finger is transformed into a thumb and is transposed to the position of the thumb with vessels and nerves being retained. The skeleton has to be shortened, rotated and abducted, followed by reconstruction of the muscles in line with the function of the new thumb. This procedure facilitates a restoration with maximal stability, sensitivity and mobility. In cases of isolated thumb hypoplasia, pollicization of the index finger yields good results persisting into adulthood. If associated aberrations are present, the outcome is less predictable because of the preexistent stiffness of the index finger. Nevertheless, associated aberrations do not represent a contraindication for index finger pollicization., (© Georg Thieme Verlag KG Stuttgart · New York.)

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

From a neuroimaging point of view, deep brain stimulation (DBS) in psychiatric disorders represents a unique source of information to probe results gained in functional, structural and molecular neuroimaging studies in vivo. However, the implementation has, up to now, been restricted by the heterogeneity of the data reported in DBS studies. The aim of the present study was therefore to provide a comprehensive and standardized database of currently used DBS targets in selected psychiatric disorders (obsessive-compulsive disorder (OCD), treatment-resistant depression (TRD), Gilles de la Tourette syndrome (GTS)) to enable topological comparisons between neuroimaging results and stimulation areas. A systematic literature research was performed and all peer-reviewed publications until the year 2012 were included. Literature research yielded a total of 84 peer-reviewed studies including about 296 psychiatric patients. The individual stimulation data of 37 of these studies meeting the inclusion criteria which included a total of 202 patients (63 OCD, 89 TRD, 50 GTS) was translated into MNI stereotactic space with respect to AC origin in order to identify key targets. The created database can be used to compare DBS target areas in MNI stereotactic coordinates with: 1) activation patterns in functional brain imaging (fMRI, phfMRI, PET, MET, EEG); 2) brain connectivity data (e.g., MR-based DTI/tractography, functional and effective connectivity); 3) quantitative molecular distribution data (e.g., neuroreceptor PET, post-mortem neuroreceptor mapping); 4) structural data (e.g., VBM for neuroplastic changes). Vice versa, the structural, functional and molecular data may provide a rationale to define new DBS targets and adjust/fine-tune currently used targets in DBS based on this overview in stereotactic coordinates. Furthermore, the availability of DBS data in stereotactic space may facilitate the investigation and interpretation of treatment effects and side effect of DBS by comparing these to neuroimaging results. The present study thus improves comparability between functional, structural and molecular data in standard stereotactic space gained in neuroimaging studies with surgical targets for DBS, which is among other possible implications of crucial importance for the definition of new targets for effective DBS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Social adjustment is impaired in depressed patients. The difficulty to adjust to social circumstances has been hypothesized to be one of the causes of depression, as well as a consequence of the disorder. Genetic variation in the serotonin transporter gene has been previously associated with social adjustment levels in patients with mood disorders., Methods: We investigated whether variations on the HTR1A (rs6295) and HTR2A (rs7997012) genes were associated with levels of social adjustment using the Social Adjustment Scale in two samples of depressed patients (total n=156)., Results: Patients carrying the GG genotype of the HTR2A-rs7997012 showed better social adjustment in areas of work and family unit bonding., Limitations: These findings did not survive correction for multiple testing and should be interpreted with caution., Conclusion: Our finding is in line with previous observations that have associated the G allele of the HTR2A-rs7997012 with higher rate of antidepressant response. The HTR2A-rs7997012 is worthy of further investigation in studies examining factors that are related to depression course and outcome., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Unlabelled: On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized., Introduction: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g., the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive., Methods: To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized., Results: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population., Conclusion: To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 μg (800 IU), which is best achieved with a supplement.

Background: Adverse life events are precipitating and maintenance factors for mood and anxiety disorders. However, the impact of such events on clinical features and treatment response is still unclear., Sampling and Methods: The aim of this study was to investigate whether specific adverse events (early parental loss and physical abuse) influence clinical features in a sample of 1,336 mood disorder patients, and whether genetic parameters interact with adverse events to influence treatment outcomes in a subsample of 252 subjects. Participants were collected in the context of a European multicenter study and treated with antidepressants at adequate doses for at least 4 weeks. We focused on two genes (BDNF and CREB1) due to prior evidence of association with treatment outcomes in the same sample., Results: Patients with a history of physical abuse had higher suicidal risk (including history of attempts), comorbid panic disorder, posttraumatic stress disorder and alcohol dependence compared to non-abused patients. Experience of early parental loss was a less detrimental type of life stressor. Treatment response was not affected by adverse events. No gene-environment interaction was found with genetic variations, using a corrected significance level., Conclusions: A limitation of the present study is that the subsample is too small for detecting gene-environment interactions. The clinical message of our findings is that mood disorder patients with a history of physical abuse showed a worse clinical profile, characterized by higher comorbid Axis I psychopathology and increased suicidal behavior., (Copyright © 2013 S. Karger AG, Basel.)

The main function of vitamin E is to protect against scavenging of reactive oxygen species; it is the primary protective agent against lipid peroxidation. Overt vitamin E deficiency is present only in patients with severe malnutrition and certain chronic diseases. The latest Recommended Dietary Allowance for vitamin E is based on the correlation between hydrogen peroxide-induced erythrocyte lysis and plasma α-tocopherol concentrations (Institute of Medicine, United States), or the prevention of lipid peroxidation (National Nutrition Societies of Germany, Austria and Switzerland, D-A-CH). According to the current recommendations, the reference plasma concentration for vitamin E is 12 - 46 µmol/L (daily intake of 15 - 30 mg α-tocopherol equivalents). Epidemiological studies suggest a beneficial effect of vitamin E on cardiovascular health at a plasma concentration of 30 µmol/L (a daily intake of ~ 50 IU). Vitamin E is also an important micronutrient for maintaining the immune system, especially in the elderly. A workshop was organized with the main objective to propose a concept for developing markers of status, functionality, and health in the field of nutritional research, in order to define desirable vitamin E requirements in healthy individuals.

Deficiencies of essential nutrients have been responsible for many epidemic outbreaks of deficiency diseases in the past. Large observational studies point at possible links between nutrition and chronic diseases. Low intake of antioxidant vitamins e. g. have been correlated to increased risk of cardiovascular diseases or cancer. The main results of these studies are indications that an intake below the recommendation could be one of the risk factors for chronic diseases. There was hardly any evidence that amounts above the RDA could be of additional benefit. Since observational studies cannot prove causality, the scientific community has been asking for placebo-controlled, randomized intervention trials (RCTs). Thus, the consequences of the epidemiological studies would have been to select volunteers whose baseline vitamin levels were below the recommended values. The hypothesis of the trial should be that correcting this risk factor up to RDA levels lowers the risk of a disease like CVD by 20 - 30 %. However, none of the RCTs of western countries was designed to correct a chronic marginal deficiency, but they rather tested whether an additional supplement on top of the recommended values would be beneficial in reducing a disease risk or its prognosis. It was, therefore, not surprising that the results were disappointing. As a matter of fact, the results confirmed the findings of the observational studies: chronic diseases are the product of several risk factors, among them most probably a chronic vitamin deficiency. Vitamin supplements could only correct the part of the overall risk that is due to the insufficient vitamin intake.

Objective: Climate, in particular sunshine, influences mood and energy levels, creating a positive upswing of mood on bright, sunny days and negative downswing in cold, dark winter seasons. Higher serotonin transporter availability in healthy human subjects in times of lesser light exposure and lower serotonin levels have been shown in winter., Methods: We examined the light-dependent variations in serotonin-1A receptor binding in limbic regions in 36 drug-naive healthy human subjects. Receptor binding was quantified using positron emission tomography and the radioligand [carbonyl-¹¹C]WAY-100635. Binding potential values were related to the amount of individual exposure to sunlight (daily duration of sunshine) and global radiation (total light intensity)., Results: We found a 20-30% lower serotonin-1A receptor binding in the group exposed to a lower amount of global light radiation. Partial correlation analysis revealed significant positive correlations between the regional postsynaptic serotonin-1A receptor binding and global radiation accumulated over a period of 5 days., Conclusions: Seasonal factors, such as daily amount of sunshine and global radiation, influence serotonin-1A receptor binding in limbic brain regions of healthy human subjects. Combined with recently demonstrated seasonal fluctuations in the serotonin transporter availability, our results underline the importance of seasonal factors in the regulation of the serotonergic transmission.

Background: The nosological and clinical implications of psychotic features in the course of mood disorders have been widely debated. Currently, no specification exists for defining a subgroup of lifetime Psychotic Mood Disorder (PMD) patients., Methods: A total of 2178 patients were examined, including subjects with Bipolar Disorder (BP) type I (n=519) and II (n=207) and Major Depressive Disorder (n=1452). Patients were divided between PMD (n=645) and non-psychotic Mood Disorders (MD) (n=1533) by the lifetime presence of at least one mood episode with psychotic features. Subjects having a depressive episode at the time of assessment were also examined: HAM-D and YMRS scores were compared between MD and PMD subjects, both with and without current psychotic features., Results: A diagnosis of BP-I, a higher familial load for BP, a higher number of mood episodes lifetime, and a higher prevalence of OCD and somatic comorbidities were all associated to PMD. A diagnosis of BP (OR=4.48) was the only significant predictor for psychosis. PMD with non-psychotic depression were apparently less severe than MD patients and had a lower rate of "non-responders" to AD treatment. Sub-threshold manic symptoms and suicidal risk were also more pronounced among PMD., Limitations: The lack of information about number and polarity of previous psychotic mood episodes may be the major limitations of our study., Conclusions: BP diagnosis is the most significant predictor for psychosis in mood disorders. Non-psychotic mood episodes in PMD patients may be characterized by a distinctive symptom profile and, possibly, a different response to treatment., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Progesterone (P) is thought to influence mood and affective states. Alterations of the inhibitory serotonin-1A (5-HT(1A)) receptor distribution are associated with depression and anxiety. This study evaluates the influence of plasma P levels on the 5-HT(1A) receptor binding in healthy male subjects., Methods: Molecular neuroimaging of the 5-HT(1A) receptor distribution using positron emission tomography and hormone assays for total plasma P and cortisol were done in a sample of 18 healthy men., Results: Plasma P levels explained up to 65% of the variability in 5-HT(1A) receptor binding in limbic regions including the amygdala, orbitofrontal cortex and retrosplenial cortex. When controlling for cortisol in the model, there was an expected decline in explained variances of 5-HT(1A) binding attributed to P., Conclusions: The results of this study provide further support for the effect of P on 5-HT(1A) receptor expression and raise the possibility that P mediates the vulnerability to mood disorders by affecting the serotonergic system., (Copyright © 2011 S. Karger AG, Basel.)

Selective serotonin reuptake inhibitors (SSRIs) represent one of the most common treatment options in major depression and anxiety disorders. By blocking the serotonin transporter, SSRIs modulate serotonergic neurotransmission as well as the function of autoreceptors and heteroreceptors. However, treatment-induced changes on a network level primarily remain unknown. Thus, we evaluated the association between serotonin-1A (5-HT1A) autoreceptors and heteroreceptors before and after SSRIs. Twenty-one patients with anxiety disorders underwent positron emission tomography using [carbonyl-11C]WAY-100635 before and after 12 weeks of escitalopram treatment; 15 of them completed the study protocol. Additionally, 36 drug-naive healthy controls were measured once. The 5-HT1A receptor binding potential (BPND) was quantified for the dorsal raphe nucleus (DRN) using a region-of-interest approach and for the entire brain by calculating parametric maps. Voxel-wise linear regression was applied between DRN autoreceptor and whole-brain heteroreceptor 5-HT1A BPND. Consistent with previous observations, healthy subjects showed widespread positive correlations of 5-HT1A BPND between autoreceptors and heteroreceptors. Comparing patients before versus after escitalopram treatment revealed enhanced associations of autoreceptor-to-heteroreceptor 5-HT1A BPND within the amygdala and hippocampus (R2=0.21-0.28 vs 0.49-0.81; p<0.05-0.001). In contrast, no significant SSRI-induced changes were found for correlations of heteroreceptor-to-heteroreceptor 5-HT1A BPND between several limbic regions. This interregional approach suggests a treatment-induced reinforcement of the association of 5-HT1A binding between autoreceptors and heteroreceptors specifically in areas involved in anxiety disorders. These findings provide complementary information about treatment effects on a network level and confirm the central role of the DRN as a prime regulatory area.

Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.

Serotonin modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT(1A)). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT(1A) receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT(1A) receptor radioligand [carbonyl-(11)C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT(1A) receptor binding potential (BP) as independent variable showed a highly significant association (r=.691, p=.002). The hypothalamic 5-HT(1A) BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant (p<.01, Bonferroni corrected threshold <.0056) between 5-HT(1A) BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT(1A) receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT(1A) receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT(1A) receptor distribution have been reported in affective disorders, future studies should focus on these interactions., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

There is an increasing interest in the underlying mechanisms of the antidepressant and anxiolytic treatment effect associated with changes in serotonergic neurotransmission after treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) in humans. The 5-HT(1A) receptor is known to play a crucial role in the pathophysiology of affective disorders, and altered 5-HT(1A) receptor binding has been found in anxiety patients. SSRI treatment raises the 5-HT level in the synaptic cleft and might change postsynaptic receptor densities. Therefore, our study in patients suffering from anxiety disorders investigated the effects of long-term treatment with escitalopram on the 5-HT(1A) receptor. A longitudinal positrone emission tomography (PET) study in 12 patients suffering from anxiety disorders was conducted. Two dynamic PET scans were performed applying the selective 5-HT(1A) receptor antagonist [carbonyl-(11)C]WAY-100635. Eight regions of interest were defined a priori (orbitofrontal cortex, amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus and cerebellum as reference). After the baseline PET scan, patients were administered escitalopram (average dose of 11.2+/-6.0 mg day(-1)) for a minimum of 12 weeks. A second PET scan was conducted after 109+/-27 days. 5-HT(1A) receptor binding potentials in 12 patients were assessed by PET applying the Simplified Reference Tissue Model.There was a significant reduction in the 5-HT(1A) receptor binding potential after a minimum of 12 weeks of escitalopram treatment in the hippocampus (P=0.006), subgenual cortex (P=0.017) and posterior cingulate cortex (P=0.034). The significance of the hippocampus region survived the Bonferroni-adjusted threshold for multiple comparisons. These PET data in humans in vivo demonstrate a reduction of the 5-HT(1A) binding potential after SSRI treatment.

Objectives: Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT(1A) receptor, and sex hormones., Experimental Design: Thirty-three healthy volunteers (16 women, aged 26.24 +/- 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl-(11)C]WAY-100635 to quantify 5-HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17beta-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions., Principal Observations: Statistical analyses revealed higher 5-HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5-HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03)., Conclusions: The present study provides first-time evidence for a specific interrelation between the 5-HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down-stream control due to higher amounts or activities of frontal 5-HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones., ((c) 2008 Wiley-Liss, Inc.)

Lateralization is a well described aspect of the human brain. A plethora of morphological, cytological and functional studies describes hemispheric asymmetry in auditory and language areas. However, no study has reported cortical lateralization in the healthy human brain in vivo on the level of neurotransmitter receptors and in relation to functional organization so far. In this study, we assessed the distribution of the main inhibitory serotonergic receptor (the 5-HT1A receptor) and analyzed its regional binding with regard to hemisphere, sex and plasma levels of sex steroid hormones (testosterone, estradiol, progesterone). We quantified the 5-HT1A receptor binding potential by positron emission tomography (PET) using the highly selective and specific radioligand [carbonyl-11C]WAY-100635 and measured hormone levels in thirty-four (16 females, 18 males) healthy right-handed subjects. The obtained data were analyzed in an automated region of interest (ROI) based approach investigating 14 auditory, language and limbic areas. We found significantly higher 5-HT1A receptor binding in the superior and middle frontal gyri of the right hemisphere, the triangular and orbital parts of the inferior frontal gyrus, the supramarginal gyrus, the superior gyrus of the temporal pole and the middle temporal gyrus. Regions of the primary and secondary auditory cortex (Heschl's gyrus and superior temporal gyrus) and the Rolandic operculum displayed significantly higher receptor binding in the left hemisphere. 5-HT1A receptor binding was 1.8-2.9% higher in right frontal ROIs and 2-3.6% higher in left primary and secondary auditory regions. There was no hemispheric difference in 5-HT(1A) receptor binding in the hippocampus, amygdala, and insula. Post-hoc testing suggested that lateralization of 5-HT1A receptor binding differed between the sexes in the triangular part of the inferior frontal gyrus. For the first time, this PET study shows lateralization of the main inhibitory receptor of the serotonergic system in functionally asymmetric organized regions of the healthy human brain in vivo.

Purpose: The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT(1A)) receptor., Methods: Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-(11)C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT(1A) receptor BP(ND) was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling., Results: The 5-HT(1A) receptor BP(ND) was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP(ND) values in every region investigated, with a borderline significant sex difference in the hypothalamus (p = 0.012, uncorrected). There was a high intersubject variability of the 5-HT(1A) receptor BP(ND) within both sexes compared to the small mean differences between men and women., Conclusions: To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT(1A) receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT(1A) receptor expression.

Quantitative ultrasound (QUS) measurements can be used to estimate osteoporotic fracture risk. The commonly used variables are the speed of sound (SOS) and the frequency dependent sound attenuation (broadband ultrasound attenuation, [BUA]) of a wave propagating through the bone, preferably the calcaneus. The technology, so far, is less suitable for direct measurement in vivo at the spine or the femur for prediction of bone mineral density (BMD) or fracture risk at the main osteoporotic fracture sites. To improve the clinical performance of QUS, we built a device for direct QUS measurements at the human femur in vivo. In vivo images of ultrasound transmission at one of the main fracture sites, the proximal femur, could be acquired. The estimated precision of SOS measurements of 0.5% achieved at the femur is comparable with the precision of peripheral QUS devices.

Quantitative ultrasound (QUS) at the calcaneus has similar power as a bone mineral density (BMD)- measurement using DXA for the prediction of osteoporotic fracture risk. Ultrasound equipment is less expensive than DXA and free of ionizing radiation. As a mechanical wave, QUS has the potential of measuring different bone properties than dual X-ray absorptiometry (DXA,) which depends on X-ray attenuation and might be developed into a tool of comprehensive assessment of bone strength. However, site-specific DXA at the proximal femur shows best performance in the prediction of hip fractures. To combine the potential of QUS with measurements directly at the femur, we developed a device for in vivo QUS measurements at this site. Methods comprise ultrasound transmission through the bone, reflection from the bone surface, and backscatter from the inner trabecular structure. The complete area of the proximal femur can be scanned except at the femoral head, which interferes with the ilium. To avoid edge artifacts, a subregion of the proximal femur in the trochanteric region was selected as measurement region. First, in vivo measurements demonstrate a good signal to noise ratio and proper depiction of the proximal femur on an attenuation image. Our results demonstrate the feasibility of in vivo measurements. Further improvements can be expected by refinement of the scanning technique and data evaluation method to enhance the potential of the new method for the estimation of bone strength.

Objective: The aim of this observational study was to evaluate the effectiveness of escitalopram in a naturalistic sample of employed people with mood and anxiety disorders., Method: Days on sick leave 3 months prior and 3 months during treatment with escitalopram were recorded and compared (mirror study design) in 2378 patients (949 men and 1376 women). A further clinical examination including the clinical global impression of severity (CGI-S) and improvement (CGI-I) scales and assessments of tolerability were used to evaluate treatment effects in a subgroup of 807 study subjects., Results: Escitalopram treatment (mean final daily dosage: 12.4+/-5.0 mg) led to a significant reduction (baseline versus end of study) of sick leave (11.0+/-12.8 days versus 5.4+/-11.0 days; p<0.001). CGI-S scores decreased from 4.7+/-0.9 at baseline to 2.4+/-1.1 after 3 months (p<0.001), the CGI-I after 3 months was 1.9+/-0.9. The incidence of adverse events after initiation of treatment with escitalopram was 13.1%, with only 1.3% of patients experiencing severe adverse events interfering with patient functioning., Conclusion: Our results suggest that escitalopram is an efficacious and overall well-tolerated treatment in a naturalistic sample of working patients. A decrease in the days on sick leave is indicative of indirect cost-effectiveness of this treatment.

Quantitative ultrasound (QUS) measurements at peripheral sites can be used to estimate osteoporotic fracture risk. However, measurements at these sites are less suitable to predict bone mineral density (BMD) or fracture risk at the central skeleton. We investigated whether direct QUS measurements at the femur would allow to estimate dual X-ray absorptiometry (DXA) BMD of the total proximal femur with errors comparable to established DXA accuracy errors. Two independent sets of femora were measured in Kiel (6 f, 4 m, age: 55-90) and Paris (19 f, 20 m age: 45-95) using different benchtop systems in the two laboratories. The femora were scanned in transverse transmission mode using focused US transducers of 500 kHz center frequency. The QUS values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements. BMD was measured using DXA. SOS and BMD correlated significantly (p<0.0001) in both data sets (R2=0.81-0.93). Correlations between BUA and BMD were also significant at p<0.001, but correlation coefficients were lower (R2=0.61-0.75). Residual errors for the estimation of BMD were 8%-10% for SOS as predictor, and 14%-16% for BUA as predictor. The residual error of 8 to 10% for the estimation of BMD from SOS is comparable to variabilities among different DXA femur subregions and accuracy errors of femoral DXA measurements caused by the impact of soft tissue. It is substantially smaller than the errors of 13% for the estimation of total femur BMD from spine BMD, 14% for the estimation of total femur BMD from calcaneus SOS or 16% for the estimation of ash weight from DXA. The results of the study show that SOS is able to predict total BMD with adequate accuracy. If femoral BMD could be obtained in vivo with comparable accuracy, femoral QUS would be suited for the assessment of bone status at one of the main osteoporotic fracture sites.

Objectives: The purpose of this study was to develop a transesophageal probe that: 1) enables on-line representation of the spatial structures of the heart, and 2) enables navigation of medical instruments., Background: Whereas transthoracic real-time 3-dimensional (3D) echocardiography could recently be implemented, there is still no corresponding transesophageal system. Transesophageal real-time 3D echocardiography would have great potential for numerous clinical applications, such as navigation of catheters., Methods: The newly developed real-time 3D system is based on a transesophageal probe in which multiple transducers are arranged in an interlaced pattern on a rotating cylinder. This enables continuous recording of a large echo volume of 70 mm in length and a sector angle of 120 degrees . The presentation of the volume-reconstructed data is made with a time lag of <100 ms. The frame rate is up to 20 Hz. In addition to conventional imaging, the observer can obtain a stereoscopic image of the structures examined with red/blue goggles., Results: It was shown in vitro on ventricle- and aorta-form agar models and in vivo that the system enables excellent visualization of the 3D structures. Shape, spatial orientation, and the navigation of various catheters (e.g., EPS-catheter, Swan-Ganz-catheter), stents, or atrial septal defect occluders could be recorded on-line and stereoscopically depicted. The size of the echo sector enables a wide field of view without changing the position of the probe., Conclusions: Transesophageal real-time 3D echocardiography can be technically realized with the system presented here. The in vitro and in vivo studies show particularly the potential for navigation in the heart and large vessels on the basis of stereoscopic images.