An investigation of the association between focal damage and global network properties in cognitively impaired and cognitively preserved patients with multiple sclerosis.

Introduction: The presence of focal cortical and white matter damage in patients with multiple sclerosis (pwMS) might lead to specific alterations in brain networks that are associated with cognitive impairment. We applied microstructure-weighted connectomes to investigate (i) the relationship between global network metrics and information processing speed in pwMS, and (ii) whether the disruption provoked by focal lesions on global network metrics is associated to patients' information processing speed. Materials and methods: Sixty-eight pwMS and 92 healthy controls (HC) underwent neuropsychological examination and 3T brain MRI including multishell diffusion (dMRI), 3D FLAIR, and MP2RAGE. Whole-brain deterministic tractography and connectometry were performed on dMRI. Connectomes were obtained using the Spherical Mean Technique and were weighted for the intracellular fraction. We identified white matter lesions and cortical lesions on 3D FLAIR and MP2RAGE images, respectively. PwMS were subdivided into cognitively preserved (CPMS) and cognitively impaired (CIMS) using the Symbol Digit Modalities Test (SDMT) z-score at cut-off value of -1.5 standard deviations. Statistical analyses were performed using robust linear models with age, gender, and years of education as covariates, followed by correction for multiple testing. Results: Out of 68 pwMS, 18 were CIMS and 50 were CPMS. We found significant changes in all global network metrics in pwMS vs HC (p < 0.05), except for modularity. All global network metrics were positively correlated with SDMT, except for modularity which showed an inverse correlation. Cortical, leukocortical, and periventricular lesion volumes significantly influenced the relationship between (i) network density and information processing speed and (ii) modularity and information processing speed in pwMS. Interestingly, this was not the case, when an exploratory analysis was performed in the subgroup of CIMS patients. Discussion: Our study showed that cortical (especially leukocortical) and periventricular lesions affect the relationship between global network metrics and information processing speed in pwMS. Our data also suggest that in CIMS patients increased focal cortical and periventricular damage does not linearly affect the relationship between network properties and SDMT, suggesting that other mechanisms (e.g. disruption of local networks, loss of compensatory processes) might be responsible for the development of processing speed deficits.

Quality of Life After Severe Burn Injury: A Case Report.

The danger of fire and electric current is underestimated by many people. The associated severe burn injuries are mainly treated in special burn centers because they are challenging and tend to have a strong impact on health-related quality of life. This case report describes a 20-year-old female severe burn victim who suffered second- to third-degree burns to approximately 80% of her total body surface. During in-patient care, we focused on inhalation trauma and anti-infective therapy, surgical management, physiotherapeutic and occupational therapy, in-patient rehabilitation measures, compression therapy and accompanying psychological co-treatment. This interdisciplinary treatment focused on restoring the best possible quality of life for burn victims.

Les dangers du feu et de l'électricité sont largement sous-estimés par la population. Les brûlures graves relèvent des centres spécialisés en raison de la complexité de leur prise en charge et de leur impact majeur sur la qualité de vie. Nous rapportons le cas d'une femme de 20 ans brûlée sur 80% de SCT (2ème et 3ème degrés). La prise en charge initiale a associé le traitement de l'inhalation de fumées, le traitement antiinfectieux, la chirurgie, la rééducation, la pressothérapie et l'accompagnement psychologique, dans le but d'optimiser la qualité de la vie à venir.

Effects of suspended coal particles on gill structure and oxygen consumption rates in a coral reef fish.

Large quantities of coal are transported through tropical regions; however, little is known about the sub-lethal effects of coal contamination on tropical marine organisms, including fish. Here, we measured aerobic metabolism and gill morphology in a planktivorous coral reef damselfish, Acanthochromis polyacanthus to elucidate the sub-lethal effects of suspended coal particles over a range of coal concentrations and exposure durations. Differences in the standard oxygen consumption rates (MO2) between control fish and fish exposed to coal particles (38 and 73 mg L-1) were minimal and generally not dose dependent; however, the MO2 of fish exposed to 38 mg coal L-1 (21 days) and 73 mg coal L-1 (31 days) were both significantly higher than the MO2 of control fish. Chronic coal exposure (31 days) altered gill structure in the higher coal treatments (73 and 275 mg L-1), with fish exposed to 275 mg L-1 exhibiting significant reductions in gill mucous and thinning of lamellar and filament epithelium. These findings contribute to our limited understanding of the potential impacts of coal on tropical reef species; however, most of the observed effects occurred at high coal concentrations that are unlikely under most coal spill scenarios. Future studies should investigate other contamination scenarios such as the impacts of chronic exposures to lower concentrations of coal.

Fine sediment and particulate organic matter: A review and case study on ridge-to-reef transport, transformations, fates, and impacts on marine ecosystems.

Studies documenting the effects of land-derived suspended particulate matter (SPM, i.e., particulate organic matter and mineral sediment) on marine ecosystems are typically disconnected from terrestrial studies that determine their origin, transport and fate. This study reviews sources, transport, transformations, fate and effects of SPM along the 'ridge-to-reef' continuum. We show that some of the SPM can be transported over long distances and transformed into large and easily resuspendible organic-rich sediment flocs. These flocs may lead to prolonged reductions in water clarity, impacting upon coral reef, seagrass and fish communities. Using the Great Barrier Reef (NE Australia) as a case study, we identify the latest research tools to determine thresholds of SPM exposure, allowing for an improved appreciation of marine risk. These tools are used to determine ecologically-relevant end-of-basin load targets and reliable marine water quality guidelines, thereby enabling enhanced prioritisation and management of SPM export from ridge-to-reef.

Scenario planning with linked land-sea models inform where forest conservation actions will promote coral reef resilience.

We developed a linked land-sea modeling framework based on remote sensing and empirical data, which couples sediment export and coral reef models at fine spatial resolution. This spatially-explicit (60 × 60 m) framework simultaneously tracks changes in multiple benthic and fish indicators as a function of land-use and climate change scenarios. We applied this framework in Kubulau District, Fiji, to investigate the effects of logging, agriculture expansion, and restoration on coral reef resilience. Under the deforestation scenario, models projected a 4.5-fold sediment increase (>7,000 t. yr-1) coupled with a significant decrease in benthic habitat quality across 1,940 ha and a reef fish biomass loss of 60.6 t. Under the restoration scenario, models projected a small (<30 t. yr-1) decrease in exported sediments, resulting in a significant increase in benthic habitat quality across 577 ha and a fish biomass gain of 5.7 t. The decrease in benthic habitat quality and loss of fish biomass were greater when combining climate change and deforestation scenarios. We evaluated where land-use change and bleaching scenarios would impact sediment runoff and downstream coral reefs to identify priority areas on land, where conservation or restoration could promote coral reef resilience in the face of climate change.

[Reliable Flaps for Congenitally Malformed Hands]. / Bewährte Lappen an der fehlgebildeten Kinderhand.

Congenital hand malformations are rare, but hand function and aesthetics cannot be improved by surgery in every affected child. However, whenever this is possible, it is important to create an individual surgical plan for each child. Growth has to be taken into account in the accurate planning of incisions and local flaps. Just because it is technically possible, not every flap should be used in the malformed child's hand. In the following article, we present a collection of reliable flaps in the surgery of the congenitally malformed hand.

[Technique of Suspension Surgery Using Palmaris Longus Tendon for Correction of Severe Blepharoptosis]. / Suspensionsoperation der Ptose des Oberlids durch die Sehne des M. palmaris longus an den M. frontalis.

Background In cases of blepharoptosis, the upper eyelid either cannot or can only be elevated insufficiently. The aetiology may be myogenic, aponeurotic, neurogenic, mechanical, or traumatic. The most common cause of congenital ptosis is myogenic, due to the improper development of the levator muscle. Methods Frontalis suspension operation as a technique of correction often uses silicone slings or fascia lata. On the basis of 3 cases, we present our method using palmaris longus tendon. Results In all 3 cases, intra- and postoperative courses were without adverse events and all cases are still relapse-free. Discussion Our technique using palmaris longus tendon for suspension of the frontalis muscle is a very good alternative to fascia lata or silicone slings. We achieved satisfactory results for eyelid opening and symmetry.

The direction of human mesenchymal stem cells into the chondrogenic lineage is influenced by the features of hydrogel carriers.

Low back pain is a major public health issue in the Western world, one main cause is believed to be intervertebral disc (IVD) degeneration. To halt/diminish IVD degeneration, cell therapy using different biomaterials e.g. hydrogels as cell carriers has been suggested. In this study, two different hydrogels were examined (in vitro) as potential cell carriers for human mesenchymal stem cells (hMSCs) intended for IVD transplantation. The aim was to investigate cell-survival and chondrogenic differentiation of hMSCs when cultured in hydrogels Puramatrix® or Hydromatrix® and potential effects of stimulation with growth hormone (GH). hMSCs/hydrogel cultures were investigated for cell-viability, attachment, gene expression of chondrogenic markers SOX9, COL2A1, ACAN and accumulation of extracellular matrix (ECM). In both hydrogel types, hMSCs were viable for 28days, expressed integrin ß1 which indicates adhesion of hMSCs. Differentiation was observed into chondrocyte-like cells, in a higher extent in hMSCs/Hydromatrix® cultures when compared to hMSCs/Puramatrix® hydrogel cultures. Gene expression analyses of chondrogenic markers verified results. hMSCs/hydrogel cultures stimulated with GH displayed no significant effects on chondrogenesis. In conclusion, both hydrogels, especially Hydromatrix® was demonstrated as a promising cell carrier in vitro for hMSCs, when directed into chondrogenesis. This knowledge could be useful in biological approaches for regeneration of degenerated human IVDs.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.

[Nerve injuries after elbow luxation fractures in childhood : Indication and timing for surgical revision]. / Nervenverletzungen nach Ellenbogenluxationsfraktur im Kindesalter : Indikation und Zeitpunkt zur operativen Revision.

BACKGROUND: Supracondylar humerus fractures are very common in pediatric populations. In cases of dislocated fractures, closed reduction and percutaneous K­wire fixation is recommended. Initially, 10-16 % of the patients also present lesion of the ulnar nerve as well as median nerve palsy in 6.4% and radial nerve palsy in 2.6 % of cases, respectively. METHOD: We present the case of a 10-year-old boy with a dislocation of the elbow and fracture of the medial epicondyle. After closed reduction and K­wire fixation from medial, he presents a median nerve palsy. That a lesion of the ulnar nerve is also present is only noticed 3½ years posttraumatically. A surgical decompression and neurolysis of the ulnar and median nerve is performed and the postoperative grip and key strength presented. DISCUSSION: With the help of the presented case we discuss the indication and the point of surgical revision. Clinical assessment and neurosonography are essential for an exact diagnosis.

["A Little Bit of Switzerland, a Little Bit of Kosovo". Swiss Immigrants from Former Yugoslavia with Type 2 Diabetes. A Qualitative Study' in Analogy to Grounded Theory]. / "Bisschen Schweiz, bisschen Kosovo". Erleben von Schweizer Migranten mit Diabetes mellitus Typ 2 aus dem ehemaligen Jugoslawien: Eine qualitative Studie in Anlehnung an die Grounded Theory.

Type 2 diabetes is on the increase among the Swiss immigrants. The cultural background of patients presents new linguistic and sociocultural barriers and gains in importance for health care. In order to develop patient-centred care, it is necessary to focus on different sociocultural aspects in everyday life and experiences of immigrants from the former republics of Yugoslavia with diabetes who have rarely been studied in Switzerland. Based on these insights the needs for counselling can be identified and nursing interventions can be designed accordingly. Using the Grounded Theory approach, 5 interviews were analysed according to the Corbin and Strauss coding paradigm. The central phenomenon found is the experience to live in 2 different cultures. The complexity arises from the tension living in 2 cultural backgrounds at the same time. It turns out that in the country of origin the immigrants adjust their disease management. The changing daily rhythm and the more traditional role model affect aspects of their disease management such as diet and/or drug therapy. The different strategies impact the person's roles, emotions, their everyday lives and their families. It provides an insight into the perspective of Swiss immigrants from the former republics of Yugoslavia suffering from diabetes. Many questions are still unanswered and further research will be required.

[Incisional hernias after median laparotomy. A concept for anatomic reconstruction of the abdominal wall]. / Bauchwandhernien nach medianer Laparotomie. Ein Konzept zur "anatomisch-funktionellen" Wiederherstellung.

The abdominal wall is a complex system of fibres and has its function in stabilisation of the lower back and pressure build-up for coughing and evacuation of the bowels. In case of incicional hernias after median laparotomy, which occur in 10-20%, reconstruction is a great challange for the surgeon. As methods of repair doubling of fascias, implantation of mesh grafts and muscle transfers have been described. In the following article we present a concept for anatomic and functional restoration of the abdominal wall in a selected patient population. Besides an exact surgical technique, the patient's compliance for weight reduction, special work-out and wearing a bodice pre- and postoperatively is essential for a good result.

Comparison of hospital-wide and unit-specific cumulative antibiograms in hospital- and community-acquired infection.

BACKGROUND: Empirical antibacterial therapy in hospitals is usually guided by local epidemiologic features reflected by institutional cumulative antibiograms. We investigated additional information inferred by aggregating cumulative antibiograms by type of unit or according to the place of acquisition (i.e. community vs. hospital) of the bacteria. MATERIALS AND METHODS: Antimicrobial susceptibility rates of selected pathogens were collected over a 4-year period in an university-affiliated hospital. Hospital-wide antibiograms were compared with those selected by type of unit and sampling time (<48 or >48 h after hospital admission). RESULTS: Strains isolated >48 h after admission were less susceptible than those presumably arising from the community (<48 h). The comparison of units revealed significant differences among strains isolated >48 h after admission. When compared to hospital-wide antibiograms, susceptibility rates were lower in the ICU and surgical units for Escherichia coli to amoxicillin-clavulanate, enterococci to penicillin, and Pseudomonas aeruginosa to anti-pseudomonal beta-lactams, and in medical units for Staphylococcus aureus to oxacillin. In contrast, few differences were observed among strains isolated within 48 h of admission. CONCLUSIONS: Hospital-wide antibiograms reflect the susceptibility pattern for a specific unit with respect to community-acquired, but not to hospital-acquired strains. Antibiograms adjusted to these parameters may be useful in guiding the choice of empirical antibacterial therapy.

Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate.

Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate.

Changing molecular epidemiology of methicillin-resistant Staphylococcus aureus in a small geographic area over an eight-year period.

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) at an international level shows that most MRSA strains belong to a few pandemic clones. At the local level, a predominance of one or two clones was generally reported. However, the situation is evolving and new clones are emerging worldwide, some of them with specific biological characteristics, such as the presence of Panton-Valentine leucocidin (PVL). Understanding these changes at the local and international levels is of great importance. Our objective was to analyze the evolution of MRSA epidemiology at multiple sites on a local level (Western Switzerland) over a period of 8 years. Data were based on MRSA reports from seven sentinel laboratories and infection control programs covering different areas. Pulsed-field gel electrophoresis was used to type MRSA isolates. From 1997 to 2004, a total of 2,256 patients with MRSA were reported. Results showed the presence of four predominant clones (accounting for 86% of patients), which could be related to known international clones (Berlin, New York/Japan, Southern Germany, and Iberian clones). Within the small geographic region, the 8-year follow-up period in the different areas showed spacio-temporal differences in the relative proportions of the four clones. Other international MRSA clones, as well as clones showing genetic characteristics identical to those of community-acquired MRSA (SCCmec type IV and the presence of PVL genes), were also identified but presumably did not disseminate. Despite the worldwide predominance of a few MRSA clones, our data showed that at a local level, the epidemiology of MRSA might be different from one hospital to another. Moreover, MRSA clones were replaced by other emerging clones, suggesting a rapid change.

[The influence of geometric visual illusions on saccadic eye movements]. / Der Einfluss geometrisch-optischer Täuschungen auf sakkadische Augenbewegungen.

BACKGROUND: The aim of this study was to investigate whether visually perceived length differences of Mueller-Lyer figures result in amplitude differences of saccadic eye movements along the figures. METHODS: Video recordings of eye movements were obtained from 35 healthy volunteers (aged 18 - 30 years) when scanning the endpoints of Mueller-Lyer targets. RESULTS: Saccades between the ends of lines with inward-pointing arrowheads had significantly greater amplitudes than saccades between the ends of lines with outward-pointing arrowheads. This bias was observed for both horizontal and vertical target orientations, and was maintained with a smaller amplitude, after fixation periods were extended from 1 s to 4 s. CONCLUSIONS: Changes in length perception by visual illusions correspond with changes in the amplitude of saccadic eye movements. Therefore, recordings of saccadic eye movements offer the opportunity to assess changes in visual object perception based on changes of central image processing at the cortical level.

Gene expression profiling reveals platelet-derived growth factor receptor alpha as a target of cell contact-dependent gene regulation in an endothelial cell-osteoblast co-culture model.

Angiogenesis plays an important role in bone development, repair, and remodelling. Neovascularization is furthermore a crucial step in bone tissue engineering because implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of the engineered tissue. We have previously described a co-cultivation system of human primary osteoblasts and human primary endothelial cells that was developed to improve neovascularization in bone tissue-engineering applications. In our present study, we have performed complementary deoxyribonucleic acid microarray analysis to analyze putative changes in osteoblastic gene expression upon co-cultivation of osteoblasts and endothelial cells. Transcriptional profiling revealed upregulation of 79 genes and downregulation of 62 genes in osteoblasts after co-cultivation with endothelial cells. To verify the microarray data, quantitative real-time reverse transcriptase polymerase chain reaction was carried out on selected genes. The expression of the platelet-derived growth factor receptor alpha gene in osteoblasts was analyzed in more detail, revealing that a cell contact-dependent mechanism, and not paracrine-acting diffusible factors, mediates the downregulation of this receptor in osteoblasts upon co-cultivation with endothelial cells. In summary, the data demonstrate complex gene-regulation mechanisms between endothelial cells and osteoblasts that are likely to play a role in bone morphogenesis.

How to make the most of history and literature in the teaching of medical humanities: the experience of the University of Geneva.

In this paper the authors discuss the benefits of history and literature in the teaching of medical humanities. They suggest that human sciences produce a common effect, which they call distancing. Distancing is the awareness that one natural way to describe a given situation does not exist and that any point of view-scientific or not-is context dependant and culturally shaped. Distancing is important to medical students, by allowing them to become aware of the specificity of their own professional point of view. The authors offer a reflection on the specificities of both historical and literary approaches and on the tools they provide for medical students. This paper assumes there is a close link between the theoretical debate on the benefits provided by human sciences and the concrete framework of a given programme. The authors describe team teaching, which has been the solution adopted in the School of Medicine at the University of Geneva to obtain the most from history and literature.