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.

[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.

[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.

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.

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.

Superdense water ice.

A new allotropic form of water ice with a density of 2.32 +/- 0.15 grams per cubic centimeter has been observed at very low pressures and for temperatures lower than 100 degrees K. It is most likely amorphous.

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.

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.

[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.

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.

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.

Oncodevelopmental enzymes of the Dunning rat prostatic adenocarcinoma.

In this paper, data are presented which demonstrate that adenylate kinase and creatine kinase are oncodevelopmental enzymes in the rat prostate. The Dunning tumor (dorsal rat prostate) was used as a model system; four sublines of the tumor (R3327-H, R3327-AT, MAT Lu, and MAT LyLu) were studied. The tumor lines were maintained as solid tumors in syngeneic rats (Copenhagen) and as monolayers in tissue culture. The appearance of adenylate kinase with malignant transformation of the dorsal prostate was demonstrated. The disappearance of the CK-M subunit of creatine kinase and decreasing levels of creatine kinase were demonstrated with increasing anaplasia. The lactate dehydrogenase (LDH) concentration increased with increasing anaplasia, and the LDH isoenzyme pattern shifted to a more glycolytic pattern (LDH-4, LDH-5). The malignant isoenzyme pattern was reversible with the use of a differentiating agent (dimethyl sulfoxide). Prostates from neonatal rats and castrated adult male rats exhibited patterns of creatine kinase and adenylate kinase similar to those of the undifferentiated tumor. The oncofetal isoenzyme pattern of the castrated rat prostate was reversible with physiological levels of exogenous testosterone.

Local aspirin analgesia in the oral cavity.

Aspirin solution applied locally to the oral cavity produces an analgesic effect on pain induced by electrical stimuli and by knife prick. Spontaneous pain is also relieved. The effect is of a local nature and can be terminated by rinsing the mouth with water, indicating that there is only a loose bond between aspirin and the mucosa. The local nature is also demonstrated by the lack of analgesia in areas of the tongue where exposure to aspirin solution is prevented by separation with a rubber-dam.

Community-acquired pneumonia. A prospective outpatient study.

We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.

Modulation of in vitro angiogenesis in a three-dimensional spheroidal coculture model for bone tissue engineering.

One of the major challenges in tissue engineering of bone substitutes remains vascularization of the transplant. We have developed a three-dimensional collagen-based coculture system to assess interactions between human endothelial cells (hECs) and human osteoblasts (hOBs) in vitro. Human umbilical vein endothelial cells (HUVECs) were grown as three-dimensional multicellular spheroids and seeded in a collagen matrix to assess sprouting of the spheroids, that is, formation of tubelike structures resembling early capillaries. Direct cell contact between hOBs and HUVECs was established by incorporating hOBs into the EC spheroids, thus forming heterogeneous cospheroids. Spatial organization of cospheroids and sprout configuration were assessed by immunohistochemical wholemount staining techniques and confocal laser microscopy. Cumulative sprout length of spheroids was quantitatively analyzed by digital imaging planimetry. In this model HUVECs and hOBs formed heterogeneous cospheroids with distinct spatial organization. The ability of HUVEC spheroids to form tubelike structures on angiogenic stimulation with vascular endothelial growth factor and basic fibroblast growth factor was suppressed in heterogeneous HUVEC/hOB cospheroids. The model system introduced in this study may be useful to assess the mechanisms involved in regulating angiogenesis during bone formation and to further investigate the mechanisms by which heterotypic cell-cell interactions inhibit endothelial tube formation for applications in bone tissue engineering.

Plasmid gene delivery to human keratinocytes through a fibrin-mediated transfection system.

We have developed a matrix-mediated transfection system to deliver plasmids to human keratinocytes. The matrix is a soluble, self-hardening fibrin matrix (Tissucol), Baxter) that has been used clinically. Recently it has been shown that full thickness burn wounds can be successfully treated with a keratinocyte fibrin glue suspension. Further, it has been demonstrated that hEGF transfected cells accelerate wound healing. In this study, we inoculated the matrix with the hEGF expression plasmid and resuspended the matrix with either cultured or noncultured human keratinocytes. We obtained successful transfection rates of these cells (up to a 100-fold increase compared to controls containing no EGF expression plasmid) in vitro. After transplantation to full thickness wounds on athymic mice we were able to show a 180-fold increase in EGF concentration compared to controls, which persisted over the entire 7-day monitored period, decreasing from 180 to 20 pg/mL at day seven. This unique approach indicates the possible utility to combine a matrix for cell transplantation with a transfection system to release therapeutic proteins in vitro and in vivo.