The Global Atmosphere-aerosol Model ICON-A-HAM2.3-Initial Model Evaluation and Effects of Radiation Balance Tuning on Aerosol Optical Thickness.

The Hamburg Aerosol Module version 2.3 (HAM2.3) from the ECHAM6.3-HAM2.3 global atmosphere-aerosol model is coupled to the recently developed icosahedral nonhydrostatic ICON-A (icon-aes-1.3.00) global atmosphere model to yield the new ICON-A-HAM2.3 atmosphere-aerosol model. The ICON-A and ECHAM6.3 host models use different dynamical cores, parameterizations of vertical mixing due to sub-grid scale turbulence, and parameter settings for radiation balance tuning. Here, we study the role of the different host models for simulated aerosol optical thickness (AOT) and evaluate impacts of using HAM2.3 and the ECHAM6-HAM2.3 two-moment cloud microphysics scheme on several meteorological variables. Sensitivity runs show that a positive AOT bias over the subtropical oceans is remedied in ICON-A-HAM2.3 because of a different default setting of a parameter in the moist convection parameterization of the host models. The global mean AOT is biased low compared to MODIS satellite instrument retrievals in ICON-A-HAM2.3 and ECHAM6.3-HAM2.3, but the bias is larger in ICON-A-HAM2.3 because negative AOT biases over the Amazon, the African rain forest, and the northern Indian Ocean are no longer compensated by high biases over the sub-tropical oceans. ICON-A-HAM2.3 shows a moderate improvement with respect to AOT observations at AERONET sites. A multivariable bias score combining biases of several meteorological variables into a single number is larger in ICON-A-HAM2.3 compared to standard ICON-A and standard ECHAM6.3. In the tropics, this multivariable bias is of similar magnitude in ICON-A-HAM2.3 and in ECHAM6.3-HAM2.3. In the extra-tropics, a smaller multivariable bias is found for ICON-A-HAM2.3 than for ECHAM6.3-HAM2.3.

Orthotic treatment of idiopathic toe walking with a lower leg orthosis with circular subtalar blocking.

BACKGROUND: There is no universally accepted treatment standard for idiopathic toe walking patients (ITW) in the current literature. None of the established methods provide homogenous satisfying results. In our department we treat ITW patients with lower leg orthoses with a circular foot unit for a total of 16 weeks. In this study we reviewed our database to evaluate the success of our treatment protocol for a 24 months follow up period. RESULTS: Twenty-two patients were included in this study. Age at the beginning of treatment was 7.0 years +/- 2.9 (range 2.5-13.1). Percentage of ITW at the beginning of treatment according to the perception of the parents was 89% +/- 22.2 (range 50-100). Immediately after the treatment with our device, percentage of ITW dropped to 11% +/- 13.2 (range 0-50). After 12 months, 73% of the patients (16/22) walked completely normal or showed ITW less than 10% of the day. After 24 months, 64% of the patients kept a normal gait (14/22). CONCLUSION: This study provides evidence that the treatment of idiopathic toe walking with lower leg orthoses with a circular foot unit results in satisfying long-term results in two thirds of the patients.

Is unilateral lower leg orthosis with a circular foot unit in the treatment of idiopathic clubfeet a reasonable bracing alternative in the Ponseti method? Five-year results of a supraregional paediatric-orthopaedic centre.

BACKGROUND: In the Ponseti treatment of idiopathic clubfoot, children are generally provided with a standard foot abduction orthosis (FAO). A significant proportion of these patients experience irresolvable problems with the FAO leading to therapeutic non-compliance and eventual relapse. Accordingly, these patients were equipped with a unilateral lower leg orthosis (LLO) developed in our institution. The goal of this retrospective study was to determine compliance with and the efficacy of the LLO as an alternative treatment measure. The minimum follow-up was 5 years. RESULTS: A total of 45 patients (75 ft) were retrospectively registered and included in the study. Compliance with the bracing protocol was 91% with the LLO and 46% with the FAO. The most common problems with the FAO were sleep disturbance (50%) and cutaneous problems (45%). Nine percent of patients experienced sleep disturbance, and no cutaneous problems occurred with the LLO. Thirteen percent of patients being treated with an FAO until the age of four (23 patients; 40 ft) underwent surgery because of relapse, defined by rigid recurrence of any of the components of a clubfoot. Fourteen percent of patients being treated with an LLO (22 patients; 35 ft), mostly following initial treatment with an FAO, experienced recurrence. CONCLUSION: Changing from FAO to LLO at any point during treatment did not result in an increased rate of surgery and caused few problems.

Androgen receptor dampens tissue factor expression via nuclear factor-κB and early growth response protein 1.

Essentials Androgen deprivation increases the rate of venous thromboembolism in prostate cancer patients. We characterized androgen receptor-mediated tissue factor regulation in prostate epithelial cells. Androgen receptor is dampening tissue factor expression in prostate epithelial cells. Androgen deprivation could enhance tissue factor expression and raise venous thromboembolism rates. SUMMARY: Background Prostate cancer is one of the leading causes of cancer death in men. Advanced prostate cancer is usually treated by androgen deprivation therapy (ADT), which is aimed at reducing circulating testosterone levels to reduce cancer growth. There is growing evidence that ADT can increase the rate of venous thromboembolism (VTE) in prostate cancer patients. The tissue factor (TF) gene is one of the most important mediators of coagulation and VTE, but, so far, there are limited data on androgen receptor (AR)-mediated TF gene expression. Objectives To characterize AR-mediated TF regulation in vitro and in vivo. Methods We used the androgen-dependent prostate cancer cell lines LNCaP and MyC-CaP to test whether TF expression is regulated by AR. Furthermore, we cloned the TF gene promoter into a luciferase reporter vector to identify the transcription factor-binding sites that mediate TF regulation downstream of AR. Finally, we used castration experiments in mice to characterize AR-mediated TF regulation in vivo. Results TF is directly regulated by AR. In LNCaP cells, nuclear factor-κB signaling and EGR1 mediate TF expression. By using castration experiments in mice, we could detect upregulation of TF and early growth response protein 1 mRNA and protein expression in prostate epithelial cells. Conclusion AR is crucial for dampening TF expression, which could be important for increased TF expression and TF-positive microvesicle release in androgen-deprived prostate cancer patients.

A novel method for automated assessment of megakaryocyte differentiation and proplatelet formation.

Transfusion of platelet concentrates represents an important treatment for various bleeding complications. However, the short half-life and frequent contaminations with bacteria restrict the availability of platelet concentrates and raise a clear demand for platelets generated ex vivo. Therefore, in vitro platelet generation from megakaryocytes represents an important research topic. A vital step for this process represents accurate analysis of thrombopoiesis and proplatelet formation, which is usually conducted manually. We aimed to develop a novel method for automated classification and analysis of proplatelet-forming megakaryocytes in vitro. After fluorescent labelling of surface and nucleus, MKs were automatically categorized and analysed with a novel pipeline of the open source software CellProfiler. Our new workflow is able to detect and quantify four subtypes of megakaryocytes undergoing thrombopoiesis: proplatelet-forming, spreading, pseudopodia-forming and terminally differentiated, anucleated megakaryocytes. Furthermore, we were able to characterize the inhibitory effect of dasatinib on thrombopoiesis in more detail. Our new workflow enabled rapid, unbiased, quantitative and qualitative in-depth analysis of proplatelet formation based on morphological characteristics. Clinicians and basic researchers alike will benefit from this novel technique that allows reliable and unbiased quantification of proplatelet formation. It thereby provides a valuable tool for the development of methods to generate platelets ex vivo and to detect effects of drugs on megakaryocyte differentiation.

[Cardiac arrest in a fitness trainer with apical hypertrophic cardiomyopathy associated with cor triatriatum sinister]. / Plötzlicher Herztod einer Fitnesstrainerin mit hypertropher Kardiomyopathie vom apikalen Typ assoziiert mit Cor triatriatum sinister.

We report on a 49-year-old fitness trainer, who was admitted to our hospital after cardiac arrest due to ventricular fibrillation. Return of spontaneous circulation was achieved after immediate cardiopulmonary resuscitation. Coronary angiography could exclude coronary artery disease. Echocardiography demonstrated the presence of apical hypertrophic cardiomyopathy, associated with cor triatriatum sinister. Cardiac magnetic resonance imaging additionally showed marked myocardial fibrosis. The patient underwent placement of an implantable cardioverter-defibrillator and was subsequently discharged for rehabilitation in good condition.

Myeloid PTEN deficiency impairs tumor-immune surveillance via immune-checkpoint inhibition.

Tumor-host interaction is determined by constant immune surveillance, characterized by tumor infiltration of myeloid and lymphoid cells. A malfunctioning or diverted immune response promotes tumor growth and metastasis. Recent advances had been made, by treating of certain tumor types, such as melanoma, with T-cell checkpoint inhibitors. This highlights the importance of understanding the molecular mechanisms underlying the crosstalk between tumors and their environment, in particular myeloid and lymphoid cells. Our aim was to study the contribution of the myeloid PI3K/PTEN-signaling pathway in the regulation of tumor-immune surveillance in murine models of cancer. We made use of conditional PTEN-deficient mice, which exhibit sustained activation of the PI3K-signaling axis in a variety of myeloid cell subsets such as macrophages and dendritic cells (DCs). In colitis-associated colon cancer (CAC), mice deficient in myeloid PTEN showed a markedly higher tumor burden and decreased survival. We attributed this observation to the increased presence of immune-modulatory conventional CD8α(+) DCs in the spleen, whereas other relevant myeloid cell subsets were largely unaffected. Notably, we detected enhanced surface expression of PD-L1 and PD-L2 on these DCs. As a consequence, tumoricidal T-cell responses were hampered or redirected. Taken together, our findings indicated an unanticipated role for the PI3K/PTEN-signaling axis in the functional regulation of splenic antigen-presenting cells (APCs). Our data pointed at potential, indirect, tumoricidal effects of subclass-specific PI3K inhibitors, which are currently under clinical investigation for treatment of tumors, via myeloid cell activation.

[Osteogenesis imperfecta]. / Osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is the most common genetic disease of bone and is characterized by fragile bones and growth disorders of varying severity. Most cases of OI are inherited autosomal dominant and caused by a mutation in the collagen type I gene. DIAGNOSTICS: Indications for OI are bone fragility, stunted growth, scoliosis, skull deformities, blue sclera, loss of hearing, dentinogenesis imperfecta and increased laxity of ligaments and skin. In most cases it is possible to make a clinical diagnosis but a skin biopsy or genetic testing can be useful; however, negative results for these tests do not exclude OI. THERAPY: Therapy must be carried out in a multidisciplinary team and includes conservative (e.g. physiotherapy, rehabilitation programs and orthopedic aids), operative (e.g. intramedullary stabilization procedures) and pharmaceutical (e.g. biphosphonates and growth hormones) procedures. PROGNOSIS: The prognosis depends on the type of OI and ranges from normal life expectations for type 1 patients up to up to perinatal mortality for type II patients.

[Determination of activity levels in patients with cerebral palsy]. / Ermittlung des Aktivitätslevels bei Patienten mit infantiler Zerebralparese.

AIM: The aim of this study is the determination of physical activity in everyday life of handicapped persons due to cerebral palsy using standardised testing procedures. METHOD: The subjects were examined according to the Conconi test on a treadmill at increasing speeds for their fitness. We used a continuous heart rate monitoring, 3-axis acceleration sensors, lactate measurements and pedography. RESULTS: Three groups of subjects could be differentiated. In one group, a rapid rise in heart rate even at lower walking speed was observed. In a second group of persons with poor motor coordination, the maximum walking speed was limited. Single subjects were not limited neither in their physical performance nor in their condition. CONCLUSION: In the physical therapy for patients with cerebral palsy one should not lose sight of possible cardiovascular limitations additional to the physical disabilities.

[Spastic foot deformities in children: surgical management]. / Spastische Fußdeformitäten im Kindesalter: Operatives Management.

Although the neurological defects associated with cerebral palsy are not progressive, secondary musculoskeletal disorders due to growth and gravity are variable. In the clinical analysis of spastic foot deformities different mechanisms that produce a variety of deformities have to be analyzed. The goals of surgical treatment are correction of the deformity, reestablishment of stability of the foot and preservation of functionally important ranges of motion and muscle strength. The most common spastic foot deformities are equinus, planovalgus, equinovarus and calcaneus. For treatment soft tissue surgery, such as muscle lengthening and transfer together with bone surgery, such as osteotomy or arthrodesis are used and combinations of these methods are often required. Subsequently postoperative plasters are necessary followed by dynamic orthotic management.

[Prolonged hospitalization versus home management for women with arrested preterm labour: a before-after study]. / Hospitalisation prolongée ou retour à domicile des menaces d'accouchement prématuré : une étude avant-après.

OBJECTIVES: To compare gestational age at birth and incidence of preterm birth inferior to 37 weeks of gestation (WG) in single pregnancies with either prolonged hospitalization, or early home discharge after arrested preterm labour. PATIENTS AND METHODS: Management of preterm labour was changed in our public academic hospital because no evidence of benefits for prolonged hospitalization was found and because adverse effects related to long-term hospitalization were described. In this retrospective before-after study, we compare the attitude A (December 2006 to April 2008), a prolonged hospitalization until 32 or 34WG, with new attitude B (May 2008 to February 2010), an early discharge home if the cervical exam was unchanged since admission. RESULTS: A total of 140 patients were included: 70 in each group. Initial hospitalization stay was significantly shorter in Group B (respectively, 5.4±5.4 days and 11.4±12.1 days; P<0.05). Preterm spontaneous delivery is 14 (20%) in group A and 21 (28.6%) in Group B (P>0.05). Gestational ages at birth were 33(5/7) and 33(0/7) WG in groups A and B, respectively (P>0.05). If we focus on patients who were discharged home in the two groups (women who did not deliver no matter the hospitalization length), the gestational age at birth (38(4/7) and 38WG; ns) and the prematurity rate inferior to 37WG (17.2% and 22.4%; ns) were statistically similar. DISCUSSION AND CONCLUSION: This study suggests that shorter hospitalization does not decrease the delivery term, nor does it increase the premature delivery incidence.

[Primary malignant bone tumors]. / Primär maligne Knochentumoren.

Among human neoplasms, primary malignant bone tumors are fairly rare. They present an incidence rate of roughly 10 cases per 1 million inhabitants per year. During childhood (<15 years), the percentage of malignant bone tumors amounts to 6% of all infantile malignancies. Only leukemia and lymphoma show a higher incidence in adolescence. Of all primary malignant bone tumors, 60% affect patients younger than 45 years and the peak incidence of all bone tumors occurs between 15 and 19 years. The most common primary malignant bone tumors are osteosarcoma (35%), chondrosarcoma (25%), and Ewing's sarcoma (16%). Less frequently (≤ 5%) occurring tumors are chordoma, malignant fibrous histiocytoma of bone, and fibrosarcoma of bone. Vascular primary malignant tumors of bone and adamantinoma are very rare. Staging of the lesion is essential for systemic therapeutic decision-making and includes complete imaging and histo-pathological confirmation of the suspected entity. In most cases, this is established by open- or image-guided biopsy. Based on this information, an interdisciplinary tumor board will determine the individual therapeutic approach. Endoprosthetic or biological reconstruction following wide tumor resection is the most common surgical therapy for primary malignant bone tumors. There is vital importance in a thorough postoperative follow-up and continous after-care by a competent tumor center which is permanentely in charge of therapy.

CSF biomarkers in posterior cortical atrophy.

OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid ß (Aß(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.

[Significance of cholesterol levels in patients 75 years or older]. / Quelle signification pour le taux de cholestérol après 75 ans?

Increasing comorbidity with aging reduces the predictive power of cardiovascular risk factors. From the age of 70 onward, total cholesterol levels decrease, perhaps associated with changes in the composition of some lipoprotein fractions. In subjects older than 75 years, being in the lowest quartile of cholesterol, insulinemia or serum albumin concentrations is associated with increased mortality. Cholesterol levels below 189 mg/dL in subjects older than 75 years should be considered an early sign of unidentified comorbidity or of rapid functional decline. HDL cholesterol levels, rather than total or LDL cholesterol, were inversely associated with increased mortality from ischemic coronary disease and stroke appears to rise as HDL cholesterol levels fall, rather than total or LDL cholesterol. On the other hand, LDL concentrations below 106 mg/dL and HDL concentrations below 36 mg/dL were associated with an increased risk of death from infectious disease. Stroke incidence, in particular, ischemic stroke, is highest in subjects older than 75 years. HDL cholesterol levels above 35 mg/dL appear to have a protective effect against ischemic stroke in subjects younger than 70 years. Two interventional drug studies investigating the effects of two statins (simvastatin and pravastatin) found that in subgroups of subjects older than 75 these drugs were associated with a reduction in all-cause mortality and cardiovascular morbidity, regardless of total cholesterol levels, but had no short-term effect on cognitive function.

Large-artery stroke in a young patient with Crohn's disease. Role of vitamin B6 deficiency-induced hyperhomocysteinemia.

An increased incidence of ischemic stroke has been reported in patients with Crohn's disease. Cerebral infarcts are usually considered as a complication of the hypercoagulable state associated with this inflammatory bowel disease (IBD). The association between Crohn's disease, hyperhomocysteinemia and large-artery stroke of the young has rarely been reported. A 39-year-old woman, with prior medical history of Crohn's disease and hypertension, presented with an ischemic stroke of the left internal carotid artery (ICA) territory. Etiological workup disclosed bilateral high-grade ICA stenosis and atheroma of the subclavian and vertebral arteries. Exhaustive search for prothrombotic factors showed inflammation, with an increased level of fibrinogen and factor IX, and a marked hyperhomocysteinemia. Both vitamin B1 and vitamin B6 plasmatic levels were decreased. Heterozygous C677T methylene-tetrahydrofolate reductase gene mutation was present. This observation highlights the combined proatherogenic effect of vitamin B deficiency-induced hyperhomocysteinemia and inflammation leading to large-artery stroke of the young in the setting of Crohn's disease. Our case report stresses the importance of vitamin deficiency screening in patients with IBD in terms of stroke prevention.