Julius Sachs (1832-1897) and the Unity of Life.
Ontology highlight
ABSTRACT:
SUBMITTER: Kutschera U
PROVIDER: S-EPMC4883976 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Background and purposeDiffusion-weighted imaging (DWI) for treatment response monitoring is feasible on hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the Elekta Unity system has an adjusted design compared to diagnostic scanners. We investigated its impact on measuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice of b-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this study is to give recommendations for accurate ADC measurements on Unity systems.Materials and methodsSignal-to-noise ratio (SNR) measurements with increasing b-values were done to determine the highest bvalue that can be measured reliably. The spatial variation of the ADC was assessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotation and irradiation was investigated by acquiring DWI images before and during treatment of 11 prostate cancer patients.ResultsOn the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, as a trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm from the iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influenced by the rotating linac or irradiation during treatment.ConclusionWe provide Unity system specific recommendations for measuring the ADC. This will increase the consistency of ADC values acquired in different centers on the Unity system, enabling large cohort studies for biomarker discovery and treatment response monitoring.
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Project description:Tay-Sachs disease belongs to the group of autosomal-recessive lysosomal storage metabolic disorders. This disease is caused by ?-hexosaminidase A (HexA) enzyme deficiency due to various mutations in ?-subunit gene of this enzyme, resulting in GM2 ganglioside accumulation predominantly in lysosomes of nerve cells. Tay-Sachs disease is characterized by acute neurodegeneration preceded by activated microglia expansion, macrophage and astrocyte activation along with inflammatory mediator production. In most cases, the disease manifests itself during infancy, the "infantile form," which characterizes the most severe disorders of the nervous system. The juvenile form, the symptoms of which appear in adolescence, and the most rare form with late onset of symptoms in adulthood are also described. The typical features of Tay-Sachs disease are muscle weakness, ataxia, speech, and mental disorders. Clinical symptom severity depends on residual HexA enzymatic activity associated with some mutations. Currently, Tay-Sachs disease treatment is based on symptom relief and, in case of the late-onset form, on the delay of progression. There are also clinical reports of substrate reduction therapy using miglustat and bone marrow or hematopoietic stem cell transplantation. At the development stage there are methods of Tay-Sachs disease gene therapy using adeno- or adeno-associated viruses as vectors for the delivery of cDNA encoding ? and ? HexA subunit genes. Effectiveness of this approach is evaluated in ? or ? HexA subunit defective model mice or Jacob sheep, in which Tay-Sachs disease arises spontaneously and is characterized by the same pathological features as in humans. This review discusses the possibilities of new therapeutic strategies in Tay-Sachs disease therapy aimed at preventing neurodegeneration and neuroinflammation.
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Project description:Tay-Sachs disease (TSD) is a fatal, recessively inherited neurodegenerative condition of infancy and early childhood. Although rare in most other populations, the carrier frequency is one in 25 in Ashkenazi Jews. Australian high-school-based TSD preconception genetic screening programs aim to screen, educate, and optimize reproductive choice for participants. These programs have demonstrated high uptake, low psychological morbidity, and have been shown to result in fewer than expected Jewish TSD-affected births over 18 years of operation. The majority of Jewish individuals of reproductive age outside of the high school screening program setting in Australia have not accessed screening. Recent recommendations advocate supplementing the community high school screening programs with general practitioner- and obstetrician-led genetic screening of Ashkenazi Jewish individuals for TSD and other severe recessive diseases for which this group is at risk. Massively parallel DNA sequencing is expected to become the testing modality of choice over the coming years.
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Project description:An increase in power consumption necessitates a low-power circuit technology to extend Moore's law. Low-power transistors, such as tunnel field-effect transistors (TFETs), negative-capacitance field-effect transistors (NC-FETs), and Dirac-source field-effect transistors (DS-FETs), have been realised to break the thermionic limit of the subthreshold swing (SS). However, a low-power rectifier, able to overcome the thermionic limit of an ideality factor (η) of 1 at room temperature, has not been proposed yet. In this study, we have realised a DS diode based on graphene/MoS2/graphite van der Waals heterostructures, which exhibits a steep-slope characteristic curve, by exploiting the linear density of states (DOSs) of graphene. For the developed DS diode, we obtained η < 1 for more than four decades of drain current (ηave_4dec < 1) with a minimum value of 0.8, and a rectifying ratio exceeding 108. The realisation of a DS diode represents an additional step towards the development of low-power electronic circuits.
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Project description:The GM2 gangliosidoses are progressive neurodegenerative disorders due to defects in the lysosomal ?-N-acetylhexosaminidase system. Accumulation of ?-hexosaminidases A and B substrates is presumed to cause this fatal condition. An authentic mouse model of Sandhoff disease (SD) with pathological characteristics resembling those noted in infantile GM2 gangliosidosis has been described. We have shown that expression of ?-hexosaminidase by intracranial delivery of recombinant adeno-associated viral vectors to young adult SD mice can prevent many features of the disease and extends lifespan. To investigate the nature of the neurological injury in GM2 gangliosidosis and the extent of its reversibility, we have examined the evolution of disease in the SD mouse; we have moreover explored the effects of gene transfer delivered at key times during the course of the illness. Here we report greatly increased survival only when the therapeutic genes are expressed either before the disease is apparent or during its early manifestations. However, irrespective of when treatment was administered, widespread and abundant expression of ?-hexosaminidase with consequent clearance of glycoconjugates, ?-synuclein and ubiquitinated proteins, and abrogation of inflammatory responses and neuronal loss was observed. We also show that defects in myelination occur in early life and cannot be easily resolved when treatment is given to the adult brain. These results indicate that there is a limited temporal opportunity in which function and survival can be improved-but regardless of resolution of the cardinal pathological features of GM2 gangliosidosis, a point is reached when functional deterioration and death cannot be prevented.
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Project description:Humeral bone loss has been shown to be a risk factor for failure after arthroscopic treatment of instability. We present the arthroscopic remplissage technique originally described by Koo and Burkhart et al. with a modification in the percutaneous anchor placement and suture tying that is reproducible and effective. We percutaneously place 2 suture anchors, which require no additional suture passing across the tissue, to create a double pulley technique, filling the defect with posterior capsule and rotator cuff. Therefore, the Hill-Sachs defect becomes extra-articular, eliminating the potential engagement of the anterior glenoid and contribution to recurrence of instability. This technique is applicable broadly for most Hill-Sachs lesions that need addressing. By not having to pass or shuttle any suture through tissue after anchor placement and by eliminating the necessity to go subacromially to retrieve or tie suture, the technique saves time and improves reproducibility. The compression of tissue into the Hill Sachs surface area also is improved by double-reinforced suturing through the double-pulley technique. The combination of these advantages creates a sound and efficient technique for remplissage.
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