Three-dimensional,three-vector-component velocimetry of cilia-driven fluid flow using correlation-based approaches in optical coherence tomography

Microscale quantification of cilia-driven fluid flow is an emerging area in medical physiology, including pulmonary and central nervous system physiology. Cilia-driven fluid flow is most completely described by a three-dimensional, three-component (3D3C) vector field. Here, we generate 3D3C velocimetry measurements by synthesizing higher dimensional data from lower dimensional measurements obtained using two separate optical coherence tomography (OCT)-based approaches: digital particle image velocimetry (DPIV) and dynamic light scattering (DLS)-OCT. Building on previous work, we first demonstrate directional DLS-OCT for 1D2C velocimetry measurements in the sub-1 mm/s regime (sub-2.5 inch/minute regime) of cilia-driven fluid flow in Xenopus epithelium, an important animal model of the ciliated respiratory tract. We then extend our analysis toward 3D3C measurements in Xenopus using both DLS-OCT and DPIV. We demonstrate the use of DPIV-based approaches towards flow imaging of Xenopus cerebrospinal fluid and mouse trachea, two other important ciliary systems. Both of these flows typically fall in the sub-100 μm/s regime (sub-0.25 inch/minute regime). Lastly, we develop a framework for optimizing the signal-to-noise ratio of 3D3C flow velocity measurements synthesized from 2D2C measures in non-orthogonal planes. In all, 3D3C OCT-based velocimetry has the potential to comprehensively characterize the flow performance of biological ciliated surfaces.OCIS codes: (110.4500) Optical coherence tomography, (120.7250) Velocimetry, (170.3340) Laser Doppler velocimetry, (170.6480) Spectroscopy, speckle     

Successful Delivery of RRT in Ebola Virus Disease

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.     

Neue Optimierungswege der allgemeinärztlichen Betreuung bei Typ-2-Diabetes

Background

The care of diabetes patients is mostly undertaken by general practitioners. In order to achieve sufficient control of blood sugar levels and blood pressure in patients and thus to avoid complications and secondary diseases, a patient-centered disease management and support of patient self-management are essential. These functions can be partially delegated.

Aim

The DIANA study is an epidemiological physician-based prospective cohort study on new approaches for optimization of general practitioner care. The objectives were to investigate the current status of diabetes care as well as the consequences of a patient-centered treatment approach on the course of diabetes. Furthermore, the effectiveness of a supportive telephone counseling service over 12 months by trained medical practice personnel was investigated.

Material and methods

The DIANA study consists of a basic survey and an interventional study. A total of 38 general medical practices with 1,146 patients diagnosed with type 2 diabetes were included. For the basic survey standardized questionnaires were completed by the patients and their physicians. Furthermore, blood samples were taken from patients for determination of HbA1c levels in a certified laboratory. Patients with HbA1c levels >?7.5?% in the basic survey were eligible for inclusion in the interventional study. In this subpopulation of 204 patients the effectiveness of an intervention with telephone support by trained personnel from the medical practices in the study was investigated. The patients who agreed to participate were randomized to either the intervention group or the control group. The control group received usual care.

Results

Mean HbA1c was 6.9?% in this sample and thus within the target corridor of the new German clinical practice guidelines on type 2 diabetes of 6.5–7.5?%. Nevertheless, about one fifth of the patients’ values were above the corridor and thus in a dissatisfactory zone. In addition, participating patients had considerable comorbidities, such as hypertension, coronary heart disease, cardiac insufficiency, and depression. Another problem was medication adherence among patients. Self-reported medication adherence was associated with poor glycemic control, especially in men. Young, employed and unmarried patients and those with depression symptoms were particularly at risk. The intervention had only limited effects. The primary outcome HbA1c decreased likewise in both groups. A decrease of systolic blood pressure was observed in the intervention group, but which was not sustained after the end of the intervention. It was only after the end of the intervention that health-related quality of life improved in the intervention group.

Conclusion

There is a large problem group of diabetes patients with an unsatisfactory metabolic situation. General practitioners should concentrate on these patients and be aware that younger, employed and single as well as depressive patients are particularly affected. A long-term accompaniment by trained personnel could be useful.     

Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II–IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III–IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II–IV astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. These findings suggest that focal radiation may be inadequate for some of these patients. Importantly, we show that clinically classic DIPGs represent a diverse histologic spectrum, including multiple cases which would fit WHO criteria of grade II astrocytoma which nevertheless behave clinically as high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests that the current WHO astrocytoma grading scheme may not appropriately predict outcome for paediatric brainstem gliomas.     

Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC

Objective  

The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations.     

VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment

Tandem mass spectrometry-based newborn screening correctly identifies individuals with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). However, a great number of healthy individuals present with identical acylcarnitine profiles during catabolism in the first three days of life. We routinely perform an enzyme activity assay as confirmation analysis in newborns identified by screening. Whereas VLCAD residual activities of less than 10% are clearly diagnostic and indicate patients at risk of clinical disease, the clinical relevance of higher residual activities is unclear. In this study we assess the molecular basis in 34 individuals with residual activities of 10-50%. We identify two pathogenic mutations in patients that result in residual activities as high as 22%, while individuals with residual activities of 25-50% either present with a heterozygous or no mutation in the VLCAD gene. In addition, confirmed heterozygous parents present with residual activities as low as 32%.