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Den historiske baggrund for den armenske tragedie og den danske missionær Maria Jacobsens virkeDen historiske baggrund for den armenske tragedie og den danske missionær Maria Jacobsens virk

Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

Introduction. Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN. Methods. Twelve-week-old male Sprague-Dawley rats were allocated to a normal chow diet or a 45% kcal high-fat diet. After eight weeks, the high-fat fed animals received a mild dose of streptozotocin to induce hyperglycemia. Four weeks after diabetes induction, the diabetic animals were allocated into three treatment groups receiving either no insulin or insulin-releasing implants in a high or low dose. During the 12-week treatment period, blood glucose and body weight were monitored weekly, whereas Hargreaves’ test was performed four, eight, and 12 weeks after treatment initiation. At study termination, several blood parameters, body composition, and neuropathy endpoints were assessed. Results. Insulin treatment lowered blood glucose in a dose-dependent manner. In addition, both doses of insulin lowered lipids and increased body fat percentage. High-dose insulin treatment attenuated small nerve fiber damage assessed by Hargreaves’ test and intraepidermal nerve fiber density compared to untreated diabetes and low-dose insulin; however, neuropathy was not completely prevented by tight glycemic control. Linear regression analysis revealed that glycemic status, circulating lipids, and sciatic nerve sorbitol level were all negatively associated with the small nerve fiber damage observed. Conclusion. In summary, our data suggest that high-dose insulin treatment attenuates small nerve fiber damage. Furthermore, data also indicate that both poor glycemic control and dyslipidemia are associated with disease progression. Consequently, this rat model of T2D seems to fit well with progression of DPN in humans and could be a relevant preclinical model to use in relation to research investigating treatment opportunities for DPN

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy

PURPOSE To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings

The first clinical treatment with kilovoltage intrafraction monitoring (KIM): A real-time image guidance method

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time image guidance method that uses widely available radiotherapy technology, i.e., a gantry-mounted x-ray imager. The authors report on the geometric and dosimetric results of the first patient treatment using KIM which occurred on September 16, 2014. METHODS: KIM uses current and prior 2D x-ray images to estimate the 3D target position during cancer radiotherapy treatment delivery. KIM software was written to process kilovoltage (kV) images streamed from a standard C-arm linear accelerator with a gantry-mounted kV x-ray imaging system. A 120° pretreatment kV imaging arc was acquired to build the patient-specific 2D to 3D motion correlation. The kV imager was activated during the megavoltage (MV) treatment, a dual arc VMAT prostate treatment, to estimate the 3D prostate position in real-time. All necessary ethics, legal, and regulatory requirements were met for this clinical study. The quality assurance processes were completed and peer reviewed. RESULTS: During treatment, a prostate position offset of nearly 3 mm in the posterior direction was observed with KIM. This position offset did not trigger a gating event. After the treatment, the prostate motion was independently measured using kV/MV triangulation, resulting in a mean difference of less than 0.6 mm and standard deviation of less than 0.6 mm in each direction. The accuracy of the marker segmentation was visually assessed during and after treatment and found to be performing well. During treatment, there were no interruptions due to performance of the KIM software. CONCLUSIONS: For the first time, KIM has been used for real-time image guidance during cancer radiotherapy. The measured accuracy and precision were both submillimeter for the first treatment fraction. This clinical translational research milestone paves the way for the broad implementation of real-time image guidance to facilitate the detection and correction of geometric and dosimetric errors, and resultant improved clinical outcomes, in cancer radiotherapy

Refraction during incipient presbyopia:the Aston Longitudinal Assessment of Presbyopia (ALAP) study

Purpose: To investigate non-cycloplegic changes in refractive error prior to the onset of presbyopia. Methods: The Aston Longitudinal Assessment of Presbyopia (ALAP) study is a prospective 2.5 year longitudinal study, measuring objective refractive error using a binocular open-field WAM-5500 autorefractor at 6-month intervals in participants aged between 33 and 45 years. Results: From the 58 participants recruited, 51 participants (88%) completed the final visit. At baseline, 21 participants were myopic (MSE -3.25 ± 2.28 DS; baseline age 38.6 ± 3.1 years) and 30 were emmetropic (MSE −0.17 ± 0.32 DS; baseline age 39.0 ± 2.9 years). After 2.5 years, 10% of the myopic group experienced a hypermetropic shift (≥0.50 D), 5% a myopic shift (≥0.50 D) and 85% had no significant change in refraction (<0.50 D). From the emmetropic group, 10% experienced a hypermetropic shift (≥0.50 D), 3% a myopic shift (≥0.50 D) and 87% had no significant change in refraction (<0.50 D). In terms of astigmatism vectors, other than J45 (p < 0.001), all measures remained invariant over the study period. Conclusion: The incidence of a myopic shift in refraction during incipient presbyopia does not appear to be as large as previously indicated by retrospective research. The changes in axis indicate ocular astigmatism tends towards the against-the-rule direction with age. The structural origin(s) of the reported myopic shift in refraction during incipient presbyopia warrants further investigation