Orofacial function and temporomandibular disorders in Parkinson's Disease: a case-controlled study.

BACKGROUND: The difficulties and challenges faced by people with Parkinson's disease (PD) in performing daily orofacial function are not systematically investigated. In this study, specific orofacial non-motor and motor symptoms and functions were systematically examined in PD patients in comparison to a matched control group. METHODS: The clinical case-controlled study was conducted from May 2021 to October 2022 and included persons with PD and age- and gender-matched persons without PD. The participants with PD were outpatients diagnosed with PD at the Department of Neurology at Bispebjerg University Hospital in Copenhagen, Denmark. The participants underwent a systematic clinical and relevant self-assessment of the orofacial function and temporomandibular disorders (TMD). The primary outcomes were objective and subjective assessments of the general orofacial function, mastication, swallowing, xerostomia and drooling. The secondary outcomes were the prevalence of TMD and orofacial pain. The difference in outcome measures between the two groups was analysed using chi-square and Mann-Whitney U test. RESULTS: The study included 20 persons with PD and 20 age- and gender-matched persons without PD. Both objectively and subjectively, persons with PD had poorer orofacial function than the control group. Persons with PD had also a significantly more severe limitation of jaw mobility and jaw function. The objective masticatory function was also significantly reduced for persons with PD compared to the control group, and 60% of persons with PD found it difficult to eat foods with certain consistencies while 0% of the control group reported that problem. Persons with PD could swallow less water per second and the average swallowing event was significantly longer for PD persons. Even though PD persons reported more xerostomia (58% for persons with PD and 20% for control persons), they also reported significantly more drooling than the control group. Additionally, orofacial pain was more prevalent in PD persons. CONCLUSIONS: Persons with PD have a compromised orofacial function. Furthermore, the study indicates a link between PD and orofacial pain. In order to screen and treat persons with PD accordingly, healthcare professionals should be aware of and address these limitations and symptoms. TRIAL REGISTRATION: The trial was approved by the Regional Committee on Research Health Ethics of the Capital Region (H-20,047,464), the Danish Data Protection Agency (514 - 0510/20-3000), and registered at ClinicalTrials.gov (NCT05356845).

Fat Grafting With Expanded Adipose-Derived Stromal Cells for Breast Augmentation: A Randomized Controlled Trial.

BACKGROUND: The main challenge with fat grafting is loss of some of the graft to postsurgery resorption. Previous studies suggest that adipose-derived stromal cells (ASCs) can improve the volume retention of fat grafts but there is a lack of randomized trials to support the use of ASCs in clinical practice. OBJECTIVES: This trial aimed to investigate whether ASCs improve fat graft volume retention in patients undergoing breast augmentation with lipofilling. METHODS: This was a double-blind, randomized controlled trial of breast augmentation with ASC-enriched fat grafting. Healthy women aged 30 to 45 years were enrolled. First, the participants underwent liposuction to obtain fat for culture expansion of ASCs. Then, the participants were randomly assigned to undergo a 300- to 350-mL breast augmentation with ASC-enriched fat grafting (10 × 106 ASCs/mL fat graft) to 1 of their breasts and placebo-enriched fat grafting of identical volume to the contralateral breast. The primary outcome was fat graft volume retention after a 1-year follow-up measured with MRI. The trial is registered at www.clinicaltrialsregister.eu (EudraCT-2014-000510-59). RESULTS: Ten participants were included in the trial; all completed the treatment and follow-up. No serious adverse events occurred. Fat graft volume retention after 1 year was 54.0% (95% CI, 30.4%-77.6%) in the breasts treated with ASC-enriched fat grafting (n = 10) and 55.9% (95% CI, 28.9%-82.9%) in the contralateral breasts treated with placebo-enriched fat grafting (n = 10) (P = 0.566). CONCLUSIONS: The findings of this trial do not support that ASC-enriched fat grafting is superior to standard fat grafting for breast augmentation.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

BACKGROUND: Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. METHODS: In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min-1·m-2. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. RESULTS: Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (P=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm3 (interquartile range, 0-118 mm3; range, 0-25 261 mm3) in the low-target group versus 29 mm3 (interquartile range, 0-143 mm3; range, 0-22 116 mm3) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P=0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P=0.71). No significant difference was observed in frequency of severe adverse events. CONCLUSIONS: Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885.

Low 5-HT1B receptor binding in the migraine brain: A PET study.

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [11C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding. Patients who reported migraine <48 hours after the PET examination were excluded from the final analysis. We defined seven brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor binding in the dorsal raphe and in the midbrain. Conclusion We report here for the first time that migraine patients have low 5-HT1B receptor binding in pain modulating regions, reflecting decreased receptor density. This is either a primary constitutive trait of the migraine brain or secondary to repeated exposure to migraine attacks. We also provide indirect support for the dorsal raphe 5-HT1B receptors being temporarily downregulated during the migraine attack, presumably in response to higher cerebral serotonin levels in the ictal phase.

An Applied Anatomical Study of the Ethmoidal Arteries: Computed Tomographic and Direct Measurements in Human Cadavers.

Computed tomography (CT) images have been used in very few studies on distances to the ethmoidal arteries in the orbit. Most other studies have included direct measurements on cadavers and frequently quote the 24-12-6 mm rule to describe distances from the anterior lacrimal crest to the anterior and posterior ethmoidal foramina (AEF and PEF), optic canal (OC), respectively. However, the large interindividual variation of distances renders absolute values less applicable in a clinical setting. Preoperative measurements on CT images may provide more precise distances than absolute rules and thus lead to safer orbital surgery. The authors hypothesize that the distances to the ethmoidal arteries and the length of the medial wall are positively correlated and that measurements of the distances from the posterior lacrimal crest (PLC) on CT images are feasible with a low intra- and interobserver variability.Fifty intact orbits from 25 Caucasian cadavers were exenterated and examined. In additional, high-resolution CT scans of 48 orbits from 24 other Caucasian nonexenterated cadavers were examined. Distances were measured from 4 different anterior landmarks to the AEF and PEF and the OC.Distances from the most anterior landmarks to the arteries were positively correlated with the length of the medial wall. Measurements of the distances from the PLC to the ethmoidal arteries on CT images were feasible with a low intra- and interobserver variability. In conclusion, iatrogenic damage to the ethmoidal arteries in the orbit may be best avoided by using CT measurements in presurgical planning.

Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I.

We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471.

Safety of magnetic resonance scanning without monitoring of patients with pacemakers.

AIMS: The objective of this study was to investigate whether it is safe to perform 1.5-Tesla magnetic resonance imaging (MRI) scans in pacemaker (PM) patients without pulse oximetry or electrocardiogram monitoring and with no special specific absorption rate (SAR) or time limits, provided that the PMs are interrogated and programmed to asynchronous mode prior to the scan. METHODS AND RESULTS: This study reports the outcome of 207 MRI scans on PM patients at Rigshospitalet, Copenhagen University Hospital from June 2010 to September 2013. All MRIs were performed with the PMs in asynchronous mode and without additional monitoring. There were no adverse events registered among the PM patients during the study period. The only statistically significant change after MRI scans was a small, but clinically insignificant increase in atrial sense. No occurrences of reprogramming to power-on-reset were registered. CONCLUSION: It is possible to perform MRI scans relatively safely in PM patients without additional monitoring or change in the normal MRI protocol, given that the PM has been assessed and reprogrammed prior to MRI. This is especially important to remember in the acute setting where MRI scans may be delayed when monitoring facilities are unavailable.

Placental Growth during Normal Pregnancy - A Magnetic Resonance Imaging Study.

OBJECTIVE: To investigate normal human placental growth longitudinally throughout the second and third trimesters using MRI. METHODS: Twenty normal, first-time singleton pregnancies were scanned 7 times between the 14th and 38th week of gestation, at 4-week intervals, using MRI. Placental volumes were measured in both sagittal and transversal slices. All placentas were weighed after delivery to make a comparative study. RESULTS: Sixteen of the 20 women had increasing placental volumes from the 14th to 38th week of gestation. The 6th and 7th scan showed that 4 women had placentas of the same size. The mean placental volume increases linearly from the 14th till the 38th week of gestation, with a constant mean growth rate of 29.97 ml/week. The median placental volume extrapolated to delivery was to 856 ml (range 602-1,050 ml). The median weight of the exsanguinated placenta after delivery was 640 g (range 500-787 g). All pregnancies were carried to term, resulting in the delivery of healthy infants with good correlation between placental size and birth weight (R = 0.56, p = 0.009). CONCLUSION: Placental growth was measured systematically in a longitudinal study through the second and third trimesters using MRI. MRI provides a safe and feasible method to measure placental growth. The mean placental growth was linear throughout the second and third trimesters.

Flow measurement at the aortic root - impact of location of through-plane phase contrast velocity mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the gold standard of cardiac volumetric measurements. Flow in the aortic root is often measured at the sinotubular junction, even though placing the slice just above valve level may be more precise. It is unknown how much flow measurements vary at different levels in the aortic root and which level corresponds best to left ventricle volumetry. METHODS: All patients were older than 70 years presenting with at least one of the following diagnoses: diabetes, hypertension, prior stroke and/or heart failure. Patients with arrhythmias during CMR and aortic stenosis were excluded from the analyses. Stroke volumes were measured volumetrically (SVref) from steady-state free precision short axis images covering the entire left ventricle, excluding the papillary muscles and including the left ventricular outflow tract. Flow sequences (through-plane phase contrast velocity mapping) were obtained at valve level (SVV) and at the sinotubular junction (SVST). Firstly, SVV and SVST were compared to each other and secondly, after excluding patients with mitral regurgitations to ensure that stroke volumes measured volumetrically would theoretically be equal to flow measurements, SVV and SVST were compared to SVref. RESULTS: Initially, 152 patients were included. 22 were excluded because of arrhythmias during scans and 9 were excluded for aortic stenosis. Accordingly, data from 121 patients were analysed and of these 63 had visually evident mitral regurgitation on cine images. On average, stroke volumes measured with flow at the sinotubular junction was 13-16 % lower than when measured at valve level (70.0 mL ±13.8 vs. 81.8 mL ±15.5). This was in excess of the expected difference caused by the outflow to the coronary arteries. In the 58 patients with no valvulopathy, stroke volumes measured at valve level (79.0 mL ±12.4) was closest to the volumetric measurement (85.4 mL ±12.0) but still significantly lower (p < 0.001). Flow measured at the ST-junction (68.1 mL ±11.6) was significantly lower than at valve level and the volumetric measurements. The mean difference between SVref-SVV (6.4 mL) and SVref-SVST (18.2 mL) showed similar variances (SD 7.4 vs. 8.1 respectively) and hence equal accuracy. CONCLUSIONS: Aortic flow measured at valve level corresponded best with volumetric measurements and on average flow measured at the sinotubular junction underestimated flow approximately 15 % compared to valve level. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02036450 . Registered 08/01/2014.

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series.

PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. MATERIALS AND METHODS: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. RESULTS: The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. CONCLUSIONS: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2.

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial.

BACKGROUND: Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts. METHODS: Healthy participants underwent two liposuctions taken 14 days apart: one for ASC isolation and ex-vivo expansion, and another for the preparation of fat grafts. Two purified fat grafts (30 mL each) taken from the second liposuction were prepared for each participant. One graft was enriched with ASCs (20 × 10(6) cells per mL fat), and another graft without ASC enrichment served as a control. The fat grafts were injected subcutaneously as a bolus to the posterior part of the right and left upper arm according to the randomisation sequence. The volumes of injected fat grafts were measured by MRI immediately after injection and after 121 days before surgical removal. The primary goal was to compare the residual graft volumes of ASC-enriched grafts with those of control grafts. This study is registered at www.clinicaltrialsregister.eu, number 2010-023006-12. FINDINGS: 13 participants were enrolled, three of whom were excluded. Compared with the control grafts, the ASC-enriched fat grafts had significantly higher residual volumes: 23·00 (95% CI 20·57-25·43) cm(3) versus 4·66 (3·16-6·16) cm(3) for the controls, corresponding to 80·9% (76·6-85·2) versus 16·3% (11·1-21·4) of the initial volumes, respectively (p<0·0001). The difference between the groups was 18·34 (95% CI 15·70-20·98) cm(3), equivalent to 64·6% (57·1-72·1; p<0·0001). No serious adverse events were noted. INTERPRETATION: The procedure of ASC-enriched fat grafting had excellent feasibility and safety. These promising results add significantly to the prospect of stem cell use in clinical settings, and indicate that ASC graft enrichment could render lipofilling a reliable alternative to major tissue augmentation, such as breast surgery, with allogeneic material or major flap surgery. FUNDING: Danish Cancer Society, Centre of Head and Orthopaedics Rigshospitalet, and Moalem Weitemeyer Bendtsen.

Single-mode pumped high air-fill fraction photonic crystal fiber taper for high-power deep-blue supercontinuum sources.

Dispersion control with axially nonuniform photonic crystal fibers (PCFs) permits supercontinuum (SC) generation into the deep-blue from an ytterbium pump laser. In this Letter, we exploit the full degrees of freedom afforded by PCFs to fabricate a fiber with longitudinally increasing air-fill fraction and decreasing diameter directly on the draw-tower. We demonstrate SC generation extending down to 375 nm in one such monolithic fiber device that is single-mode at 1064 nm at the input end.

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study.

BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM. MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity. RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32) and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

The decrease of cardiac chamber volumes and output during positive-pressure ventilation.

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.

von Hippel-Lindau disease: deafness due to a non-MRI-visible endolymphatic sac tumor despite targeted screening.

OBJECTIVE: Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the challenges of prophylactic ELST screening and to explore the role of audiometry in pre-symptomatic ELST screening. DESIGN: For a period of 17 years our patient was screened for ELSTs with inner-ear MRI (magnetic resonance imaging), audiometry, and clinical interviews. STUDY SAMPLE: A male vHL patient who became deaf in one ear due to a radiologically undetectable ELST. RESULTS: Despite annual MRIs, the ELST was not visible until four months after onset of deafness when it appeared as a 1.4 × 1.4 mm tumor mass. Although his hearing was objectively within normal limits for the first 14 years, a distinct pattern of low-frequency hearing loss could retrospectively be seen at all audiometries. CONCLUSIONS: Audiometry is a candidate screening tool for detection of non-symptomatic pre-MRI-visible ELSTs, and we have initiated an international collaborative study to further determine its application. At present, we suggest an ELST screening protocol of yearly audiological assessment and inner ear MRI.

The role of phase coherence in seeded supercontinuum generation.

The noise properties of a supercontinuum can be controlled by modulating the pump with a seed pulse. In this paper, we numerically investigate the influence of seeding with a partially phase coherent weak pulse or continuous wave. We demonstrate that the noise properties of the generated supercontinuum are highly sensitive to the degree of phase noise of the seed and that a nearly coherent seed pulse is needed to achieve a coherent pulse break-up and low noise supercontinuum. The specific maximum allowable linewidth of the seed laser is found to decrease with increasing pump power.

Intravenous immunoglobulin treatment in a patient with adrenomyeloneuropathy.

BACKGROUND: Adrenomyeloneuropathy (AMN) is one of several phenotypes of the adrenoleukodystrophy spectrum caused by mutations in the ABCD1 gene on the X chromosome. An inflammatory component is part of the disease complex ranging from severe childhood CNS demyelination to spinal cord and peripheral nerve degeneration. CASE PRESENTATION: We present a patient with clinical progressive AMN and severe lower limb pain. Longitudinal brain magnetic resonance spectroscopy showed a constant slightly elevated myoinositol/total creatine ratio during the five year treatment period, probably reflecting demyelination, microglial activation and gliosis, indicating an inflammatory response. The pain was refractory to conventional therapy but intravenous immunoglobulin (IVIG) treatment was highly efficient. CONCLUSION: IVIG may be considered as a last resort for treatment of refractory pain in AMN patients with indications of an inflammatory component.

An fMRI-compatible system for targeted electrical stimulation.

BACKGROUND: Neuromodulation is a rapidly expanding therapeutic option considered within neuropsychiatry, pain and rehabilitation therapy. Combining electrostimulation with feedback from fMRI can provide information about the mechanisms underlying the therapeutic effects, but so far, such studies have been hampered by the lack of technology to conduct safe and accurate experiments. Here we present a system for fMRI compatible electrical stimulation, and the first proof-of-concept neuroimaging data with deep brain stimulation (DBS) in pigs obtained with the device. NEW METHOD: The system consists of two modules, placed in the control and scanner room, connected by optical fiber. The system also connects to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) while we acquired BOLD responses in the STN and neocortex. RESULTS: We found that the system delivered robust electrical stimuli to the implanted electrode in sync with the preprogrammed fMRI sequence. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the STN. COMPARISONS WITH EXISTING METHOD: The system solves three major problems related to electric stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference with the MRI scanner. CONCLUSIONS: The fMRI compatible electrical stimulator circumvents previous problems related to electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters, and can be customized to electroceutical applications beyond DBS.

Endurance Training Improves GLP-1 Sensitivity and Glucose Tolerance in Overweight Women.

Context and objective: Obesity and inactivity are risk factors for developing impaired glucose tolerance characterized by insulin resistance and reduced beta-cell function. The stimulatory effect of glucagon-like peptide 1 (GLP-1) on insulin secretion is also impaired in obese, inactive individuals. The aim of this study was to investigate whether endurance training influences beta-cell sensitivity to GLP-1. Participants and intervention: Twenty-four female participants, age 46 ±â€…2 years, body mass index 32.4 ±â€…0.9 kg/m2, and maximal oxygen consumption 24.7 ±â€…0.8 mL/kg/min participated in a 10-week exercise training study. Methods: Beta-cell sensitivity to GLP-1 was assessed in a subset of participants (n = 6) during a 120-minute hyperglycemic glucose clamp (8.5 mM) including a 1-hour GLP-1 (7-36 amide) infusion (0.4 pmol/kg/min). Changes in glucose tolerance, body composition, and cardiorespiratory fitness were assessed by oral glucose tolerance tests (OGTTs), dual-energy X-ray absorptiometry scans, magnetic resonance scans, and maximal oxygen consumption (VO2max) tests, respectively. Results: The c-peptide response to infusion of GLP-1 increased 28 ±â€…3% (P < 0.05) toward the end of the hyperglycemic clamp. The insulin response remained unchanged. Training improved glucose tolerance and reduced GLP-1, insulin, and glucagon levels during the OGTTs. Training increased VO2max (from 24.7 ±â€…0.8 to 27.0 ±â€…0.7 mL/kg/min; P < 0.05) and reduced visceral fat volume (from 4176 ±â€…265 to 3888 ±â€…266 cm3; P < 0.01). Conclusion: Along with improved glycemic control, endurance training improved beta-cell sensitivity to GLP-1 in overweight women. The study was deemed not to constitute a clinical trial and was not registered as such.