Effects of Tissue Temperature and Injury on ADC during Therapeutic Hypothermia in Newborn Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: ADC changes are useful in detecting ischemic brain injury, but mechanisms other than tissue pathology may affect the kinetic movement and diffusion of water molecules. We aimed to determine the effects of brain temperature on the corresponding ADC in infants undergoing therapeutic hypothermia. MATERIALS AND METHODS: Brain temperature and ADC values in the basal ganglia, thalamus, cortical GM, and WM were analyzed during and after therapeutic hypothermia. The study cohort was categorized as having no-injury or injury. Among infants without injury, the correlation between ADC values and temperature was analyzed using the Pearson correlation. Intrasubject comparison of ADC changes during and after therapeutic hypothermia were analyzed, excluding patients who had an MR image interval of >5 days to minimize the effects of injury evolution. RESULTS: Thirty-nine infants with hypoxic-ischemic encephalopathy were enrolled (23 no-injury; 16 injury). The median ADC was significantly lower during therapeutic hypothermia (837; interquartile range, 771-928, versus 906; interquartile range, 844-1032 ×10-6mm2/s; P < .001). There was no difference in the ADC between the no-injury and injury groups during therapeutic hypothermia (823; interquartile range, 782-868, versus 842; interquartile range, 770-1008 ×10-6mm2/s; P = .4). In the no-injury group, in which ADC is presumed least affected by the evolution of injury, the median ADC was significantly lower during therapeutic hypothermia (826; interquartile range, 771-866, versus 897; interquartile range, 846-936 ×10-6mm2/s; P < .001). There was a moderate correlation between temperature and ADC in the no-injury group (during therapeutic hypothermia: Spearman ρ, 0.48; P < .001; after therapeutic hypothermia: ρ, 0.4; P < .001). CONCLUSIONS: Aside from brain injury, reduced tissue temperature may also contribute to diffusion restriction on MR imaging in infants undergoing therapeutic hypothermia.

Comparison of the effect of oxygen supplementation using flow-by or a face mask on the partial pressure of arterial oxygen in sedated dogs.

AIMS To compare the effect of oxygen supplementation using flow-by or a face mask on the partial pressure of arterial oxygen (PaO2) in sedated dogs. METHODS Twenty healthy dogs weighing >15 kg, of mixed sex and breed, were enrolled in a randomised cross-over study. Each dog was sedated with I/M 0.015 mg/kg medetomidine and 0.5 mg/kg methadone. Twenty minutes later dogs were exposed to two 5-minute treatment periods of oxygen supplementation separated by a 15-minute washout period during which dogs were allowed to breathe room air. During the treatment periods, oxygen was delivered at a flow rate of 3 L/minute either through a face mask (face mask oxygenation), or via a tube held 2 cm from the dog's nares (flow-by oxygenation). The order in which the treatments were administered was randomised. Arterial blood was collected for blood gas analysis and rectal temperature measured at four times: prior to commencing treatments, after each treatment, and at the end of the 15 minutes washout period between treatments. RESULTS The mean PaO2 in arterial samples taken from the dogs after face mask oxygen supplementation was 371.3 (SE 13.74) mmHg which was higher than in samples taken after they received flow-by oxygen supplementation (182.2 (SE 6.741) mmHg; p<0.001). The mean PaO2 in samples taken after receiving either form of oxygen supplementation was higher than in samples taken after the dogs had been breathing room air (82.43 (SE 2.143) mmHg; p<0.001). There was no association between sex, age, weight or breed of dogs and blood gas parameters or rectal temperature (p>0.05). CONCLUSIONS Oxygen supplementation delivered using a face mask was more effective at increasing PaO2 than flow-by oxygen supplementation. Flow-by oxygen supplementation at a distance of 2 cm from the nose may be a suitable alternative when the use of a face mask is not tolerated by the patient.

Pubertal development of estradiol-induced hypothalamic progesterone synthesis.

In females, a hallmark of puberty is the luteinizing hormone (LH) surge that triggers ovulation. Puberty initiates estrogen positive feedback onto hypothalamic circuits, which underlie the stimulation of gonadotropin releasing hormone (GnRH) neurons. In reproductively mature female rodents, both estradiol (E2) and progesterone (P4) signaling are necessary to stimulate the surge release of GnRH and LH. Estradiol membrane-initiated signaling facilitates progesterone (neuroP) synthesis in hypothalamic astrocytes, which act on E2-induced progesterone receptors (PGR) to stimulate kisspeptin release, thereby activating GnRH release. How the brain changes during puberty to allow estrogen positive feedback remains unknown. In the current study, we hypothesized that a critical step in estrogen positive feedback was the ability for estradiol-induced neuroP synthesis. To test this idea, hypothalamic neuroP levels were measured in groups of prepubertal, pubertal and young adult female Long Evans rats. Steroids were measured with liquid chromatography tandem mass spectrometry (LC-MS/MS). Hypothalamic neuroP increases from pre-puberty to young adulthood in both gonad-intact females and ovariectomized rats treated with E2. The pubertal development of hypothalamic E2-facilitated progesterone synthesis appears to be one of the neural switches facilitating reproductive maturation.

The role of the vaginal microbiome in gynaecological cancer.

Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynaecologic malignancies. Further, we suggest that it may be possible to expand the use of probiotics in the treatment of gynaecological cancers. TWEETABLE ABSTRACT: A review of the research to date on the relation between the vaginal microbiome and gynaecological cancers.

New understanding on the contribution of the central otolithic system to eye movement and skew deviation.

The otolith organs consist of the utricle and saccule. The utricle mediates the utriculo-ocular reflex by detecting horizontal head translation and static head tilt. Skew deviation is a vertical strabismus caused by imbalance of the utriculo-ocular reflex pathway and is commonly caused by lesions in the brainstem or cerebellum. It is associated with abnormal utriculo-ocular reflexes including asymmetric reduction of the translational vestibulo-ocular and ocular counterroll responses. Skew deviation is also associated with head position-dependent changes in ocular torsion and vertical strabismus. The reduction in ocular torsion and vertical strabismus when changing from an upright to supine position in skew deviation allows us to devise a new bedside 'upright-supine test' to differentiate skew deviation from fourth nerve palsy and other causes of vertical strabismus.

Cerebral diffusion tensor MR tractography in tuberous sclerosis complex: correlation with neurologic severity and tract-based spatial statistical analysis.

BACKGROUND AND PURPOSE: The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. MATERIALS AND METHODS: In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. RESULTS: NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = -.70; r = -.75), bilateral PF (r = -.66; r = -.68), and MWT (r = -.71; r = -.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. CONCLUSIONS: Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression.

The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.

Single center retrospective analysis of BU-based conditioning regimens in allogeneic transplantation.

We performed a single institution retrospective analysis of 114 patients treated with BU-based pretransplant conditioning regimens. Oral BU was administered to 76 patients (total dose 16 mg/kg or 8 mg/kg) and i.v. BU to 38 others (total dose 12.8 mg/kg or 6.4 mg/kg). Either CY (n=74) or fludarabine (n=40) was given in combination with BU. Median age was 35 years in the oral BU group and 48.5 years with i.v. BU (P<0.001). OS and PFS rates at 3-years post HSCT were not different in patients who received either i.v. or oral BU (OS: 41.3 vs 44.0% (P=0.981); PFS: 52.7 vs 54.7% (P=0.526), respectively). The i.v. BU, however, was associated with a significantly shorter time to engraftment (13.5 days vs 16 days, respectively; P<0.001). There were no significant differences in survival or 100-day mortality for patients who received either CY or fludarabine, in combination with BU. After adjustment for confounders, multivariate analysis showed that age of transplant (P=0.002), donor type (sibling or unrelated; P=0.003), GVHD (P<0.05) and route of administration (P=0.023) were significant risk factors for OS. The i.v. BU used in an older age group yielded equivalent survival compared with oral BU used in a younger population.

Static ocular counterroll reflex in skew deviation.

OBJECTIVE: The static ocular counterroll (OCR) reflex generates partially compensatory torsional eye movements during head roll. It is mediated by the utricle in the inner ear. Skew deviation is a vertical strabismus thought to be caused by imbalance in the utriculo-ocular pathway. We hypothesized that if skew deviation is indeed caused by damage to this reflex pathway, patients with skew deviation would show abnormal OCR. METHODS: Eighteen patients with skew deviation caused by brainstem or cerebellar lesions and 18 normal participants viewed a target at 1 m. Ocular responses to static passive head roll-tilts of approximately 20° were recorded using search coils. Static OCR gain was calculated as the change in torsional eye position divided by the change in head position during sustained head roll. Perception of the subjective visual vertical (SVV) was also measured. RESULTS: Group mean OCR gain was reduced by 45% in patients. At an individual level, OCR gains were asymmetric between eyes and between torsional directions in 90% of patients. In addition, the hypotropic eye incyclotorting gain was lower than the hypertropic eye excyclotorting gain during head roll toward the hypotropic eye in 94% of patients. No consistent pattern of gain asymmetry was found during head roll toward the hypertropic eye. The SVV was tilted toward the hypotropic eye. CONCLUSION: Static OCR gain is significantly reduced in skew deviation. Interocular and directional gain asymmetries are also prevalent. The asymmetries provide further evidence that disruption of the utriculo-ocular pathway is a mechanism for skew deviation.

Effects of swimming on eye hand coordination and balance in the elderly.

OBJECTIVE: To evaluate the effects of swimming on upper extremity motor control, and balance in elderly population. DESIGN: Cross-sectional study. SETTING: The biomechanical laboratory in a tertiary hospital. PARTICIPANTS: The swimming group consisted of 20 swimmers (n_20, 65.4 ± 5.5 years) who received regular swimming exercise for more than 2 years. The control group consisted of 34 healthy active subjects (n_34, 67.4 ± 5.7 years) who have regular exercises other than swimming. MEASUREMENTS: The eye hand coordination was evaluated by calculating the mean reaction time required in accurately pointing onto the center of the target sensors that come in three different sizes (1 cm, 1.5 cm, and 2 cm in diameter). The SMART Balance Master device was used to measure posture balance. The maximal stability, center of pressure (COP) velocity, and percentage ankle strategy were obtained under six different balance conditions. RESULTS: In the testing of upper extremity motor control, the swimming group had significant shorter mean reaction time as compared with the control group in all three target sensor sizes (p < 0.05). In balance testing, the swimming group had significant greater percentage of ankle strategy during eyes closed and fixed support (EC), and sway-referenced vision and support (SVSS) conditions as compared with the control group (p < 0.05). CONCLUSION: Regular swimming exercise may result in improved eye hand coordination as faster and more accurate repetitive movements. Swimming may also result in improved balance function under few complicated balance conditions.

Differentiating Components of Cerebral Arteriovenous Malformations Using T1-Weighted Gradient Recall Echo MR Imaging.

Cerebral arteriovenous malformation (AVM) typically shows signal void on conventional MR images, making differentiation of each component difficult. We analyzed the MR signal intensity of AVM components on T1-weighted gradient recalled echo pulse sequence images. We retrospectively studied 29 patients with AVM between 2006 and 2008. Patients were excluded if they had 1) intracranial hemorrhage, 2) previous intervention for AVM. All patients underwent MR study on a 3T system (Magentom TIM Trio, Siemens). Pulse sequences included T1-weighted gradient recalled echo (T1GRE), T2-weighted (T2), time-of-flight (TOF), and contrast-enhanced T1-weighted (cT1) images. Digital subtracted angiography (DSA) was performed in all patients as a diagnostic standard. Signal intensity of each AVM component was recorded and compared between pulse sequences. Nine patients were studied (five men; mean age 39.1 years) and nine AVM were identified (mean size, 3.9 cm). Three different signal intensities (hypo-, iso-, and hyper-intensity) were observed in all nine patients on T1GRE. Only one signal intensity was seen on T2 (flow void) and cT1 images (hyperintensity) in nine patients. Two different signal intensities were observed in all seven patients with TOF images. The T1GRE image showed the largest number of different signal intensities of AVM when compared with other pulse sequences, thus providing clearer structural delineation. Routine use of the T1GRE pulse sequence can help pre-therapeutic planning or follow-up of AVM.

Cloning and regulation of expression of the Na+-Cl--taurine transporter in gill cells of freshwater Japanese eels.

Our previous studies have demonstrated the hypertonic-induced expression of osmotic stress transcription factor and the regulatory volume increase (RVI) response in gill cells isolated from freshwater eels. In this study, we aimed to clone one of the organic osmolyte transporters, the Na+-Cl--taurine transporter (TauT), and to characterize its expression in anisosmotic conditions, using both in vivo and in vitro approaches. A cDNA clone encoding TauT was isolated from gill tissues of Japanese eels, Anguilla japonica. The deduced amino acid sequence shows 88-90% identity to other reported piscine TauT sequences. Our data indicated that TauT mRNA was detectable in both freshwater and seawater fish gills. The expression level of TauT mRNA increased in gills of seawater-acclimating fish. A high abundance of TauT protein was found to be localized in seawater gill chloride cells. Using primary gill cell culture, expression of the gene was induced when the ambient osmolarity was raised from 320 to 500 mosmol l(-1). Hypertonic treatment of the culture caused an increase of F-actin distribution in the cell periphery. Treatment of the cells with colchicine or cytochalasin D significantly reduced TauT transcript level following hypertonic exposure. The inhibition of myosin light chain (MLC) kinase by ML-7 had a significant additive effect on hypertonic-induced TauT expression. Collectively, the data of this study reveal, for the first time, the regulation of TauT expression in gill cells of euryhaline fish. We have demonstrated the involvement of ionic strength, the cytoskeleton and MLC kinase in the regulation of TauT expression. The results shed light on the osmosensing and hyperosmotic adaptation in fish gills.

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors.

Non-integrating lentiviral vectors show considerable promise for gene therapy applications as they persist as long-term episomes in non-dividing cells and diminish risks of insertional mutagenesis. In this study, non-integrating lentiviral vectors were evaluated for their use in the adult and fetal central nervous system of rodents. Vectors differentially pseudotyped with vesicular stomatitis virus, rabies and baculoviral envelope proteins allowed targeting of varied cell populations. Efficient gene delivery to discrete areas of the brain and spinal cord was observed following stereotactic administration. Furthermore, after direct in utero administration (E14), sustained and strong expression was observed 4 months into adulthood. Quantification of transduction and viral copy number was comparable when using non-integrating lentivirus and conventional integrating vector. These data support the use of non-integrating lentiviral vectors as an effective alternative to their integrating counterparts in gene therapy applications, and highlight their potential for treatment of inherited and acquired neurological disorders.

Differentiation between classic and atypical meningiomas with use of diffusion tensor imaging.

BACKGROUND AND PURPOSE: The differentiation between classic and atypical meningiomas may have implications in preoperative planning but may not be possible on the basis of conventional MR imaging. Our hypothesis was that classic and atypical meningiomas have different patterns of intratumoral water diffusion that will allow for differentiation between them. MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 12 classic and 12 atypical meningiomas. Signal intensity of solid-enhancing tumor regions on diffusion-weighted trace images and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps was assessed. Regions of interest (ROIs) were placed in solid-enhancing regions, peritumoral edema, and contralateral normal-appearing white matter (NAWM) to measure tensor metrics including major (lambda(1)), intermediate (lambda(2)) and minor eigenvalues (lambda(3)) and FA and ADC values. Distribution of tensor shapes within enhancing tumors was calculated for all tumors. Differences between classic and atypical meningiomas in tumor signal intensity, intratumoral and peritumoral tensor metrics, as well as tensor shapes distribution were statistically analyzed. RESULTS: A significantly greater proportion of atypical meningiomas were isointense and hypointense on ADC maps (P = .007). Classic meningiomas had significantly lower FA (P = .012), higher ADC (P = .011), greater lambda(2) (P = .020) and lambda(3) (P = .003). There was significantly more spherical diffusion in classic than in atypical meningiomas (P = .020). All diffusion tensor metrics for peritumoral edema of the 2 tumor groups did not differ. CONCLUSION: DTI showed that intratumoral microscopic water motion is less organized in classic than in atypical meningiomas. This feature may allow for noninvasive differentiation between classic and atypical meningiomas.

Laser spectroscopy of iridium monoboride.

High resolution laser induced fluorescence spectrum of IrB in the spectral region between 545 and 610 nm has been recorded and analyzed. Reacting laser-ablated iridium atoms with 1% B(2)H(6) seeded in argon produced the IrB molecule. This is the first experimental observation of the IrB molecule. Four vibronic transition bands, (v,0) with v=0-3 of an electronic transition system, have been observed. Spectra of all four isotopic molecules, (191)Ir(10)B, (193)Ir(10)B, (191)Ir(11)B, and (193)Ir(11)B, were recorded. Isotopic relationships confirmed the carrier of the spectra and the vibrational quantum number assignment. Preliminary analysis of rotational lines showed that these vibronic bands are with Omega' = 2 and Omega" = 3. The electronic transition identified is assigned as the [16.5](3)Pi(2)-X(3)Delta(3) system. Partially resolved hyperfine structure which conforms to the Hund's case a(beta) coupling scheme has been observed and analyzed. The bond length r(0) of the lower X(3)Delta(3) state of IrB was determined to be 1.7675 A.

Localization in the frontal plane is not susceptible to manipulation of afferent feedback via the Jendrassik Maneuver.

We have previously shown that registered vergence eye position is altered while participants perform the Jendrassik Maneuver (JM). We proposed that the altered eye position signal registration is due to the effect of the JM which changes the gain of the sensory feedback from the eye muscles, possibly via the activity of non-twitch motoneurons. We conducted two studies to further extend and clarify one of our previous findings by examining whether the JM also affects registered eye position during localization in the frontal plane. Since the non-twitch motoneurons do not receive premotor input from areas involved in the programming of saccades, we hypothesized that localization responses associated with the saccadic system should not be affected by the JM. The data confirmed our prediction. We propose that the non-twitch motoneurons are involved in parametric adjustment of the proprioceptive feedback loops of the vergence but not the version eye movements.

Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging.

BACKGROUND AND PURPOSE: Differentiating between primary cerebral lymphoma and glioblastoma multiforme (GBM) based on conventional MR imaging sequences may be impossible. Our hypothesis was that there are significant differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between lymphoma and GBM, which will allow for differentiation between them. MATERIALS AND METHODS: Preoperative diffusion tensor imaging (DTI) was performed in 10 patients with lymphoma and 10 patients with GBM. Regions of interest were placed in only solid-enhancing tumor areas and the contralateral normal-appearing white matter (NAWM) to measure the FA and ADC values. The differences in FA and ADC between lymphoma and GBM, as well as between solid-enhancing areas of each tumor type and contralateral NAWM, were analyzed statistically. Cutoff values of FA, FA ratio, ADC, and ADC ratio for distinguishing lymphomas from GBMs were determined by receiver operating characteristic curve analysis. RESULTS: FA and ADC values of lymphoma were significantly decreased compared with NAWM. Mean FA, FA ratio, ADC (x10(-3) mm(2)/s), and ADC ratios were 0.140 +/- 0.024, 0.25 +/- 0.04, 0.630 +/- 0.155, and 0.83 +/- 0.14 for lymphoma, respectively, and 0.229 +/- 0.069, 0.40 +/- 0.12, 0.963 +/- 0.119, and 1.26 +/- 0.13 for GBM, respectively. All of the values were significantly different between lymphomas and GBM. Cutoff values to differentiate lymphomas from GBM were 0.192 for FA, 0.33 for FA ratio, 0.818 for ADC, and 1.06 for ADC ratio. CONCLUSIONS: The FA and ADC of primary cerebral lymphoma were significantly lower than those of GBM. DTI is able to differentiate lymphomas from GBM.

Spinal cord arteriovenous malformation presenting as chest pain in a child.

STUDY DESIGN: A case report of spinal arteriovenous malformation presented as chest pain in a child. OBJECTIVES: To illustrate the atypical clinical presentation as right chest pain in a child with spinal cord arteriovenous malformation. SETTING: Chang Gung Memorial Hospital and Chang Gung University, Taiwan. CASE REPORT: An 8-year-old boy was diagnosed with spinal cord arteriovenous malformation after paraplegia. However, early diagnosis was delayed for the atypical initial clinical presentation as chest pain. After surgery and rehabilitation for 6 months, the patient could walk without assistance. CONCLUSIONS: Correct diagnosis of spinal cord arteriovenous malformations is sometimes difficult in children with atypical presentations. Early diagnosis relies on detailed examination and high index of suspicion.

Radiation-induced skull base leiomyosarcoma presenting with intracerebral haemorrhage.

Radiation-induced neoplasm including meningioma, glioma and sarcoma, is an uncommon but known consequence after therapeutic irradiation of pituitary tumour. Radiation-induced leiomyosarcoma due to previous sellar irradiation has only been reported once in the literature. We herein present the second case of radiation-induced leiomyosarcoma that happened 17 years after radiation therapy for pituitary adenoma. The case is unique in its initial presentation, i.e. acute intracerebral haemorrhage. To the best of our knowledge, such an acute and severe presentation has never been reported in radiation-induced neoplasm following radiotherapy for pituitary adenoma.