Effects of age, HIV, and HIV-associated clinical factors on neuropsychological functioning and brain regional volume in HIV+ patients on effective treatment.

It is yet unclear if people infected with human immunodeficiency virus (HIV+) on stable, combined antiretroviral therapies (cARTs) decline with age at the same or greater rate than healthy people. In this study, we examined independent and interactive effects of HIV, age, and HIV-related clinical parameters on neuropsychological functioning and brain regional volume in a sizable group of Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell count, CD4 cell count during participation in the study, duration of HIV infection, or duration of cART along with age. Ninety-one HIV+ and 95 control (HIV-) volunteers ages 23-75 completed a battery of neuropsychological tests, and 54 HIV+ and 62 HIV- of these volunteers participated in a brain imaging assessment. Regional brain volume in the cortical and subcortical regions was measured using voxel-based morphometry. We have found that HIV and older age were independently related to lower attention, working memory, nonverbal fluency, and visuomotor dexterity. Older age but not HIV was associated with less volume in several cortical and subcortical brain regions. In the oldest HIV+ participants, age had a moderating effect on the relationship between the duration of cART and visuomotor performance, such as that older age decreased speed of visuomotor performance along with every year on cART. Such results may reflect the efficacy of cART in preventing HIV-associated brain damage. They also highlight the importance of monitoring neuropsychological functioning and brain structure in HIV+ patients. This is particularly important in older patients with long adherence to cART.

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

Reduced small world brain connectivity in probands with a family history of epilepsy.

BACKGROUND AND PURPOSE: The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). METHODS: Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. RESULTS: A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. CONCLUSION: Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations.

Repetitive transcranial magnetic stimulation induced modulations of resting state motor connectivity in writer's cramp.

BACKGROUND AND PURPOSE: Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). METHODS: Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. RESULTS: Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. CONCLUSIONS: It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy.

Reliability of unstable periodic orbit based control strategies in biological systems.

Presence of recurrent and statistically significant unstable periodic orbits (UPOs) in time series obtained from biological systems is now routinely used as evidence for low dimensional chaos. Extracting accurate dynamical information from the detected UPO trajectories is vital for successful control strategies that either aim to stabilize the system near the fixed point or steer the system away from the periodic orbits. A hybrid UPO detection method from return maps that combines topological recurrence criterion, matrix fit algorithm, and stringent criterion for fixed point location gives accurate and statistically significant UPOs even in the presence of significant noise. Geometry of the return map, frequency of UPOs visiting the same trajectory, length of the data set, strength of the noise, and degree of nonstationarity affect the efficacy of the proposed method. Results suggest that establishing determinism from unambiguous UPO detection is often possible in short data sets with significant noise, but derived dynamical properties are rarely accurate and adequate for controlling the dynamics around these UPOs. A repeat chaos control experiment on epileptic hippocampal slices through more stringent control strategy and adaptive UPO tracking is reinterpreted in this context through simulation of similar control experiments on an analogous but stochastic computer model of epileptic brain slices. Reproduction of equivalent results suggests that far more stringent criteria are needed for linking apparent success of control in such experiments with possible determinism in the underlying dynamics.

Resection and reconstruction of malignant tumor involving sternum.

We present a series of four cases of chest wall tumor, which underwent sternum resection. The methods of resection and reconstruction chest wall defect are discussed and the final outcome highlighted.

Polymodal therapy for high grade gliomas: a case report of favourable outcomes following intraoperative radiation therapy.

High grade gliomas, frequently with their infiltrative nature, often make the outcome from neurosurgical intervention alone unsatisfactory. It is recognized that adjuvant radiochemotherapy approaches offer an improved prognosis. For these reasons, we opted for surgical debulking, intraoperative radiation therapy (IORT) in combination with whole brain irradiation therapy and chemotherapy (temozolamide cycles) in the management of a 42 year-old lady with Glioblastoma Multiforme (GBM). Her troublesome symptoms improved after 3 months of this polymodal therapy and remained independently functional for more than two years.

Drought hotspot maps and regional drought characteristics curves: Development of a novel framework and its application to an Indian River basin undergoing climatic changes.

Drought is one of the significant natural disasters that incurs billion dollars of economic damage every year. Among all, agricultural drought needs critical attention for drought monitoring due to its direct effect on crop yield and management of irrigation water. Most of the previous studies focused on regionalizing drought using k-means, hierarchal, fuzzy, and entropy-based clustering techniques. However, these techniques are not suitable where the clusters are not separated distinctively, and the number of clusters cannot be estimated automatically. In this study, we have developed agricultural drought hotspot maps using Soil moisture deficit index (SMDI) and the regional severity (S), duration (D), and frequency (F) curves using complex network algorithm for the future warming climate (2041-2070) of the Mahanadi River basin (MRB) in India. We have used a modified dynamic Budyko (DB) hydrological model to simulate daily soil moisture at a spatial scale of 0.25° × 0.25° using input from four GCMs for the RCP 4.5 scenario. The modified DB model was calibrated and validated for the study area. The model proved to be capable of simulating the soil moisture dynamics over the basin and also effectively captured the historical droughts occurred in the basin. The drought hotspot maps of the basin suggest that the northern, south-eastern, and central parts of the basins are going to experience more number of droughts. The results suggest that for most of the clusters, the regional S-D-F curve can be utilized to understand the future drought characteristics at site-specific as well as regional scale, as the confidence band is found to be very narrow. Overall, our study provides a framework to develop regional S-D-F curve.

LINAC based radiosurgery and radiotherapy for neurosurgical diseases: what have we learnt so far.

BACKGROUND: Stereotactic radiosurgery uses a single fraction high dose radiation while stereotactic radiotherapy uses multifractionated lower dose focused radiation. MATERIALS AND METHODS: Radiosurgery used rigid CRW head frame while stereotactic radiotherapy utilized GTC or HNL relocatable frames. Stereotactic planning and radiation involved Radionics X-plan and LINAC system. RESULTS: Since December 2001, we have treated 83 lesions from 77 patients using either radiosurgery or fractionated stereotactic radiotherapy. Eighty six percent (86%) of our treated lesions showed favourable outcomes with median follow-up of 32 months (0-7 years). CONCLUSIONS: Our lessons from LINAC precision radiation therapy uphold its value as a promising and effective tool in treating a range of nervous system pathologies.

Functional connectivity of human striatum: a resting state FMRI study.

Classically regarded as motor structures, the basal ganglia subserve a wide range of functions, including motor, cognitive, motivational, and emotional processes. Consistent with this broad-reaching involvement in brain function, basal ganglia dysfunction has been implicated in numerous neurological and psychiatric disorders. Despite recent advances in human neuroimaging, models of basal ganglia circuitry continue to rely primarily upon inference from animal studies. Here, we provide a comprehensive functional connectivity analysis of basal ganglia circuitry in humans through a functional magnetic resonance imaging examination during rest. Voxelwise regression analyses substantiated the hypothesized motor, cognitive, and affective divisions among striatal subregions, and provided in vivo evidence of a functional organization consistent with parallel and integrative loop models described in animals. Our findings also revealed subtler distinctions within striatal subregions not previously appreciated by task-based imaging approaches. For instance, the inferior ventral striatum is functionally connected with medial portions of orbitofrontal cortex, whereas a more superior ventral striatal seed is associated with medial and lateral portions. The ability to map multiple distinct striatal circuits in a single study in humans, as opposed to relying on meta-analyses of multiple studies, is a principal strength of resting state functional magnetic resonance imaging. This approach holds promise for studying basal ganglia dysfunction in clinical disorders.

Radiation effects on the intima-media thickness of the common carotid artery in post-radiotherapy patients with head and neck malignancy.

BACKGROUND: Post-radiation large vessel injury has not received as much attention as microvascular irradiation injury. A few studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy to the head and neck. However, in most of these studies, the irradiated subjects also had other major risk factors for atherosclerosis. In this study, irradiated subjects with major risk factors such as hypertension, diabetes, history of previous cerebrovascular accident and connective tissue disorder were excluded. OBJECTIVE: To show in a cross-sectional study if radiotherapy to the carotid area has any effect on the IMT of the common carotid artery. SUBJECTS AND METHODS: 13 patients with head and neck malignancies who had completed radiotherapy to the carotid region at least 1 year previously underwent ultrasound of the carotid artery. IMT measurements were compared with those of 13 healthy controls, matched for age, sex and race, with no history of radiotherapy. RESULTS: The irradiated subjects had significantly larger IMT measurements (mean 0.74 mm) than the non-irradiated subjects (mean 0.46 mm). The difference was significant (p<0.001) with a confidence interval of 95%. CONCLUSIONS: This study shows that there is a measurable, significant (p<0.001) increase in IMT of the common carotid artery after radiotherapy for head and neck malignancy compared with non-irradiated matched controls. This knowledge is important for risk-benefit assessment of prophylactic or therapeutic neck irradiation. Increased awareness of this complication should provide an opportunity to intervene and prevent future cerebrovascular accidents in the majority of such patients.

Stochastic multiscale model for carbonate rocks.

A multiscale model for the diagenesis of carbonate rocks is proposed. It captures important pore scale characteristics of carbonate rocks: wide range of length scales in the pore diameters; large variability in the permeability; and strong dependence of the geometrical and transport parameters on the resolution. A pore scale microstructure of an oolithic dolostone with generic diagenetic features is successfully generated. The continuum representation of a reconstructed cubic sample of side length 2mm contains roughly 42 x 10{6} crystallites and pore diameters varying over many decades. Petrophysical parameters are computed on discretized samples of sizes up to 1000{3}. The model can be easily adapted to represent the multiscale microstructure of a wide variety of carbonate rocks.

An extensive sinonasal osteosarcoma mimicking chondrosarcoma.

Osteosarcoma is a rare tumour in the sinonasal region. Early diagnosis is essential for adequate management and better prognosis and this requires a meticulous histopathological examination. Reported is a case of osteosarcoma misdiagnosed as chondrosarcoma and treated by surgery followed by radiotherapy. However, appropriate diagnosis and pre-operative chemotherapy would have been significant in the prognosis. The pitfall of accurate diagnosis and the subsequent treatment is discussed in order to find the ways to maximize five years survival which is not more than 25% in this type of lesions.

Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study.

BACKGROUND AND PURPOSE: Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation. MATERIALS AND METHODS: Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex. RESULTS: Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102). CONCLUSIONS: This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.

Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring.

Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.

Prognostic factors of differentiated thyroid cancer patients in Hospital Universiti Sains Malaysia.

INTRODUCTION: The aim of this study was to identify the prognostic factors that influence the survival of differentiated thyroid cancer patients treated at Hospital Universiti Sains Malaysia (HUSM). METHODS: A total of 178 patients diagnosed with and treated for differentiated thyroid cancer in HUSM between January 1974 and July 2003 were included in this retrospective cohort study. The additional follow-up period was one year after the end of the recruitment phase. The data was collected from the medical records of the patients. RESULTS: The overall five- and ten-year relative survivals of differentiated thyroid cancer patients in HUSM were 90.6 percent (95 percent confidence interval [CI] 84.4-94.4) and 85.3 percent (95 percent CI 76.0-91.2), respectively. The significant prognostic factors for differentiated thyroid cancer were age (hazard ratio [HR] 6.9; 95 percent CI 1.7-28.6), loss of appetite (HR 10.9; 95 percent CI 2.7-43.7), tumour size (HR 3.7; 95 percent CI 1.1-13.8), regional recurrences (HR 3.2; 95 percent CI 1.1-9.8), high-risk stage (HR 19.9; 95 percent CI 4.4-90.4), and treatment (HR 0.2; 95 percent CI: 0.1-0.5). CONCLUSION: The survival rates obtained in this study were slightly lower than other studies but the pattern of survival rates between groups were similar. Prognostic factors identified in this study were similar to those of other studies, suggesting that the experience of HUSM was almost similar with that of other institutions.

Aggressive giant cell tumour of bone.

INTRODUCTION: The surgical treatment of Stage III or aggressive giant cell tumour of the bone, whether to perform intralesional or en-bloc resection, remains controversial. The aim of this study is to identify the effectiveness of en-bloc resection for local control and final oncological outcome of the disease. METHODS: The data of 20 consecutive patients with Stage III giant cell tumour were retrospectively reviewed to determine the local control and oncological outcome after treatment with wide resection. RESULTS: The majority of the patients presented late with mean duration of symptoms of 24 months, and four patients presented with recurrences. All patients were treated with wide resection except for two patients who underwent ablative surgery due to major neurovascular involvement. Ten patients required free vascularised tissue transfer to cover massive soft tissue defect. Local recurrence occurred in one patient who was again treated with wide resection and vascularised flap. Six patients had pulmonary metastases. Two patients with resectable disease were treated with thoracoscopic surgery and they remained disease-free 36 months after surgery. Two patients with multiple lung metastases were treated with chemotherapy and the disease remained non-progressive. The remaining two patients who refused chemotherapy showed radiological progression, and one succumbed to the disease with massive haemoptysis. CONCLUSION: Aggressive giant cell tumour of bone should be treated with wide resection for better local control, and treatment of pulmonary metastases is mandatory for overall prognosis.

Early Malaysian experience on the use of head and neck localizers in the precision radiotherapy of intra and extra cranial sites for first 28 cases.

Precision Radiotherapy at high doses require a fixed, referable target point. The frame system fulfills the required criteria by making the target point relocatable and fixed within a stereotactic space. Since December 2001, we have treated 28 central and peripheral nervous system lesions using either radiosurgery as a single high dose fraction or fractionated 3-dimensional conformal radiotherapy using a lower dose and a multi-leaf collimator. Various pathological lesions either benign or malignant were treated. Eighty six percent of our treated lesions showed growth restraint, preventing them from causing new symptoms with a median follow-up duration of 20.5 months. However, the true benefit from this technique would require a long-term follow-up to document the progress.

A new relaxed state in horse methemoglobin characterized by crystallographic studies.

A new relaxed state has been characterized in the crystals of horse methemoglobin grown at neutral pH at low ionic concentration and their low humidity variants. The crystals provide an example for improvement in X-ray diffraction quality with reduced solvent content. Only the classical R state has been so far observed in liganded horse hemoglobin. The state characterized in the present study lies in between the R state and the R2 state characterized earlier in liganded human hemoglobin. The results presented here, along with those of earlier studies, suggest that relaxed and tense hemoglobin can access ensembles of states.

Abdominal aorta and inferior vena cava thromboses in advanced stage of malignant fibrous histiocytoma.

Asymptomatic simultaneous thrombosis of abdominal aorta and inferior vena cava is a rare complication in advanced malignancy. We described an incidental finding of this clinical entity in our patient who presented with advance stage of malignant fibrous hystiocytoma of soft tissue and pathological fracture. The radiological evaluation with spiral computed tomography scan of abdominal aorta and inferior vena cava are presented and the subsequent management highlighted.