Neurosurgical oncology: advances in operative technologies and adjuncts

Modern glioma surgery has evolved around the central tenet of safely maximizing resection. Recent surgical adjuncts have focused on increasing the maximum extent of resection while minimizing risk to functional brain. Technologies such as cortical and subcortical stimulation mapping, intraoperative magnetic resonance imaging, functional neuronavigation, navigable intraoperative ultrasound, neuroendoscopy, and fluorescence-guided resection have been developed to augment the identification of tumor while preserving brain anatomy and function. However, whether these technologies offer additional long-term benefits to glioma patients remains to be determined. Here we review advances over the past decade in operative technologies that have offered the most promising benefits for glioblastoma patients.     

Odontogenic carcinoma: a functional genomic comparison with oral mucosal squamous cell carcinoma

Intraosseous squamous cell carcinomas of the mandible arise de novo or secondary to a tumor or transformed cyst epithelium. Current diagnostic tests frequently fail to distinguish between these tumors, leading to confusing classification schemes. We report the functional genomic analysis of a mandibular odontogenic carcinoma. Malignant keratinocytes from the lesion were isolated using laser capture microdissection. Target sample generated from the total RNA of the LCM-procured cells was used to hybridize high-density oligonucleotide arrays. Functional genomic analysis of the odontogenic carcinoma database compared with four oral mucosal squamous cell carcinoma gene expression databases was performed. Preliminary results suggest a small subset of genes distinguish this odontogenic carcinoma from oral mucosal epidermoid carcinomas.     

Strategic marketing in the UK tobacco industry

Tobacco-industry marketing has played a central part in the global spread of tobacco use and addiction. Although the absolute size of the tobacco market has dwindled, the industry is still immensely successful, largely due to sophisticated and manipulative marketing strategies. The UK tobacco industry identifies target groups and builds enduring relationships based on careful brand management. Potential customers are exposed to brands which are likely to appeal to them most. Tobacco companies tailor their products to target markets by altering the content of tar and nicotine, and by adding flavourings to produce a distinctive taste. Marketing strategies ensure that the products are promoted heavily at the point of sale, and directed advertising and sponsorship agreements are used to increase the visibility of the brand and strengthen its image. Tobacco companies also target non-consumer organisations such as retailers and policy makers with the aim of creating the best possible business environment for tobacco sales. We review published evidence, internal-advertising-agency documents, and observational data about tobacco promotion, and discuss the use of targeted marketing strategies in the UK.     

The development and psychometric validation of the central sensitization inventory

Central sensitization (CS) has been proposed as a common pathophysiological mechanism to explain related syndromes for which no specific organic cause can be found. The term "central sensitivity syndrome (CSS)" has been proposed to describe these poorly understood disorders related to CS. The goal of this investigation was to develop the Central Sensitization Inventory (CSI), which identifies key symptoms associated with CSSs and quantifies the degree of these symptoms. The utility of the CSI, to differentiate among different types of chronic pain patients who presumably have different levels of CS impairment, was then evaluated. Study 1 demonstrated strong psychometric properties (test-retest reliability = 0.817; Cronbach's alpha = 0.879) of the CSI in a cohort of normative subjects. A factor analysis (including both normative and chronic pain subjects) yielded 4 major factors (all related to somatic and emotional symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the CSI was administered to 4 groups: fibromyalgia (FM); chronic widespread pain without FM; work-related regional chronic low back pain (CLBP); and normative control group. Analyses revealed that the patients with FM reported the highest CSI scores and the normative population the lowest (P < 0.05). Analyses also demonstrated that the prevalence of previously diagnosed CSSs and related disorders was highest in the FM group and lowest in the normative group (P < 0.001). Taken together, these 2 studies demonstrate the psychometric strength, clinical utility, and the initial construct validity of the CSI in evaluating CS-related clinical symptoms in chronic pain populations.     

The influence of head motion on intrinsic functional connectivity MRI

Functional connectivity MRI (fcMRI) has been widely applied to explore group and individual differences. A confounding factor is head motion. Children move more than adults, older adults more than younger adults, and patients more than controls. Head motion varies considerably among individuals within the same population. Here we explored the influence of head motion on fcMRI estimates. Mean head displacement, maximum head displacement, the number of micro movements (> 0.1 mm), and head rotation were estimated in 1000 healthy, young adult subjects each scanned for two resting-state runs on matched 3T scanners. The majority of fcMRI variation across subjects was not linked to head motion. However, head motion had significant, systematic effects on fcMRI network measures. Head motion was associated with decreased functional coupling in the default and frontoparietal control networks — two networks characterized by coupling among distributed regions of association cortex. Other network measures increased with motion including estimates of local functional coupling and coupling between left and right motor regions — a region pair sometimes used as a control in studies to establish specificity. Comparisons between groups of individuals with subtly different levels of head motion yielded difference maps that could be mistaken for neuronal effects in other contexts. These effects are important to consider when interpreting variation between groups and across individuals.     

The serendipitous discovery of the brain's default network

One of the most unexpected findings by functional neuroimaging has been the discovery of the brain's default network - a set of brain regions that is spontaneously active during passive moments. The default network's discovery was a fortunate accident that occurred due to the inclusion of rest control conditions in early PET and functional MRI studies. At first, the network was ignored. Later, its presence was shunned as evidence of an experimental confound. Finally, it emerged as a mainstream target of focused study. Here, I describe a personal perspective of the default network's serendipitous discovery.     

Interventions for Children with Pervasive Developmental Disorders in Low and Middle Income Countries

Background Although interventions for children with pervasive developmental disorders (PDD) have been the focus of research effort and evidence reviews in many Western countries, this evidence has not been assessed in the context of low‐ and middle‐income (LAMI) countries especially in terms of the fit with different cultures and resources. Method As a part of the WHO MH‐GAP project, we carried out a systematic review of published literature relating to interventions for PDD in LAMI countries. Given the small amount of direct evidence found, we supplemented the review with findings from existing relevant evidence reviews to draw practical recommendations. Results We found only four controlled studies evaluating an intervention for children with PDD in a LAMI country. These studies all evaluated different interventions. A systematic search of controlled studies of evidence‐based parenting training interventions (Incredible Years and Triple P) in non‐LAMI countries identified two studies both indicating successful outcomes. Conclusions The evidence base for interventions for PDDs in LAMI countries is sparse, and to inform practical and future research recommendations, it is important to consider potentially deliverable behavioural parent training interventions. Such interventions need to be explored in LAMI countries when delivered in primary and secondary healthcare contexts.     

Measurement of orientation and susceptibility ratios using a polarization-resolved second-harmonic generation holographic microscope

Three-dimensional second-harmonic fields, sample orientation, and susceptibility ratios of biological samples are measured using polarization-resolved second-harmonic generation (SHG) microscopy. The three-dimensional (3D) polarization is gathered by measurement of a series of holograms for which excitation and analyzer polarizations are systematically varied, and the 3D SHG field is recovered through numerical back propagation. Harmonophore orientation is resolved in 3D from a sub-set of polarization-resolved SHG holograms. We further expand on previous approaches for the determination of susceptibility ratios, adding the calculation of multiple ratio values to allow intrinsic verification.OCIS codes: (090.1995) Digital holography, (180.4315) Nonlinear microscopy, (110.3010) Image reconstruction techniques     

Traumatic brain injury and trichloroethylene exposure interact and produce functional, histological, and mitochondrial deficits

Mitochondria play a pivotal role in the development of pathology associated with Parkinson's disease (PD), traumatic brain injury (TBI), and following exposure to the environmental toxin trichloroethylene (TCE). Evidence from humans indicates that both TBI and TCE can play a role in the development of PD and that each of these insults result in significant mitochondrial dysfunction. In the current studies we hypothesized that exposure to both TCE and TBI would result in increased pathology associated with PD. To test this hypothesis, 16 week old male Fischer 344 rats were administered TCE for either one or two weeks by oral gavage. Following exposure to TCE, rats were subjected to either a sham, mild (1.0mm), or moderate (2.0mm) controlled cortical impact TBI. Given the strong connection between mitochondrial function and PD, TBI, and TCE, tissue from the striatum and substantia nigra were analyzed 6h after the TBI. Neither TCE exposure, TBI, nor the combination of the two insults resulted in mitochondrial deficits at 6h post-TBI in the substantia nigra. Unlike the substantia nigra, the striatum exhibited significant mitochondrial dysfunction. Exposure to TCE alone for two weeks resulted in approximately a 75% reduction in mitochondrial function (p<0.05) in the striatum whereas TBI alone resulted in approximately a 30% reduction in striatal mitochondrial function. Following 1 week exposure to TCE followed by TBI, there was a significant reduction (50%) in mitochondrial function (p<0.05) which required the presence of both insults. Beginning 12 days after the injury significant motor impairment was observed with Rotarod testing. Animals exposed to TCE and a moderate TBI exhibited performance which was approximately 50% of controls (p<0.01). Cylinder testing revealed that at 30 days post-injury animals exposed to TCE and a moderate TBI also had about a 34% reduction in the usage of the contralateral fore paw and this impairment was significantly worse than both control animals and animals exposed to TCE and a mild TBI (p<0.05). At 30 days post-injury there was a 13-17% reduction in the number of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (p<0.05), which was the result of protein loss and not cell death. Loss of TH positive neurons did not result in changes in striatal TH fiber density or levels of the dopamine transporter or type-2 dopamine receptor. Additionally, exposure to TCE prior to the TBI did not increase the loss of cortical tissue, indicating regional specificity for TCE induced deficits. These studies provide further evidence for the connection between TCE, TBI, and PD and lend support to the concept that PD develops from a multifactorial injury scenario.     

Sexuality and sex education of adolescents with intellectual disability: mothers' attitudes, experiences, and support needs

Few studies have considered families' views about adolescents' sexual development. The authors compared attitudes and behaviors of mothers of young people with (n = 30) and without intellectual disability (n = 30). Both groups placed similar importance on dealing with their children's developing sexuality and were similarly confident in doing so. Mothers of young people with intellectual disability held more cautious attitudes about contraception, readiness to learn about sex, and decisions about intimate relationships. Mothers expressed concerns about their children with intellectual disability and sexual vulnerability. They had also spoken about fewer sexual topics with their children and began these discussions when their children were older. The findings can inform more sensitive supports and materials to help families deal with the sexual development of their offspring.