Adenosquamous carcinoma of the facial bones,skull base,and calvaria: CT and MR manifestations.

A 62-year-old woman had proptosis of the right eye, decreased visual acuity of the left eye, and no other focal neurologic deficits. She had a grand mal seizure 1 month before admission. The CT and MR studies showed extensive bone destruction of the margins of the right orbit, the floor of the middle cranial fossa, the right cavernous sinus, and much of the calvaria. There was considerable dural disease and tumor in the right orbit, paranasal sinuses, and scalp, as well as mucoceles of the left ethmoidal sinus with desiccated secretions. The diagnosis was adenosquamous carcinoma, an aggressive tumor related to both squamous cell carcinoma and adenocarcinoma.     

Evidence to Practice for Mental Health Task-Sharing: Understanding Readiness for Change among Accredited Social Health Activists in Sehore District,Madhya Pradesh,India

Involvement of community health workers (CHWs) within task-sharing to bridge the mental health treatment gap has been proven to be efficacious in randomized controlled trials. The impact of mental health programs based on task-sharing paradigm greatly depends on the performance of CHWs which, in-turn, is influenced by their readiness for change. However, there is dearth of literature assessing the role of readiness for change as an important predicator of CHW performance. The aim of this study is to examine the applicability of the readiness for change model and investigate its cultural and contextual nuances among Accredited Social Health Activists (ASHAs), a cadre of CHWs in India, to understand their engagement in mental health task-sharing. We conducted in-depth, semi-structured interviews with a purposive sample of n?=?12 key informants including ASHAs and other healthcare professionals in Sehore district, India. The interview guide consisted of open-ended questions based on the readiness for change factors including ASHAs’ attitudes towards their role in mental health care, perception of capability to implement mental health task-sharing, of support from the public health system, etc. Framework analysis with a combined inductive-deductive approach was employed to code the data and generate themes. Participants endorsed three readiness for change themes relevant to task-sharing among ASHAs including change valence or value ascribed to task-sharing, change-efficacy or the perceived ability to implement task-sharing, and job valence or value ascribed to their regular job role. In addition, they provided insights into the culturally and contextually salient aspects of these factors. Themes of personal empowerment, gaining respect and trust from community, professional duty, relationship with supervisors, and lack of resources availability were majorly highlighted. This is the first study to qualitatively investigate the applicability of the readiness for change model and its culture- and context-specific nuances among a cadre of non-specialist health workers in India. Our findings posit that implementation science models should strongly consider the culture and context within which they are being applied to enhance fit and relevance. Further, our results should be taken into consideration to adapt and validate measurement tools and build readiness for change in this population.

     

MRI of the paranasal sinuses and nasal cavity

In the evaluation of soft tissue masses of the paranasal sinuses and nasal cavity, MR has excelled, not only in sensitivity, but in specificity. Without question, MR has improved the diagnostic accuracy for distinguishing neoplasms from inflammatory diseases. This improved discrimination is primarily due to the combination of the superior soft tissue contrast of MRI and the widely disparate T2-relaxation values between the neoplasms and inflammatory processes indigenous to this anatomic area. MR's expanding role as the primary imaging modality for clinical problems in the sinonasal region will accompany the decrease in exam time and increase in spatial resolution. In the past few years there has been a rapid expansion in MRI's utility for a variety of clinical situations in the sinonasal region. This trend should accelerate, especially with the decrease in exam time and increase in spatial resolution that will accompany other expeditious technologic advancements.     

Crosstalk between oligodendrocytes and cerebral endothelium contributes to vascular remodeling after white matter injury

After stroke and brain injury, cortical gray matter recovery involves mechanisms of neurovascular matrix remodeling. In white matter, however, the mechanisms of recovery remain unclear. In this study, we demonstrate that oligodendrocytes secrete matrix metalloproteinase-9 (MMP-9), which accelerates the angiogenic response after white matter injury. In primary oligodendrocyte cultures, treatment with the proinflammatory cytokine interleukin-1β (IL-1β) induced an upregulation and secretion of MMP-9. Conditioned media from IL-1β-stimulated oligodendrocytes significantly amplified matrigel tube formation in brain endothelial cells, indicating that MMP-9 from oligodendrocytes can promote angiogenesis in vitro. Next, we asked whether similar signals and substrates operate after white matter injury in vivo. Focal white matter injury and demyelination was induced in mice via stereotactic injection of lysophosphatidylcholine into corpus callosum. Western blot analysis showed that IL-1β expression was increased in damaged white matter. Immunostaining demonstrated MMP-9 signals in myelin-associated oligodendrocytic basic protein-positive oligodendrocytes. Treatment with an IL-1β-neutralizing antibody suppressed the MMP-9 response in oligodendrocytes. Finally, we confirmed that the broad spectrum MMP inhibitor GM6001 inhibited angiogenesis around the injury area in this white matter injury model. In gray matter, a neurovascular niche promotes cortical recovery after brain injury. Our study suggests that an analogous oligovascular niche may mediate recovery in white matter.     

Possible involvement of free radicals in the differential neurobehavioral responses to stress in male and female rats

The effect of restraint stress (RS) on neurobehavioral and brain oxidative stress parameters, and their modulation by antioxidants were evaluated in male and cycling female rats. Exposure to RS suppressed both open arm entries and open arm time in the elevated plus maze and these changes were more marked in males than in females. Assay of brain homogenates revealed that the behavioral suppression was associated with similar differential increases in malondialdehye (MDA) and decreases in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels in males and females. Pretreatment with alpha-tocopherol (25 and 50 mg/kg) and N-acetylcysteine (100 and 200 mg/kg), attenuated the stress induced alteration of behavioral and oxidative stress markers in a consistent manner in both male and female rats. These findings suggest that males may be more susceptible than females to stress induced neurobehavioral changes and free radicals may exert a regulatory influence in such gender dependent responses to stress.     

APOE and LRPAP1 gene polymorphism and risk of Parkinson’s disease

Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson’s disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI_95%) = 1.067–1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI_95% = 1.137–6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI_95% = 1.621–10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI_95% = 0.897–0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.     

Voxel-based morphometry in the detection of dysplasia and neoplasia in childhood epilepsy: Limitations of grey matter analysis

The purpose of this exploratory investigation was to evaluate voxel-based morphometry (VBM) in detecting lesions underlying childhood epilepsy, and to establish the optimal image processing and statistical parameters in this context. The patients were 16 children (10 boys) aged 5.9 to 15.2 years (mean 11.3 years) with epilepsy and focal cortical dysplasia (FCD) or neoplasia. The control group comprised 24 normal children (12 boys), age matched to the patients. MRI volumes were spatially normalised to a custom template and segmented into grey matter (GM) and white matter. Using statistical parametric mapping, the GM segment from each patient was then contrasted with the mean GM segment of the control group utilising different VBM post-processing methods. Maps showing increased/decreased areas of GM concentration or volume were generated and compared with visually identified lesions. The results indicated that conservative VBM parameters of linear normalisation with no modulation produced the highest rates of lesion detection, which were identical for FCD and neoplasia at 5/8 lesions. These preliminary data suggest that VBM analysis of GM using conservative parameters can usually detect FCD and neoplasia in the MRI of children with epilepsy, but sensitivity may be inadequate for routine clinical application. Further refinement of the technique may be necessary.     

Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for δ-GABAA receptors

The sedative and hypnotic agent 4,5,6,7‐tetrahydroisoxazolo[4,5‐c]pyridine‐3‐ol (THIP) is a GABA_A receptor (GABA_AR) agonist that preferentially activates δ‐subunit‐containing GABA_ARs (δ‐GABA_ARs). To clarify the role of δ‐GABA_ARs in mediating the sedative actions of THIP, we utilized mice lacking the α₁‐ or δ‐subunit in a combined electrophysiological and behavioural analysis. Whole‐cell patch‐clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of ?60 mV. Application of bicuculline to wild‐type (WT) VB neurones revealed a GABA_AR‐mediated tonic current of 92 ± 19 pA, which was greatly reduced (13 ± 5 pA) for VB neurones of δ^0/0 mice. Deletion of the δ‐ but not the α₁‐subunit dramatically reduced the THIP (1 μm )‐induced inward current in these neurones (WT, ?309 ± 23 pA; δ^0/0, ?18 ± 3 pA; α₁^0/0, ?377 ± 45 pA). Furthermore, THIP selectively decreased the excitability of WT and α₁^0/0 but not δ^0/0 VB neurones. THIP did not affect the properties of miniature inhibitory post‐synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose‐dependent manner. The effect of THIP on rotarod performance was blunted for δ^0/0 but not α₁^0/0 mice. We previously reported that deletion of the α₁‐subunit abolished synaptic GABA_A responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic δ‐GABA_ARs vs. synaptic α₁‐subunit‐containing GABA_ARs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP.