Introduction of a newly created AW stereotactic frame: a phantom-based accuracy evaluation and an initial experience in clinical usage.

BACKGROUND: A new stereotactic frame was created in 2015, based on a linear algorithm. It is called Albert Wong (AW) frame. A simple AW stereo-calculator was also designed based on Excel® (Microscoft Corporation, Redmond, WA) programme for the frame. OBJECTIVE: The aim of this study is to test the accuracy of the AW frame by a direct head to head comparison with CRW® frame (Integra Life Sciences, Plainsboro, NJ) on a phantom. METHODS: This is a prospective pilot cross-sectional phantom study with a total of 42 (21 for AW and 21 for CRW®) laboratory testings performed in 2017 at our institute to compare the accuracies of both frames in a consecutive manner. A phantom (BL phantom) was newly created, where targets can be placed at different heights and positions on a platform attached under the frame for accuracy testing comparing between the AW and CRW® frames. RESULTS: A comparable accuracy testing results were observed between the AW and CRW® frames of 0.64 mm versus 1.07 mm respectively. Approval from the local ethics committee for a clinical trial was obtained. We report on three case illustrations who had the AW frame-based biopsies with definitive diagnoses and without any post-biopsy related complication. CONCLUSION: AW frame successfully demonstrated a good accuracy of 0.64 mm in phantom testing using the BL phantom by a linear algorithmic calculation. The clinical trial with three patients demonstrated definitive diagnoses and safety with its use.

Development of a novel peptide to prevent entry of SARS-CoV-2 into lung and olfactory bulb cells of hACE2 expressing mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has caused a global pandemic Coronavirus Disease 2019 (COVID-19). Currently, there are no effective treatments specifically for COVID-19 infection. The initial step in SARS-CoV-2 infection is attachment to the angiotensin-converting enzyme 2 (ACE2) on the cell surface. We have developed a protein peptide that effectively disrupts the binding between the SARS-CoV-2 spike protein and ACE2. When delivered by nasal spray, our peptide prevents SARS-CoV-2 spike protein from entering lung and olfactory bulb cells of mice expressing human ACE2. Our peptide represents a potential novel treatment and prophylaxis against COVID-19.

Chronic Subdural Hematoma Caused by Calvarial and Dural Metastasis from Uterine Leiomyosarcoma.

Uterine Leiomyosarcoma (uLMS) is an aggressive tumor with poor clinical outcome. Skull and dural metastasis from uterine uLMS is exceptionally rare. We report a 60-year-old woman who had a 6 months' history of per vaginal bleed and abdominal pain who presented to us in a confused state and raised intracranial pressure symptoms with swelling over her right frontal-temporal region. She underwent excision of the right frontal-temporal tumor and evacuation of a right subdural hematoma (SDH), which greatly improved her condition. Postoperatively, she underwent adjuvant radiotherapy and chemotherapy. This case highlights the importance of clinical suspicion to diagnose patients with this rare metastasis to this region and the appropriate subsequent treatment. We herein report a rare case of metastatic uLMS with skull and dural metastasis that presented with SDH.

Do inhabitants profit from integrating a public health focus in urban renewal programmes? A Dutch case study.

BACKGROUND: Urban renewal traditionally involves policy sectors such as housing, transport, and employment, which potentially can enhance the health of residents living in deprived areas. Additional involvement of the public health sector might increase the health impact of these urban renewal activities. This study evaluates the health impact of an additional focus on health, under the heading of Healthy District Experiments (HDE), within districts where an urban renewal programme was carried out. METHODS: We evaluated changes in health outcomes before the start of the HDE and after implementation, and compared these changes with health changes in control areas, e.g. districts from the urban renewal programme where no additional HDE was implemented. Additionally, we gathered information on the content of the experiments to determine what types of activities have been implemented. RESULTS: The additional activities from the HDE were mostly aimed at strengthening the health care in the districts and at promoting physical activity. When we compared the prevalence in general health, mental health, overweight, obesity, smoking, and physical activity during the study period between the HDE districts and control districts, we found no significant differences in the rate of change. The study is limited by a small sample size and the cross-sectional nature of the data. These and other limitations are discussed. CONCLUSION: We found no evidence for a beneficial health impact of the activities that were initiated with a specific focus on health, within a Dutch urban renewal programme. Specific attention for network management and the integration of such activities in the wider programme, as well as an allocated budget might be needed in order to sort a health impact.

Novel use of robotics and navigation for anterior lumbar total disc replacement surgery.

The ability to navigate the anterior lumbar disc space may improve clinical outcomes and implant longevity. However, no robotic navigation systems are presently authorized by the U.S. Food and Drug Administration to assist with anterior retroperitoneal lumbar interbody surgery. Furthermore, no studies to date have investigated such an application of this technology. This study examines the application of robotic navigation to anterior lumbar total disc replacement surgery to improve retroperitoneal exposure and orientation of the anterior lumbar spine, enhance coronal plane centralization of the implant, optimize surgical trajectory, and mitigate radiologic exposure. Postoperative outcomes of a small cohort of patients undergoing anterior lumbar total disc replacement surgery using robotic navigation were analyzed. The results of the study revealed that a modified use of the aforementioned robot-assisted surgical technology enhances coronal plane centralization and trajectory, all while mitigating radiologic exposure, resulting in more accurate placement of the implant within the intervertebral space at each level.

Factors affecting diagnostic yield in stereotactic biopsy for brain lesions: a 5-year single-center series.

The objective of this study is to determine the factors that are associated with the diagnostic yield of stereotactic brain biopsy. A retrospective analysis was performed on 50 consecutive patients who underwent stereotactic brain biopsies in a single institute from 2014 to 2019. Variables including age, gender, lesion topography and characteristics, biopsy methods, and surgeon's experience were analyzed along with diagnostic rate. This study included 31 male and 19 female patients with a mean age of 48.4 (range: 1-76). Of these, 25 underwent frameless brain-suite stereotactic biopsies, 15 were frameless Portable Brain-lab® stereotactic biopsies and 10 were frame-based CRW® stereotactic biopsies. There was no statistical difference between the diagnostic yield of the three methods. The diagnostic yield in our series was 76%. Age, gender, and biopsy methods had no impact on diagnostic yield. Periventricular and pineal lesion biopsies were significantly associated with negative diagnostic yield (p = 0.01) whereas larger lesions were significantly associated with a positive yield (p = 0.01) with the mean volume of lesions in the positive yield group (13.6 cc) being higher than the negative yield group (7 cc). The diagnostic yields seen between senior and junior neurosurgeons in the biopsy procedure were 95% and 63%, respectively (p = 0.02). Anatomical location of the lesion, volume of the lesion, and experience of the surgeon have significant impacts on the diagnostic yield in stereotactic brain biopsy. There was no statistical difference between the diagnostic yield of the three methods, age, gender, and depth of lesion.

Outpatient Versus Inpatient Anterior Lumbar Spine Surgery: A Multisite, Comparative Analysis of Patient Safety Measures.

BACKGROUND: The frequency and complexity of spinal surgery performed in an ambulatory surgery center (ASC) is increasing. However, safety and efficacy data of most spinal procedures adapted to the ASC are sparse and have focused on anterior cervical surgery. The purpose of this study was to compare the 90-day complication and readmission rates of anterior lumbar spine surgery performed in an ASC or inpatient setting. METHODS: We performed a retrospective comparative analysis of 226 consecutive anterior lumbar surgeries (283 levels treated) completed in an ASC (n = 124) or in an inpatient tertiary care hospital (n = 102) over a 3-year period. These included anterior lumbar interbody fusion (ALIF), artificial disc replacement (ADR), and hybrids. Patients undergoing simultaneous or staged posterior procedures within 3 months were excluded. Patient demographics and surgical parameters between the two surgical settings were compared. Ninety-day medical complications and readmission rates were assessed. One-way analysis of variance and Chi-square analysis were used. A P value of less than .05 was considered statistically significant. RESULTS: The two study groups had similar baseline characteristics. While there was a trend toward fewer complications, reoperations, and readmissions for the ASC cohort, the differences were not statistically significant. There were 7 intraoperative complications (5.6% minor vascular injury) in the inpatient cohort and 0 in the ASC cohort. The overall 90-day postoperative complication rate was 5.6% for the inpatient cohort and 0.9% for the ASC cohort. The 90-day readmission rate was 1.9% in the ASC cohort and 1.6% in the inpatient cohort. The 90-day reoperation rate was 0.8% for the inpatient cohort and 0% in the ASC cohort. The average hospital stay was 2.3 ± 1.5 days for the inpatient cohort. CONCLUSION: The 90-day readmission rates were lower for outpatients than for inpatients, while the complication and reoperation rates were similar. Our results demonstrate that anterior lumbar procedures, including single-level and multilevel ALIF, ADR, and hybrid procedures, can be performed safely in an ASC. This has significant cost savings implications for the ASC setting.

Vacuum Drains versus Passive Drains versus No Drains in Decompressive Craniectomies-A Randomized Controlled Trial on Subgaleal Drain Complication Rates (VADER Trial).

OBJECTIVE: Subgaleal drains are generally deemed necessary for cranial surgeries including decompressive craniectomies (DCs) to avoid excessive postoperative subgaleal hematoma (SGH) formation. Many surgeries have moved away from routine prophylactic drainage but the role of subgaleal drainage in cranial surgeries has not been addressed. METHODS: This was a randomized controlled trial at 2 centers. A total of 78 patients requiring DC were randomized in a 1:1:1 ratio into 3 groups: vacuum drains (VD), passive drains (PD), and no drains (ND). Complications studied were need for surgical revision, SGH amount, new remote hematomas, postcraniectomy hydrocephalus (PCH), functional outcomes, and mortality. RESULTS: Only 1 VD patient required surgical revision to evacuate SGH. There was no difference in SGH thickness and volume among the 3 drain types (P = 0.171 and P = 0.320, respectively). Rate of new remote hematoma and PCH was not significantly different (P = 0.647 and P = 0.083, respectively), but the ND group did not have any patient with PCH. In the subgroup analysis of 49 patients with traumatic brain injury, the SGH amount of the PD and ND group was significantly higher than that of the VD group. However, these higher amounts did not translate as a significant risk factor for poor functional outcome or mortality. VD may have better functional outcome and mortality. CONCLUSIONS: In terms of complication rates, VD, PD, and ND may be used safely in DC. A higher amount of SGH was not associated with poorer outcomes. Further studies are needed to clarify the advantage of VD regarding functional outcome and mortality, and if ND reduces PCH rates.

Disrupting the α7nAChR-NR2A protein complex exerts antidepressant-like effects.

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Most antidepressant medications target the serotonin and norepinephrine transporters, but a significant minority of patients do not respond to treatment and novel therapeutic targets are needed. We previously identified a protein complex composed of the α7 nicotinic acetylcholine receptor (nAChR) and NMDA glutamate receptors (NMDARs), through which α7nAChR upregulates NMDAR function. Disruption of the α7nAChR-NMDAR complex with an interfering peptide blocked α7nAChR-mediated upregulation of NMDAR function and cue-induced reinstatement of nicotine seeking in rat models of relapse. Here we report that disrupting the α7nAChR-NMDAR complex with the interfering peptide also has antidepressant-like effects in the forced swim test (FST), a common rat behaviour screening test for antidepressant effects. Furthermore, the interfering peptide significantly increases extracellular signal-regulated kinase (ERK) activity in the animals subjected to the FST. Our results provide a novel potential therapeutic target for the development of new antidepressant medications.

Enhancing proteasomal processing improves survival for a peptide vaccine used to treat glioblastoma.

Despite its essential role in antigen presentation, enhancing proteasomal processing is an unexploited strategy for improving vaccines. pepVIII, an anticancer vaccine targeting EGFRvIII, has been tested in several trials for glioblastoma. We examined 20 peptides in silico and experimentally, which showed that a tyrosine substitution (Y6-pepVIII) maximizes proteasome cleavage and survival in a subcutaneous tumor model in mice. In an intracranial glioma model, Y6-pepVIII showed a 62 and 31% improvement in median survival compared to control animals and pepVIII-vaccinated mice. Y6-pepVIII vaccination altered tumor-infiltrating lymphocyte subsets and expression of PD-1 on intratumoral T cells. Combination with anti-PD-1 therapy cured 45% of the Y6-pepVIII-vaccinated mice but was ineffective for pepVIII-treated mice. Liquid chromatography-tandem mass spectrometry analysis of proteasome-digested pepVIII and Y6-pepVIII revealed that most fragments were similar but more abundant in Y6-pepVIII digests and 77% resulted from proteasome-catalyzed peptide splicing (PCPS). We identified 10 peptides that bound human and murine MHC class I. Nine were PCPS products and only one peptide was colinear with EGFRvIII, indicating that PCPS fragments may be a component of MHC class I recognition. Despite not being colinear with EGFRvIII, two of three PCPS products tested were capable of increasing survival when administered independently as vaccines. We hypothesize that the immune response to a vaccine represents the collective contribution from multiple PCPS and linear products. Our work suggests a strategy to increase proteasomal processing of a vaccine that results in an augmented immune response and enhanced survival in mice.

Endoscopic Endonasal Approach in Clival Chordoma Surgery: Case Series.

Chordomas are rare and slow-growing locally destructive bone tumors that can develop in the craniospinal axis. It is commonly found in the sacrococcygeal region whereas only 25-35% are found in the clival region. Headache with neurological deficits are the most common clinical presentations. Complete surgical resection either via open or endoscopic endonasal approaches are the main mode of treatment. Here, we report a series of 5 cases of clival chordomas which was managed via endoscopic endonasal approaches in our center. A retrospective analysis of patients who had undergone endoscopic endonasal resection of clival chordoma in Sarawak General Hospital from 2014 to 2018. A total of 5 cases were operated on endoscopically via a combine effort of both the otorhinolaryngology team and the neurosurgical team during the study period from year 2013 to 2018. From our patient, 2 were female and 3 were male patients. The main clinical presentation was headache, squinting of eye and nasopharyngeal fullness. All our patient had endoscopic endonasal debulking of clival tumor done, with average of hospital stay from 9 - 23 days. Pos-operatively, patients were discharged back well. Endoscopic endonasal resection of clival chordomas gives good surgical resection results with low morbidity rates and therefore can be considered as a surgical option in centers where the surgical specialties are available.

Clinical Outcome of Tuberculous Meningitis with Hydrocephalus - A Retrospective Study.

BACKGROUND: To study the clinical outcome of tuberculous meningitis with hydrocephalus (TBMH) and the factors contributing to its poor clinical outcome. METHODS: Clinical data of 143 adult patients diagnosed with TBM over a 6-year period in two tertiary hospitals in Malaysia were retrospectively reviewed. Relevant clinical and radiological data were studied. Patients with TBMH were further analysed based on their clinical grade and rendered treatment to identify associated factors and outcome of this subgroup of patients. The functional outcome of patients was assessed at 12 months from treatment. RESULTS: The mean age of patients was 35.6 (12.4) years old, with a male gender predominance of 67.1%. Forty-four percent had TBMH, of which 42.9% had surgical intervention. In the good modified Vellore grade, 76.5% was managed medically with concurrent anti-tuberculosis treatment (ATT), steroids and osmotic agents. Four patients had surgery early in the disease as they did not respond to medical therapy and reported a good outcome subsequently. Poor outcome (65.2%) was seen in the poor modified Vellore grade despite medical and surgical intervention. Multivariate model multiple Cox regression showed significant results for seizure (adjusted hazard ratio [aHR]: 15.05; 95% CI: 3.73, 60.78), Glasgow coma scale (GCS) (aHR: 0.79; 95% CI: 0.70, 0.89) and cerebrospinal fluid (CSF) cell count (aHR: 1.11; 95% CI: 1.05, 1.17). CONCLUSION: Hydrocephalus was seen in 44% of patients in this study. GCS score, seizure and high CSF cell count were factors associated with a poor prognosis in TBM. Patients with TBMH treated medically (TBMHM) had better survival function compared to TBMH patients undergoing surgical intervention (TBMHS) (P-value < 0.001). This retrospective study emphasises that TBMH is still a serious illness as 47.6% of the patients had poor outcome despite adequate treatment.

Neurosurgical Services in the Northern Zone of Sarawak in Malaysia: The Way Forward Amid the COVID-19 Pandemic.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has set a huge challenge to the delivery of neurosurgical services, including the transfer of patients. We aimed to share our strategy in handling neurosurgical emergencies at a remote center in Borneo island. Our objectives included discussing the logistic and geographic challenges faced during the COVID-19 pandemic. METHODS: Miri General Hospital is a remote center in Sarawak, Malaysia, serving a population with difficult access to neurosurgical services. Two neurosurgeons were stationed here on a rotational basis every fortnight during the pandemic to handle neurosurgical cases. Patients were triaged depending on their urgent needs for surgery or transfer to a neurosurgical center and managed accordingly. All patients were screened for potential risk of contracting COVID-19 prior to the surgery. Based on this, the level of personal protective equipment required for the health care workers involved was determined. RESULTS: During the initial 6 weeks of the Movement Control Order in Malaysia, there were 50 urgent neurosurgical consultations. Twenty patients (40%) required emergency surgery or intervention. There were 9 vascular (45%), 5 trauma (25%), 4 tumor (20%), and 2 hydrocephalus cases (10%). Eighteen patients were operated at Miri General Hospital, among whom 17 (94.4%) survived. Ninety percent of anticipated transfers were avoided. None of the medical staff acquired COVID-19. CONCLUSIONS: This framework allowed timely intervention for neurosurgical emergencies (within a safe limit), minimized transfer, and enabled uninterrupted neurosurgical services at a remote center with difficult access to neurosurgical care during a pandemic.

Clustering of chronic hepatitis B screening intentions in social networks of Moroccan immigrants in the Netherlands.

BACKGROUND: Early detection, identification, and treatment of chronic hepatitis B through screening is vital for those at increased risk, e.g. born in hepatitis B endemic countries. In the Netherlands, Moroccan immigrants show low participation rates in health-related screening programmes. Since social networks influence health behaviour, we investigated whether similar screening intentions for chronic hepatitis B cluster within social networks of Moroccan immigrants. METHODS: We used respondent-driven sampling (RDS) where each participant ("recruiter") was asked to complete a questionnaire and to recruit three Moroccans ("recruitees") from their social network. Logistic regression analyses were used to analyse whether the recruiters' intention to request a screening test was similar to the intention of their recruitees. RESULTS: We sampled 354 recruiter-recruitee pairs: for 154 pairs both participants had a positive screening intention, for 68 pairs both had a negative screening intention, and the remaining 132 pairs had a discordant intention to request a screening test. A tie between a recruiter and recruitee was associated with having the same screening intention, after correction for sociodemographic variables (OR 1.70 [1.15-2.51]). CONCLUSIONS: The findings of our pilot study show clustering of screening intention among individuals in the same network. This provides opportunities for social network interventions to encourage participation in hepatitis B screening initiatives.

Radiation-induced malignant rhabdoid tumour of the hypothalamus in an adult: A case report.

BACKGROUND: Rhabdoid tumours of the central nervous system are highly malignant and extremely rare in adults. To the best of our knowledge, only 87 cases of malignant rhabdoid tumour have been reported to date, inclusive of 4 cases with presumed radiation-induced aetiology. We report a case of malignant rhabdoid tumour in an adult with presumed radiation-induced aetiology to enrich the armamentarium of this disease entity, which may have some implications for early diagnosis and treatment of this rare disease in the future. CASE SUMMARY: A 27-year-old male, who was exposed to cranial irradiation at the age of 4 years as part of the treatment for acute lymphoblastic leukaemia, presented with symptoms of raised intracranial pressure for one week. Brain magnetic resonance imaging revealed a heterogeneously enhancing lesion at the hypothalamus. Stereotactic biopsy was performed. Histopathological examination of the lesion showed malignant rhabdoid tumour. The disease progressed rapidly, with manifestation of leptomeningeal spread. He was started on craniospinal irradiation but treatment was suspended after 5.4 Gy, as he developed myelosuppression. His clinical condition deteriorated rapidly, and he succumbed to his illness within 2 mo. CONCLUSION: This fifth case of radiation-induced central nervous system rhabdoid tumour re-enforces the aggressive nature of this disease with poor prognosis.

Does Putting Back Hyperostotic Bone Flap in Meningioma Surgery Cause Tumor Recurrence? An Observational Prospective Study.

BACKGROUND: Replacing the skull defect with synthetic materials for hyperostotic bone secondary to meningioma is recommended owing to the possibility of tumor invasion. In our institution, neurosurgeons have been putting back the refashioned hyperostotic bone flap after meningioma excision because of budget constraints. The aim of this study was to review the long-term meningioma recurrence rate in these patients. METHODS: This was a nonrandomized, prospective observational study conducted from September 2011 to January 2015 on patients with intracranial convexity and parasagittal meningiomas. Preoperative computed tomography brain scans were obtained in all patients to confirm bony hyperostosis. Intraoperatively, part of the hyperostotic bone was sent for histopathologic examination. The rest of the bone flap was refashioned by drilling off the hyperostotic part. The bone flap was put back over the craniotomy site after soaking in distilled water. All patients were followed up for tumor recurrence. RESULTS: The study included 34 patients with convexity or parasagittal meningioma World Health Organization grade I-II who underwent Simpson grade Ia and IIa excision. Median follow-up was 63.5 months (mean 64.9 ± 9.4 months). The hyperostotic bone flap showed presence of tumor in 35% of patients. There were 2 patients with parasagittal meningiomas after Simpson grade IIa resections who developed tumor recurrences. CONCLUSIONS: Our study found that meningioma recurrence was unlikely when autologous cranioplasty was done with refashioned hyperostotic bone. This could be done in the same setting with meningioma excision. There was no recurrence in convexity meningiomas at mean 5-year follow-up.

Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease.

BACKGROUND: Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases. RESULTS: Extending our recent findings of oscillating cytosine modifications (osc-modCs) in mice, in this study, we show that osc-modCs are also prevalent in human neutrophils. Osc-modCs may play a role in gene regulation, can explain parts of intra- and inter-individual epigenetic variation, and are signatures of aging. Finally, we show that osc-modCs are linked to three complex diseases and provide a new interpretation of cross-sectional epigenome-wide association studies. CONCLUSIONS: Our findings suggest that loss of balance between cytosine methylation and demethylation during the circadian cycle can be a potential mechanism for complex disease. Additional experiments, however, are required to investigate the possible involvement of confounding effects, such as hidden cellular heterogeneity. Circadian rhythmicity, one of the key adaptations of life forms on Earth, may contribute to frailty later in life.

Generation of regulable EGFRvIII targeted chimeric antigen receptor T cells for adoptive cell therapy of glioblastoma.

Adoptive immunotherapy using chimeric antigen receptors-modified T cells (CAR-T) is a promising approach for cancer treatment. However, CARs currently applied in the clinics cannot be effectively regulated and the safety of CAR-T cell therapies remains a major concern. To improve the safety of CAR-T cells, we designed a synthetic splitting CAR (ssCAR) that can regulate T cell functions exogenously. Epidermal growth factor receptor variant III (EGFRvIII) was used as a molecular target for ssCAR. Our results indicate that both EGFRvIII and small molecule are needed for the activation of the ssCAR-T cells. AP21967 dose-dependently increased the expression of T cell activation, production of cytokines and extent of cell lysis. In conclusion, the gene switch designed in this study allows for temporal and spatial control over engineered T cells in a dose-and time-dependent manner by AP21967. Our work demonstrates the feasibility and improved safety profile of this novel treatment approach.

Gravity-guided Stereotactic Brain Biopsy.

INTRODUCTION: This study describes a technique using gravity for guidance in stereotactic brain biopsy. This will be especially useful in hospitals where the stereotactic equipment is unavailable. OBJECTIVES: The aim of this study is to describe the technique, develop a formula to define its limits of accuracy, and report on its clinical application. METHODS: Using the positioning laser grid lines on the computed tomography scanner, a small metallic marker is placed on the scalp at the intended biopsy site. The distance between the tumor and the inner table of the bone is measured. In the operating theater, the patient is positioned such that the tip and the bridge of the nose are aligned in a horizontal position. The patient's two eyebrows or the orbital canthi are aligned in a vertical line. Simultaneously, the posterior borders of the two pinnae are aligned vertically. Gravity is used to guide the biopsy needle through the marked burr hole into the target. Seven patients had biopsies. One was for targeting the craniopharyngioma cyst to place an Ommaya catheter. The fraction of error or error fraction (EF), was developed for verification of its limits of accuracy. RESULTS: All the biopsies were diagnostic and the Ommaya catheter was correctly sited. The EFs at α = 5° were all predictive of the limits of accuracy of this technique. CONCLUSION: This is the first reported gravity-guided stereotactic brain surgery. The outcome in all the eight cases showed that it was within the limits of its accuracy. EF can be calculated to ensure accuracy. This technique is helpful if a commercial stereotactic system is not available.

T cell LFA-1-induced proinflammatory mRNA stabilization is mediated by the p38 pathway kinase MK2 in a process regulated by hnRNPs C, H1 and K.

Activation of the ß2 integrin lymphocyte function-associated antigen-1 (LFA-1) in T cells induces stabilization of proinflammatory AU-rich element (ARE)-bearing mRNAs, by triggering the nuclear-to-cytoplasmic translocation of the mRNA-binding and -stabilizing protein HuR. However, the mechanism by which LFA-1 engagement controls HuR localization is not known. Here, we identify and characterize four key regulators of LFA-1-induced changes in HuR activity: the p38 pathway kinase MK2 and the constitutive nuclear proteins hnRNPs C, H1 and K. LFA-1 engagement results in rapid, sequential activation of p38 and MK2. Post-LFA-1 activation, MK2 inducibly associates with both hnRNPC and HuR, resulting in the dissociation of HuR from hnRNPs C, H1 and K. Freed from the three hnRNPs, HuR translocates from the nucleus to the cytoplasm, and mediates the stabilization of labile cytokine transcripts. Our results suggest that the modulation of T cell cytokine mRNA half-life is an intricate process that is negatively regulated by hnRNPs C, H1 and K and requires MK2 as a critical activator.