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Objective: This was a prospective and randomized study to compare the use of Human Patient Simulator (HPS) and conventional didactic teaching in enhancing medical undergraduates, understanding of crisis recognition and resuscitation. Methods: Following Research and Ethics Committee approval, 80 final year medical students were enrolled. The students were computer-randomized into two groups: - Group A for conventional teaching and Group B for Human Patient Simulator training. All the students were trained separately on four topics, i.e. tachycardia, asystole, ventricular fibrillation and heart block; 30 minutes for each topic. A 2-hour common lecture on all the topics was given prior to training. All trainings were conducted on one day. After a washout period of two days, the students were given a 75 minutes written test on crisis recognition and resuscitation. Results: The results were analyzed using SPSS version 14. Of the 80 students enrolled, 77 students followed the whole process of training. Group B with the Human Patient Simulator training (n = 37) achieved higher average mark compared to Group A with conventional training (n = 40), i.e. 70.22% vs 65.98%. This result was statistically significant (p < 0.05). However, there was no significant difference between the two groups' achievement when their results, which comprised of two components, crisis recognition and resuscitation, were analyzed separately. Conclusion: In conclusion, HPS was able to enhance the understanding of medical students in terms of crisis recognition and resuscitation. However, more researches are needed to further reveal its potential. [ABSTRACT FROM AUTHOR]

Individuals with Parkinson's disease (PD) exhibit a variety of impairments in nonmotor symptoms including emotional processing and cognitive control that have implications for speech production. The present study sought to investigate whether impairments in cognitive processing in individuals with PD impact emotional sentence production as indicated by changes in speech rate. Thirty-six individuals (20 individuals with PD, 16 healthy controls) completed subtests 8A and 8B of the Florida Emotional Expressive Battery (FEEB) to elicit speech samples in five different emotional tones (happy, sad, angry, fear, and neutral). Sentences contained either semantically emotional or neutral information, resulting in conditions of congruency (same semantics-tone) and incongruency (different semantics-tone). Speech rate was impacted by the emotional tone of all participants. Individuals with PD demonstrated faster speech rates under conditions of conflicting semantic information than healthy older adults. Changes in speech rate under emotional conditions were not influenced by global measures of cognition or depression. The results of this study indicate that individuals with PD struggle to manage irrelevant information present during emotional speech production. Speech rate is a simple, easy-to-measure metric that may reflect cognitive processing impairments in PD., Competing Interests: None declared., (Thieme. All rights reserved.)

The Nurse Professional Development Model (NPD) has been utilized to improve quality of care for several conditions. Patients with Parkinson's Disease (PD) are susceptible to higher risks while in the hospital. Educational efforts for this patient population are challenged by the small, disbursed number of patients as well as increased turn-over and reliance on temporary nursing staff. To properly care for this patient group, any education has to be hospital wide and ongoing for maintenance of competency. We have used the NPD Model to initiate education for new incoming nurses as well as for continued education for a program that requires hospital-wide reach. Our utilization of the NPD Model for this high risk, low volume patient population has helped us improve the safety of this patient population in the hospital. With this manuscript we detail the need and the educational platform with the hope of it serving as a reference for other institutions facing similar challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bobek, Pascarelli, Cocoziello and Azmi.)

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson's disease (PWP). For example, EHR systems can help identify Parkinson's disease (PD) patients across the hospital by flagging a patient's diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems. In 2020, the Parkinson's Foundation, a national and international leader in PD research, education, and advocacy, and Epic, a leading EHR vendor with more than 35% market share in the United States, launched a partnership to reduce risks to hospitalized PWP using standardized EHR-based solutions. This article discusses that project which included leadership from physician informaticists, movement disorders specialists, hospital quality officers, the Parkinson's Foundation and members of the Parkinson's community. We describe the best practice solutions developed through this project. We highlight those that are currently available as standard defaults or options within the Epic EHR, discuss the successes and limitations of these solutions, and consider opportunities for scalability in environments beyond a single EHR vendor. The Parkinson's Foundation and Epic launched a partnership to develop best practice solutions in the Epic EHR system to improve safety for PWP in the hospital. The goal of the partnership was to create the EHR tools that will have the greatest impact on outcomes for hospitalized PWP., Competing Interests: AW is a volunteer member of the Epic Neuroscience Specialty Steering Board. BW serves as Section Head of Movement Disorders at the Cleveland Clinic. Over the years, he has received research grants from the NIH and Parkinson’s Foundation. He has served as site investigator and/or co-investigator for clinical research studies sponsored by grants from Industry to Cleveland Clinic. Currently, he is the site PI for Neuroderm (Mitsubishi Tanabe Pharma), Discern (Great Lakes Neurotech/NIH R44), Tempo 2, and Tempo 3 studies (Cerevel Therapeutics) and a grant from the Parkinson’s Foundation to improve the inpatient care of People with PD. He has served as a consultant or speaker for Medtronic, Boston Scientific, and Abbott. AB Director of Strategic Initiatives, Parkinson’s Foundation EB Associate Director of Strategic Initiatives, Parkinson’s Foundation. KA was supported by the Michael J Fox Edmund J. Safra Fellowship in Movement Disorders from July 2017–July 2019. She previously served as Investigator and/or medical monitor for clinical trials supported by Aptinyx Inc. Genentech Roche Ltd., EIP Pharma Inc., Michael J Fox foundation for PD research, NINDS, and Acadia Pharmaceuticals Inc., and Biogene. She previously served as Co-I of a Lewy Body Dementia Association Research Center of Excellence site. The work presented here was supported by a Parkinson Foundation Community Grant (awarded to IR). IR serves as Director of the University of Rochester Parkinson’s Foundation Center of Excellence and her contributions to this article were supported by a Parkinson’s Foundation Community Grant, Parkinson’s Disease Hospital Optimization Project (PD-HOP) for which she served as PI. IR has received research and/or training grants from NIH, Parkinson’s Foundation and the Michael J. Fox Foundation. IR has served as a site investigator and/or co-investigator for clinical research studies sponsored by grants from Industry to the University of Rochester, currently including F. Hoffmann-La Roche Ltd., Acadia Pharm, and Jazz Pharmaceuticals. KM is an employee of Epic, a health IT software company which licenses electronic health record software and provides related services to health care organizations that pay Epic for such software and services. She and Epic have no financial disclosures or conflicts of interest related to this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wu, Walter, Brooks, Buetow, Amodeo, Richard, Mundth and Azmi.)

Background: Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital., Material and Methods: We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed., Results: 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group ( p <.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p <0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time ( p <0.001 for all comparisons)., Conclusion: This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications., Competing Interests: JMP is employed and hold equity in Superior Medical Experts, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Azmi, Cocoziello, Ruzicka, Clar, Pederson, Jacob, Thomas, Rocco, Bobek, Pereira-Argenziano, Roth and Thomas.)

Vitamin D deficiency is a hot topic as it affects about 50% of the world's population. Beyond its extra-osseous effects, notably on the cardiovascular system. In recent years many epidemiological studies have looked at the role of vitamin D status in modulating blood pressure. It appears that there is an inverse association between serum vitamin D levels and blood pressure. It is in this context that our prospective study on the Moroccan population allows having global knowledge of the association between vitamin D and arterial hypertension. This is a descriptive study of vitamin D status in Moroccan hypertensive patients in whom blood samples were taken for serum 25(OH)D determination. The data collected were anonymised and entered into SPSS software. X2 and ANOVA tests were used to investigate the existence of correlations between vitamin D status and age, age at menopause, body mass index, sex and hypertension.  1015 hypertensive patients were included in this study with a female predominance of 84.2%, mainly over 50 years old in 80.8%, of whom 31.5% were overweight or obese, 13.2% had a hypertensive parent and 70.8% had vitamin D deficiency. Vitamin D regulates at least 3% of the human genome with receptors throughout the body, including vascular smooth muscle cells, vascular endothelium and cardiomyocytes, where it acts by vasodilation and by blocking the renin-angiotensin-aldosterone system (RAAS) to lower blood pressure. There is a relationship between low serum vitamin D levels and high blood pressure. Our study concluded that there is an association between hypovitaminosis D and the pathology of hypertension. However, further randomised studies are needed and in the meantime, clinicians could propose it in the therapeutic arsenal of Moroccan hypertensive patients.

The major roles of vitamin D in the genesis of breast cancer and as an immunomodulator against acute and chronic infections have been the subject of much research in recent years. A low vitamin D status could decrease the function of blocking the cell multiplication cycle of the cancer process and weaken the immune system. In this context, we were interested in the implication of vitamin D status in women with human papilloma virus (HPV)-induced breast cancer. Our study included 63 women, 53 with breast cancer and 10 healthy women, and we measured the plasma 25(OH)D3 level and looked for the presence of HPV by PCR in our population. 90.6% had low serum 25(OH)D3 levels and HPV was found in 41% of cases. In this regard, the data in the literature are discordant. Vitamin D status could explain the concomitance of the two conditions, breast cancer and HPV; it would be desirable to broaden the sample in order to better define its impact.

This paper introduces a novel robust adaptive fault detection and diagnosis (FDD) observer design approach for a class of nonlinear systems with parametric uncertainty, unknown system fault and time-varying internal delays. The conditions for the existence of the proposed FDD are obtained based on the well-known Linear Matrix Inequalities (LMI) technique. Using Lyapunov stability theory, the adaptation laws for updating the observer weights and unknown faults estimation are derived based on which the convergence of the state estimation error to zero and asymptotic stability of the error dynamics are proven. Toward this, a new structural algorithm for FDD observer design is also derived based on LMIs. The performance of the proposed method is also investigated while applying to some industrial systems. Simulation results illustrate superior performance of the proposed method for the systems subject to time-varying unknown delays on states, uncertainty in nonlinear system modeling and unknown system faults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction There has been a recent increase in the number of spinal procedures that can be performed in ambulatory surgical centers (ASCs). Studies have found that patients who undergo procedures at ASCs tend to have lower complication rates following procedures, including lower infection rates. Furthermore, ASCs offer significantly lower costs of procedures to patients and health insurance companies as compared to the costs of procedures performed in a hospital. Despite precautions and screening in place by ASCs, patients may be hesitant to undergo procedures outside of the hospital. Conversely, the ongoing COVID-19 pandemic has created hesitancy for many to go to the hospital for care due to the presence of COVID patients.  Objective To assess patient preferences in the location of elective spine procedures between ASCs and hospitals, the authors conducted a survey of spine surgery candidates in a single practice. Methods A survey measuring patient age, vaccination status, fear of contracting COVID-19, and preference of surgery location was given to spinal surgery candidates at a single practice between fall 2021 and winter 2022. Statistical differences between the means of response groups were measured by a two-sample Z-score test. Results A total of 58 surveys were completed by patients. No difference in preference was observed by age. A difference was observed between genders, with 66% of females preferring ASCs to 40% of males (α=0.03). Patients with a fear of contracting COVID-19 preferred to have their procedure performed in an ASC. No difference was observed in location due to vaccination status, but unvaccinated patients had a significantly lower fear of contracting COVID-19 (α=0.02). Conclusion The differences in patient preferences have no clear cause, highlighting the need for better patient education in regard to the risks and benefits of each location of surgery. The fear of contracting COVID-19 on the day of surgery appears to be more ideological than rational for unvaccinated patients, who had less fear of contracting COVID-19 than vaccinated patients, despite being more likely to contract COVID-19 than vaccinated patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Cassimatis et al.)

Alzheimer's disease (AD) and other forms of dementia can have a large impact on patients, their families, and for the society as a whole. Current medical treatments have not shown enough potential in treating or altering the course of the disease. Deep brain stimulation (DBS) has shown great neuromodulatory potential in Parkinson's disease, and there is a growing body of evidence for justifying its use in cognitive disorders. At the same time there is mounting interest at less invasive and alternative modes of neuromodulation for the treatment of AD. This manuscript is a brief review of the infrastructure of memory, the current understanding of the pathophysiology of AD, and the body of preclinical and clinical evidence for noninvasive and invasive neuromodulation modalities for the treatment of cognitive disorders and AD in particular., Competing Interests: None

Background: Patients with Parkinson's Disease (PD) are at higher risk of complications when admitted to the hospital. Delays in PD medications and use of contraindicated medications contribute to the increased risk and prolong their lengths of stay (LOS). Using a hospital-wide PD protocol, we aimed to ensure PD medications were placed with "custom" timing to resemble the home schedules, and also to avoid ordering or administering contraindicated medications., Material and Methods: 569 patients admitted in 2017 and 2018, were reviewed retrospectively. Mean age was 76.5 (SD 10.6), 332 were males and 237 were females. Charts were reviewed to assess if A) PD medications were ordered with custom timing, B) if not, were the orders changed to custom timed C) if contraindicated medications were ordered, and D) if they were administered. We also assessed the actual/expected length of stay during this time period. Chi Square and post hoc analyses were done to compare time points. Poisson regression analysis was done to assess relative improvement of variables., Results: There was a 2.7 fold increase in orders placed with custom timing in 2018 compared to 2017 (RR = 2.651, 95%CI: 1.860-3.780, p < 0.0001), and a 3.2 fold increase in correction of non-custom orders in the same time period (RR = 3.246, 95%CI: 1.875-1.619, p < 0.0001). We also observed a decrease in the actual/expected LOS ratio from 1.54  to 1.32  (p < 0.05)., Conclusion: By utilizing an established platform for quality improvement, we were able to improve adherence to the home medication regimen timing in admitted PD patients. Our findings also suggests that adherence to a strict medication regimen protocol may decrease LOS for this patient population., Competing Interests: None., (© 2020 The Author(s).)

Background: Patients with Parkinson disease (PD) admitted to the hospital for any reason are at a higher risk of hospital-related complications. Frequent causes include delays in administering PD medications or use of contraindicated medications. The Joint Commission Disease-Specific Care (DSC) program has been used to establish a systematic approach to the care of specific inpatient populations. Once obtained, this certification demonstrates a commitment to patient care and safety, which is transparent to the public and can improve quality of care., Methods: We formalized our efforts to improve the care of hospitalized patients with PD by pursuing Joint Commission DSC. An interprofessional team was assembled to include nurses, therapists, physicians, pharmacists, performance improvement specialists, and data analysts. The team identified quality metrics based on clinical guidelines. In addition, a large educational campaign was undertaken. Application to the Joint Commission for DSC resulted in a successful June 15, 2018 site visit. To our knowledge, this is the first DSC program in PD in an acute care hospital., Conclusion: Using the established platform of DSC certification from the Joint Commission, we developed a program based on relevant metrics that aims to address medication management of patients with PD admitted to the hospital. Our hope is to improve the care of this vulnerable patient population.

Background: Intraoperative magnetic resonance imaging (ioMRI) has led to significant advancements in neurosurgery with improved accuracy, assessment of the extent of resection, less invasive surgical alternatives, and real-time confirmation of targeting as well delivery of therapies. The costs associated with developing ioMRI units in the surgical suite have been obstacles to the expansion of their use. More recently, the development of hybrid interventional MRI (iMRI) units has become a viable alternative. The process of designing, developing, and implementing operations for these units requires the careful integration of environmental, technical, and safety elements of both surgical and MR practices. There is a paucity of published literature providing guidance for institutions looking to develop a hybrid iMRI unit, especially with a limited footprint in the radiology department., Methods: The experience of designing, developing, and implementing an iMRI in a preexisting space for neurosurgical procedures at a single institution in light of available options and the literature is described., Results: The development of the unit was accomplished through the engagement of a multidisciplinary team of stakeholders who utilized existing guidelines and recommendations and their own professional experience to address issues including physical layout, equipment selection, operations planning, infection control, and oversight/review, among others., Conclusion: Successful creation of an iMRI program requires multidisciplinary collaboration in integrating surgical and MR practice. The authors' aim is that the experience described in this article will serve as an example for facilities or neurosurgical departments looking to navigate the same process., Competing Interests: The corresponding author has a consulting agreement with Medtronic Inc and Abbott Scientific. All of the other authors certify that they have no conflicts of interest.

Background: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers., Methods: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration., Results: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003)., Conclusion: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial., Level of Evidence: Therapeutic/care management, level III.

Background: Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented., Methods: DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison., Results: For the iMRI-guided patients, mean "Off" UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative "On" medication, "On" stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3)., Conclusion: iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

Objective: We examine the effect of intracranial air on stereotactic accuracy during bilateral deep brain stimulation (DBS) surgery for Parkinson's disease (PD). We also assess factors that may predict an increased risk of intracranial air during these surgeries., Methods: 32 patients with PD underwent bilateral DBS surgery. The technique used for implantation of the leads has been standardized in over 800 subthalamic nucleus (STN) implantations. For lead implantation, the goal of the neurophysiological technique is identification of the STN and its borders with 3 microelectrode recording (MER) tracks. We examined the number of tracks and the degree of deviation from the planned target on each side. Total intracranial air (TIA) was then compared in these groups. We also examined the relationship between the TIA and length of surgery, ventricular volume and the degree of atrophy., Results: Side 2 in this series required more MER tracks. The TIA was larger in patients with more than 3 MER tracks on side 2 of surgery. There was more deviation from the target on side 2. In addition, the TIA in patients with >1 mm of vector deviation on side 2 was more than in those without. The TIA correlated with the number of tracks on side 2 as well as with the degree of the second euclidean deviation on side 2. There was a correlation of degree of atrophy with TIA., Conclusion: In bilateral STN DBS for PD, intracranial air may contribute to error in stereotactic accuracy especially on the second side. In addition, there is a correlation between the accumulated volume of intracranial air and the degree of cerebral atrophy., (Copyright © 2011 S. Karger AG, Basel.)

Movement disorders, such as Parkinson's disease, tremor, and dystonia, are among the most common neurological conditions and affect millions of patients. Although medications are the mainstay of therapy for movement disorders, neurosurgery has played an important role in their management for the past 50 years. Surgery is now a viable and safe option for patients with medically intractable Parkinson's disease, essential tremor, and dystonia. In this article, we provide a review of the history, neurocircuitry, indication, technical aspects, outcomes, complications, and emerging neurosurgical approaches for the treatment of movement disorders.

Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species.

Objective: We previously demonstrated the capability to obtain functional magnetic resonance imaging (MRI) scans of the motor cortex in healthy volunteers using a low-field mobile operating room-based MRI scanner with 0.12-T field strength. Using an expanded (0.15-T), but still mobile, version of this system, our goal was to acquire data showing activation of other areas of functionally important cortex., Methods: Five healthy volunteers were scanned with the low-field scanner using finger tapping, hand touch, silent word generation, text listening, and visual stimulation paradigms. The data was analyzed offline using publicly available software. For comparison, the volunteers were then scanned with a 3-T diagnostic MRI scanner., Results: Significant cortical activation was demonstrated on 16 out of 22 images obtained on the operating room-based scanner. Motor activation was most robust, followed by silent word generation, text listening, and hand touch paradigms. The correlation coefficients compared favorably with the images obtained on the 3-T scanner. The signal changes were higher for images obtained with the low-field, mobile scanner compared with those performed with the 3-T diagnostic MRI scanner., Conclusion: Functional MRI scans of multiple cortical areas can be acquired with a low-field strength magnet designed for intraoperative imaging. Further refinement of this technique may allow for the acquisition of true intraoperative functional MRI scans immediately, before, and even during cranial surgery in select patients.

A possible outbreak of beriberi occurred at a drug detention and rehabilitation centre, Pusat Serenti Bukit Cabang, Perlis, Malaysia in February 2004. This outbreak was identified following the presentation of a large number of inmates at a health centre with signs and symptoms of ankle oedema and shortness of breath. Further investigations revealed the death of three inmates at the General Hospital with similar clinical presentations during the period from October 2003 till February 2004. A cross sectional comparative study was carried out at the rehabilitation centre to find out the prevalence of thiamine deficiency among the inmates both symptomatic and asymptomatic. A total of 154 inmates were examined (57 symptomatic and 97 asymptomatic cases). It was found that 74% from the sample study (114 cases) had thiamine deficiency (44 symptomatic and 70 asymptomatic). Further statistical analysis showed that ankle oedema is consistent with the diagnosis of thiamine deficiency but lack sensitivity (p < 0.05, sensitivity 24.6%, specificity 95%). This outbreak could have been triggered by poor diet intake of thiamine by the inmates coupled with possible intake of certain thiamine antagonists in their diet.

Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity using tetrodotoxin (TTX) and voltage-gated Ca(2+) channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca(2+) in astrocytes. Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling. Our results show an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.

Study Design: This retrospective study involves 26 patients with degenerative cervical myelopathy who were surgically treated by anterior corpectomy, titanium mesh cage (TMC) filled with autogenous bone, and anterior plate +/- posterolateral plate and fusion., Objectives: This study was conducted to determine the indications, efficacy, and complication rate associated with performing corpectomy to achieve anterior decompression of neural elements or for removing anterior lesions., Summary of Background Data: This retrospective study involves patients with degenerative cervical myelopathy who were surgically treated by > or =2-level anterior corpectomy, TMC filled with autogenous bone, and anterior plate +/- posterolateral plate and fusion. The purpose was to evaluate and compare the results in terms of neurologic recovery and function and effectivity of TMC as a structural support., Methods: Twenty-six patients with degenerative cervical myelopathy who had surgical treatment and average 30 months (range, 24-52 months) follow up were included. The mean age was 64.9 years (range, 55-74 years) and average period between myelopathic symptoms and surgery was 2.8 years (range, 6 months-5 years). Preoperative evaluation of every patient consisted of anterior-posterior, lateral, bilateral oblique, flexion, and extension radiographs, computed tomography reconstructions and magnetic resonance imaging of the cervical spine, Doppler ultrasound of the carotid arteries, vertebral artery magnetic resonance angiography, neurologic examination, and electromyography. Degree of pre- and postoperative myelopathy was determined according to the scoring systems developed by Nurick and Japanese Orthopedic Association (JOA). Twelve patients had a mild balance problem and difficulty while walking but were able to perform their daily activities. Fourteen patients had spastic quadriparesis ambulating on either crutches or with wheelchairs. Of these, 11 experienced bladder disturbance as well. Surgical treatment in 18 patients consisted of anterior decompressive corpectomy, structural TMC, and anterior plate stabilization in 14 patients who had 2-level corpectomy. Posterior plate stabilization without laminectomy was added to this procedure in another 4 patients who had 3- or more level corpectomy. The remaining 8 patients had first laminectomy and posterolateral plate, then anterior corpectomy, TMC, and anterior plate on the same stage. Corpectomy levels were between C3 and T1, and anterior corpectomy, structural TMC, and anterior plating was the procedure that all patients had in common., Results: Mean sagittal Cobb angle (C2-C7) was 9 degrees (range, 0-23 degrees) before surgery, 17.1 degrees (range, 11-22 degrees) on the third postoperative month, and 16.9 degrees (range, 10-22 degrees) at last follow-up. The difference in sagittal alignment on the third month and last follow up was not statistically significant (P > 0.05). Average preoperative Nurick score was 3.5 (range, 2-5) and JOA score was 7 (range, 1-14). Major and statistically significant neurologic recovery was within the first 3 months, and average Nurick and JOA scores at 3 months were 2 (range, 0-3) and 11 (range, 8-17) (P < 0.001), respectively. All patients had improved neurologic status at final follow up. As confirmed by plain radiographs and computed tomography reconstructions, solid fusion was achieved across the TMC with no settling or migration, and we had no implant-related complication or failure. As major complications, 1 (3.8%) early deep posterior infection developed but responded to early debridement and antibiotics. Also, 3 patients (11.5%) had transient C5 nerve root injury. At final follow up, all patients were able to ambulate without support and maintain their daily activities., Conclusions: Anterior decompression provides good neurologic recovery in patients with degenerative cervical myelopathy. TMC provides good structural support, and solid fusion can be achieved with TMC and anterior plate (for < or =2-level corpectomy) and/or posterior plate (> or =3-level corpectomy). There is increased risk of C5 nerve root injury when first laminectomy and posterolateral plate stabilization are performed.

The interleukin-2 mRNA is a labile transcript containing AU-rich elements that is transiently stabilized by CD28 receptor signaling. For a number of proto-oncogenes and cytokines, the HuR protein has been shown to avidly bind the AU-rich elements that confer instability upon their mRNAs. HuR was originally thought to participate in mRNA degradation but subsequent studies indicated that it actually functions to stabilize mRNA. Binding of HuR to the mouse interleukin-2 mRNA has not been studied. We tested if HuR binds the interleukin-2 mRNA and whether such binding is related to CD28-mediated stabilization of the mRNA. First, we confirm that T cell receptor signaling, which is sufficient to induce interleukin-2 transcription, also triggers translocation of HuR from the nucleus to the cytoplasm. Interestingly, T cell receptor-triggered translocation is selective as heterogeneous nuclear ribonucleoprotein A1 does not shuttle under the same conditions. Engagement of both the T cell and CD28 receptors, which enhance interleukin-2 transcription and induce stabilization of the mRNA, did not further increase the level of cytoplasmic HuR. Using an in vitro binding assay, we demonstrate that HuR binds the interleukin-2 mRNA and localize binding to a sequence downstream of the single nonameric AU-rich element that is present in its 3'-untranslated region. However, we conclude that HuR binding to the interleukin-2 mRNA, both in vitro and in vivo, is not associated with alterations in mRNA stability.

Anterior cervical decompression and fusion has gained popularity because of its applicability to a variety of cervical spine disorders. The authors of long-term follow-up studies have demonstrated the development of degenerative changes in segments adjacent to fusion. So-called adjacent-segment disease causes symptomatic deterioration in up to 25% of the patients who have undergone anterior cervical decompression and fusion for cervical spondylotic myelopathy. The causes of this condition are debated in the literature. The authors provide a review of the available literature on the pathogenesis, prevention, and treatment of postarthrodesis adjacent-segment degenerative disease.

Background: Functional magnetic resonance imaging (fMRI) has been used for preoperative planning and intraoperative surgical navigation. However, most experience to date has been with preoperative images acquired on high-field echoplanar MRI units. We explored the feasibility of acquiring fMRI of the motor cortex with a dedicated low-field intraoperative MRI (iMRI)., Methods: Five healthy volunteers were scanned with the 0.12-tesla PoleStar N-10 iMRI (Odin Medical Technologies, Israel). A finger-tapping motor paradigm was performed with sequential scans, acquired alternately at rest and during activity. In addition, scans were obtained during breath holding alternating with normal breathing. The same paradigms were repeated using a 3-tesla MRI (Siemens Corp., Allandale, N.J., USA). Statistical analysis was performed offline using cross-correlation and cluster techniques. Data were resampled using the 'jackknife' process. The location, number of activated voxels and degrees of statistical significance between the two scanners were compared., Results: With both the 0.12- and 3-tesla imagers, motor cortex activation was seen in all subjects to a significance of p < 0.02 or greater. No clustered pixels were seen outside the sensorimotor cortex. The resampled correlation coefficients were normally distributed, with a mean of 0.56 for both the 0.12- and 3-tesla scanners (standard deviations 0.11 and 0.08, respectively). The breath holding paradigm confirmed that the expected diffuse activation was seen on 0.12- and 3-tesla scans., Conclusions: Accurate fMRI with a low-field iMRI is feasible. Such data could be acquired immediately before or even during surgery. This would increase the utility of iMRI and allow for updated intraoperative functional imaging, free of the limitations of brain shift., (Copyright 2003 S. Karger AG, Basel)

Recently, magnetic resonance imagers (MRIs) with 3-tesla magnets were approved for clinical use. The spatial accuracy of these high-resolution scanners has yet to be proven. In the present study, a computed tomography (CT)- and MRI-compatible phantom was scanned on a CT, a 1.5-tesla MRI and a 3-tesla MRI scanner. The model was registered to the images using an infrared-based surgical navigation system. The distance between the predicted position of the navigation probe tip and the actual target on the image was measured on the x, y and z axes for 13 points on each image. Error was compared across imaging modalities, peripheral versus central targets and along each axis. We found that 3-tesla MRI scans are accurate as stereotactic data sets., (Copyright 2003 S. Karger AG, Basel)

A demographic and obstetric profile of pregnant mothers attending antenatal clinics in kelantan over period of one year was determined by a retrospective study of 10,032 registered pregnant mothers. The prevalence of risk factors related to the age of the mother, parity, weight, haemoglobin level, bad obstetric history and pregnancy related diseases were determined. Prevalence of teenage pregnancy and primigravida accounted for 4.3 and 17.2 percent respectively. Nearly 3.9 percent of the mothers weighed less than 40 kg and 44.5 percent of mothers were found to be anaemic (Hb less than 11g/d) at the first antenatal visit. Only 3.2 percent of the mothers did not have any designated risk factor. Previous bad obstetric history and pregnancy related disease accounted for 17.1 and 3.5 percent of mothers respectively.