Nickel-cadmium cells

A high energy density nickel cadmium cell of aerospace quality was designed. The approach used was to utilize manufacturing techniques which produce highly uniform and controlled starting materials in addition to improvements in the overall design. Parameters controlling the production of plaque and both positive and negative plate were studied. Quantities of these materials were produced and prototype cells were assembled to test the proposed design

The Evaluation of PMP22 and Protein 0, Examinations for Early Disability Detection in Leprosy Patients

Introduction: Leprosy is a chronic infectious disease caused by Mycobacterium leprae that has a predilection for peripheral nerves, especially Schwann cells. Leprosy medications may only eradicate the bacteria without preventing or recovering peripheral nerve damage. Previous studies proved that Krox-20 could be a useful diagnostic tool for early peripheral nerve damage detection in leprosy.nObjective: To analyse and to determine PMP22, and P0 cut-off points as diagnostic tools of early disability in leprosy. Methods: We examined ambulatory patients at Kediri Leprosy Hospital, Indonesia. We employed WHO’s criteria to assess the degree of disability and measured the study variables using ELISA. We then determine the cut-off value using Receiver Operating Characteristic curve. Results: From overall patients (n=79), 36 patients had 0-degree of disability, and 43 patients had 1-degree of disability. The ROC curve analysis revealed cut-off values for PMP22 and P0 at 4,42 pg/mL and 11,39 pg/mL, respectively. The mean value for all variables in patients with 0-degree of disability were higher than that in patients with 1-degree of disability at 12,56 pg/mL vs 4,24 pg/mL (p<0,05) and at 9,85 pg/mL vs 2,86 pg/mL, respectively (p<0,05). Conclusion: Leprosy is a chronic infectious disease that brings forth many degrees of disability secondary to peripheral nerve invasion, particularly Schwann cells. Hence, early detection of peripheral nerve damage becomes crucial. The evaluation of PMP22 and P0 examinations is useful to identify early peripheral nerve damage in leprosy

Hot spots policing of small geographic areas effects on crime

Background In recent years, crime scholars and practitioners have pointed to the potential benefits of focusing crime prevention efforts on crime places. A number of studies suggest that there is significant clustering of crime in small places, or “hot spots,” that generate half of all criminal events. Researchers have argued that many crime problems can be reduced more efficiently if police officers focused their attention to these deviant places. The appeal of focusing limited resources on a small number of high-activity crime places is straightforward. If crime can be prevented at these hot spots, then citywide crime totals could be reduced. Objectives To assess the effects of focused police crime prevention interventions at crime hot spots. The review also examined whether focused police actions at specific locations result in crime displacement (i.e., crime moving around the corner) or diffusion (i.e., crime reduction in surrounding areas) of crime control benefits. Search Methods A keyword search was performed on 15 abstract databases. Bibliographies of past narrative and empirical reviews of literature that examined the effectiveness of police crime control programs were reviewed and forward searches for works that cited seminal hot spots policing studies were performed. Bibliographies of past completed Campbell systematic reviews of police crime prevention efforts were reviewed and hand searches of leading journals in the field were completed. Experts in the field were consulted and relevant citations were obtained. Selection Criteria To be eligible for this review, interventions used to control crime hot spots were limited to police-led prevention efforts. Suitable police-led crime prevention efforts included traditional tactics such as directed patrol and heightened levels of traffic enforcement as well as alternative strategies such as aggressive disorder enforcement and problem-oriented policing. Studies that used randomized controlled experimental or quasiexperimental designs were selected. The units of analysis were limited to crime hot spots or high-activity crime “places” rather than larger areas such as neighborhoods. The control group in each study received routine levels of traditional police crime prevention tactics. Data Collection and Analysis Sixty-five studies containing 78 tests of hot spots policing interventions were identified and full narratives of these studies were reported. Twenty-seven of the selected studies used randomized experimental designs and 38 used quasiexperimental designs. A formal meta-analysis was conducted to determine the crime prevention effects in the eligible studies. Random effects models were used to calculate mean effect sizes. Results Sixty-two of 78 tests of hot spots policing interventions reported noteworthy crime and disorder reductions. The meta-analysis of key reported outcome measures revealed a small statistically significant mean effect size favoring the effects of hot spots policing in reducing crime outcomes at treatment places relative to control places. The effect was smaller for randomized designs but still statistically significant and positive. When displacement and diffusion effects were measured, a diffusion of crime prevention benefits was associated with hot spots policing. Authors\u27 Conclusions The extant evaluation research suggests that hot spots policing is an effective crime prevention strategy. The research also suggests that focusing police efforts on high-activity crime places does not inevitably lead to crime displacement; rather, crime control benefits may diffuse into the areas immediately surrounding the targeted locations

The Evaluation of PMP22 and Protein 0, Examinations for Early Disability Detection in Leprosy Patients

Introduction: Leprosy is a chronic infectious disease caused by Mycobacterium leprae that has a predilection for peripheral nerves, especially Schwann cells. Leprosy medications may only eradicate the bacteria without preventing or recovering peripheral nerve damage. Previous studies proved that Krox-20 could be a useful diagnostic tool for early peripheral nerve damage detection in leprosy.nObjective: To analyse and to determine PMP22, and P0 cut-off points as diagnostic tools of early disability in leprosy. Methods: We examined ambulatory patients at Kediri Leprosy Hospital, Indonesia. We employed WHO’s criteria to assess the degree of disability and measured the study variables using ELISA. We then determine the cut-off value using Receiver Operating Characteristic curve. Results: From overall patients (n=79), 36 patients had 0-degree of disability, and 43 patients had 1-degree of disability. The ROC curve analysis revealed cut-off values for PMP22 and P0 at 4,42 pg/mL and 11,39 pg/mL, respectively. The mean value for all variables in patients with 0-degree of disability were higher than that in patients with 1-degree of disability at 12,56 pg/mL vs 4,24 pg/mL (p<0,05) and at 9,85 pg/mL vs 2,86 pg/mL, respectively (p<0,05). Conclusion: Leprosy is a chronic infectious disease that brings forth many degrees of disability secondary to peripheral nerve invasion, particularly Schwann cells. Hence, early detection of peripheral nerve damage becomes crucial. The evaluation of PMP22 and P0 examinations is useful to identify early peripheral nerve damage in leprosy

Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism

BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. RESULTS: 17β-Estradiol (17β-E(2)), but not 17α-estradiol (17α-E(2)), was protective against this combined neurotoxicity. Progesterone (PROG) afforded limited neuroprotection, as did dihydrotestosterone (DHT). The efficacy of 5α-testosterone (T)-mediated neuroprotection was robust, similar to that provided by 17β-E(2. )In the presence of the specific estrogen receptor (ER) antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. CONCLUSION: Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists

Teleneurology service provided via tablet technology: 3-year outcomes and physician satisfaction

© James Cook University. Introduction: This study aimed to demonstrate that teleneurology consultations conducted via tablet technology are an efficient and cost-effective means of managing acute neurologic emergencies at community-based hospitals and that utilizing such technology yields high community physician satisfaction. Method: During a 39-month period, Vanderbilt University Medical Center in Tennessee USA, provided teleneurology services to 10 community-based hospitals that lacked adequate neurology coverage. Hospitalists at one community-based hospital were not comfortable treating any patient with a neurologic symptom, resulting in 100% of those patients being transferred. This facility now retains more than 60% of neurology patients. For less than US$1200, these hospitals were able to meet the only capital expenditure required to launch this service: the purchase of handheld tablet computers. Real-time teleneurology consultations were conducted via tablet using two-way video conferencing, radiologic image sharing, and medical record documentation. Community physicians were regularly surveyed to assess satisfaction. Results: From February 2014 to May 2017, 3626 teleneurology consultations were conducted. Community physicians, in partnership with neurologists, successfully managed 87% of patients at the community-based hospital. Only 13% of patients required transfer to another facility for a higher level of care. The most common diagnoses included stroke (34%), seizure (11%), and headache/migraine (6%). The average time for the neurologist to answer a request for consultation page and connect with the community physician was 10.6 minutes. Ninety-one percent of community physicians were satisfied or somewhat satisfied with the overall service. Conclusion: In the assessment of neurology patients, tablets are a more cost-effective alternative to traditional telehealth technologies. The devices promote efficiency in consultations through ease of use and low transfer rates, and survey results indicate community physician satisfaction

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. CONCLUSION: Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions

Dopamine Neuron Stimulating Actions of a GDNF Propeptide

BACKGROUND: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed. METHODS AND FINDINGS: Here we present the neurobiological actions of dopamine neuron stimulating peptide-11 (DNSP-11), an 11-mer peptide from the proGDNF domain. In vitro, DNSP-11 supports the survival of fetal mesencephalic neurons, increasing both the number of surviving cells and neuritic outgrowth. In MN9D cells, DNSP-11 protects against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-induced cell death, significantly decreasing TUNEL-positive cells and levels of caspase-3 activity. In vivo, a single injection of DNSP-11 into the normal adult rat substantia nigra is taken up rapidly into neurons and increases resting levels of dopamine and its metabolites for up to 28 days. Of particular note, DNSP-11 significantly improves apomorphine-induced rotational behavior, and increases dopamine and dopamine metabolite tissue levels in the substantia nigra in a rat model of PD. Unlike GDNF, DNSP-11 was found to block staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing the release of cytochrome c from mitochondria. CONCLUSIONS: Collectively, these data support that DNSP-11 exhibits potent neurotrophic actions analogous to GDNF, making it a viable candidate for a PD therapeutic. However, it likely signals through pathways that do not directly involve the GFRalpha1 receptor

Ibudilast, a Pharmacologic Phosphodiesterase Inhibitor, Prevents Human Immunodeficiency Virus-1 Tat-Mediated Activation of Microglial Cells

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorders (HAND) occur, in part, due to the inflammatory response to viral proteins, such as the HIV-1 transactivator of transcription (Tat), in the central nervous system (CNS). Given the need for novel adjunctive therapies for HAND, we hypothesized that ibudilast would inhibit Tat-induced excess production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) in microglial cells. Ibudilast is a non-selective cyclic AMP phosphodiesterase inhibitor that has recently shown promise as a treatment for neuropathic pain via its ability to attenuate glial cell activation. Accordingly, here we demonstrate that pre-treatment of both human and mouse microglial cells with increasing doses of ibudilast inhibited Tat-induced synthesis of TNFα by microglial cells in a manner dependent on serine/threonine protein phosphatase activity. Ibudilast had no effect on Tat-induced p38 MAP kinase activation, and blockade of adenosine A2A receptor activation did not reverse ibudilast's inhibition of Tat-induced TNFα production. Interestingly, ibudilast reduced Tat-mediated transcription of TNFα, via modulation of nuclear factor-kappa B (NF-κB) signaling, as shown by transcriptional activity of NF-κB and analysis of inhibitor of kappa B alpha (IκBα) stability. Together, our findings shed light on the mechanism of ibudilast's inhibition of Tat-induced TNFα production in microglial cells and may implicate ibudilast as a potential novel adjunctive therapy for the management of HAND

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data

Background/Aims: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. Methods: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ϵ4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. Results: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). Conclusion: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool