Validity of Accelerometer-Based Sensor System for Muscle Tightness Estimation through Vibration on the Upper Limb.

Spasticity is a condition that profoundly impacts the ability to perform everyday tasks. However, its diagnosis requires trained physicians and subjective evaluations that may vary depending on the evaluator. Focal vibration of spastic muscles has been proposed as a non-invasive, pain-free alternative for spasticity modulation. We propose a system to estimate muscular tightness based on the propagation of elastic waves in the skin generated by focal vibration of the upper limb. The developed system generates focalized displacements on the biceps muscle at frequencies from 50 to 200 Hz, measures the vibration acceleration on the vibration source (input) and the distant location (output), and extracts features of ratios between input and output. The system was tested on 5 healthy volunteers while lifting 1.25 - 11.25 kg weights to increase muscle tone resembling spastic conditions, where the vibration frequency and weight were selected as explanatory variables. An increase in the ratio of the root mean squares proportional to the weight was found, validating the feasibility of the current approach to estimating muscle tightness.Clinical Relevance- This work presents the feasibility of a vibration-based system as an alternative method to objectively diagnose the degree of spasticity.

Imidacloprid Induces Histopathological Damage in the Midgut, Ovary, and Spermathecal Stored Spermatozoa of Queens After Chronic Colony Exposure.

Bee colony health is declining as a result of several factors, including exposure to pesticides. The development and strength of honey bee colonies depend on the reproductive success of queen bees. Because flowers are sources of food for bees, foragers can accidentally collect and carry contaminated pollen and nectar to their hives; and this may compromise the longevity and the life span of individuals. Thus, the present study aimed to observe the action of imidacloprid in the midgut and ovaries of Apis mellifera queens, as well as the effects on sperm stored in their spermatheca. To this end, the apiary was divided into three experimental groups: control, commercial imidacloprid, and active ingredient imidacloprid. For toxicity assays, a sucrose solution containing 1 µg/L of imidacloprid was offered to the colonies for 42 days. A control group received only food in the same period. In both treatments with imidacloprid, the midgut of queens showed modifications in the external musculature and cellular alterations. Such changes could lead to the nonrecovery of the epithelium and subsequently malabsorption of nutrients. Moreover, the digestive cells of queen bees exposed to the commercial imidacloprid presented pyknotic nuclei, suggesting a cell death process. The main alterations observed in the ovaries of these reproductive bees treated with commercial imidacloprid were degeneration and resorption of the ovariole content, which probably affected their fertilization and colony development. There were no significant changes in the spermatozoa morphology for both treatments with imidacloprid, but this insecticide may interfere with the development and reproductive success of A. mellifera colonies because it affects the morphology and function of essential organs for the survival of queens. Environ Toxicol Chem 2022;41:1637-1648. SETAC.

Antioxidant nanomedicine with cytoplasmic distribution in neuronal cells shows superior neurovascular protection properties.

This study investigated whether nitroxide radical (4-amino-TEMPOL)-containing nanoparticles (RNPs; antioxidant nanomedicine) can prevent neurovascular unit impairment caused by reactive oxygen species (ROS) after cerebral ischemia-reperfusion. C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO). The mice were randomly divided and administered intra-arterial RNPs injection (9 mg/kg, 7 µM/kg), edaravone (3 mg/kg, 17 µM/kg), or phosphate-buffered saline (control group). Survival rate and neurological score were evaluated 24 h post-injection. RNPs distribution was determined using immunofluorescence staining and blood-brain barrier (BBB) disruption using Evans blue extravasation assay. Effect of RNPs and edaravone on microglia polarization into microglia M1 and M2 was evaluated. We also determined multiple ROS-scavenging activities in brain homogenates of RNPs- and edaravone-treated animals using an electron spin resonance-based spin-trapping method. Compared with edaravone, RNPs significantly improved the survival rate and neurological deficit, inhibited BBB disruption and supported polarization of microglia into M2 microglia. RNPs were localized in endothelial cells, the perivascular space, neuronal cell cytoplasm, astrocytes, and microglia. Scavenging capacities of hydroxyl, alkoxyl, and peroxyl radicals were significantly higher in the RNPs-treated group. RNPs show promising results as a future neuroprotective nanomedicine approach for cerebral ischemia-reperfusion injury.

Novel neuroprotection using antioxidant nanoparticles in a mouse model of head trauma.

INTRODUCTION: Free radicals and reactive oxygen species are related to deteriorating pathological conditions after head trauma because of their secondary effects. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) scavenges free radicals; however, this molecule is also toxic. Here, we have evaluated the neuroprotective effect of antioxidant nanoparticles, which consisted of a novel core-shell type nanoparticle containing 4-amino-TEMPO, that is, redox-active nitroxide radical-containing nanoparticles (RNPs). METHODS: Institute of Cancer Research mice were subjected to a head-impact procedure, randomly divided into four groups and intravenously (3 mg/kg) administered phosphate-buffered saline, TEMPO, micelle (a self-assembling block copolymer micelle without a TEMPO moiety), or RNP through the tail vein immediately thereafter and intraperitoneally at days 1, 3, and 5 after traumatic brain injury (TBI). The RNP distribution was detected by rhodamine labeling. Cognitive behavior was assessed using the neurological severity score and a rotarod test at days 1, 3, and 7 following TBI, and contusion volume was measured at day 7 after TBI. Free radical-scavenging capacity was analyzed by electron paramagnetic resonance on day 1 after TBI, and immunostaining was used to observe mobilization of microglia (Iba-1) and rescued neuronal cells (NeuN). RESULTS: Redox-active nitroxide radical-containing nanoparticle was detected in the microvessels around the injured area in the brain. Cognitive behavior assessment was significantly better, and contusion volume was significantly smaller in the RNP group compared with the other groups. Superoxide anion scavenging capacity was significantly higher in the RNP group, and neuronal loss was significantly suppressed around the injured area at day 7 after TBI. Furthermore, in the RNP group, neurodegenerative microglia production was suppressed at days 3 and 7 after TBI, whereas neuroprotective microglia production was higher at day 7 after TBI. CONCLUSION: The RNP administration after TBI improved cognitive behavior and reduced contusion volume by improving reactive oxygen species scavenging capacity. Therefore, RNP may have a neuroprotective effect after TBI. LEVEL OF EVIDENCE: Therapeutic test.

Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment - Synergistic effect of thrombolysis and antioxidant.

The medical treatment for stroke has advanced greatly in recent years. Thrombolytic therapy with tissue plasminogen activator (t-PA) is one of the mainstream treatments, but it still has many problems, including short half-life, and t-PA-induced reperfusion and oxidative injuries. To broaden the therapeutic window of t-PA and reduce its associated oxidative stress after reperfusion, t-PA-installed, nitroxide radical-containing, self-assembled polyion complex nanoparticles (t-PA@iRNP) were designed. Encapsulation of t-PA in the self-assembled antioxidant nanoparticles improved its bioavailability and extended its therapeutic window. To suppress reactive oxygen species (ROS) in the ischemic penumbra area, the low-molecular-weight nitroxide antioxidant 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was covalently conjugated with the nanoparticle matrix, thus suppressing oxidative damage in the brain after reperfusion. t-PA and nitroxide radicals were confined and protected in the core of t-PA@iRNP, thereby preventing their rapid metabolism and excretion out of the body after systemic circulation for prolonged period. The nano-sized formulation prevented non-specific internalization of t-PA@iRNP in healthy cells, thereby preserving the normal function of redox reactions in the cells, especially important redox reactions such as electron transport chains. This improved pharmacological performance of t-PA@iRNP remarkably extended the in vivo half-life of t-PA in systemic circulation. Using a mouse model of photo-thrombotic middle cerebral artery occlusion, we found that t-PA@iRNP treatment, compared with naked t-PA, void iRNP, or t-PA@niRNP (non-ROS scavenging nanoparticle as a control), significantly suppressed increases in cerebral infarct volume and improved neurological deficit after brain ischemia. t-PA-induced subarachnoid hemorrhage was also suppressed by t-PA@iRNP treatment through elimination of overproduced ROS. Based on these data, t-PA@iRNP presents therapeutic potential through synergistic effect of thrombolysis and antioxidant effects for preventing and treating ischemia-reperfusion injury.

Reshaping of Bilateral Gait Coordination in Hemiparetic Stroke Patients After Early Robotic Intervention.

Hemiparetic gait is a common condition after stroke which alters importantly the quality of life of stroke survivors. In recent years, several robotic interventions have been developed to support and enhance rehabilitation strategies for such population. The Hybrid Assistive Limb® (HAL) robot suit is a unique device able to collect in real time bioelectric signals from the patient to support and enhance voluntary gait. HAL has been used before in early stages of stroke showing gait improvement after the intervention. However, evaluation of the coordination of gait has not been done yet. Coordination is a key factor for an adequate gait performance; consequently, its changes may be closely related to gait recovery. In this study, we used planar covariation to evaluate coordination changes in hemiparetic stroke patients after early HAL intervention. Before starting, impaired intersegmental coordination for the paretic and non-paretic side was evident. HAL intervention was able to induce recovery of the covariation loop shape and deviation from the covariation plane improving intersegmental coordination. Also, there was a tendency of recovery for movement range evidenced by comparison of peak elevation angles of each limb segment of the patients before and after HAL intervention, and also when compared to healthy volunteers. Our results suggest that early HAL intervention contributed to the improvement of gait coordination in hemiparetic stroke patients by reinforcing central pattern generators and therefore reshaping their gait pattern. Trial registration: UMIN000022410 2016/05/23.

Preliminary in vivo magnetofection data using magnetic calcium phosphate nanoparticles immobilizing DNA and iron oxide nanocrystals.

The data reported herein are in association with our research article entitled "Rapid one-pot fabrication of magnetic calcium phosphate nanoparticles immobilizing DNA and iron oxide nanocrystals using injection solutions for magnetofection and magnetic targeting" (Shubhra et al. 2017) [1]. This article reports morphological and gene delivery (in vitro and preliminary in vivo) data of those calcium phosphate (CaP) naonparticles (NPs) with various iron oxide (IO) contents, named as CaP-Fe(1), CaP-Fe(2), CaP-Fe(3), CaP-Fe(4), and CaP-Fe(5), which were prepared via coprecipitation in supersaturated CaP solutions with nominal Fe concentrations 6.97, 13.94, 27.87, 55.74, and 139.35 µg/mL, respectively. Morphological data of four different NPs: CaP-Fe(1), CaP-Fe(2), CaP-Fe(4), and CaP-Fe(5) are shown here. Data of the luciferase reporter gene expression assay show the effects of the coprecipitation time and the dosage of the CaP-Fe(3) NPs on gene expression levels of CHO-K1 cells transfected by the NPs without external magnetic field. It is demonstrated using digital and microscopic images that the CaP-Fe(3) NPs localize near the periphery of the external magnet that was placed under the cell culture plate. Using the CaP-Fe(3) NPs, animal experiments were conducted to obtain preliminary in vivo magnetofection data.

Reshaping of Gait Coordination by Robotic Intervention in Myelopathy Patients After Surgery.

The Ossification of the Posterior Longitudinal Ligament (OPLL) is an idiopathic degenerative spinal disease which may cause motor deficit. For patients presenting myelopathy or severe stenosis, surgical decompression is the treatment of choice; however, despite adequate decompression residual motor impairment is found in some cases. After surgery, there is no therapeutic approach available for this population. The Hybrid Assistive Limb® (HAL) robot suit is a unique powered exoskeleton designed to predict, support, and enhance the lower extremities performance of patients using their own bioelectric signals. This approach has been used for spinal cord injury and stroke patients where the walking performance improved. However, there is no available data about gait kinematics evaluation after HAL therapy. Here we analyze the effect of HAL therapy in OPLL patients in acute and chronic stages after decompression surgery. We found that HAL therapy improved the walking performance for both groups. Interestingly, kinematics evaluation by the analysis of the elevation angles of the thigh, shank, and foot by using a principal component analysis showed that planar covariation, plane orientation, and movement range evaluation improved for acute patients suggesting an improvement in gait coordination. Being the first study performing kinematics analysis after HAL therapy, our results suggest that HAL improved the gait coordination of acute patients by supporting the relearning process and therefore reshaping their gait pattern.

Neurovascular Unit Protection From Cerebral Ischemia-Reperfusion Injury by Radical-Containing Nanoparticles in Mice.

BACKGROUND AND PURPOSE: Reperfusion therapy by mechanical thrombectomy is used to treat acute ischemic stroke. However, reactive oxygen species generation after reperfusion therapy causes cerebral ischemia-reperfusion injury, which aggravates cerebral infarction. There is limited evidence for clinical efficacy in stroke for antioxidants. Here, we developed a novel core-shell type nanoparticle containing 4-amino-4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (nitroxide radical-containing nanoparticles [RNPs]) and investigated its ability to scavenge reactive oxygen species and confer neuroprotection. METHODS: C57BL/6J mice underwent transient middle cerebral artery occlusion and then received RNPs (9 mg/kg) through the common carotid artery. Infarction size, neurological scale, and blood-brain barrier damage were visualized by Evans blue extravasation 24 hours after reperfusion. RNP distribution was detected by rhodamine labeling. Blood-brain barrier damage, neuronal apoptosis, and oxidative neuronal cell damage were evaluated in ischemic brains. Multiple free radical-scavenging capacities were analyzed by an electron paramagnetic resonance-based method. RESULTS: RNPs were detected in endothelial cells and around neuronal cells in the ischemic lesion. Infarction size, neurological scale, and Evans blue extravasation were significantly lower after RNP treatment. RNP treatment preserved the endothelium and endothelial tight junctions in the ischemic brain; neuronal apoptosis, O2- production, and gene oxidation were significantly suppressed. Reactive oxygen species scavenging capacities against OH, ROO, and O2- improved by RNP treatment. CONCLUSIONS: An intra-arterial RNP injection after cerebral ischemia-reperfusion injury reduced blood-brain barrier damage and infarction volume by improving multiple reactive oxygen species scavenging capacities. Therefore, RNPs can provide neurovascular unit protection.

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms.

Age-associated neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3-4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.

Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

Eventos adversos relacionados con el cuidado de enfermería / Adverse events related to nursing care

Introducción: la seguridad en la atención en salud se ha convertido en una prioridad mundial, por lo cual es importantecaracterizar los eventos adversos con elfin de tomar las medidas pertinentes para prevenirlos. Objetivo: caracterizar la población que presentó los eventos adversos, describiendo las características relacionadas con el paciente, el ambiente yel personal de enfermería. Métodos: análisis descriptivo de una cohorte hospitalariapiloto sobre los eventos adversos relacionados con el cuidado de enfermería, en Bucaramanga, Colombia. Fueron incluidos 198 pacientes, a quienes se les aplicó en las primeras horas de hospitalización un formato que evaluaba posibles factores de riesgo para la ocurrencia de eventos adversos: úlceras por presión, caídas, flebitis y retiros de dispositivos terapéuticos. Resultados: las características que prevalecieron con respecto al pacientefueron: lasalteraciones en el estado de ánimo, el confinamiento a la camay la dieta especial; en cuanto al ambiente, la falta de insumos para la prevención de UPP y timbres. El promedio de pacientes por enfermera profesional fue de 27,3 y en personal auxiliar de enfermería de 9,1. Conclusiones: el conocer las características que estuvieron presentes en los pacientes que desarrollaron un evento adverso, es una primera aproximación sobre la problemática y un elemento importante para que las organizaciones de salud tengan mayores argumentos e inviertan en prácticas más seguras(AU)

Introduction: safety in health care has become a priority in many countries. It is important to inquire about those fact involved in its occurrence for the organizations to respond appropriately to prevent them. Objective: To characterize the population who presented adverse events, describing the characteristics related to the patient, the environment and the nursing staff. Methodology: descriptive analysis of a cohort pilot hospital about adverse events related to nursing care, in Bucaramanga, Colombia. Results: Prevalent events found in patients were alterations in mood, confinement to bed and need for special diet; in the environment events were: lack of inputs for pressure ulcers prevention and lack of nurse call buttons. The average number of patients per nurse practitioner was 27.3 and auxiliary nurses of 9.1. Conclusions: The knowledge about the characteristics that were present in the patients who developed an adverse event, is a first approximation of the problem and an important element for health organizations have more arguments for investing in safer practices(AU)

Depression, Anxiety and Somatic Complaints in Colombian Children Living in Rural Communities / Depresión, ansiedad y síntomas somáticos en niños que viven en comunidades rurales colombianas

Introduction: In Colombia, children are frequently exposed to traumatic events; however, there are no data regarding the impact on depression, anxiety and somatic correlates of such exposure in children living in rural communities. Objective: To investigate the somatic complaints and symptoms of depression and anxiety among children exposed to traumatic events in a rural community of Colombia. Methods: Design: Cross-Sectional study. Participants: Two hundred and ninety-three Colombian children aged eight to 18 years. Main Outcome Measures: Standardized measures were administered to assess children's depression, anxiety, physical symptoms and exposure to traumatic events. Depression: CDI (Children's Depression Inventory); anxiety: SCARED (The Screen for Child Anxiety Related Emotional Disorders); somatic complaints: CBCL (Child Behavior Checklist, Somatic Complaints scale) and reporting traumatic events during the K-SADS-PL (Diagnostic Interview for Children and Adolescents). Results: Ninety-one of the 293 children (31.1%) reported somatic complaints. The most common somatic complaint was in the gastrointestinal category (35/91). One hundred and seventy eight children (60.5%) had observed traumatic events, including homicides during the last month. Two hundred five (69.9%) of the children showed depressive symptom profiles above established norms, and 239 (81.6%) exhibited anxiety symptoms according to their own reports. The correlation between depression and traumatic events, anxiety and somatic complaints, and between anxiety and depression were statistically significant (p<0.005). Conclusions: As the first study of its kind in children living in rural communities in Colombia, it demonstrates a clear impact of traumatic events on mental health. Information that somatic complaints are commonly an expression of underlying depression and anxiety may facilitate the treatment and thereby help avoid unnecessary medical workups and sequelae from traumatized children. It is important for physicians to probe for "hidden" symptoms in traumatized children.

Introducción: En Colombia, los niños están expuestos con frecuencia a eventos traumáticos, sin embargo, no hay datos sobre el impacto de la depresión, la ansiedad y la correlación somática de dicha exposición en niños que viven en comunidades rurales. Objetivo: investigar las alteraciones somáticas, síntomas de depresión y ansiedad en los niños expuestos a eventos traumáticos en una comunidad rural de Colombia. Metodología: Diseño: Estudio transversal; Participantes: Doscientos noventa y tres niños colombianos de ocho a 18 años. Principales medidas de resultado: se aplicaron medidas estandarizadas para evaluar la depresión infantil, ansiedad, síntomas físicos y la exposición a eventos traumáticos. Depresión:CDI (Children's Depression Inventory)). Ansiedad: SCARED (The Screen for Child Anxiety Related Emotional Disorders), Enfermedades somáticas: CBCL (Child Behavior Checklist, Somatic Complaints scale) e informar los eventos traumáticos durante el K -SADS -PL (Diagnostic Interview for Children and Adolescents). Resultados: Noventa y uno de los 293 niños ( 31,1 % ) informaron de síntomas somáticos. La queja somática más común estuvo en la categoría gastrointestinal (35/ 91). Ciento setenta y ocho niños ( 60,5 % ) habían observado los acontecimientos traumáticos, incluyendo homicidios durante el último mes. Doscientos cinco ( 69,9 % ) de los niños mostraron perfiles de síntomas depresivos por encima de las normas establecidas, y 239 ( 81,6 % ) presentaban síntomas de ansiedad según sus propios informes. La correlación entre la depresión y los eventos traumáticos, la ansiedad y quejas somáticas, y entre la ansiedad y la depresión fueron estadísticamente significativas ( p < 0,005 ). Conclusiones: como el primer estudio de su tipo en los niños que viven en comunidades rurales de Colombia , demuestra un claro impacto de eventos traumáticos en la salud mental. La afirmación que las quejas somáticas son comúnmente una expresión de la depresión y la ansiedad subyacente puede facilitar el tratamiento y de ese modo ayudar a evitar abordajes médicos innecesarios y secuelas en los niños traumatizados . Es importante para los médicos explorar los síntomas "ocultos" en los niños traumatizados.

Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

Cerebral capillary endothelial cells are covered by the VEGF-expressing foot processes of astrocytes.

Molecules that have crucial functions in both nervous and vascular systems have attracted keen attention recently, and the name "angioneurins" has been proposed. The most striking example of angioneurins is vascular endothelial growth factor A (VEGF), which was originally identified as a key regulator of angiogenesis and has only recently been found to have important functions in the nervous system. In this study, we compared VEGF expression in the vasculature in the brain with that in the aorta and the vasculature in the kidney in mice. In larger vessels containing smooth muscle cells, VEGF was expressed by smooth muscle cells covering the lining of endothelial cells, both in and outside the brain. In cerebral capillaries lacking smooth muscle cells, endothelial cells were closely covered by VEGF-expressing foot processes of astrocytes, whereas capillaries were surrounded by VEGF-expressing processes of podocytes in the renal glomeruli. We also found that cultured cerebral microvessel endothelial cells do not express VEGF, whereas cultured cortical astrocytes do express VEGF.

A multicenter study of bipolar disorder among emergency department patients in Latin-American countries.

OBJECTIVE: This multicenter study estimated the prevalence of bipolar disorder (BPD) among emergency department (ED) patients in Latin America. METHODS: To identify patients with BPD, a combination of DSM IV-criteria interview and the Mood Disorder Questionnaire (MDQ) was used. Data from 1,505 patients from hospitals in Argentina, Brazil, Chile, Colombia, and Mexico was analyzed. RESULTS: The prevalence ofBPD in this sample was 5.2% (95% CI = 4.5% to 6.9%). The mean age was 37 years (response rate of 83.0%). Compared to non-BPD patients, BPD patients were more likely to report asthma (16.7% vs. 9%), thyroid problems (12.8% vs. 5.8%), seizures (23.1% vs. 3.0%), obesity (39.7% vs. 26.9%), alcohol abuse (30.8% vs. 10.0%), attention deficit hyperactivity disorders (50.0% vs. 12.0%), depression (81.6% vs. 45.7%), obsessive compulsive disorder (20.1% vs. 3.0%), panic disorders (23.1% vs. 12.3%), phobic disorders (11.2% vs. 3.1%), and any anxiety disorder (82.1 % vs. 41.8%; all p < or = 0.05). Suicidal plans and attempts were also significant higher in the bipolar group (11.5% vs. 2.8% and 10.3% vs. 1.8% respectively). Multivariate analysis identified ADHD, depression, alcohol abuse, anxiety disorder, and last month suicide plans and attempts to be independently associated with BPD. CONCLUSION: Our study supports that BPD is prevalent in ED in Latin-American countries and that comorbidity is the rule, not the exception. Patients presenting at ED with irritability, anxiety, pressure speech, euphoria, with suicidal tendencies, involved in risky behaviors, alcohol abuse, dependence or those with history of mental health hospitalization in the past 12 months must be assessed for comorbid BPD.

Experimental investigation of encephalomyosynangiosis using gyrencephalic brain of the miniature pig: histopathological evaluation of dynamic reconstruction of vessels for functional anastomosis. Laboratory investigation.

OBJECT: Encephalomyosynangiosis (EMS) is a surgical treatment for moyamoya disease that is widely used to provide increased intracranial blood flow via revascularization by arterial anastomosis from the external carotid artery. However, the angiogenic mechanism responsible for the revascularization induced by EMS has not been systematically evaluated. In this study the authors investigated the chronological angiogenic changes associated with EMS to clarify the favorable factors and identify revascularization mechanisms by using an experimental internal carotid artery occlusion (ICAO) model in the miniature pig. METHODS: Fourteen miniature pigs were used, 11 of which underwent ICAO before transcranial surgery for EMS was performed. Animals were allowed to recover for 1 week (4 pigs) or 4 weeks (7 pigs) after EMS. Control group animals were treated in the same way, but without occlusion (3 pigs). Magnetic resonance imaging, angiography, and histological investigation were performed. RESULTS: One week after EMS, on histological examination of both the ICAO and control groups it was found that the transplanted temporal muscle had adhered to the arachnoid via a granulation zone, which was enriched with immune cells such as macrophages associated with the angiogenic process. Four weeks after EMS, angiography and histological examination of the ICAO group showed patent anastomoses between the external carotid artery and the cortical arteries without any detectable boundary between the temporal muscle and the cerebral cortex. In contrast, histological examination of the control group found scar tissue between the cerebral cortex and temporal muscle. CONCLUSIONS: The initial step for formation of anastomoses resembles the process of wound healing associated with repair processes such as active proliferation of macrophages and angiogenesis within the new connective tissue. Functional revascularization requires a suitable environment (such as tissue containing vascular beds) and stimulus (such as ischemia) to induce vascular expansion.

Experimental model of lacunar infarction in the gyrencephalic brain of the miniature pig: neurological assessment and histological, immunohistochemical, and physiological evaluation of dynamic corticospinal tract deformation.

BACKGROUND AND PURPOSE: Lacunar infarction accounts for 25% of ischemic strokes, but the pathological characteristics have not been investigated systematically. A new experimental model of lacunar infarction in the miniature pig was developed to investigate the pathophysiological changes in the corticospinal tract from the acute to chronic phases. METHODS: Thirty-five miniature pigs underwent transcranial surgery for permanent anterior choroidal artery occlusion. Animals recovered for 24 hours (n=7), 2 (n=5), 3 (n=2), 4 (n=2), 6 (n=1), 7 (n=7), 8 (n=2), and 9 days (n=1), 2 weeks (n=2), 4 weeks (n=3), and more than 4 weeks (n=3). Neurology, electrophysiology, histology, and MRI were performed. Seven additional miniature pigs underwent transient anterior choroidal artery occlusion to study muscle motor-evoked potentials and evaluate corticospinal tract function during transient anterior choroidal artery occlusion. RESULTS: The protocol had a 91.4% success rate in induction of internal capsule infarction 286+/-153 mm(3) (mean+/-SD). Motor-evoked potentials revealed the presence of penumbral tissue in the internal capsule after 6 to 15 minutes anterior choroidal artery occlusion. Total neurological deficit scores of 15.0 (95% CI, 13.5 to 16.4) and 3.4 (0.3 to 6.4) were recorded for permanent anterior choroidal artery occlusion and sham groups, respectively (P<0.001, maximum score 25) with motor deficit scores of 3.4 (95% CI, 2.9 to 4.0) and 0.0 (CI, 0.0 to 0.0), respectively (P<0.001, maximum score 9). Histology revealed that the internal capsule lesion expands gradually from acute to chronic phases. CONCLUSIONS: This new model of lacunar infarction induces a reproducible infarct in subcortical white matter with a measurable functional deficit and evidence of penumbral tissue acutely.