Acute toxicity of essential oils of Aloysia triphylla (L'Hér.) Britton, Lippia gracilis Schauer, and Piper aduncum L. in Colossoma macropomum (Cuvier, 1818).

The aim of this study was to determine the acute toxicity of the essential oils (EOs) of Aloysia triphylla, Lippia gracilis and Piper aduncum in juvenile tambaqui (Colossoma macropomum), and evaluate the possible histopathological alterations in their gills. For the acute toxicity tests, juvenile tambaqui (n=24/treatment) were distributed in six treatments with three replicates, which comprised the control and five EO concentrations of A. triphylla (60, 80, 100, 120 and 140 mg L-1), L. gracilis (35, 40, 45, 50 and 55 mg L-1) and P. aduncum (42.5, 45, 47.5, 50 and 52.5 mg L-1), with an exposure period of 4 h. The mortality rate and severity of damage to the tambaqui gills were proportional to the increase in the concentration of the EO, with LC50-4 h values estimated at 109.57 mg L -1 for A. triphylla, 41.63 mg L -1 for L. gracilis and 48.17 mg L -1 for P. aduncum. The main morphological damages observed in the gills of the tambaqui exposed to the three EOs, were Grade I: hypertrophy and hyperplasia of lamellar epithelial cells, lamellar fusion, epithelial detachment, capillary dilation and constriction, proliferation of chloride cells and mucosal cells and edema; in low frequency Grade II damage as epithelial rupture and lamellar aneurysm. Necrosis (Grade III damage) was observed only in gill lamellae exposed to P. aduncum EO (47.5, 50.0 and 52.5 mg L-1). Concentrations of EOs below LC50-4 h can be used sparingly, for short periods of exposure for the treatment of diseases in tambaqui breeding.

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

Comorbidities associated with COVID-19 mortality in adults in Lima, Peru: a retrospective cohort study. / Comorbilidades asociadas a la mortalidad por COVID-19 en adultos en Lima, Perú: un estudio de cohorte retrospectiva.

OBJECTIVES.: Motivation for the study. During the COVID-19 pandemic, the mortality rate from this disease was higher in adults and the elderly. Therefore, it is important to identify the factors that were associated with mortality from COVID-19 in adults, by age group. Main findings. Chronic neurological disease, kidney disease, liver disease, and cancer increased the risk of dying from COVID-19 in the three age groups we analyzed, which were made up of hospitalized patients from Lima and Callao. The risk of mortality associated with comorbidities was higher in patients aged 18 to 29. Implications. This study helps to identify the groups of patients with the highest risk of death from COVID-19, according to age group and type of comorbidity. . To evaluate comorbidities associated with mortality in adult patients hospitalized due to COVID-19 in hospitals in Lima and Callao. MATERIALS AND METHODS.: In this retrospective cohort study, we analyzed data from adult patients hospitalized due to COVID-19 reported to the National Epidemiological Surveillance System of the Peruvian Ministry of Health from March to October 2020. We estimated relative risks with 95% confidence intervals using Poisson regression models with robust variance to assess comorbidities associated with mortality by age group: young adults (18-29 years), adults (30-59 years) and older adults (≥60 years). RESULTS.: We included 2366 young adults, 23,781 adults and 25,356 older adults. Older adults had the highest mortality (63.7%) compared to adults (27.1%) and young adults (8.5%). Regardless of age group, the presence of neurological disease, renal disease, liver disease, and cancer was associated with an increased risk of mortality. Additionally, cardiovascular disease was also a risk factor in young adults; obesity, diabetes, cardiovascular disease, chronic lung disease, and immunodeficiency in adults; and obesity and chronic lung disease in the elderly. CONCLUSIONS.: Regardless of age groups, individuals with chronic neurologic disease, renal disease, liver disease, and cancer were at high risk of death from COVID-19.

OBJETIVOS.: Motivation for the study. During the COVID-19 pandemic, the mortality rate from this disease was higher in adults and the elderly. Therefore, it is important to identify the factors that were associated with mortality from COVID-19 in adults, by age group. Main findings. Chronic neurological disease, kidney disease, liver disease, and cancer increased the risk of dying from COVID-19 in the three age groups we analyzed, which were made up of hospitalized patients from Lima and Callao. The risk of mortality associated with comorbidities was higher in patients aged 18 to 29. Implications. This study helps to identify the groups of patients with the highest risk of death from COVID-19, according to age group and type of comorbidity. . Evaluar las comorbilidades asociadas a la mortalidad en pacientes adultos hospitalizados por COVID-19 de diferentes grupos de edad en hospitales de Lima y Callao. MATERIALES Y MÉTODOS.: En este estudio de cohorte retrospectiva analizamos datos de pacientes adultos hospitalizados por COVID-19, notificados al Sistema Nacional de Vigilancia Epidemiológica del Ministerio de Salud de Perú de marzo a octubre del 2020. Se estimaron riesgos relativos con intervalos de confianza al 95% mediante modelos de regresión de Poisson con varianza robusta para evaluar las comorbilidades asociadas a la mortalidad por grupos de edad: jóvenes (18-29 años), adultos (30-59 años) y mayores (≥60 años). RESULTADOS.: Se incluyeron 2366 jóvenes, 23781 adultos y 25356 adultos mayores en el análisis. Los adultos mayores presentaron la mortalidad más alta (63,7%) en comparación con adultos (27,1%) y jóvenes (8,5%). Independientemente del grupo de edad, la presencia de enfermedad neurológica, enfermedad renal, enfermedad hepática y cáncer se asoció a un mayor riesgo de mortalidad. Adicionalmente, la enfermedad cardiovascular fue también un factor de riesgo en los jóvenes; la obesidad, la diabetes, la enfermedad cardiovascular, la enfermedad pulmonar crónica y la inmunodeficiencia en los adultos; y la obesidad y la enfermedad pulmonar crónica en los mayores. CONCLUSIONES: Independientemente de los grupos de edad, los individuos con enfermedad neurológica crónica, enfermedad renal, enfermedad hepática y cáncer tendrían un alto riesgo de morir por la COVID-19.

Revisión sistemática y metaanálisis de los efectos hemodinámicos del etomidato frente a otros sedantes en pacientes sometidos a secuencia de intubación rápida / A systematic review and meta-analysis of the hemodynamic effects of etomidate versus other sedatives in patients undergoing rapid sequence intubation

Introducción: La secuencia de intubación rápida es una técnica de protección y rescate de la vía aérea que requiere el uso de sedantes para propiciar un adecuado escenario durante la intubación orotraqueal. Son utilizados diferentes sedantes inductores, siendo el etomidato el más común por sus cualidades farmacocinéticas y farmacodinámicas, donde resalta su estabilidad hemodinámica. Sin embargo, en comparación con otros sedantes esta superioridad es controvertida. Materiales y métodos: Se realizó un metaanálisis con un protocolo definido a priori y siguiendo las etapas de la guía PRISMA. Se calculó la diferencia de medias de la presión arterial sistólica antes y después de la administración del sedante, además de un metaanálisis de riesgos relativos de hipotensión. Resultados: Se incluyeron 10 estudios en los cuales la incidencia de hipotensión en el grupo de pacientes que recibió el etomidato osciló entre el 6,4% y el 75,2%, mientras que en los que recibieron otros sedantes osciló entre el 24,0% y el 65,9%. En los metaanálisis de diferencia de medias no se hallaron diferencias significativas de la presión arterial sistólica durante la preintubación 0,01mmHg (IC 95%: –0,90; 0,92), ni en la postintubación 0,98mmHg (IC 95%: –0,24; 2,20). Además, el metaanálisis de riesgos relativos indica que el riesgo de hipotensión es igual a un RR 1,19 (IC 95%: 0,92-1,54) entre quienes recibieron el etomidato y aquellos que recibieron los otros sedantes. Conclusiones: El riesgo de hipotensión posterior a la secuencia de intubación rápida con etomidato no presenta diferencias significativas comparado con otros sedantes. Sin embargo, hay heterogeneidad en los estudios incluidos.(AU)

Introduction: Rapid sequence intubation is an airway rescue and protection technique in which different sedatives are used to perform orotracheal intubation. Etomidate, due to its pharmacokinetic and pharmacodynamic qualities, particularly hemodynamic stability, is the most widely used sedative in this scenario. However, its superiority over other sedatives is controversial. Materials and methods: We performed a meta-analysis using a pre-designed protocol and PRISMA guidelines to evaluate the mean difference between systolic blood pressure before and after administration of the sedative. We also analyzed the relative risks of hypotension. Results: Ten studies were included. The incidence of hypotension in patients receiving etomidate ranged from 6.4% to 75.2%, and between 24.0% and 65.9% in patients receiving other sedatives. No significant differences were found in the mean difference in systolic blood pressure during pre-intubation 0.01mmHg (95% CI: –0.90; 0.92) or in post-intubation 0.98mmHg (95% CI: –0.24; 2.20). The relative risk analysis showed that the risk of hypotension is equal to an RR of 1.19 (95% CI: 0.92-1.54) between those who received etomidate and those who received the other sedatives. Conclusions: The risk of hypotension after rapid intubation sequence with etomidate does not differ significantly compared to other sedatives. However, the studies included in this review were heterogeneous.(AU)

A systematic review and meta-analysis of the hemodynamic effects of etomidate versus other sedatives in patients undergoing rapid sequence intubation.

INTRODUCTION: Rapid sequence intubation is an airway rescue and protection technique in which different sedatives are used to perform orotracheal intubation. Etomidate, due to its pharmacokinetic and pharmacodynamic qualities, particularly hemodynamic stability, is the most widely used sedative in this scenario. However, its superiority over other sedatives is controversial. MATERIALS AND METHODS: We performed a meta-analysis using a pre-designed protocol and PRISMA guidelines to evaluate the mean difference between systolic blood pressure before and after administration of the sedative. We also analyzed the relative risks of hypotension. RESULTS: Ten studies were included. The incidence of hypotension in patients receiving etomidate ranged from 6.4% to 75.2%, and between 24.0% and 65.9% in patients receiving other sedatives. No significant differences were found in the mean difference in systolic blood pressure during pre-intubation 0.01 mm Hg (95% CI: -0.90; 0.92) or in post-intubation 0.98 mmHg (95% CI: -0.24; 2.20). The relative risk analysis showed that the risk of hypotension is equal to an RR of 1.19 (95% CI: 0.92-1.54) between those who received etomidate and those who received the other sedatives. CONCLUSIONS: The risk of hypotension after rapid intubation sequence with etomidate does not differ significantly compared to other sedatives. However, the studies included in this review were heterogeneous.

Supraclavicular nerve entrapment by the external jugular vein: An unreported finding.

OBJECTIVE: We aim to describe the supraclavicular nerve's vascular entrapment by the external jugular vein as an unreported anatomical finding. CASE DESCRIPTION: In a routine cadaveric dissection, the superficial emergence of the first division of the left supraclavicular nerve emerged along a duct formed through the external jugular vein. No other vascular or neural anatomical abnormalities were found in the surrounding structures. CONCLUSION: This unreported vascular entrapment of the supraclavicular nerve by the external jugular may harbour clinical implications for surgical and endovascular procedures on the external jugular vein and in refractory thoracic and scapular waist pain.

Synthesis and characterization of C60 and C70 acetylace-tone monoadducts and study of their photochemical properties for potential application in solar cells / Síntesis y caracterización de monoaductos de C60 y C70 con acetilacetona y estudio de sus propiedades fotoquímicas para su posible aplicación en células solares / Sínteses e caracterização de monoadutos de C60 e C70 com acetilacetona e estudo das suas propriedades fotoquímicas para a sua possível aplicação em células solares

Abstract We report on the synthesis of C60 and C70 monoadducts at room temperature through the Bingel reaction; employing acetylacetone as ligand; in presence of DBU (1,8-Diazabicyclo [5.4.0] undec-7-ene), carbon tetrabromide (CBr4), and o-dichlorobenzene. Diacetylmethane-[C60-Ih]-fullerene-[5,6] and diacetylmethane-[C70-D5h]-fullerene-[5,6] monoadducts were obtained with yields of 69% and 44%, respectively. The products were purified by column chromatography (CC, on silica gel, using hexane, carbon disulfide, and chloroform as eluents at room temperature) and characterized by Nuclear Magnetic Resonance ('H and 13C), Fourier-Transform Infrared (FT-IR) and UV-Visible spectroscopies, Matrix-assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) Mass spectrometry, Cyclic Voltammetry (CV), and Osteryoung Square Wave Voltammetry (OSWV). Both compounds showed irreversible reduction peaks controlled by diffusion, with LUMO energy levels of -3.09 eV, -3.13 eV for C60, and C70 monoadducts, respectively. These values are comparable with the -3.99 eV of PC61BM. The synthetized adducts were incorporated into inverted-type perovskite solar cells and were used as electron transporting materials (ETM) obtaining power conversion efficiencies (PCE) of 8.5% and 14.0% for the C60 and C70 monoadducts, respectively. When C60 is replaced by a lower symmetrical fullerene such as C70 an improved light absorption in the visible region is observed.

Resumen Reportamos la síntesis de monoadductos de C60 y C70 a temperatura ambiente a través de la reacción de Bingel, empleando acetilacetona como ligando, en presencia de DBU (1,8-diazabiciclo [5.4.0] undec-7-eno), tetrabromuro de carbono (CBr4) y o-diclorobenceno. Se obtuvieron monoadductos de diacetilmetano-[C -I.]-fullereno-[5,6] y diacetilmetano-[C70-D5h]-fullereno-[5,6] con rendimientos del 69% y 44%, respectivamente. Los productos se purificaron por cromatografía en columna (CC, usando silica gel, hexano, disulfuro de carbono y cloroformo como fase móvil, a temperatura ambiente) y se caracterizaron por resonancia magnética nuclear (1H y 13C), infrarrojo con transformada de Fourier (FT-IR), espectroscopia UV-Visible, espectrometría de masas, desorción/ionización láser asistida por matriz - tiempo de vuelo (MALDI-TOF), voltametría cíclica (CV) y voltametría de onda cuadrada de Osteryoung (OSWV). Ambos compuestos mostraron picos de reducción irreversibles controlados por difusión, con niveles de energía LUMO de -3,09 eV y -3,13 eV para los monoadductos C60 y C70, respectivamente. Estos valores son comparables con el -3,99 eV de PC61BM. Los aductos sintetizados se incorporaron a las células solares de perovskita de tipo inversa y se usaron como materiales de transporte de electrones (ETM) obteniendo eficiencias de conversión de energía (PCE) de 8,5% y 14,0% para los monoaductos C60 y C70, respectivamente. Cuando el C60 se reemplaza por un fullereno menos simétrico como el C70, se observa una absorción de luz mejorada en la región visible.

Resumo Reportamos a sínteses de monoadutos de C60 e C70 a temperatura ambiente através da reação de Bingel, utilizando acetilacetona como ligando, na presença de DBU (1,8-diazabiciclo [5.4.0] undec-7-eno), tetrabromuro de carbono (CBr4) e o-diclorobenzeno. Foram obtidos monoadutos de diacetilmetano-[C60-IJ-fulereno-[5,6] e diacetilmetano-[C70-D5J-fulereno-[5,6] com rendimentos de 69% e 44%, respectivamente. Os produtos se purificaram por cromatografia em coluna (CC, usando sílica gel, hexano, dissulfeto de carbono e clorofórmio como fase móvel à temperatura ambiente ) e se caracterizaram por ressonância magnética nuclear OH e 13C), infra-vermelho com transformada de Fourier (FT-IR), espectroscopia UV-Visível, espectrometria de massas, ionização e dessorção a laser assistida por matriz-tempo de voo (MALDI-TOF), voltametria cíclica (CV) e voltametria de onda quadrada de Osteryoung (OSWV). Ambos compostos mostraram picos de redução irreversíveis controlados por difusão, com níveis de energia LUMO de -3,09 eV, -3,13 eV para os monoadutos C60 e C70, respectivamente. Estos valores são comparáveis com -3,99 eV de PC61BM. Os adutos sintetizados se incorporaram nas células solares de perovskita de tipo inversa e se usaram como materiais de transporte de eletrões (ETM) obtendo eficiências de conversão de energia (PCE) de 8,5% e 14,0% para os monoadutos C60 e C70, respectivamente. Quando o C60 se substitui por um fulereno menos simétrico como o C70, se observa uma absorção de luz melhorado na região visível.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

Molecular dissection of TNFR-TNFα bidirectional signaling reveals both cooperative and antagonistic interactions with p75 neurotrophic factor receptor in axon patterning.

During neural development, complex organisms rely on progressive and regressive events whereby axons, synapses, and neurons are overproduced followed by selective elimination of a portion of these components. Tumor necrosis factor α (TNFα) together with its cognate receptor (Tumor necrosis factor receptor 1; TNFR1) have been shown to play both regressive (i.e. forward signaling from the receptor) and progressive (i.e. reverse signaling from the ligand) roles in sympathetic neuron development. In contrast, a paralog of TNFR1, p75 neurotrophic factor receptor (p75NTR) promotes mainly regressive developmental events in sympathetic neurons. Here we examine the interplay between these paralogous receptors in the regulation of axon branch elimination and arborization. We confirm previous reports that these TNFR1 family members are individually capable of promoting ligand-dependent suppression of axon growth and branching. Remarkably, p75NTR and TNFR1 physically interact and p75NTR requires TNFR1 for ligand-dependent axon suppression of axon branching but not vice versa. We also find that p75NTR forward signaling and TNFα reverse signaling are functionally antagonistic. Finally, we find that TNFα reverse signaling is necessary for nerve growth factor (NGF) dependent axon growth. Taken together these findings demonstrate several levels of synergistic and antagonistic interactions using very few signaling pathways and that the balance of these synergizing and opposing signals act to ensure proper axon growth and patterning.

Local Hemodynamic Conditions Associated with Focal Changes in the Intracranial Aneurysm Wall.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics has been associated with wall histology and inflammation. We investigated associations between local hemodynamics and focal wall changes visible intraoperatively. MATERIALS AND METHODS: Computational fluid dynamics models were constructed from 3D images of 65 aneurysms treated surgically. Aneurysm regions with different visual appearances were identified in intraoperative videos: 1) "atherosclerotic" (yellow), 2) "hyperplastic" (white), 3) "thin" (red), 4) rupture site, and 5) "normal" (similar to parent artery), They were marked on 3D reconstructions. Regional hemodynamics was characterized by the following: wall shear stress, oscillatory shear index, relative residence time, wall shear stress gradient and divergence, gradient oscillatory number, and dynamic pressure; these were compared using the Mann-Whitney test. RESULTS: Hyperplastic regions had lower average wall shear stress (P = .005) and pressure (P = .009) than normal regions. Flow conditions in atherosclerotic and hyperplastic regions were similar but had higher average relative residence time (P = .03) and oscillatory shear index (P = .04) than thin regions. Hyperplastic regions also had a higher average gradient oscillatory number (P = .002) than thin regions. Thin regions had lower average relative residence time (P < .001), oscillatory shear index (P = .006), and gradient oscillatory number (P < .001) than normal regions, and higher average wall shear stress (P = .006) and pressure (P = .009) than hyperplastic regions. Thin regions tended to be aligned with the flow stream, while atherosclerotic and hyperplastic regions tended to be aligned with recirculation zones. CONCLUSIONS: Local hemodynamics is associated with visible focal wall changes. Slow swirling flow with low and oscillatory wall shear stress was associated with atherosclerotic and hyperplastic changes. High flow conditions prevalent in regions near the flow impingement site characterized by higher and less oscillatory wall shear stress were associated with local "thinning" of the wall.

Connections between the median and ulnar nerves evidenced by electromyography in Lima, Peru, 2016. / Conexiones entre los nervios mediano-cubital por electromiografía en Lima (Perú), 2016.

INTRODUCTION: Connections are common communications between 2similar anatomical elements. Some of the most common are in the forearm between the median and ulnar nerves and are clinically important because they produce variations in motor and sensory innervation and can cause confusion when diagnosing peripheral nerve pathology. METHOD: Descriptive, cross-sectional, observational study. A total of 127 patients older than 18 years were studied, electromyography was performed on the upper limbs and the frequency of presentation of the connections was obtained. RESULT: The Riche-Cannieu connection was present in 16.5% of the total patients studied, of which 42.9% presented in the left arm and 89.3% in isolation. The Marinacci connection was the second in frequency with 15.7%, of which 40% was presented in the left arm and 45.8% coexisted with another connection. The Berrettini connection was the third in frequency with 9.4%, 50% presented in the left arm and 53.3% of the sample was found in isolation. Martin-Grüber's connection was the least frequent at 7.1% of our cases, of which 44.5% presented bilaterally and 90% associated with another connection. CONCLUSION: It is concluded that of the 4types of connection studied the most frequent in our environment was the Riche-Cannieu with predominance of the left arm and in isolation.

Enhancing the Therapeutic Potential of Olfactory Ensheathing Cells in Spinal Cord Repair Using Neurotrophins.

Autologous olfactory ensheathing cell (OEC) transplantation is a promising therapy for spinal cord injury; however, the efficacy varies between trials in both animals and humans. The main reason for this variability is that the purity and phenotype of the transplanted cells differs between studies. OECs are susceptible to modulation with neurotrophic factors, and thus, neurotrophins can be used to manipulate the transplanted cells into an optimal, consistent phenotype. OEC transplantation can be divided into 3 phases: (1) cell preparation, (2) cell administration, and (3) continuous support to the transplanted cells in situ. The ideal behaviour of OECs differs between these 3 phases; in the cell preparation phase, rapid cell expansion is desirable to decrease the time between damage and transplantation. In the cell administration phase, OEC survival and integration at the injury site, in particular migration into the glial scar, are the most critical factors, along with OEC-mediated phagocytosis of cellular debris. Finally, continuous support needs to be provided to the transplantation site to promote survival of both transplanted cells and endogenous cells within injury site and to promote long-term integration of the transplanted cells and angiogenesis. In this review, we define the 3 phases of OEC transplantation into the injured spinal cord and the optimal cell behaviors required for each phase. Optimising functional outcomes of OEC transplantation can be achieved by modulation of cell behaviours with neurotrophins. We identify the key growth factors that exhibit the strongest potential for optimizing the OEC phenotype required for each phase.

Olfactory Ensheathing Cells for Spinal Cord Injury: Sniffing Out the Issues.

Olfactory ensheathing cells (OECs) are glia reported to sustain the continuous axon extension and successful topographic targeting of the olfactory receptor neurons responsible for the sense of smell (olfaction). Due to this distinctive property, OECs have been trialed in human cell transplant therapies to assist in the repair of central nervous system injuries, particularly those of the spinal cord. Though many studies have reported neurological improvement, the therapy remains inconsistent and requires further improvement. Much of this variability stems from differing olfactory cell populations prior to transplantation into the injury site. While some studies have used purified cells, others have used unpurified transplants. Although both preparations have merits and faults, the latter increases the variability between transplants received by recipients. Without a robust purification procedure in OEC transplantation therapies, the full potential of OECs for spinal cord injury may not be realised.

Water-equivalence of gel dosimeters for radiology medical imaging.

International dosimetry protocols are based on determinations of absorbed dose to water. Ideally, the phantom material should be water equivalent; that is, it should have the same absorption and scatter properties as water. This study presents theoretical, experimental and Monte Carlo modeling of water-equivalence of Fricke and polymer (NIPAM, PAGAT and itaconic acid ITABIS) gel dosimeters. Mass and electronic densities along with effective atomic number were calculated by means of theoretical approaches. Samples were scanned by standard computed tomography. Photon mass attenuation coefficients and electron stopping powers were examined. Theoretical, Monte Carlo and experimental results confirmed good water-equivalence for all gel dosimeters. Overall variations with respect to water in the low energy radiology range (up to 130 kVp) were found to be less than 3% in average.

Theory, simulation and experiments for precise deflection control of radiotherapy electron beams.

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control.