BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation.

Moderate acute intermittent hypoxia (mAIH) elicits a form of phrenic motor plasticity known as phrenic long-term facilitation (pLTF), which requires spinal 5-HT2 receptor activation, ERK/MAP kinase signaling, and new brain-derived neurotrophic factor (BDNF) synthesis. New BDNF protein activates TrkB receptors that normally signal through PKCθ to elicit pLTF. Phrenic motor plasticity elicited by spinal drug administration (e.g., BDNF) is referred to by a more general term: phrenic motor facilitation (pMF). Although mild systemic inflammation elicited by a low lipopolysaccharide (LPS) dose (100 µg/kg; 24 h prior) undermines mAIH-induced pLTF upstream from BDNF protein synthesis, it augments pMF induced by spinal BDNF administration through unknown mechanisms. Here, we tested the hypothesis that mild inflammation shifts BDNF/TrkB signaling from PKCθ to alternative pathways that enhance pMF. We examined the role of three known signaling pathways associated with TrkB (MEK/ERK MAP kinase, PI3 kinase/Akt, and PKCθ) in BDNF-induced pMF in anesthetized, paralyzed, and ventilated Sprague Dawley rats 24 h post-LPS. Spinal PKCθ inhibitor (TIP) attenuated early BDNF-induced pMF (≤30 min), with minimal effect 60-90 min post-BDNF injection. In contrast, MEK inhibition (U0126) abolished BDNF-induced pMF at 60 and 90 min. PI3K/Akt inhibition (PI-828) had no effect on BDNF-induced pMF at any time. Thus, whereas BDNF-induced pMF is exclusively PKCθ-dependent in normal rats, MEK/ERK is recruited by neuroinflammation to sustain, and even augment downstream plasticity. Because AIH is being developed as a therapeutic modality to restore breathing in people living with multiple neurological disorders, it is important to understand how inflammation, a common comorbidity in many traumatic or degenerative central nervous system disorders, impacts phrenic motor plasticity.NEW & NOTEWORTHY We demonstrate that even mild systemic inflammation shifts signaling mechanisms giving rise to BDNF-induced phrenic motor plasticity. This finding has important experimental, biological, and translational implications, particularly since BDNF-dependent spinal plasticity is being translated to restore breathing and nonrespiratory movements in diverse clinical disorders, such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS).

The Role of Emotions in Classroom Conflict Management. Case Studies Geared Towards Improving Teacher Training.

The purpose of this paper is twofold: firstly, to explore the emotional aspects underlying classroom conflict management, and secondly, to apply these notions to the contrasted analysis of two case studies. Our findings underscore the importance of examining teachers' emotional regulation to better understand their performance when dealing with conflicts that affect classroom climate. In the final section, we make suggestions for introducing this perspective into initial teacher training through the use of Virtual Reality, a scenario that would allow pre-service teachers to experiment, record and reflect on affective and attitudinal issues that are decisive for effective classroom conflict management.

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons.

Cholinergic transmission shapes the maturation of glutamatergic circuits, yet the developmental sources of acetylcholine have not been systematically explored. Here, we have used Cre-recombinase-mediated genetic labeling to identify and map both mature and developing CNS neurons that express choline acetyltransferase (ChAT). Correction of a significant problem with a widely used ChatCre transgenic line ensures that this map does not contain expression artifacts. ChatCre marks all known cholinergic systems in the adult brain, but also identifies several brain areas not usually regarded as cholinergic, including specific thalamic and hypothalamic neurons, the subiculum, the lateral parabrachial nucleus, the cuneate/gracilis nuclei, and the pontocerebellar system. This ChatCre fate map suggests transient developmental expression of a cholinergic phenotype in areas important for cognition, motor control, and respiration. We therefore examined expression of ChAT and the vesicular acetylcholine transporter in the embryonic and early postnatal brain to determine the developmental timing of this transient cholinergic phenotype, and found that it mirrored the establishment of relevant glutamatergic projection pathways. We then used an intersectional genetic strategy combining ChatCre with Vglut2Flp to show that these neurons adopt a glutamatergic fate in the adult brain. The transient cholinergic phenotype of these glutamatergic neurons suggests a homosynaptic source of acetylcholine for the maturation of developing glutamatergic synapses. These findings thus define critical windows during which specific glutamatergic circuits may be vulnerable to disruption by nicotine in utero, and suggest new mechanisms for pediatric disorders associated with maternal smoking, such as sudden infant death syndrome.

Advances in cellular and integrative control of oxygen homeostasis within the central nervous system.

Mammals must continuously regulate the levels of O2 and CO2 , which is particularly important for the brain. Failure to maintain adequate O2 /CO2 homeostasis has been associated with numerous disorders including sleep apnoea, Rett syndrome and sudden infant death syndrome. But, O2 /CO2 homeostasis poses major regulatory challenges, even in the healthy brain. Neuronal activities change in a differentiated, spatially and temporally complex manner, which is reflected in equally complex changes in O2 demand. This raises important questions: is oxygen sensing an emergent property, locally generated within all active neuronal networks, and/or the property of specialized O2 -sensitive CNS regions? Increasing evidence suggests that the regulation of the brain's redox state involves properties that are intrinsic to many networks, but that specialized regions in the brainstem orchestrate the integrated control of respiratory and cardiovascular functions. Although the levels of O2 in arterial blood and the CNS are very different, neuro-glial interactions and purinergic signalling are critical for both peripheral and CNS chemosensation. Indeed, the specificity of neuroglial interactions seems to determine the differential responses to O2 , CO2 and the changes in pH.

Systemic inflammation inhibits serotonin receptor 2-induced phrenic motor facilitation upstream from BDNF/TrkB signaling.

Although systemic inflammation induced by even a low dose of lipopolysaccharide (LPS, 100 µg/kg) impairs respiratory motor plasticity, little is known concerning cellular mechanisms giving rise to this inhibition. Phrenic motor facilitation (pMF) is a form of respiratory motor plasticity elicited by pharmacological agents applied to the cervical spinal cord, or by acute intermittent hypoxia (AIH; 3, 5-min hypoxic episodes); when elicited by AIH, pMF is known as phrenic long-term facilitation (pLTF). AIH consisting of moderate hypoxic episodes (mAIH, arterial Po2 = 35-55 mmHg) elicits pLTF via the Q pathway to pMF, a mechanism that requires spinal serotonin (5HT2) receptor activation and new brain-derived neurotrophic factor (BDNF) protein synthesis. Although mild systemic inflammation attenuates mAIH-induced pLTF via spinal p38 MAP kinase activation, little is known concerning how p38 MAP kinase activity inhibits the Q pathway. Here, we confirmed that 24 h after a low LPS dose (100 µg/kg ip), mAIH-induced pLTF is greatly attenuated. Similarly, pMF elicited by intrathecal cervical injections of 5HT2A (DOI; 100 µM; 3 × 6 µl) or 5HT2B receptor agonists (BW723C86; 100 µM; 3 × 6 µl) is blocked 24 h post-LPS. When pMF was elicited by intrathecal BDNF (100 ng, 12 µl), pMF was actually enhanced 24 h post-LPS. Thus 5HT2A/2B receptor-induced pMF is impaired downstream from 5HT2 receptor activation, but upstream from BDNF/TrkB signaling. Mechanisms whereby LPS augments BDNF-induced pMF are not yet known. NEW & NOTEWORTHY These experiments give novel insights concerning mechanisms whereby systemic inflammation undermines serotonin-dependent, spinal respiratory motor plasticity, yet enhances brain-derived neurotrophic factor (BDNF)/TrkB signaling in phrenic motor neurons. These insights may guide development of new strategies to elicit functional recovery of breathing capacity in patients with respiratory impairment by reducing (or bypassing) the impact of systemic inflammation characteristic of clinical disorders that compromise breathing.

Spinal BDNF-induced phrenic motor facilitation requires PKCθ activity.

Spinal brain-derived neurotrophic factor (BDNF) is necessary and sufficient for certain forms of long-lasting phrenic motor facilitation (pMF). BDNF elicits pMF by binding to its high-affinity receptor, tropomyosin receptor kinase B (TrkB), on phrenic motor neurons, potentially activating multiple downstream signaling cascades. Canonical BDNF/TrkB signaling includes the 1) Ras/RAF/MEK/ERK MAP kinase, 2) phosphatidylinositol 3-kinase (PI3K)/Akt, and 3) PLCγ/PKC pathways. Here we demonstrate that spinal BDNF-induced pMF requires PLCγ/PKCθ in normal rats but not MEK/ERK or PI3K/Akt signaling. Cervical intrathecal injections of MEK/ERK (U0126) or PI3K/Akt (PI-828; 100 µM, 12 µl) inhibitor had no effect on BDNF-induced pMF (90 min after BDNF; U0126 + BDNF: 59 ± 14%, PI-828 + BDNF: 59 ± 8%, inhibitor vehicle + BDNF: 56 ± 7%; all P ≥ 0.05). In contrast, PKCθ inhibition with theta inhibitory peptide (TIP; 0.86 mM, 12 µl) prevented BDNF-induced pMF (90 min after BDNF; TIP + BDNF: -2 ± 2%; P ≤ 0.05 vs. other groups). Thus BDNF-induced pMF requires downstream PLCγ/PKCθ signaling, contrary to initial expectations.NEW AND NOTEWORTHY We demonstrate that BDNF-induced pMF requires downstream signaling via PKCθ but not MEK/ERK or PI3K/Akt signaling. These data are essential to understand the sequence of the cellular cascade leading to BDNF-dependent phrenic motor plasticity.

Análisis de la composición corporal empleando parámetros bioeléctricos en la población deportiva cubana / Body composition analysis using bioelectrical parameters in Cuban sporting population

Objetivos: La propuesta de este estudio es proveer datos de parámetros bioeléctricos de la población deportiva cubana, particularmente: resistencia (R), reactancia (Xc), impedancia (Z), ángulo de fase (AF), y los componentes del vector impedancia de acuerdo al análisis del vector bioeléctrico (BIVA), estableciendo valores de referencia en atletas de alto rendimiento. Material y método: Se les realizó el análisis de bioimpedancia eléctrica (BIA) a 943 deportistas cubanos (620 masculinos, 323 femeninos) de 26 deportes diferentes. Los parámetros bioeléctricos R, Xc, Z y PA fueron obtenidos a una frecuencia de 50-kHz y en la gama de 1 a 1.000 kHz usando un analizador multifrecuencia. De estos parámetros, fueron calculados cinco índices (R/Estatura, Xc/ Estatura, Z/Estatura, reactancia en paralelo, y resistencia en paralelo) a 50 kHz. Se obtuvo el análisis del vector de bioimpedancia eléctrica (BIVA) y se realizó un modelado Cole-Cole. Una vez estimado R/Estatura y Xc/Estatura, fue realizado el análisis de BIVA. La media y la desviación estándar fueron calculadas para todas las variables. La prueba t fue usada para detectar las diferencias entre ambos sexos.Los BIVA fueron comparados usando la T2 de Hotelling. Para contrastar la hipótesis nula de igualdad entre los parámetros examinados, se empleó el nivel de significación de p <0,05. Resultados: En comparación a la población masculina, la población femenina tuvo mayor R, R/Estatura, Xc, Xc/Estatura, Z, Z/Estatura y menor PA (p<0,05). La precisión de BIVA fue diferente entre los sexos (p <0,05) y de acuerdo al índice de masa corporal (≤25 y >25). Las diferencias entre deportes estuvieron relacionadas al valor de Z y AF. Conclusiones: El estudio mostró que la variabilidad de R, Xc, Z y AF dependió del género, de las características de la masa corporal de la población estudiada, y del deporte

Objectives: The purpose of this study is to provide data on bioelectrical parameters in Cuban sport population, particularly: resistance (R), reactance (Xc), impedance (Z), impedance vector component according to bioelectrical impedance vector analysis (BIVA) and phase angle (PhA), establishing references values on athletes of high performance level. Material and method: We performed bioelectrical impedance analysis (BIA) in 943 Cuban athletes (620 male, 323 female) of 26 sports modalities. Bioelectric parameters R, Xc, Z and PhA were obtained at 50-kHz frequency and multi-frequency from 1 to 1000 kHz using a multi-frequency measuring device. From these parameters, five bioimpedance ratios were calculated (R/Height, Xc/ Height, Z/ Height, the reactance paralate, and resistence paralate) at 50 kHz. Bioelectrical impedance vectors analysis (BIVA) and Cole-Cole modeled were performed. Once R/Height and Xc/Height were estimated, the BIVA was performed. Mean and standard deviations were calculated for all variables. Unpaired t-test was used to detect differences between sexes. BIVA vectors were compared using Hotelling’s T2 test. To eliminate a null hypothesis about the equality of the examined parameters, we used the level of probability of p<0.05. Results: Compared to male population, female population had higher R, R/ Height, Xc, Xc/ Height, Z, Z/ Height and lower PhA. The accuracy of specific BIVA was different in the two sexes (p<0.05) and according to the Body Mass Index (≤25 and >25). Differences between sports were found in order to Z and PhA. Conclusions: The study showed that variability of R, Xc, Z and PhA measures depends on gender, body mass characteristics of the study population, and sport

Adenosine-dependent phrenic motor facilitation is inflammation resistant.

Phrenic motor facilitation (pMF), a form of respiratory plasticity, can be elicited by acute intermittent hypoxia (i.e., phrenic long-term facilitation, pLTF) or direct application of drugs to the cervical spinal cord. Moderate acute intermittent hypoxia (mAIH; 3 × 5-min episodes of 35-50 mmHg arterial Po2, 5-min normoxic intervals) induces pLTF by a serotonin-dependent mechanism; mAIH-induced pLTF is abolished by mild systemic inflammation induced by a low dose of lipopolysaccharide (LPS; 100 µg/kg ip). In contrast, severe acute intermittent hypoxia (sAIH; 3 × 5-min episodes of 25-30 mmHg arterial Po2, 5-min normoxic intervals) elicits pLTF by a distinct, adenosine-dependent mechanism. Since it is not known if systemic LPS blocks the mechanism giving rise to sAIH-induced pLTF, we tested the hypothesis that sAIH-induced pLTF and adenosine 2A (A2A) receptor-induced pMF are insensitive to mild systemic inflammation elicited by the same low dose of LPS. In agreement with our hypothesis, neither sAIH-induced pLTF nor cervical intrathecal A2A receptor agonist (CGS-21680; 200 µM, 10 µl × 3)-induced pMF were affected 24 h post-LPS. Pretreatment with intrathecal A2A receptor antagonist injections (MSX-3; 10 µM, 12 µl) blocked sAIH-induced pLTF 24 h post LPS, confirming that pLTF was adenosine dependent. Our results give insights concerning the differential impact of systemic inflammation and the functional significance of multiple cascades capable of giving rise to phrenic motor plasticity. The relative resistance of adenosine-dependent pMF to inflammation suggests that it provides a "backup" system in animals lacking serotonin-dependent pMF due to ongoing inflammation associated with systemic infections and/or neural injury.NEW & NOTEWORTHY This study gives novel insights concerning how a mild systemic inflammation impacts phrenic motor plasticity (pMF), particularly adenosine-dependent pMF. We suggest that since this adenosine-dependent pathway is insensitive to systemic inflammation, it represents an alternative or "backup" mechanism of pMF when other mechanisms are suppressed.

Un enfoque comparativo del pasado y presente de la otitis externa maligna en pacientes diabéticos / A comparative approach of the past and present of malignant external otitis treatment on diabetic patients with quinolones

Se realiza un estudio en pacientes con otitis externa maligna del diabético en el Servicio de Otorrinolaringología del Hospital General Docente de Guantánamo entre 1990-2013, con el objetivo de comparar los resultados antes y después de la incorporación de las quinolonas al tratamiento. El universo estuvo formado por 45 pacientes: 25 del Grupo I, entre 1990-2000, tratados con antibióticos convencionales y 20 del Grupo II, entre 2001-2013, tratados con quinolonas. Las variables estudiadas son: edad y sexo, tipo de diabetes, cuadro clínico, glucemia al ingreso, bacteriología, tratamiento, entre otras. En el Grupo I predominó el dolor nocturno e intenso; se utilizó la combinación de Betalactámicos aminoglucósidos, el mayor número tuvo una estadía hospitalaria entre 31 y 40 días. En el grupo II el dolor fue menos intenso y soportable, la quinolona se utilizó en el 80 por ciento y en 12 pacientes, la estadía resultó inferior a 10 días. La Pseudomona A. se aisló en el 75.5 por ciento de los cultivos. La utilización de las Quinolonas tuvo un gran impacto en los enfermos, desde la modificación del dolor, reversión con prontitud del cuadro clínico; ausencia de complicaciones y disminución de la estadía hospitalaria(AU)

A study is performed on diabetic patients with malignant external otitis in the Department of Otolaryngology, at the General Teaching Hospital Dr Agostino Neto from 1990 to 2013, in order to compare results before and after incorporation of quinolone treatment. The universe consisted of 45 patients: 25 Group I, from 1990 to 2000, treated with conventional antibiotics and 20 Group II, from 2001 to 2013, receiving quinolones. The variables studied were: age, sex, type of diabetes, clinical, admission glycemia, bacteriology, treatment, among others. In Group I prevailed night and intense pain; the combination of beta-lactam was used - aminoglycosides, many patients had a hospital stay between 31 and 40 days. In group II the pain was less intense and endurable, quinolone was used in 80 percent and in 12 patients, the stay was less than 10 days. A. Pseudomonas was isolated in 75.5 percent of cultures. The use of quinolones had a great impact on patients, since the reduction of pain, reversal of the clinical symptoms; absence of complications and reduced of hospital stay(AU)

Churg-Strauss syndrome associated with acalculous cholecystitis and liver involvement.

We describe a 65-year-old man who had liver involvement with Churg-Strauss syndrome. He was admitted to the hospital because of fever, weight loss, dyspnea, abdominal pain, skin lesions and paraesthesias. His past medical history revealed a diagnosis of acalculous cholecystitis that had been made eight months earlier. Microscopic examination of a gall bladder biopsy specimen obtained at that time revealed an increase in extravascular eosinophils. There was evidence of a new bilateral pulmonary disease with bronchoconstriction and a transient infiltrated lesion in the right upper lung. The patient's white cell count was 14 620 per cubic millimetre, with 39% eosinophils (5800 per cubic millimetre) and 39% neutrophils. IgE was 503 g/L (normal range, 0 to 100 g/L). Liver function tests were mildly elevated. Fine needle liver biopsy showed active interface hepatitis. A diagnosis of Churg-Strauss syndrome was made. In this patient the syndrome occurred in a rare association with hepatitis, likely due to immunologic events in the liver. The patient was successfully treated with 60 mg/day of prednisolone monotherapy.