Murine modeling of menstruation identifies immune correlates of protection during Chlamydia muridarum challenge.

The menstrual cycle influences the risk of acquiring sexually transmitted infections (STIs), including Chlamydia trachomatis (C. trachomatis), although the underlying immune contributions are poorly defined. A mouse model simulating the immune-mediated process of menstruation could provide valuable insights into tissue-specific determinants of protection against chlamydial infection within the cervicovaginal and uterine mucosae comprising the female reproductive tract (FRT). Here, we used the pseudopregnancy approach in naïve C57Bl/6 mice and performed vaginal challenge with Chlamydia muridarum (C. muridarum) at decidualization, endometrial tissue remodeling, or uterine repair. This strategy identified that the time frame comprising uterine repair correlated with robust infection and greater bacterial burden as compared with mice on hormonal contraception, while challenges during endometrial remodeling were least likely to result in a productive infection. By comparing the infection site at early time points following chlamydial challenge, we found that a greater abundance of innate effector populations and proinflammatory signaling, including IFNγ correlated with protection. FRT immune profiling in uninfected mice over pseudopregnancy or in pig-tailed macaques over the menstrual cycle identified NK cell infiltration into the cervicovaginal tissues and lumen over the course of endometrial remodeling. Notably, NK cell depletion over this time frame reversed protection, with mice now productively infected with C. muridarum following challenge. This study shows that the pseudopregnancy murine menstruation model recapitulates immune changes in the FRT as a result of endometrial remodeling and identifies NK cell localization at the FRT as essential for immune protection against primary C. muridarum infection.

Neurotoxicity associated with oxidative stress and inflammasome gene expression induced by allethrin in SH-SY5Y cells.

Pyrethroids, including allethrin, have largely been used as commercial insecticides. The toxicity of allethrin is little known, but it is assumed that, as occurs with other pyrethroids, it could cause alterations of the nervous system and pose both occupational and non-occupational health hazards. To evaluate the neurotoxicity of allethrin we used the MTT assay of SH-SY5Y neuroblastoma cells to determine cell viability. Dose-dependent reductions of cell viability served to compare the vehicle-group and the IC50 for allethrin, which was 49.19 µM. ROS production increased significantly at concentrations of 10-200 µM of allethrin, and NO levels were significantly increased by the effect of allethrin at a minimum concentration of 50 µM. Lipid peroxidation increased by the effect of allethrin at concentrations of 25, 50, 100, and 200 µM. Caspase 3/7 activity was induced by allethrin concentrations of 50, 100, and 200 µM. Here, we suggest that allethrin might affect the inflammasome complex (Caspase-1, NLRP3, and PYDC1) and apoptosis (Bax and Bcl-2) gene expression by mRNA fold change expression levels shown in Caspase-1 (2.46-fold), NLRP3 (1.57-fold), PYDC1 (1.48-fold), and Bax (2.1-fold). These results demonstrated that allethrin induced neurotoxicity effects on SH-SY5Y cells through activation of inflammasome pathways, cell death, and oxidative stress.

CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels.

Decreased NAD+ levels have been shown to contribute to metabolic dysfunction during aging. NAD+ decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD+ homeostasis. Here we show that an increase in CD38 in white adipose tissue (WAT) and the liver during aging is mediated by accumulation of CD38+ immune cells. Inflammation increases CD38 and decreases NAD+. In addition, senescent cells and their secreted signals promote accumulation of CD38+ cells in WAT, and ablation of senescent cells or their secretory phenotype decreases CD38, partially reversing NAD+ decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD+ through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that, through its ecto-enzymatic activity, decreases levels of NMN and NAD+.

Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet.

Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Here, we evaluated the in vivo response of beta cells in the pancreatic islets of 8-week-old C57Bl/6J CAV1 KO mice subjected to a control diet (CD, 14% kcal fat) or a HFD (60% kcal fat) for 12 weeks. We observed that CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels, impaired glucose tolerance and were insulin resistant. Some of these alterations were also observed in mice on CD. Interestingly, KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. These in vivo results suggest that although the CAV1 KO mice are metabolically unhealthy, they adapt better to a HFD than WT mice. To shed light on the possible signaling pathway(s) involved, MIN6 murine beta cells expressing (MIN6 CAV) or not expressing (MIN6 Mock) CAV1 were incubated with the saturated fatty acid palmitate in the presence of mitogen-activated protein kinase inhibitors. Western blot analysis revealed that CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. Moreover, all the MAPK inhibitors partially restored MIN6 viability, but the effect was most notable with the ERK inhibitor. In conclusion, our results suggest that CAV1 KO mice adapted better to a HFD despite their altered metabolic state and that this may at least in part be due to reduced beta cell damage. Moreover, they indicate that the ability of CAV1 to increase sensitivity to FFAs may be mediated by MAPK and particularly ERK activation.

Optimizing a Noninvasive Oral Sampling Technique for Semicaptive Neotropical Primates in Peru.

Disease surveillance in Neotropical primates (NP) is limited by the difficulties associated with anesthetizing NP for sample collection in remote settings. Our objective was to optimize a noninvasive method of oral sampling from semicaptive NP in Peru. We offered 40 NP at Taricaya Rescue Centre in Madre de Dios, Peru ropes coated in various attractants and measured variables (acceptance of the rope, chewing time, and volume of fluid eluted from ropes) that may affect sample acquisition and quality. We preserved samples by direct freezing in liquid nitrogen or by storing samples in RNA stabilization reagent at room temperature. Sample integrity was measured by testing for mammalian cytochrome b with the use of conventional PCR. The NP successfully chewed on a rope in 82% (125/152) of trials. Overall sample integrity was high, with 96% (44/46) of samples (both directly frozen and stored in stabilization reagent) testing positive for cytochrome b. The number of times that an individual NP was exposed to the rope procedure and NP age were associated with higher acceptance rates and the NP successfully chewing on the rope. We conclude that ropes serve as a feasible noninvasive method of obtaining oral samples from NP at rescue centers and could be used in future studies to evaluate population genetics and for pathogen surveillance for population health monitoring.

Low dose intrathecal morphine for hip arthroplasty / Dosis baja de morfina intratecal para artroplastía de cadera

OBJETIVES: 100 mcg intrathecal morphine (ITM) for hip arthroplasty provides adequate functional recovery and reduces associated complications but is not exempt from opioid-related adverse effects. We evaluate efficacy of a reduced dose of ITM (80 mcg) in terms of anesthetic quality, postoperative analgesia, complication rates and early recovery. METHODS: Case-control study. Patients under hip arthroplasty were treated on a specific protocol, using neuraxial anesthesia with hyperbaric bupivacaine 10.5-13.5 mg plus 80 mcg ITM versus controls with 100 mcg ITM. Demographic variables, intra and perioperative course were extracted from medical records. Pain severity and morphine associated complications were blindly assessed at regular intervals postoperatively. p < 0.01 were considered significant. RESULTS: 82 patients were analyzed. Mean age was 64.21 years, 62.20% women and 70.73% ASA-2. Main endoprosthesis indication was arthrosis (58.53%). No statistically significant differences in demographic and operative data were found between groups, including surgical time, ambulation time, length of stay, and patient satisfaction for pain management. Mean VAS for pain during first 24 hours was 0.24 for the low ITM group and 0.22 for control. Rescue intravenous morphine was the same between groups. Compared to 80 mcg ITM, 100 mcg showed trends for higher complication rates for respiratory depression (OR 2.58, CI 95% 0.45-14.54, p = 0.28), nausea without vomiting (OR 1.82, CI 95% 0.82-4.01, p = 0.13), urinary retention (OR 2.02, CI 95% 0.88-4.61, p = 0.09) and significantly higher rates of pruritus (OR 3.55, CI 95% 1.61-7.82, p < 0.01). CONCLUSIONS: 80 mcg ITM during spinal anesthesia for hip arthroplasty provided comparable postoperative analgesia and lower incidence of opioid-related adverse effects.

OBJETIVOS: 100 mcg morfina intratecal (ITM), en artroplastia de cadera, proporciona una recuperación funcional adecuada y reduce complicaciones asociadas, pero no está exento de efectos adversos conocidos asociados a opioides. Evaluamos eficacia de reducir dosis (80 mcg ITM) en términos de calidad anestésica, analgesia, complicaciones y recuperación postoperatoria. MÉTODOS: Estudio de casos y controles. Pacientes sometidos a artroplastia de cadera fueron tratados con anestesia espinal con bupivacaína hiperbárica 10,5-13,5 mg más 80 mcg ITM y controles de manera similar pero con 100 mcg ITM. Variables demográficas, así como intra y perioperatorio, se extrajeron de registros médicos. Severidad del dolor, y complicaciones asociadas a ITM, se evaluaron a ciegas según protocolo, p < 0,01 fue considerado significativo. RESULTADOS: 82 pacientes analizados. Edad promedio fue 64,21 años, 62,20% fueron mujeres y 70,73% ASA-2. Principal indicación de prótesis fue artrosis (58,53%). No se encontraron diferencias estadísticas entre variables demográficas, tiempo quirúrgico, tiempo deambulación, duración hospitalización y satisfacción paciente. EVA promedio dolor, primeras 24 horas, fue 0,24 para grupo 80 mcg ITM y 0,22 para control (100 mcg ITM). Morfina intravenosa de rescate fue similar entre grupos. En comparación con 80 mcg, 100 mcg presentó mayores tasas de complicaciones para depresión respiratoria (OR 2,58, IC95% 0,45-14,54, p = 0,28), náuseas y vómitos (OR 1,82, CI95% 0,82-4,01, p = 0,13), retención urinaria (OR 2,02, CI95% 0,88-4,61, p = 0,09) y prurito (OR 3,55, CI95% 1,61-7,82, p < 0,01). CONCLUSIONES: 80 mcg ITM, en anestesia espinal para artroplastia cadera, proporciona analgesia postoperatoria comparable a 100 mcg pero con menor incidencia de efectos adversos relacionados a opioides.

Parche de sangre epidural torácico, de alto volumen, para el tratamiento del Síndrome de Hipotensión Intracraneana Espontánea secundario a fuga cervical de líquido cefalorraquídeo, ¿mejora el período asintomático?. Reporte de caso / High blood volume thoracic epidural patch for the treatment of spontaneous intracranial hypotension syndrome due to cervical cerebrospinal fluid leak, It prolongs the asymptomatic period?. A case report

Mujer de 50 años, con historia de 3 semanas de cefalea ortostática progresiva y síntomas neurológicos inespecíficos, confirmándose higroma subdural a nivel C5 con fuga de líquido cefalorraquídeo compatible con Síndrome de Hipotensión Intracraneal Espontánea (SHIE). Tratamiento médico inicial sin respuesta. Se realiza parche sanguíneo epidural (PSE) a nivel torácico con 20 ml de sangre directo a través de trocar epidural, observándose respuesta terapéutica completa en seguimiento hasta 8 meses. Creemos que un PSE torácico ofrece las ventajas de uno cervical y lumbar y, por lo tanto, debe considerarse una alternativa terapéutica eficaz en este síndrome especialmente en pacientes anatómicamente complejos.

A 50-year-old woman, with a history of three-week orthostatic headache and nonspecific neurological symptoms, has a subdural hygroma at C5 level with a cerebrospinal fluid leakage compatible with Spontaneous Intracranial Hypotension Syndrome (SIHS). Initial conservative treatment has no response. A thoracic epidural blood patch (EBP) is performed, with a 20ml blood volume spread through an epidural needle, with a complete therapeutic response up-to 8 months. We believe that a higher blood volume patch through a thoracic approach gives the advantages of cervical and lumbar EBP, and, therefore, should be considered as a therapeutic alternative especially in technical anatomically difficult patients.

Educación Médica Continua SOPNIA. Experiencia de Implementación de Cursos E-Learning en Neurología Pediátrica / Continuing medical education SOPNIA. Experience of implementing e-learning courses in Pediatric Neur

Resumen: El programa de Educación Médica Continua (EMC) de SOPNIA consiste en actividades científicas orientadas a la actualización permanente en Neurología y Psiquiatría de niños y adolescentes. Está dirigido a socios SOPNIA, médicos especialistas en Neurología Pediátrica, Psiquiatría de la Infancia y Adolescencia y médicos especialistas certificados de especialidades afines (1).Este programa desde el año 2014 inicia cursos de capacitación de post grado vía e-learning, ya que este sistema permite flexibilidad de tiempo, mayores oportunidades para acceso, favorece el desarrollo de competencias y destrezas específicas como el estudio autorregulado, con una modalidad 100% on-line a través de nuestra plataforma vía página web de SOPNIA. Se analiza experiencia realizada Palabras clave: educación médica continua, Psiquiatría infantil, Neurología pediátrica, curso e-learning, educación en página web.

The continued medical education program (EMC) of SOPNIA consists of scientific activities aimed at updating physicians on pediatric neurology and psychiatry. It is aimed at SOPNIA members, specialists in pediatric neurology, child and adolescent psychiatry and certified physicians of related medial specialties.Since 2014, this program began graduate training via e-learning, for this system allows time flexibility, greater access opportunity, favors the development of specific skills and competencies such as self-regulated study, with a 100% online mode through our platform via SOPNIA website. We analyze our experience.Key words: continued medical education, child and adolescent psychiatry, pediatric neurology, e-learning, online education, website education

Aproximación clínica al diagnóstico diferencial de los trastornos del movimiento en la infancia / Clinical approach to the differential diagnosis of childhood movement disorders

El control del movimiento implica redes complejas que relacionan diferentes aspectos de la neuroanatomía, bioquímica, fisiología de los ganglios basales, cerebelo y sus conexiones. En la aproximación clínica de este tipo de trastorno debemos orientarnos según el tipo de movimiento hacia la etiología y, si bien, lo clásico es definir estos trastornos según el tipo de movimiento, existen otras propuestas de un sistema de clasificación que los divide en 4 categorías principales que incluyen: Trastornos Transitorios del Desarrollo, Trastornos del Movimiento Paroxísticos, Trastornos de movimiento secundarios a causas no hereditarias y Trastornos Hereditarios-Metabólicos, que será el enfoque de esta revisión. Palabras claves: desórdenes del movimiento, tics, movimientos paroxísticos, movimientos transitorios del desarrollo. Movimientos hereditarios-metabólicos

The motion control involves complex networks that relate different aspects of neuroanatomy, biochemistry, physiology of the basal ganglia, cerebellum and its connections. The clinical approach of this type of disorder is guided to etiology by the type of movement, and while these disorders have been classically defined according to the type of movement, there is another proposed classification system that divides them in 4 main categories that include: transient developmental movement disorders, paroxysmal movement disorders, non-hereditary and hereditary-metabolic movement disorders, which will be the focus of this review. Key words: disordes of movements, tics, movements of hereditary and metabolic disorders, transient movements of the development