Tratamiento mediante neurólisis ecoguiada con fenol 6 % acuoso del componente álgico por neuromas postamputación: a propósito de un caso / Treatment by ultrasound-guided neurolysis with 6 % aqueous phenol of the pain component for post-amputation neuromas: report of a clinical case

Introducción: El tratamiento del dolor producido por neuromas es en sí complejo. Las opciones de tratamiento una vez se ha descartado la vía quirúrgica son pocas, si bien el impacto que dicho dolor produce en la vida de los pacientes obliga a buscar en estos casos alternativas que ofrezcan un control aceptable del mismo. El objetivo es presentar la neurólisis como una alternativa eficaz para el dolor por neuromas. Caso clínico: Reporte de caso, descriptivo y retrospectivo, de paciente perteneciente al Sistema Nacional de Salud, llevado a cabo por la Unidad de Dolor del Servicio de Anestesiología y Reanimación del Hospital Universitario Joan XXIII.Paciente de 59 años a quien, tras rechazar la cirugía, se le realizó neurólisis ecoguiada con fenol al 6 % acuososo para el tratamiento del dolor por neuromas derivados de la amputación de ambos miembros superiores. Discusión: La infiltración con fenol 6 % acuoso puede llegar a disminuir considerablemente el dolor durante un tiempo igual o superior a los 6 meses, otorgando una mejoría significativa en la calidad de vida de los pacientes.(AU)

Introduction: Magement of pain caused by neuromas is in itself complex. The treatment options once the surgical route has been ruled out are few, although the impact that this pain produces in the lives of patients makes it necessary to look for alternative cases that offer acceptable control of it. The objective is to present neurolysis as an effective alternative for pain due to neuromas. Case report: Descriptive and retrospective case report of a patient belonging to the National Health System, carried out by the Pain Unit of the Anesthesiology and Resuscitation Service of the Hospital Universitario Joan XXIII. 59-year-old patient who, after refusing surgery, underwent ultrasound-guided neurolysis with 6 % aqueous phenol for the treatment of pain due to neuromas derived from the amputation of both upper limbs. Discusion: Infiltration with 6 % aqueous phenol can considerably reduce pain, for a time equal to or greater than 6 months, granting a significant improvement in the quality of life of patients.(AU)

Tyramine Acts Downstream of Neuronal XBP-1s to Coordinate Inter-tissue UPRER Activation and Behavior in C. elegans.

In C. elegans, expression of the UPRER transcription factor xbp-1s in neurons cell non-autonomously activates the UPRER in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPRER activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPRER activation and extended longevity, and exposure to stress led to splicing and activation of xbp-1 in these neurons. In addition, we found that neuronal xbp-1s modulates feeding behavior and reproduction, dependent upon tyramine synthesis. XBP-1s therefore remodels neuronal signaling to coordinately modulate intestinal physiology and stress-responsive behavior, functioning as a global regulator of organismal responses to stress.

Neuronal XBP-1 Activates Intestinal Lysosomes to Improve Proteostasis in C. elegans.

The unfolded protein response of the endoplasmic reticulum (UPRER) is a crucial mediator of secretory pathway homeostasis. Expression of the spliced and active form of the UPRER transcription factor XBP-1, XBP-1s, in the nervous system triggers activation of the UPRER in the intestine of Caenorhabditis elegans (C. elegans) through release of a secreted signal, leading to increased longevity. We find that expression of XBP-1s in the neurons or intestine of the worm strikingly improves proteostasis in multiple tissues, through increased clearance of toxic proteins. To identify the mechanisms behind this enhanced proteostasis, we conducted intestine-specific RNA-seq analysis to identify genes upregulated in the intestine when XBP-1s is expressed in neurons. This revealed that neuronal XBP-1s increases the expression of genes involved in lysosome function. Lysosomes in the intestine of animals expressing neuronal XBP-1s are more acidic, and lysosomal protease activity is higher. Moreover, intestinal lysosome function is necessary for enhanced lifespan and proteostasis. These findings suggest that activation of the UPRER in the intestine through neuronal signaling can increase the activity of lysosomes, leading to extended longevity and improved proteostasis across tissues.

[Two new cases of Leigh syndrome caused by mutation m.13513G> A in the MTND5 gene]. / Dos nuevos casos de sindrome de Leigh por mutacion m.13513G>A en el gen MTND5.

TITLE: Dos nuevos casos de sindrome de Leigh por mutacion m.13513G>A en el gen MTND5.

Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells.

BACKGROUND: Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division. METHODS AND FINDINGS: Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented. CONCLUSIONS: Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis.

Fitness trade-offs and environmentally induced mutation buffering in isogenic C. elegans.

Mutations often have consequences that vary across individuals. Here, we show that the stimulation of a stress response can reduce mutation penetrance in Caenorhabditis elegans. Moreover, this induced mutation buffering varies across isogenic individuals because of interindividual differences in stress signaling. This variation has important consequences in wild-type animals, producing some individuals with higher stress resistance but lower reproductive fitness and other individuals with lower stress resistance and higher reproductive fitness. This may be beneficial in an unpredictable environment, acting as a "bet-hedging" strategy to diversify risk. These results illustrate how transient environmental stimuli can induce protection against mutations, how environmental responses can underlie variable mutation buffering, and how a fitness trade-off may make variation in stress signaling advantageous.

Predicting mutation outcome from early stochastic variation in genetic interaction partners.

Many mutations, including those that cause disease, only have a detrimental effect in a subset of individuals. The reasons for this are usually unknown, but may include additional genetic variation and environmental risk factors. However, phenotypic discordance remains even in the absence of genetic variation, for example between monozygotic twins, and incomplete penetrance of mutations is frequent in isogenic model organisms in homogeneous environments. Here we propose a model for incomplete penetrance based on genetic interaction networks. Using Caenorhabditis elegans as a model system, we identify two compensation mechanisms that vary among individuals and influence mutation outcome. First, feedback induction of an ancestral gene duplicate differs across individuals, with high expression masking the effects of a mutation. This supports the hypothesis that redundancy is maintained in genomes to buffer stochastic developmental failure. Second, during normal embryonic development we find that there is substantial variation in the induction of molecular chaperones such as Hsp90 (DAF-21). Chaperones act as promiscuous buffers of genetic variation, and embryos with stronger induction of Hsp90 are less likely to be affected by an inherited mutation. Simultaneously quantifying the variation in these two independent responses allows the phenotypic outcome of a mutation to be more accurately predicted in individuals. Our model and methodology provide a framework for dissecting the causes of incomplete penetrance. Further, the results establish that inter-individual variation in both specific and more general buffering systems combine to determine the outcome inherited mutations in each individual.

Community structure of lice (Insecta: Phthiraptera) from two sympatric gull species: kelp gull (Larus dominicanus) and Franklin's gull (Larus pipixcan) in Talcahuano, Chile.

A total of 1,177 lice of four species were collected from 124 kelp gulls (Larus dominicanus) and 137 lice of the same four species from 60 Franklin's gulls (Larus pipixcan). The louse Saemundssonia lari (O Fabricius) (Phthiraptera: Philopteridae) was the most numerous on both gull species, with infestation rates of 4.9 on kelp gulls and 1.8 on Franklin's gulls. The second most abundant louse was Quadraceps punctatus (Burmeister), with a high infestation rate but low prevalence on kelp gulls; those parameters were much lower among lice from Franklin's gulls. The composition and community structure of the lice were similar on both host species, but not their infestation rates. In addition, the feather mite Zachvatkinia larica Mironov (Acari: Avenzoariidae) is recorded from kelp gulls and Franklin's gulls for the first time, while the gamasid mite Larinyssus sp. is recorded from kelp gulls, also for the first time. The population parameters of all species of ectoparasites are discussed.

Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells.

Protein homeostasis maintains proper intracellular balance by promoting protein folding and clearance mechanisms while minimizing the stress caused by the accumulation of misfolded and damaged proteins. Chronic expression of aggregation-prone proteins is deleterious to the cell and has been linked to a wide range of conformational disorders. The molecular response to misfolded proteins is highly conserved and generally studied as a cell-autonomous process. Here, we provide evidence that neuronal signaling is an important modulator of protein homeostasis in post-synaptic muscle cells. In a forward genetic screen in Caenorhabditis elegans for enhancers of polyglutamine aggregation in muscle cells, we identified unc-30, a neuron-specific transcription factor that regulates the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We used additional sensors of protein conformational states to show that defective GABA signaling or increased acetylcholine (ACh) signaling causes a general imbalance in protein homeostasis in post-synaptic muscle cells. Moreover, exposure to GABA antagonists or ACh agonists has a similar effect, which reveals that toxins that act at the neuromuscular junction are potent modifiers of protein conformational disorders. These results demonstrate the importance of intercellular communication in intracellular homeostasis.

Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling.

The available experimental data support the hypothesis that the cap cells (CpCs) at the anterior tip of the germarium form an environmental niche for germline stem cells (GSCs) of the Drosophila ovary. Each GSC undergoes an asymmetric self-renewal division that gives rise to both a GSC, which remains associated with the CpCs, and a more posterior located cystoblast (CB). The CB upregulates expression of the novel gene, bag of marbles (bam), which is necessary for germline differentiation. Decapentaplegic (Dpp), a BMP2/4 homologue, has been postulated to act as a highly localized niche signal that maintains a GSC fate solely by repressing bam transcription. Here, we further examine the role of Dpp in GSC maintenance. In contrast to the above model, we find that an enhancer trap inserted near the Dpp target gene, Daughters against Dpp (Dad), is expressed in additional somatic cells within the germarium, suggesting that Dpp protein may be distributed throughout the anterior germarium. However, Dad-lacZ expression within the germline is present only in GSCs and to a lower level in CBs, suggesting there are mechanisms that actively restrict Dpp signaling in germ cells. We demonstrate that one function of Bam is to block Dpp signaling downstream of Dpp receptor activation, thus establishing the existence of a negative feedback loop between the action of the two genes. Moreover, in females doubly mutant for bam and the ubiquitin protein ligase Smurf, the number of germ cells responsive to Dpp is greatly increased relative to the number observed in either single mutant. These data indicate that there are multiple, genetically redundant mechanisms that act within the germline to downregulate Dpp signaling in the Cb and its descendants, and raise the possibility that a Cb and its descendants must become refractory to Dpp signaling in order for germline differentiation to occur.

[Television watching habits in children in Cantabria]. / Hábito televisivo en los niños de Cantabria.

OBJECTIVE: To determine television viewing habits in Cantabrian children and the influence of these habits on their health and development. MATERIAL AND METHODS: A transversal survey was carried out in the parents of 796 children aged 2-13 years old with the help of 47 primary care pediatricians. The chi-square, Mann-Whitney and Kruskal-Wallis tests as well as multiple regression analysis were used for the statistical analysis. RESULTS: Children aged 2-5 years old watched television for 9 hours/week, those aged 6-9 years watched 12.5 hours/ week and those aged 10-13 years watched 14.6 hours/week. Nineteen percent of the families had three or more televisions in their homes. The presence of a television, computer or video games in the child's room increased with age and was 15%, 9% and 10%, respectively. Girls aged 10-13 years were more likely to have computers in their rooms (20% versus 9% of boys of the same age),while boys aged 10-13 were more likely to have video games than girls (22% versus 12%, respectively). Twenty-seven percent of the children watched television alone, 29% watched it while having breakfast and 36% while having lunch or dinner. Fifty-eight percent of the children never ate sweets while watching television and only 1% habitually did so. Obese children and those with a chronic illness watched television more (4.5 and 3 hours/week, respectively) than healthy children. Children with lower school performance watched more television (2.85 hours/week) p < 0.001). CONCLUSIONS: Pediatricians should carry out health education on the number of hours children should spend in front of the television, advising a limit of less than 2 hours/day (the ideal time would be less than 1 hour/day). Parents should watch television with their children, discuss the programs with them and teach them to be critical. The presence of television sets in children's rooms should be avoided and television should not be used as a nanny.

Valoración de la conducta de los niños de Cantabria mediante el cuestionario de Eyberg / Evaluation of Cantabrian children`s behaviour using the Eyberg child behaviour inventoryambulatory

ANTECEDENTES: El pediatra de atención primaria debe ser capaz de detectar las alteraciones de conducta en los niños, ya que estos problemas se hallan presentes en aproximadamente un 50 por ciento de las consultas pediátricas. Para ello es necesario disponer de un instrumento útil y de fácil cumplimentación como es el cuestionario de Eyberg sobre la conducta infantil. OBJETIVO: Conocer la prevalencia de alteraciones de la conducta infantil mediante la utilización del cuestionario de Eyberg y su posible influencia por determinadas variables (edad, sexo, estudios de los padres, televisión, lectura y rendimiento escolar).MATERIAL Y MÉTODOS: Estudio transversal realizado en junio de 1998 mediante cumplimentación por parte de los padres de 796 niños de 2-13 años, de la versión española del cuestionario de Eyberg para el cribado de las alteraciones de conducta en los niños. Todos los niños incluidos procedían de las consultas pediátricas ubicadas en los centros de salud de Cantabria, colaborando 47 pediatras de atención primaria. RESULTADOS: Un 17,2 por ciento de los niños de Cantabria de 2-13 años presenta anomalías de conducta, siendo similar por grupos de edad y sexo, excepto en las niñas mayores (10-13 años), que son las que menos trastornos de conducta manifiestan (p < 0,011). La conducta más frecuentemente referida fue "le cuesta estar quieto un momento" (25,6 por ciento) y la que menos, "pega a los padres" (0,4 por ciento). Se asoció una menor frecuencia de alteraciones de conducta a tener menos edad, ser niña, nivel de formación mayor de los padres y haber comenzado a ver la televisión más tardíamente, mientras que se asoció con mayor frecuencia de conductas alteradas el hecho de un mayor número de horas dedicadas a ver televisión. Hasta 2,84 horas más a la semana ven la televisión los niños con alteraciones de la conducta en comparación con los demás niños, siendo esta diferencia de 4,99 horas más a la semana en los niños de 10-13 años. CONCLUSIÓN: La prevalencia de alteraciones de la conducta encontrada en nuestra población hace necesaria la utilización del cuestionario de Eyberg en los controles de salud que realiza el pediatra de atención primaria (AU)

Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers (MERRF).

OBJECTIVES: We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy in blood samples of 13 individuals belonging to a three family generation of myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected patients and the 8 unaffected relatives. MATERIAL AND METHODS: DNA was extracted from blood and muscle of the proband and from blood of 12 maternal relatives. A PCR restriction analysis method was used to detect the mutation. RESULTS: The proband had the complete MERRF phenotype. The phenotype in three other individuals in the maternal lineage was consistent with the MERRF syndrome. The remaining were asymptomatic. The np 8344 mutation was observed in muscle and blood of the proband, and in blood from every one of 12 maternal relatives, ranging from 44% to 83% of mutated genomes. Symptomatic individuals had higher levels (P < 0.001) of mutated mtDNA than asymptomatic maternal relatives. However, high proportions of mutant genomes (up to 63%) were found in asymptomatic relatives. CONCLUSIONS: Although there seems to be a gene dosage effect in MERRF, we found no absolute relationship between the relative proportion of mutant genomes in blood and clinical severity. Factors other than gene dosage in blood may account for the differences in clinical phenotype.

Lack of alloimmunization to D antigen in D-negative immunosuppressed liver transplant recipients.

BACKGROUND: Orthotopic liver transplantation (OLT) sometimes requires large amounts of blood. An adequate supply of Rh-negative blood for Rh-negative patients is not always available. STUDY DESIGN AND METHODS: Seventeen Rh-negative patients, out of 327 receiving OLT in this hospital, received from 5 to 41 units of Rh-positive red cells during surgery. Each of the 17 patients was followed for 7 weeks to 70 months after OLT for detection of unexpected antibodies. Cyclosporin A and prednisone, azathioprine, and adjunctive rabbit antilymphocyte globulin or monoclonal OKT3 antibody were used to prevent graft rejection. RESULTS: Evidence of immunization, either to D or to antigens in the rest of the red cell antigen systems, did not appear in any patients. CONCLUSION: It is hypothesized that cyclosporin A affects the immune humoral response, inhibiting lymphocyte activation and the primary immune response; consequently, Rh-positive blood may be transfused to Rh-negative OLT recipients so treated with little or no risk of alloimmunization.