Pure quartic modulational instability in weakly nonlocal birefringent fibers.

The modulational instability (MI) phenomenon is theoretically investigated in birefringent optical media with pure quartic dispersion and weak Kerr nonlocal nonlinearity. We find from the MI gain that instability regions are more expanded due to nonlocality, which is confirmed via direct numerical simulations showing the emergence of Akhmediev breathers (ABs) in the total energy context. In addition, the balanced competition between nonlocality and other nonlinear and dispersive effects exclusively gives the possibility of generating long-lived structures which deepens our understanding of soliton dynamics in pure-quartic dispersive optical systems and opens new investigation routes in fields related to nonlinear optics and lasers.

Higher-order dispersion and nonlinear effects of optical fibers under septic self-steepening and self-frequency shift.

We investigate the modulational instability (MI) of a continuous wave (cw) under the combined effects of higher-order dispersions, self steepening and self-frequency shift, cubic, quintic, and septic nonlinearities. Using Maxwell's theory, an extended nonlinear Schrödinger equation is derived. The linear stability analysis of the cw solution is employed to extract an expression for the MI gain, and we point out its sensitivity to both higher-order dispersions and nonlinear terms. In particular, we insist on the balance between the sixth-order dispersion and nonlinearity, septic self-steepening, and the septic self-frequency shift terms. Additionally, the linear stability analysis of cw is confronted with the stability conditions for solitons. Different combinations of the dispersion parameters are proposed that support the stability of solitons and the occurrence of MI. This is confronted with full numerical simulations where the input cw gives rise to a broad range of behaviors, mainly related to nonlinear patterns formation. Interestingly, under the activation of MI, a suitable balance between the sixth-order dispersion and the septic self-frequency shift term is found to highly influence the propagation direction of the optical wave patterns.

Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4.

HCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV-infected patients from GS-US-337-1119 and GS-US-342-1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep-sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS-US-337-1119 and 116 patients enrolled in GS-US-342-1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS-US-337-1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance-associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2-4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS-US-342-1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested. LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates.

[A training medication errors room: simulate to better train health professionals]. / La chambre des erreurs médicamenteuses: simuler pour mieux former.

BACKGROUND: Medication errors (ME) could lead to severe adverse events. Hospital staff have to gain practical knowledge and ME preventing methods. Simulation is a teaching method more and more used in health system. The aim of this study was to create an error patient room which represents a factitious patient room with ME for health professionals of the hospital. METHOD: Chosen according 3 criteria (errors already observed, "never events" related errors, errors associated with frequent issues), 21 ME were designed concerning the different steps of the medication process (prescribing, dispensing and administration) and took place in a patient room reserved for training. Seven sessions were proposed from april to june 2014. All health professionals were invited to participate on a voluntary basis. Training session was not time limit. An individual debriefing was done after each session. RESULTS: Forty-six health professional participated of 13 different hospitals' departments: 7 medicine residents, 26 nurses and 13 persons of the pharmacy staff (8 pharmacy technicians, 3 pharmacy students and 2 pharmacists). EM rate ranged of 33% (medicine residents), 50% (nurses) to 47% (pharmacy staff). DISCUSSION - CONCLUSION: The training ME room represents an easy, useful and reusable simulating tool, to train health professional and to improve their knowledge's and practical methods. This learning tool is developed in order to provide patient safety. This successful study will be evaluated by satisfaction questionnaire. Future sessions will be programmed.

[Individualized pharmaceutical consultations in the management of chemotherapy-induced nausea and vomiting]. / Place des consultations pharmaceutiques individualisées dans la prise en charge des nausées et vomissements chimio-induits.

In order to prevent and control the chemotherapy-induced nausea and vomiting (CINV), the military hospital Percy (Clamart, France) developed a systematic "CINV consultation". With 1.500 consultations conducted in 2013, the aim of this study was to confront professional practices and the patient's point of view to assess the efficiency of this procedure and consider a restructuring to optimize it. A preliminary study was conducted: 30 medical records of patients who had chemotherapy cure during 2013 have been analysed and 30 patients have completed an evaluation questionnaire anonymously. Patients were very satisfied (63%) or satisfied (37%) of these consultations. Most of them (71%) said the consultations were useful before every cure, while 27% thought that the consultation at first cure or when the chemotherapy protocol changed was enough. CINV consultations were estimated as complementary of the medical consultation for 93% of the patients. Most of the patients (70%) never had CINV or just at the first cure. Furthermore, the anti-emetic treatment was adapted to the new chemotherapy emetic level in only 53% of protocol changes. Patients have expressed a real interest in these CINV consultations and the benefits they could get from them. Moreover, patients' side effects are stabilized faster thanks to those pharmaceutical interviews. In fact, it seems that these consultations are mostly needed for the first cure (until patient stabilization) and when there is a chemotherapy protocol change.

[Review of medication errors: a case in an intensive care unit]. / Revue des erreurs médicamenteuses (REMED) : une première en service de réanimation.

OBJECTIVE: The authors conducted for the first time a medication error review (REMED) following a medication error occurred in an intensive care unit. The aim of this study was to assess this first REMED. STUDY DESIGN: Descriptive study. METHODS: The analysis of the medication error, consisting in the administration of Clottafact(®) instead of Aclotine(®), was performed using the REMED method. RESULTS: The medication error was characterized as "proved error" and "missed before administration". Four main causes were identified: poor quality of drug storage, homophony between Aclotine(®) and Clottafact(®), non-compliance with good practices, and need of hemofiltration for the patient. At least, this REMED analysis led to the establishment of four improvements measures. CONCLUSION: The educational aspect of the REMED was clearly appreciated by all the different health care workers who participated to the analysis. Even if medication errors may occur at the different steps of the medication process, the REMED is a very good tool to improve the care quality and also to reduce the drug iatrogenic risk.

Generation of pulse trains in nonlinear optical fibers through the generalized complex Ginzburg-Landau equation.

We consider a higher-order complex Ginzburg-Landau equation, with the fourth-order dispersion and cubic-quintic nonlinear terms, which can describe the propagation of an ultrashort subpicosecond or femtosecond optical pulse in an optical fiber system. We investigate the modulational instability (MI) of continuous wave solution of this equation. Several types of modulational instability gains are shown to exist in both the anomalous and normal dispersion regimes. We find that depending on the sign of the fourth-order dispersion coefficient, the MI appears for normal and anomalous dispersion regime. Simulations of the full system demonstrate that the development of the MI leads to establishment of a regular or chaotic array of pulses, a chain of well-separated peaks with continuously growing or decaying amplitudes depending on the sign of the loss/gain coefficient and higher-order dispersions terms. Comparison of the calculations with reported numerical results shows a satisfactory agreement.

[Celiac disease associated with antiphospholipid syndrome]. / Enfermedad celiaca asociada a síndrome antifosfolípido.

INTRODUCTION: celiac disease may be associated with pathologies of immune etiology. We present its association with antiphospholipid syndrome. CASE 1: a 26-year-old female was diagnosed with celiac disease. Six months later she became pregnant, and experienced fetal death. The following year she became pregnant again. IgG anticardiolipin antibodies: 20 GPL U/ml (normal value < 11), and IgM anticardiolipin antibodies: 9 MPL U/ml (n. v. < 10). Hematological tests were otherwise uneventful. Medicated with acetylsalicylic acid she had a normal pregnancy. CASE 2: a 48-year-old female diagnosed with celiac disease presented with thrombosis in her left lower limb and renal infarction. Hematological tests showed no prothrombotic alterations (antiphospholipid antibodies were not measured). A year and a half later she had thrombosis in a finger of her hand. IgG anticardiolipin antibodies: 10 GPL (n. v. < 13), and IgM anticardiolipin antibodies: 35 MPL (n. v. < 12). CASE 3: a 38-year-old female was diagnosed with celiac disease. Some time later she experienced two spontaneous abortions and a transient ischemic cerebral attack. Nowadays, she is in her sixth month of pregnancy. IgM anticardiolipin antibodies: 75 MPL/ml (n. v. up to 20), and IgG anticardiolipin antibodies within normal values. Hematological tests revealed no other prothrombotic alterations. DISCUSSION: antiphospholipid syndrome is characterized by arterial and venous thrombosis, and spontaneous fetal death. Its association with celiac disease has been described in few cases. Celiac disease is associated with spontaneous fetal death; consequently, we hypothesize that antiphospholipid syndrome may be one of the causes for this event.

Enfermedad celiaca asociada a síndrome antifosfolípido / No disponible

Introducción: la enfermedad celiaca puede asociarse a patologíasde etiología inmunológica. Presentamos su asociación consíndrome antifosfolípido.Caso 1: mujer, 26 años, diagnosticada de enfermedad celiaca.Seis meses después queda embarazada, presentando muertefetal. Al año siguiente nuevo embarazo. Anticuerpos anticardiolipinaIgG: 20 GPL U/ml (valor normal < 11) y anticardiolipinaIgM: 9 MPL U/ml (v.n. < 10). Estudio hematológico sin otras alteracionesprotrombóticas. Medicada con ácido acetilsalicílicopresenta embarazo normal.Caso 2: mujer, 48 años, diagnosticada de enfermedad celiaca,presentó trombosis de extremidad inferior e infarto renal. Examenhematológico sin alteraciones protrombóticas (no se dosaronanticuerpos antifosfolípidos). Año y medio después trombosis dededo de mano. Anticuerpos anticardiolipina IgG: 10 GPL (v.n. <13) y anticardiolipina IgM: 35 MPL (v.n. < 12).Caso 3: mujer, 38 años, diagnosticada de enfermedad celiaca.Posteriormente dos abortos espontáneos y un accidente isquémicotransitorio cerebral. Actualmente está en el sexto mes deembarazo, anticuerpos anticardiolipina IgM 75 MPL/ml (v.n. hasta20) y anticardiolipina IgG en valores normales. El estudio hematológicono evidenció otras alteraciones protrombóticas.Discusión: el síndrome antifosfolípido se caracteriza portrombosis arterial y venosa y muerte fetal espontánea. Su asociacióna enfermedad celiaca ha sido descrita en pocos casos. La enfermedadceliaca se asocia a muerte fetal espontánea, pudiéndosehipotetizar que el síndrome antifosfolípido podría ser una de lascausas de este fenómeno

Introduction: celiac disease may be associated with pathologies of immune etiology. We present its association with antiphospholipidsyndrome.Case 1: a 26-year-old female was diagnosed with celiac disease.Six months later she became pregnant, and experienced fetaldeath. The following year she became pregnant again. IgG anticardiolipinantibodies: 20 GPL U/ml (normal value < 11), andIgM anticardiolipin antibodies: 9 MPL U/ml (n. v. < 10). Hematologicaltests were otherwise uneventful. Medicated with acetylsalicylicacid she had a normal pregnancy.Case 2: a 48-year-old female diagnosed with celiac diseasepresented with thrombosis in her left lower limb and renal infarction.Hematological tests showed no prothrombotic alterations(antiphospholipid antibodies were not measured). A year and ahalf later she had thrombosis in a finger of her hand. IgG anticardiolipinantibodies: 10 GPL (n. v. < 13), and IgM anticardiolipinantibodies: 35 MPL (n. v. < 12).Case 3: a 38-year-old female was diagnosed with celiac disease.Some time later she experienced two spontaneous abortionsand a transient ischemic cerebral attack. Nowadays, she is inher sixth month of pregnancy. IgM anticardiolipin antibodies:75 MPL/ml (n. v. up to 20), and IgG anticardiolipin antibodieswithin normal values. Hematological tests revealed no other prothromboticalterations.Discussion: antiphospholipid syndrome is characterized byarterial and venous thrombosis, and spontaneous fetal death. Itsassociation with celiac disease has been described in few cases.Celiac disease is associated with spontaneous fetal death; consequently,we hypothesize that antiphospholipid syndrome may beone of the causes for this event (AU)

La salud pública en la historia de Chile / Public health in the history of Chile

El presente trabajo expone una visión sinóptica del proceso de construcción de un cuerpo de conocimientos y un sistema organizacional complejo, orientados al enfrentamiento de las amenazas al bienestar y el nivel de salud de la población chilena desde los inicios de la República hasta nuestro días. Se detallan las diferentes entidades mórbidas que han afectado a la sociedad chilena, enfatizándose la profunda interrelación entre éstas y las condiciones de pobreza, marginalidad e inequidad, así como las variadas propuestas de solución emergidas en contextos históricos particulares. Asimismo se pone de relieve el rol del estamento médico -a través de su incipiente participación desde fines del siglo XIX en la esfera política-, en catalizar procesos de cambio y toma de conciencia social respecto al tema. (AU)

Hiperplexia y pseudotetania en la encefalopatía de Hashimoto / Hyperlexia and pseudotetanus in Hashimoto´s encephalopathy

No disponible

No disponible

Developmental regulation of tyrosine phosphorylation of the nicotinic acetylcholine receptor in Torpedo electrocyte.

Tyrosine phosphorylation is thought to play a critical role in the clustering of acetylcholine receptors (AChR) at the developing neuromuscular junction. Yet, in vitro approaches have led to conflicting conclusions regarding the function of tyrosine phosphorylation of AChR beta subunit in AChR clustering. In this work, we followed in situ the time course of tyrosine phosphorylation of AChR in developing Torpedo electrocyte. We observed that tyrosine phosphorylation of the AChR beta and delta subunits occurs at a late stage of embryonic development after the accumulation of AChRs and rapsyn in the membrane and the onset of innervation. Interestingly, in the mature postsynaptic membrane, we observed two populations of AChR differing both in their phosphotyrosine content and distribution. Our data are consistent with the notion that tyrosine phosphorylation of the AChR is related to downstream events in the pathway regulating AChR accumulation rather than to initial clustering events.

Effects of training on exercise-induced muscle damage and interleukin 6 production.

To address the question of whether the increased plasma concentration of interleukin 6 (IL-6) following strenuous muscular work could be related to exercise-induced muscle damage, 5 moderately active male volunteers underwent two isokinetic exercise sessions in the eccentric mode, separated by a period of 3 weeks during which the subjects underwent five training sessions. Before training, exercise was followed by severe muscle pain (delayed-onset muscle soreness; DOMS), and by significant increases in plasma IL-6 level and serum myoglobin concentration (SMb) (P < 0.001). After training, postexercise DOMS and SMb values were significantly lower than those measured before training. There was no significant difference between plasma IL-6 levels measured at the same time points before and after training. We conclude that the hypothetical relationship between exercise-induced muscle damage and increased postexercise levels of circulating IL-6 is not substantiated by the present results.

Targeting of acetylcholine receptor and 43 kDa rapsyn to the postsynaptic membrane in Torpedo marmorata electrocyte.

In this study we have investigated the intracellular routing of two major components of the postsynaptic membrane in Torpedo electrocytes, the nicotinic acetylcholine receptor and the extrinsic 43 kDa protein rapsyn, and of a protein from the non-innervated membrane, the Na+,K+ ATPase. We isolated subpopulations of post-Golgi vesicles (PGVs) enriched either in AChR or in Na+,K+ ATPase. Rapsyn was associated to AChR-containing PGVs suggesting that both AChR and rapsyn are targeted to intracellular organelles in the secretory pathway before delivery to the postsynaptic membrane. In vitro assays further show that rapsyn-containing PVGs do bind more efficiently to microtubules compared to Na+,K+ ATPase-enriched PVGs. These data provide evidence in favor of the contribution of the secretory pathway to the delivery of synaptic components.

Polarized sorting of nicotinic acetylcholine receptors to the postsynaptic membrane in Torpedo electrocyte.

Several regulatory mechanisms contribute to the accumulation and maintenance of high concentrations of acetylcholine receptors (AChR) at the postsynaptic membrane of the neuromuscular junction, including compartmentalized gene transcription, targeting, clustering and anchoring to the cytoskeleton. The targeting of the AChR to the postsynaptic membrane is likely to involve a polarized sorting in the exocytic pathway. In this work, we used the electrocyte of Torpedo marmorata electric organ to study the intracellular trafficking of neosynthesized AChR and its delivery to the postsynaptic membrane. Gradient centrifugation and immunoisolation techniques have led to the isolation of two populations of post-Golgi transport vesicles (PGVs) enriched in proteins of either the innervated (AChR) or non-innervated (Na,K-ATPase) membrane domains of the cell. Immunolabelling of these vesicles at the EM level disclosed that very few PGVs contained both proteins. In AChR-enriched vesicles, high sialylation of AchR molecules, an expected post-translational modification of proteins exiting the trans-Golgi network, and the presence of a marker of the exocytic pathway (Rab6p), indicate that these vesicles are carriers engaged in the Golgi-to-plasma membrane transport. These data suggest that AChR and Na,K-ATPase are sorted intracellularly most likely within the trans-Golgi network. Furthermore, EM analysis and immunogold-labelling experiments provided in situ evidence that the AChR-containing PGVs are conveyed to the postsynaptic membrane, possibly by a microtubule-dependent transport mechanism. Our data therefore provide the first evidence that the targeting of receptors for neurotransmitters to synaptic sites could be contributed by intracellular sorting and polarized delivery in the exocytic pathway.

Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans.

To examine whether endotoxaemia accompanying long-term, strenuous physical exercise is involved in exercise-induced increase in plasma tumour necrosis factor alpha (TNF-alpha) concentration and polymorphonuclear neutrophil (PMN) activation, 14 male recreational athletes [mean age 28 (SEM 1) years] were studied. Exercise consisted of a 1.5-km river swim, a 40-km bicycle race, and a 10-km road race. Mean time to complete the race was 149.8 (SEM 4.8) min. The plasma concentrations of granulocyte myeloperoxidase (MPO) and TNF-alpha were significantly higher than baseline values immediately and 1 h after exercise (P<0.001). Both variables returned to pre-race levels the day after exercise. Marked, transient decreases in plasma concentrations of anti-lipopolysaccharide (LPS) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies directed against a panel of selected smooth gram-negative LPS were observed after the race, reaching in most cases minimal values in the blood sample drawn immediately following the completion of the triathlon. There was no significant correlation between the magnitude of PMN activation, as assessed by the increase in plasma concentrations of MPO, and the humoral markers of endotoxaemia and TNF-alpha. An inverse, highly significant relationship between the increase in plasma TNF-alpha concentrations and the changes in circulating anti-LPS IgM antibodies concentrations was observed (r = -0.7; P<0.01). These findings suggest that exercise-induced endotoxaemia was involved in the release of TNF-alpha, that the magnitude of the TNF-alpha response to exercise was down-regulated by anti-LPS antibodies of the IgM class, and that the production of TNF-alpha and endotoxaemia did not seem to play a role in the activation of circulating PMN in the exercising subjects.

Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia.

To address the question of whether translocation of bacterial lipopolysaccharide (LPS) into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN) activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race) were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO]), were significantly higher immediately after exercise and one hour later-than baseline values (P<0.001). This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26; P=0.383) and temporal association between [MPO] and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.