Eventos adversos en recién nacidos hospitalizados en una Unidad de Cuidados Intermedios / Adverse events among newborns hospitalized in an Intermediate Care Unit / Eventos adversos em recém-nascidos hospitalizados em una Unidade de Cuidados Intermediários

Resumen Introducción: Los recién nacidos (RN) conforman uno de los grupos poblacionales más vulnerables. El riesgo de ocurrencia de un evento adverso durante su hospitalización se incrementa por diversos factores. Objetivo: Identificar los eventos adversos en recién nacidos hospitalizados en una unidad de cuidados intermedios en 2018. Metodología: Estudio de tipo descriptivo, diseño transversal y retrospectivo, realizado en la Unidad de Cuidados Intermedios Neonatales del Instituto Nacional Materno Perinatal durante el 2018. Se elaboró una ficha de recolección de datos que constó de nueve ítems correspondientes a procedimientos realizados por el personal de enfermería. Se utilizó un análisis univariado de los datos, presentados en tablas y gráficos. Resultados: Fueron analizados 73 eventos adversos, la menor edad gestacional fue de 32 semanas, con un máximo de 28 días de hospitalización. 60% de eventos se produjo en los RN más lábiles y con situación de salud compleja, de los cuales, 58% fueron infecciones asociadas a catéter percutáneo o periférico, cuyo germen frecuente fue Sthapylococcus coagulasa negativo. Solo 20.5% de eventos adversos fueron reportados. Discusión: Los resultados obtenidos coinciden con otras investigaciones en que los factores intrínsecos de los recién nacidos contribuyen en la aparición de eventos adversos; de igual manera concuerdan en la necesidad de prevenirlos y notificarlos. Conclusiones: La prematuridad, el tiempo de hospitalización en una unidad crítica y de exposición a diversos procedimientos, incrementaron el riesgo de ocurrencia de eventos adversos en recién nacidos. Detectar oportunamente estos acontecimientos es importante, así como fomentar la cultura de reporte, con el fin de evitarlos.

Abstract Introduction: Newborns are one of the most vulnerable populations, and their risk of suffering an adverse event during their hospital stay is influenced by diverse factors. Objective: To identify the adverse events among newborns hospitalized in an Intermediate Care Unit in 2018. Methodology: This is a descriptive, transversal, and retrospective study carried out in a Newborn Intermediate Care Unit of the Maternal and Perinatal National Institute during 2018. A data gathering chart with 9 items related to the corresponding nursing procedures was designed. A univariate data analysis was calculated, and the results were shown in tables and graphs. Results: 73 adverse events were analyzed. The lowest gestational age was 32 weeks, and the longest hospitalization was 28 days. 60% of these events were related to the more delicate and with the more complex situation newborns; and 58% of these were related to percutaneous or peripheral catheter infections and the most frequent pathogen was Coagulase-Negative Staphylococcus. Only 28.5% of the events were reported. Discussion: These findings are in line with the results of other research studies. Addressing the diverse factors which contribute to the adverse events in newborns in Intermediate Care Units is suggested. Conclusions: Being premature and the length of the hospital stay increase the risk of adverse events in newborns. It is critical to promote a culture of events reporting.

Resumo Introdução: Os recém-nascidos (RN) constituem um dos grupos populacionais mais vulneráveis. O risco de ocorrência de um evento adverso durante sua hospitalização é incrementado por diversos fatores. Objetivo: Identificar os eventos adversos em recém-nascidos hospitalizados em una unidade de cuidados intermediários em 2018. Metodologia: Estudo de tipo descritivo, desenho transversal e retrospectivo, realizado na Unidade de Cuidados Intermediários Neonatais do Instituto Nacional Materno Perinatal durante 2018. Foi elaborada uma ficha de coleta de dados que constou de nove itens correspondentes a procedimentos realizados pelo pessoal de enfermagem. Utilizou-se uma análise univariáda dos dados, apresentados em tabelas e gráficos. Resultados: Foram analisados 73 eventos adversos, a menor idade gestacional foi de 32 semanas, com máximo de 28 dias de internação. 60% dos eventos produziram-se nos RN mais lábeis e em situação de saúde complexa, dos quais, 58% foram infecções associadas a cateter percutâneo ou periférico, cujo germe frequente foi o Sthapylococcus coagulase negativo. Apenas 20.5% de eventos adversos foram relatados. Discussão: Os resultados obtidos coincidem com outras pesquisas em que os fatores intrínsecos dos recém-nascidos contribuem no aparecimento de eventos adversos; aliás, concordam com a necessidade de preveni-los e notificá-los. Conclusões: A prematuridade, o tempo de hospitalização em uma unidade crítica e de exposição a diversos procedimentos, incrementaram o risco de ocorrência de eventos adversos em recém-nascidos. É importante detectar estes acontecimentos oportunamente, assim como fomentar a cultura de notificação, a fim de evitá-los.

Single-shot d-scan technique for ultrashort laser pulse characterization using transverse second-harmonic generation in random nonlinear crystals.

We demonstrate a novel dispersion-scan (d-scan) scheme for single-shot temporal characterization of ultrashort laser pulses. The novelty of this method relies on the use of a highly dispersive crystal featuring antiparallel nonlinear domains with a random distribution and size. This crystal, capable of generating a transverse second-harmonic signal, acts simultaneously as the dispersive element and the nonlinear medium of the d-scan device. The resulting in-line architecture makes the technique very simple and robust, allowing the acquisition of single-shot d-scan traces in real time. The retrieved pulses are in very good agreement with independent frequency-resolved optical grating measurements. We also apply the new single-shot d-scan to a terawatt-class laser equipped with a programmable pulse shaper, obtaining an excellent agreement between the applied and the d-scan retrieved dispersions.

Universal route to optimal few- to single-cycle pulse generation in hollow-core fiber compressors.

Gas-filled hollow-core fiber (HCF) pulse post-compressors generating few- to single-cycle pulses are a key enabling tool for attosecond science and ultrafast spectroscopy. Achieving optimum performance in this regime can be extremely challenging due to the ultra-broad bandwidth of the pulses and the need of an adequate temporal diagnostic. These difficulties have hindered the full exploitation of HCF post-compressors, namely the generation of stable and high-quality near-Fourier-transform-limited pulses. Here we show that, independently of conditions such as the type of gas or the laser system used, there is a universal route to obtain the shortest stable output pulse down to the single-cycle regime. Numerical simulations and experimental measurements performed with the dispersion-scan technique reveal that, in quite general conditions, post-compressed pulses exhibit a residual third-order dispersion intrinsic to optimum nonlinear propagation within the fiber, in agreement with measurements independently performed in several laboratories around the world. The understanding of this effect and its adequate correction, e.g. using simple transparent optical media, enables achieving high-quality post-compressed pulses with only minor changes in existing setups. These optimized sources have impact in many fields of science and technology and should enable new and exciting applications in the few- to single-cycle pulse regime.

Small Ruminant Lentiviruses in Sheep: Pathology and Tropism of 2 Strains Using the Bone Marrow Route.

The objective of this work was to comparatively study the tissue tropism and the associated pathology of 2 autochthonous small ruminant lentivirus (SRLV) field strains using an experimental infection in sheep through the bone marrow. Fifteen male, SRLV-free lambs of the Rasa Aragonesa breed were inoculated with strain 697 (nervous tissue origin, animals A1-A6), with strain 496 (articular origin, animals B1-B6), or with uninfected culture medium (C1-C3). Clinical, serologic, and polymerase chain reaction (PCR) evaluations were performed periodically. Two lambs from each infected group and a control animal were euthanized at 134, 273, and 319 days postinfection. Tissues were analyzed by gross and histopathologic evaluation; immunohistochemistry for CD3, CD4, CD8, CD68, and FoxP3 cell markers; lung morphometric evaluation; and tissue proviral quantification by PCR. All infected animals became positive either by enzyme-linked immunosorbent assay and/or PCR, with group B lambs showing the highest serologic values and more consistently positive PCR reactions. Group A lambs showed representative lung lesions but only mild histopathologic changes in the central nervous system (CNS) or in carpal joints. Contrarily, group B lambs demonstrated intense carpal arthritis and interstitial pneumonia but an absence of lesions in the CNS. Proviral copies in tissues were detected only in group B lambs. Experimental infection with these SRLV strains indicates that strain 496 is more virulent than strain 697 and more prone to induce arthritis, whereas strain 697 is more likely to reproduce encephalitis in Rasa Aragonesa lambs. Host factors as well as viral factors are responsible for the final clinicopathologic picture during SRLV infections.

A Dual-Colour Architecture for Pump-Probe Spectroscopy of Ultrafast Magnetization Dynamics in the Sub-10-femtosecond Range.

Current time-resolution-limited dynamic measurements clearly show the need for improved techniques to access processes on the sub-10-femtosecond timescale. To access this regime, we have designed and constructed a state-of-the-art time-resolved magneto-optic Kerr effect apparatus, based on a new dual-color scheme, for the measurement of ultrafast demagnetization and precessional dynamics in magnetic materials. This system can operate well below the current temporal ranges reported in the literature, which typically lie in the region of around 50 fs and above. We have used a dual-colour scheme, based on ultra broadband hollow-core fibre and chirped mirror pulse compression techniques, to obtain unprecedented sub-8-fs pump and probe pulse durations at the sample plane. To demonstrate the capabilities of this system for ultrafast demagnetization and precessional dynamics studies, we have performed measurements in a ferrimagnetic GdFeCo thin film. Our study has shown that the magnetization shows a sudden drop within the first picosecond after the pump pulse, a fast recovery (remagnetization) within a few picoseconds, followed by a clear oscillation or precession during a slower magnetization recovery. Moreover, we have experimentally confirmed for the first time that a sub-10-fs pulse is able to efficiently excite a magnetic system such as GdFeCo.

Single-shot implementation of dispersion-scan for the characterization of ultrashort laser pulses.

We demonstrate a single-shot ultrafast diagnostic, based on the dispersion-scan (d-scan) technique. In this implementation, rather than translating wedges to vary the dispersion as in scanning d-scan, the pulse to be measured experiences a spatially varying amount of dispersion in a prism. The resulting beam is then imaged into a second-harmonic generation crystal and an imaging spectrometer is used to measure the two-dimensional trace, which is analyzed using the d-scan retrieval algorithm. We compare the single-shot implementation with the scanning d-scan for the measurement of sub-3.5-fs pulses from a hollow core fiber pulse compressor. We show that the retrieval algorithm used to extract amplitude and phase of the pulse provides comparable results, proving the validity of the new single-shot implementation in the near single-cycle regime.

Carrier-envelope-phase insensitivity in high-order harmonic generation driven by few-cycle laser pulses.

We present evidence for self-stabilization of the relative spectral phase of high-order harmonic emission against intensity variations of the driving field. Our results demonstrate that, near the laser focus, phase matching of the harmonic field from a macroscopic target can compensate for the intensity dependence of the intrinsic phase of the harmonics emitted by a single radiator. As a consequence, we show experimentally and theoretically the insensitivity of the harmonic spectra produced at the laser focus against variations of the carrier-envelope phase (CEP) of a sub-two-cycle driving field. In addition, the associated attosecond pulse trains exhibit phase locking against CEP changes of the few-cycle driver.

Tratamiento con vitamina E en pacientes con esteatohepatitis no alcohólica / Vitamin E Treatment for Patients with Nonalcoholic Steatohepatitis

La esteatohepatitis no alcohólica se caracteriza histológicamente por el balonamiento de los hepatocitos, la inflamación lobulillar y la esteatosis. Al sospechar este diagnóstico es importante la exclusión de otras causas de lesión hepática principalmente el consumo excesivo de alcohol; sin embargo, la biopsia es el único método disponible hasta el momento para confirmar el diagnóstico. Para el tratamiento de esta enfermedad, la vitamina E debe ser considerada una terapia de primera línea debido a que en diversos ensayos clínicos se ha observado que aunque sin un impacto significativo en la fibrosis, a dosis de 800 UI día mejora la histología en adultos no diabéticos con NASH confirmado por biopsia. A pesar de los beneficios demostrados con el uso de este medicamento se debe tener en cuenta que no reemplaza los cambios en la dieta y el ejercicio, y que por el contrario, representa un complemento a estas medidas.

Nonalcoholic Steatohepatitis (NASH) is characterized histologically by the ballooning of hepatocytes, lobular inflammation and steatosis. If this diagnosis is suspected, it is important to exclude other causes of liver damage, especially excessive consumption of alcohol. Nevertheless, to date, a biopsy is the only method available to confirm the diagnosis. Vitamin E should be considered a first-line therapy for treatment of this disease because several clinical studies have shown that a dose of 800 UI/day improves the histology of non-diabetic adults suffering from NASH even when there is no significant impact on fibrosis. These results were confirmed by biopsies. Despite the proven benefits of the use of this drug, it is important to be aware that its use cannot replace changes in diet and exercise but rather should be seen as a complement to these measures.

An insight into a combination of ELISA strategies to diagnose small ruminant lentivirus infections.

A single broadly reactive standard ELISA is commonly applied to control small ruminant lentivirus (SRLV) spread, but type specific ELISA strategies are gaining interest in areas with highly prevalent and heterogeneous SRLV infections. Short (15-residue) synthetic peptides (n=60) were designed in this study using deduced amino acid sequence profiles of SRLV circulating in sheep from North Central Spain and SRLV described previously. The corresponding ELISAs and two standard ELISAs were employed to analyze sera from sheep flocks either controlled or infected with different SRLV genotypes. Two outbreaks, showing SRLV-induced arthritis (genotype B2) and encephalitis (genotype A), were represented among the infected flocks. The ELISA results revealed that none of the assays detected all the infected animals in the global population analyzed, the assay performance varying according to the genetic type of the strain circulating in the area and the test antigen. Five of the six highly reactive (57-62%) single peptide ELISAs were further assessed, revealing that the ELISA based on peptide 98M (type A ENV-SU5, consensus from the neurological outbreak) detected positives in the majority of the type-A specific sera tested (Se: 86%; Sp: 98%) and not in the arthritic type B outbreak. ENV-TM ELISAs based on peptides 126M1 (Se: 82%; Sp: 95%) and 126M2 0,65 0.77 (Se: 68%; Sp: 88%) detected preferentially caprine arthritis encephalitis (CAEV, type B) and visna/maedi (VMV, type A) virus infections respectively, which may help to perform a preliminary CAEV vs. VMV-like typing of the flock. The use of particular peptide ELISAs and standard tests individually or combined may be useful in the different areas under study, to determine disease progression, diagnose/type infection and prevent its spread.

Ovine TRIM5α can restrict visna/maedi virus.

The restrictive properties of tripartite motif-containing 5 alpha (TRIM5α) from small ruminant species have not been explored. Here, we identify highly similar TRIM5α sequences in sheep and goats. Cells transduced with ovine TRIM5α effectively restricted the lentivirus visna/maedi virus DNA synthesis. Proteasome inhibition in cells transduced with ovine TRIM5α restored restricted viral DNA synthesis, suggesting a conserved mechanism of restriction. Identification of TRIM5α active molecular species may open new prophylactic strategies against lentiviral infections.

Visna/Maedi virus genetic characterization and serological diagnosis of infection in sheep from a neurological outbreak.

An extensive outbreak characterized by the appearance of neurological symptoms in small ruminant lentivirus (SRLV) infected sheep has been identified in Spain, but the genetic characteristics of the strain involved and differential diagnostic tools for this outbreak remain unexplored. In this work, 23 Visna-affected naturally infected animals from the outbreak, 11 arthritic animals (both groups presenting anti-Visna/Maedi virus serum antibodies), and 100 seronegative animals were used. Eight of the Visna-affected animals were further studied post-mortem by immunohistochemistry. All had lesions in spinal cord, being the most affected part of the central nervous system in six of them. A representative strain of the outbreak was isolated. Together with other proviral sequences from the outbreak the virus was assigned to genotype A2/A3. In vitro culture of the isolate revealed that viral production was slow/low in fibroblast-like cells but it was high in blood monocyte-derived macrophages. The long terminal repeat (LTR) of the viral genome of this isolate lacked an U3-duplication, but its promoter activity in fibroblast-like cells was normal compared to other strains. Thus, viral production could not be inferred from the LTR promoter activity in this isolate. Analysis of the viral immunodominant epitopes among SRLV sequences of the outbreak and other known sequences allowed the design of a synthetic SU peptide ELISA that detected the Visna affected animals, representing a tool of epidemiological interest to control viral spread of this highly pathogenic strain.

Recombinant small ruminant lentivirus subtype B1 in goats and sheep of imported breeds in Mexico.

Nucleotide sequences of small ruminant lentiviruses (SRLVs) were determined in sheep and goats, including progeny of imported animals, on a farm in Mexico. On the basis of gag-pol, pol, env and LTR sequences, SRLVs were assigned to the B1 subgroup, which comprises caprine arthritis-encephalitis virus (CAEV)-like prototype sequences mainly from goats. In comparison with CAEV-like env sequences of American and French origin, two putative recombination events were identified within the V3-V4 and V4-V5 regions of the env gene of a full length SRLV sequence (FESC-752) derived from a goat on the farm.

Sub-two-cycle pulses by soliton self-compression in highly nonlinear photonic crystal fibers.

We demonstrate the direct generation of sub-two-cycle pulses by soliton self-compression of femtosecond pulses from a Ti:sapphire laser at 85 MHz using a 4.85-mm-long highly nonlinear photonic crystal fiber. Sub-nanojoule, 41 fs input pulses were compressed down to 4.6 fs without additional phase compensation schemes. To our knowledge, these are the shortest pulses obtained by soliton-effect compression of a laser oscillator. Efficient, near-dispersionless collimation of the fiber output was achieved with a simple lens and an octave-spanning double-chirped mirror pair. The full electric field of the compressed pulses was retrieved with a genetic algorithm applied to spectral and interferometric autocorrelation measurements, and the results are well described by numerical simulations.

Antibody-based diagnosis of small ruminant lentivirus infection in seminal fluid.

Antibody-based diagnosis of small ruminant lentiviruses (SRLVs) has been efficiently achieved using serum and milk, but not semen, for which polymerase chain reaction (PCR) has been proposed as a confirmatory technique. This work, involving 296 ovine (Ovis aries) and caprine (Capra hircus) semen donors, investigates whether seminal fluid (SF) can be reliably used in antibody-based SRLV diagnosis. First, a gold standard was established to assess the infection status and determine the sensitivity and specificity of three commercial enzyme-linked immunosorbent assays (ELISAs) in serum testing using Western blot and PCR as confirmatory tests. For SF testing, both gold standard and serum testing results were used as reference. The performance of SF testing was affected not only by the ELISA assay sensitivity (related to antigen spectrum) compared with that of the gold standard (as it occurred in serum testing) but also by SF sample quality and SF working dilution. Nonturbid SF samples, commonly collected in artificial insemination centers (AICs), were required. Compared with serum, SF testing had a decreased sensitivity in two of the ELISA assays (with original serum working dilutions

Use of B7 costimulatory molecules as adjuvants in a prime-boost vaccination against Visna/Maedi ovine lentivirus.

RNA transcripts of the B7 family molecule (CD80) are diminished in blood leukocytes from animals clinically affected with Visna/Maedi virus (VMV) infection. This work investigates whether the use of B7 genes enhances immune responses and protection in immunization-challenge approaches. Sheep were primed by particle-mediated epidermal bombardment with VMV gag and env gene recombinant plasmids together with plasmids encoding both CD80 and CD86 or CD80 alone, boosted with gag and env gene recombinant modified vaccinia Ankara virus and challenged intratracheally with VMV. Immunization in the presence of one or both of the B7 genes resulted in CD4+ T cell activation and antibody production (before and after challenge, respectively), but only immunization with CD80 and CD86 genes together, and not CD80 alone, resulted in a reduced number of infected animals and increased early transient cytotoxic T lymphocytes (CTL) responses. Post-mortem analysis showed an immune activation of lymphoid tissue in challenge-target organs in those animals that had received B7 genes compared to unvaccinated animals. Thus, the inclusion of B7 genes helped to enhance early cellular responses and protection (diminished proportion of infected animals) against VMV infection.

Phylogenetic analysis of SRLV sequences from an arthritic sheep outbreak demonstrates the introduction of CAEV-like viruses among Spanish sheep.

Small ruminant lentiviruses (SRLVs) cause different clinical forms of disease in sheep and goats. So far in Spain, Maedi visna virus-like (MVV-like) sequences have been found in both species, and the arthritic SRLV disease has never been found in sheep until a recent outbreak. Knowing that arthritis is common in goats, it was of interest to determine if the genetic type of the virus involved in the sheep arthritis outbreak was caprine arthritis encephalitis virus-like (CAEV-like) rather than MVV-like. Alignment and phylogenetic analyses on nucleotide and deduced amino acid sequences from SRLV of this outbreak, allowed a B2 genetic subgroup assignment of these SRLV, compatible with a correspondence between the virus genetic type and the disease form. Furthermore, an isolate was obtained from the arthritic outbreak, its full genome was CAEV-like but the pol integrase region was MVV-like. Although its LTR lacked a U3 repeat sequence and had a deletion in the R region, which has been proposed to reduce viral replication rate, its phenotype in sheep skin fibroblast cultures was rapid/high, thus it appeared to have adapted to sheep cells. This outbreak study represents the first report on CAEV-like genetic findings and complete genome analysis among Spanish small ruminants.

Systemic DNA immunization against ovine lentivirus using particle-mediated epidermal delivery and modified vaccinia Ankara encoding the gag and/or env genes.

To determine whether systemic immunization with plasmid DNA and virus vector against visna/maedi virus (VMV) would induce protective immune responses, sheep were immunized with VMV gag and/or env sequences using particle-mediated epidermal bombardment and injection of recombinant modified vaccinia Ankara. The results showed that immunization induced both humoral and cell-mediated responses prior to and after virus challenge. The vaccination protocol did not prevent infection, but immunization with the gag gene or a combination of gag and env genes resulted in significantly reduced provirus loads in blood and mediastinal lymph node, respectively. Provirus loads in lung and draining lymph node were unaffected, but p25 expression was undetectable in lungs of animals immunized with a combination of gag and env genes. Analysis of target tissues for lesions at post-mortem showed that immunization with the env gene caused a significant increase in lesion score, while the gag gene or a combination of gag and env genes had no effect. Inclusion of the ovine interferon-gamma gene in the initial priming mixture had minimal effect on immune responses, provirus load, or lesion development, although it resulted in a decreased p25 expression in the lung. The results thus show that systemic immunization with gag or a combination of gag and env genes reduces provirus load in blood and lymphoid tissue, respectively whereas env immunization has no effect on provirus load but increased lesion development.

Mucosal immunization against ovine lentivirus using PEI-DNA complexes and modified vaccinia Ankara encoding the gag and/or env genes.

Sheep were immunized against Visna/Maedi virus (VMV) gag and/or env genes via the nasopharynx-associated lymphoid tissue (NALT) and lung using polyethylenimine (PEI)-DNA complexes and modified vaccinia Ankara, and challenged with live virus via the lung. env immunization enhanced humoral responses prior to but not after VMV challenge. Systemic T cell proliferative and cytotoxic responses were generally low, with the responses following single gag gene immunization being significantly depressed after challenge. A transient reduction in provirus load in the blood early after challenge was observed following env immunization, whilst the gag gene either alone or in combination with env resulted in significantly elevated provirus loads in lung. However, despite this, a significant reduction in lesion score was observed in animals immunized with the single gag gene at post-mortem. Inclusion of IFN-gamma in the immunization mixture in general had no significant effects. The results thus showed that protective effects against VMV-induced lesions can be induced following respiratory immunization with the single gag gene, though this was accompanied by an increased pulmonary provirus load.

Nonintrusive phase stabilization of sub-two-cycle pulses from a prismless octave-spanning Ti:sapphire laser.

Carrier-envelope (CE) phase-stabilized sub-two-cycle pulses are generated from a 500 MHz compact prismless octave-spanning laser without extracavity nonlinear optical processes distorting the laser output. The necessary f and 2f spectral components are generated intracavity and coupled out independently from the main pulse through specially designed cavity mirrors, resulting in a 55 dB CE beat note (100 kHz resolution bandwidth). The in-loop CE phase error (integrated from 2.5 mHz to 10 MHz) is 67 mrad, equivalent to a timing jitter between carrier and envelope of 28 as at 790 nm.

Cascaded highly nondegenerate four-wave-mixing phenomenon in transparent isotropic condensed media.

Broad-bandwidth light pulses with different frequencies, extending from the IR to the UV, are simultaneously generated when two noncollinear, ultrafast laser pulses from a visible dual-frequency laser propagate through bulk isotropic transparent media such as common glass. This phenomenon, which is believed to have been previously unreported, can be explained by a cascade of highly nondegenerate four-wave-mixing processes and corresponds to a coherent scattering effect with geometrically minimized phase mismatch. Frequency-upconverted beams were observed up to the 11th order.