Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available.

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles? / ¿Debe permanecer la clorhexidina oral en los paquetes de prevención de la neumonía asociada al respirador?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available (AU)

La neumonía asociada al respirador (VAP) está relacionada con una elevada mortalidad, mayor duración de la ventilación mecánica y costes elevados. Estudios recientes han cuestionado la seguridad y la eficacia de la clorhexidina oral para prevenir la VAP. Hemos intentado verificar si los efectos adversos de esta sustancia superan sus beneficios. Se realizaron búsquedas en diversas bases de datos y se seleccionaron estudios que habían investigado el uso de la clorhexidina oral y su impacto sobre la mortalidad. En los metaanálisis de los ensayos aleatorizados a doble ciego no se encontró ninguna asociación entre clorhexidina oral y tasas de VAP más bajas; sin embargo, sí se informó de un aumento significativo de la mortalidad. Se especula que la clorhexidina puede causar daño a varias partes del organismo y citotoxicidad. Pese a que todavía podría ser beneficiosa en entornos específicos, no se dispone de evidencias sólidas para recomendar su aplicación rutinaria para todos los pacientes sometidos a ventilación mecánica; por lo tanto, dada la posibilidad de ocasionar daños, sería mejor seguir el principio de no maleficencia hasta que se disponga de más estudios (AU)

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available.

Cryopreservation of In Vitro-Grown Shoot Tips of the Medicinal Species Cleome Spinosa (Cleomaceae) Applying Vitrification-Based Techniques.

BACKGROUND: Few cryopreservation studies have been reported with the genus Cleome. Due to the use of C. spinosa in traditional medicine and its valuable pharmacological potential, the long-term conservation of the species will allow the safe maintenance of its germplasm. OBJECTIVE: This study compares two vitrification-based techniques on the cryopreservation of shoot tips of C. spinosa. MATERIALS AND METHODS: The effect of sucrose preculture and different vitrification solutions was evaluated using vitrification and V Cryo-plate techniques. The supplementation of recovery medium with BAP was also assessed. RESULTS: The V Cryo-plate proved to be the most efficient technique. Treatment of shoot tips with PVS2 at 0°C resulted in a higher regeneration response after cryopreservation when compared to treatment with PVS2 and PVS3 at 25°C. The highest survival (83.3%) and recovery (76.6%) were achieved for shoot tips exposed to PVS2 for 90 min at 0°C and recovered on MS medium supplemented with 0.5 mg L-1 BAP for 2 weeks. CONCLUSION: Plants regenerated from cryopreserved shoot tips maintained their in vitro multiplication capacity and showed a normal phenotypic aspect, demonstrating the efficiency of the cryopreservation protocol.

Positive state observer for the automatic control of the depth of anesthesia-Clinical results.

The depth of anesthesia (DoA) is a crucial feature in general anesthesia. Nowadays the DoA is usually evaluated by the bispectral index (BIS). According to the surgical procedure, different reference levels for the BIS may be clinically required. This can be achieved by the simultaneous administration of an analgesic (e.g. remifentanil) and an hypnotic (eg propofol). As a contribution to the effort of automating the processes of drug delivery in general anesthesia, in this paper, a positive state observer is designed for the implementation of a control scheme proposed for the automatic administration of propofol and of remifentanil, in order to track a desired level for the BIS. It is proved and illustrated by simulations that the controller-observer scheme has a very good performance. This scheme was implemented, tested and evaluated both by means of simulations and for a set of patients during surgical procedures.

Evaluation of the effects of the solution used for electrochemical dissolution of nickel-titanium endodontic files on dentine structure, microhardness and cell viability.

AIM: To evaluate the effects of the [NaF 12 g L-1  + NaCl 1 g L-1 ] solution used in the electrochemical dissolution process of fractured endodontic files, as well as its NiTi-containing product, on dentine hardness, topography and human fibroblast viability. METHODOLOGY: Sixty single-rooted human teeth were evaluated for dentine microhardness using the Vickers hardness test and the area and number of dentinal tubules by scanning electron microscopy. The samples were divided according to the dentine surface treatment: distilled water; 17% EDTA; [NaF 12 g L-1  + NaCl 1 g L-1 ]; and 17% EDTA + [NaF 12 g L-1  + NaCl 1 g L-1 ]. Thirty-six single-rooted human teeth were divided according to the irrigation protocol: Dulbecco's Modified Eagle's Medium + 10% foetal bovine serum; 5.25% NaOCl; [NaF 12 g L-1  + NaCl 1 g L-1 ]; and [NaF 12 g L-1  + NaCl 1 g L-1  + NiTi]. The extracts in contact with the apical foramen were used in the MTT assay to evaluate human fibroblast viability, with dilutions of 100%, 50%, 25% and 12.5%. Statistical tests used were paired t-tests, one-way anova, Tukey's test, Kruskal-Wallis test and Dunn's post-test. RESULTS: The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution did not modify dentine microhardness or the average dentinal tubule area. However, EDTA induced changes in dentine structure and microhardness (P < 0.05). The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution, and its NiTi-containing product had lower cytotoxicity than NaOCl at dilutions of 25% and 50% (P < 0.01). CONCLUSIONS: The [NaF 12 g L-1  + NaCl 1 g L-1 ] solution did not alter dentine microhardness or damage the dentine structure. It also demonstrated lower cytotoxicity than NaOCl.

Factors associated with the quality of life of mothers of preterm infants with very low birth weight: a 3-year follow-up study.

AIM: To analyze possible factors associated with the quality of life (QoL) of mothers of preterm infants with very low birth weight (VLBW) during the first 3 years after delivery. METHODS: The World Health Organization Quality of Life (WHOQOL)-bref scores were compared and correlated with maternal and infant-related sociodemographic and clinical variables at maternal discharge (T0) and at 6 (T1), 12 (T2), 24 (T3), and 36 (T4) months after delivery. Multiple linear regression models were fitted to investigate the effect of these variables on the mothers' QoL. RESULTS: The WHOQOL-BREF physical domain scores were higher at T1 and T2 compared to T0 (p = 0.013). Maternal variables that contributed to maternal QoL scores (p < 0.05) were stable marital union (b = 13.60; T0), family income (b = -12.75; T3), Evangelical religion (b = 8.11; T4), and beck depression inventory (BDI) score (-1.42 ≤ b ≤ -0.36; T0, T1, T2, T3, and T4). Infants' variables that most affected maternal QoL (p < 0.05) were posthemorrhagic hydrocephalus (PHH) (-18.84 ≤ b ≤ -10.05; T1, T2, and T4), bronchopulmonary dysplasia (BPD) (b = -7.41; T2), female gender (b = 8.09; T2), and SNAPPE severity score (b = -0.23; T3). CONCLUSION: Mothers of preterm infants with VLBW exhibited transient improvements in physical well-being during the first year after delivery. The presence of depressive symptoms in mothers and the diagnosis of PHH or BPD were negatively associated with QoL. Social, religious, and economic aspects were also important factors for the QoL of mothers of preterm infants with VLBW.

Ophthalmologic manifestations of Hallermann-Streiff-Francois syndrome: report of four cases.

PurposeHallermann-Streiff-Francois syndrome (HSS) is a rare genetic disorder characterised by ocular and craniofacial anomalies. The purpose of this report is to highlight the ophthalmological features in four such patients and outcomes of cataract surgery.Patients and methodsRetrospective review of medical records of patients with cataract and/or microcornea due to HSS was done. Presenting features, ocular findings, ocular motility and visual outcomes were noted.ResultsWe identified four children with microcornea/cataract who had associated clinical features suggestive of HSS. Mean age at presentation was 25.5±27.8 months. Three children presented with poor vision in both eyes and one with strabismus. All patients had a microcornea and microphthalmos. Three patients had a membranous cataract. Horizontal corneal diameter ranged from 5.5 to 10.5 mm and axial length ranged from 12 to 18 mm. Three patients had associated strabismus. Three patients underwent lens extraction and two underwent strabismus surgery. Best corrected visual acuity (BCVA) improved from fixing, following light to a median post-operative BCVA of 20/380. One eye developed retinal detachment.ConclusionChildren with HSS present with membranous cataracts, microcornea and microphthalmos and present surgical challenges. Though the patients were mostly left aphakic, all showed moderate visual improvement.

Alveolar hemorrhage in systemic lupus erythematosus: a cohort review.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.

Pattern strabismus and torsion needs special surgical attention.

Pattern strabismus is relatively common in strabismus practice. Although it is classically used to include A and V patterns, the term has been expanded to include additional vertically incomitant horizontal strabismus. This article reviews the clinical features, etiopathogenesis, and surgical options for the patients with pattern strabismus.

Controlling the depth of anesthesia by a novel positive control strategy.

In this paper a positive control law is designed for multi-input positive systems that ensures asymptotic tracking of a desired output reference value. This control law can be viewed as a generalization of another one proposed in the literature for the control of the total mass in SISO compartmental systems, but is suitable for a wider class of positive systems. The controller proposed here is applied to the control of the depth of anesthesia (DoA), by means of the administration of propofol and remifentanil, when using a parameter parsimonious Wiener model recently introduced in the literature. Its performance is illustrated by realistic simulations.

Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used.

Exploring the potential of Burkholderia sacchari to produce polyhydroxyalkanoates.

AIM: Evaluation of the capability of Burkholderia sacchari to incorporate different monomers into polyhydroxyalkanoates (PHA). METHODS AND RESULTS: Thirty different carbon sources were evaluated as cosubstrates for B. sacchari growing on glucose with the intention to promote the incorporation of different monomers into the PHA produced by this species. With odd-numbered fatty acids, incorporation of the 3HV monomer was achieved, up to 65 mol% in the case of valerate. With 4-hydroxybutyrate, incorporation of 4HB was obtained, representing 9·1 mol%. With hexanoic acid, the production of P3HB-co-3HHx was achieved, containing up to 1·6 mol% of 3HHx. The molar fraction of 3HHx was found to be dependent on the ratio of glucose to hexanoic acid supplied. Metabolic flux analysis revealed a high efficiency of B. sacchari in converting carbon sources into P3HB-co-3HHx. Nevertheless, hexanoic acid was only poorly converted to 3HHx. CONCLUSIONS: Burkholderia sacchari is able to incorporate 3HV, 4HB and 3HHx in PHA containing mainly 3HB. The 3HHx content of P3HB-co-3HHx can be controlled by varying the glucose to hexanoic acid ratio. Burkholderia sacchari is highly efficient in converting carbon sources into PHA; however, only 2% of the hexanoic acid supplied could be converted to 3HHx. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report describing an approach to modulate the composition of P3HB-co-3HHx produced by bacteria using mixtures of carbohydrate and hexanoic acid as carbon source.

Evaluation of cytotoxicity and up-regulation of gelatinases in human fibroblast cells by four root canal sealers.

AIM: To investigate the effects of root canal sealers on the cytotoxicity and gelatinolytic activity of matrix metalloproteinases (MMPs) in human fibroblasts. METHODOLOGY: Human fibroblasts (MRC5, 3×10(5) cells per well) were incubated directly or indirectly with AH Plus, Endomethasone N, Pulp Canal Sealer EWT or Sealapex for 30 min, 1, 4 or 24 h (time-points). The cytotoxicity of all root canal sealers was determined by counting viable cells using the trypan blue exclusion assay. Supernatants of cell cultures incubated with root sealers directly or indirectly were collected after each time-point to determine the levels of MMP-2 and MMP-9 gelatinolytic activity by gelatin zymography. Data were analysed using anova and the Tukey's tests. RESULTS: Cells secreted MMP-2 after periods of 4 and 24 h; however, there were no significant differences between the sealers. Secretion of gelatinases was elevated by root canal sealers in direct contact with the cell monolayer when compared to indirect contact (P < 0.05). At the time-points tested, no gelatinolytic activity could be detected in the control group without the sealers. The cytotoxicity results revealed that all sealers were cytotoxic in both contact forms. Sealapex had the lowest cytotoxicity and AH Plus the most cytotoxicity. CONCLUSIONS: All root canal sealers induced the expression of MMP-2 in MRC5 fibroblasts. AH Plus had the highest cytotoxicity amongst the tested sealers, but all were associated with cytotoxic effects.

Automatic analysis of macroarrays images.

The analysis of dot blot (macroarray) images is currently based on the human identification of positive/negative dots, which is a subjective and time consuming process. This paper presents a system for the automatic analysis of dot blot images, using a pre-defined grid of markers, including a number of ON and OFF controls. The geometric deformations of the input image are corrected, and the individual markers detected, both tasks fully automatically. Based on a previous training stage, the probability for each marker to be ON is established. This information is provided together with quality parameters for training, noise and classification, allowing for a fully automatic evaluation of a dot blot image.

Association of variant alleles of MBL2 gene with vasoocclusive crisis in children with sickle cell anemia.

Vasoocclusive crisis (VOC) is the major cause of morbidity and mortality in sickle cell anemia (SCA), which is caused by the occlusion of blood vessels, followed by ischemia or infarct, resulting in progressive damage to organs. However, this clinical manifestation is variable, indicating that this process could be influenced by modifier genes. The gene MBL2 which codes for mannose-binding lectin (MBL) has been associated with modifications in the progression of infectious and inflammatory vascular diseases. The aim of this study was to determine the frequency of the polymorphisms of exon 1 (alleles A/O) and promoter region -221 (alleles Y/X) of MBL2 in children with SCA and to verify their association with VOC. The determination of the polymorphism of exon 1 and the promoter region of MBL2 was performed by SYBR GREEN((R)) and Taqman((R)) system, respectively. In the patients with SCA, the frequency of the genotype related to high production of MBL was 0.46 (YA/YA) and for intermediate/low production was 0.54 (YA/XA, XA/XA, YA/YO, XA/YO, YO/YO). The frequency of the genotypes and haplotypes of MBL2 in patients with SCA did not differ from control individuals. The populations were in Hardy-Weinberg equilibrium. The patients were divided into two groups. The groups were separated by the frequency of VOC, which was defined by the total of VOC episodes divided by the age of the children at the end of this study. Since, we choose a cut point in FVOC <1 (n=48) (which we considered of mild presentation of disease) and FVOC >or=1 (n=39) (higher severity). In children with SCA, the frequency of the genotypes of MBL2 of intermediate/low expression for MBL was associated with FVOC >or=1 (p=0.0188 OR=3.15 CI=1.19-8.50). The results suggest that MBL2 polymorphism at promoter and first exon of MBL2 associated with low serum levels and structural alterations of MBL could modify the phenotype of the child with SCA related to VOC.