Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection

Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection

Efficacy and tolerability of pregabalin as preventive treatment for migraine: a 3-month follow-up study

Migraine is a common neurological disorder and epidemiological studies have documented its high social and economic impact. Unfortunately, preventive treatment is often insufficient to substantially reduce migraine frequency or it is not well tolerated. Antiepileptic drugs are increasingly used in migraine prevention. However, data on efficacy and tolerability of pregabalin in patients with migraine are still lacking. Our aim was to evaluate efficacy and tolerability of pregabalin in patients with migraine. We recruited 47 patients who started pregabalin at 75 mg/day, which was titrated to 300 mg/day as tolerated. A total of six patients (13%) reported one or more side effects during the intake of pregabalin; however, three of them discontinued pregabalin, because side effects were intolerable and persistent. Statistically significant reduction in migraine frequency compared to baseline (p < 0.001) was evident after 1 and 3 months of treatment. A greater frequency reduction was observed in those patients who increased the dosage within the first month of therapy. Our data suggest that pregabalin may be well tolerated and may represent an alternative preventive treatment in migraneurs. Limitations of the present study were a small sample size and an uncontrolled, open-label design; further randomized case–control studies are warranted to confirm our findings

Physical properties and antimicrobial activity of bioactive film based on whey protein and Lactobacillus curvatus 54M16 producer of bacteriocins

The objective of the work was to study the viability and antimicrobial activity of bacteriocin-producing lactic acid bacteria (LAB) incorporated into whey protein/inulin/gelatine (WP) edible films in presence or absence of nutrient (modified MRS broth). Moreover, the role of the cell on the film structure and properties has been investigated. The results of the work showed that WP-based films were able to ensure a high viability of the bacteriocin-producing strain L. curvatus 54M16 during 28 days of storage at 4 �C. The addition of nutrient in the film matrix slightly affected the viability of the cells, but it was critical for the antimicrobial activity of the films. Films in presence of nutrient showed a good antimicrobial activity against L. innocua C6 as in vitro system as on cooked ham. The presence of LAB has a significant effect on the structure of the film: it reduced the viscosity of the film forming solution and improved the elasticity and the percentage of elongation. Whereas, no effect was observed for water vapour transmission rate and solubility. Thus, WP-based films in presence of modified MRS broth can be used as effective delivery and carrier systems for lactic acid bacteria to develop bioactive edible film or coating with antimicrobial properties

The Prognostic Value of Pyrosequencing-Detected MGMT Promoter Hypermethylation in Newly Diagnosed Patients with Glioblastoma

O6-methylguanine-DNA-methyltransferase (MGMT) has emerged as a relevant predictor of therapeutic response and good prognosis in patients with glioblastoma (GBM). Transcriptionally active MGMT rapidly removes the alkyl adducts, preventing the formation of cross-links and thereby causing resistance to alkylating drugs. Studies with pyrosequencing (PSQ) showed that this technique has a higher reproducibility and sensitivity than other techniques. However, the definition of a prognostically relevant threshold for the percentage of MGMT methylation remains one of the most critical issues in the use of PSQ analysis. The aim of this study was to define the cut-off value correlated with good favourable prognostic outcomes. We retrospectively analyzed 51 patients (33 males, 18 females) with GBM who underwent surgery or biopsy. The Receiver Operating Characteristics analysis showed that the best possible criteria for PSQ-detected percentage of MGMT methylation that predicted progression-free survival (PFS) and overall survival (OS) were 19% and 13%, respectively. Patients with ≤19% of PSQ-detected MGMT had a shorter PFS (HR: 0.24, &lt; 0.01); those ones with ≤13% had a shorter OS (HR: 0.33, &lt; 0.05). Our study reinforces the importance of MGMT in the management of GBM patients, but future studies with larger sample sizes are warranted to confirm our findings

The LiberAction Project: Implementation of a Pediatric Liberation Bundle to Screen Delirium, Reduce Benzodiazepine Sedation, and Provide Early Mobilization in a Human Resource-Limited Pediatric Intensive Care Unit

Background: Delirium, bed immobilization, and heavy sedation are among the major contributors of pediatric post-intensive care syndrome. Recently, the Society of Critical Care Medicine has proposed the implementation of daily interventions to minimize the incidence of these morbidities and optimize children functional outcomes and quality of life. Unfortunately, these interventions require important clinical and economical efforts which prevent their use in many pediatric intensive care units (PICU). Aim: First, to evaluate the feasibility and safety of a PICU bundle implementation prioritizing delirium screening and treatment, early mobilization (&lt;72 h from PICU admission) and benzodiazepine-limited sedation in a human resource-limited PICU. Second, to evaluate the incidence of delirium and describe the early mobilization practices and sedative drugs used during the pre- and post-implementation periods. Third, to describe the barriers and adverse events encountered during early mobilization. Methods: This observational study was structured in a pre- (15th November 2019-30th June 2020) and post-implementation period (1st July 2020-31st December 2020). All patients admitted in PICU for more than 72 h during the pre and post-implementation period were included in the study. Patients were excluded if early mobilization was contraindicated. During the pre-implementation period, a rehabilitation program including delirium screening and treatment, early mobilization and benzodiazepine-sparing sedation guidelines was developed and all PICU staff trained. During the post-implementation period, delirium screening with the Connell Assessment of Pediatric Delirium scale was implemented at bedside. Early mobilization was performed using a structured tiered protocol and a new sedation protocol, limiting the use of benzodiazepine, was adopted. Results: Two hundred and twenty-five children were enrolled in the study, 137 in the pre-implementation period and 88 in the post-implementation period. Adherence to delirium screening, benzodiazepine-limited sedation and early mobilization was 90.9, 81.1, and 70.4%, respectively. Incidence of delirium was 23% in the post-implementation period. The median cumulative dose of benzodiazepines corrected for the total number of sedation days (mg/kg/sedation days) was significantly lower in the post-implementation period compared with the pre-implementation period: [0.83 (IQR: 0.53-1.31) vs. 0.74 (IQR: 0.55-1.16), p = 0.0001]. The median cumulative doses of fentanyl, remifentanil, and morphine corrected for the total number of sedation days were lower in the post-implementation period, but these differences were not significant. The median number of mobilizations per patient and the duration of each mobilization significantly increased in the post-implementation period [3.00 (IQR: 2.0-4.0) vs. 7.00 (IQR: 3.0-12.0); p = 0.004 and 4 min (IQR: 3.50-4.50) vs. 5.50 min (IQR: 5.25-6.5); p &lt; 0.0001, respectively]. Barriers to early mobilization were: disease severity and bed rest orders (55%), lack of physicians' order (20%), lack of human resources (20%), and lack of adequate devices for patient mobilization (5%). No adverse events related to early mobilization were reported in both periods. Duration of mechanical ventilation and PICU length of stay was significantly lower in the post-implementation period as well as the occurrence of iatrogenic withdrawal syndrome. Conclusion: This study showed that the implementation of a PICU liberation bundle prioritizing delirium screening and treatment, benzodiazepine-limited sedation and early mobilization was feasible and safe even in a human resource-limited PICU. Further pediatric studies are needed to evaluate the clinical impact of delirium, benzodiazepine-limited sedation and early mobilization protocols on patients' long-term functional outcomes and on hospital finances

In Vitro-Produced Equine Blastocysts Exhibit Greater Dispersal and Intermingling of Inner Cell Mass Cells than In Vivo Embryos

In vitro production (IVP) of equine embryos is increasingly popular in clinical practice but suffers from higher incidences of early embryonic loss and monozygotic twin development than transfer of in vivo derived (IVD) embryos. Early embryo development is classically characterized by two cell fate decisions: (1) first, trophectoderm (TE) cells differentiate from inner cell mass (ICM); (2) second, the ICM segregates into epiblast (EPI) and primitive endoderm (PE). This study examined the influence of embryo type (IVD versus IVP), developmental stage or speed, and culture environment (in vitro versus in vivo) on the expression of the cell lineage markers, CDX-2 (TE), SOX-2 (EPI) and GATA-6 (PE). The numbers and distribution of cells expressing the three lineage markers were evaluated in day 7 IVD early blastocysts ( n = 3) and blastocysts ( n = 3), and in IVP embryos first identified as blastocysts after 7 (fast development, n = 5) or 9 (slow development, n = 9) days. Furthermore, day 7 IVP blastocysts were examined after additional culture for 2 days either in vitro ( n = 5) or in vivo (after transfer into recipient mares, n = 3). In IVD early blastocysts, SOX-2 positive cells were encircled by GATA-6 positive cells in the ICM, with SOX-2 co-expression in some presumed PE cells. In IVD blastocysts, SOX-2 expression was exclusive to the compacted presumptive EPI, while GATA-6 and CDX-2 expression were consistent with PE and TE specification, respectively. In IVP blastocysts, SOX-2 and GATA-6 positive cells were intermingled and relatively dispersed, and co-expression of SOX-2 or GATA-6 was evident in some CDX-2 positive TE cells. IVP blastocysts had lower TE and total cell numbers than IVD blastocysts and displayed larger mean inter-EPI cell distances; these features were more pronounced in slower-developing IVP blastocysts. Transferring IVP blastocysts into recipient mares led to the compaction of SOX-2 positive cells into a presumptive EPI, whereas extended in vitro culture did not. In conclusion, IVP equine embryos have a poorly compacted ICM with intermingled EPI and PE cells; features accentuated in slowly developing embryos but remedied by transfer to a recipient mare