Novel strategy for the revalorization of olive (Olea europaea) residues based on the extraction of bioactive peptides

This work proposes a new strategy for the revalorization of residual materials from table-olive and olive oil production based on the extraction of bioactive peptides. Enzymatic hydrolysates of olive seed protein isolate were prepared by treatment with five different proteases: Alcalase, Thermolysin, Neutrase, Flavourzyme and PTN. Although all hydrolysates presented antioxidant properties, Alcalase was the enzyme that yielded the hydrolysate with the highest antioxidant capacity. All hydrolysates showed antihypertensive capacity, obtaining IC50 values from 29 to 350 mu g/ml. Thermolysin was the enzyme which yielded the hydrolysate with the highest ACE-inhibitory capacity. Hydrolysates were fractionated by ultrafiltration showing a high concentration of short chain peptides, which exhibited significantly higher antioxidant and antihypertensive capacities than fractions with higher molecular weights. Peptides in most active fractions were identified by LC-MS/MS, observing homologies with other recognized antioxidant and antihypertensive peptides. Finally, their antioxidant and antihypertensive capacities were evaluated after in vitro gastrointestinal digestion. (C) 2014 Elsevier Ltd. All rights reserved

Clozapine use during pregnancy and lactation: A case-series report

The current prescription of clozapine in psychotic women of reproductive age makes it crucial to understand its pharmacokinetics during pregnancy and lactation as well as its risk profile for neonatal outcome. The aim of this case series was to provide new evidence on the pharmacokinetic features of clozapine that determine its passage through the placenta and amniotic fluid, as well as the neonatal clozapine elimination half-life (t1/2). This case series demonstrates for the first time that clozapine might show partial placental passage similar to other atypical antipsychotics. Clozapine levels decreased during the first few days in nursing infants. The half-life of clozapine in neonates was slightly higher than previously estimated. Clozapine use in pregnancy may be associated with diabetes mellitus, especially if there is a family history of this disease. Although no acute toxicological effects were observed in the intrauterine exposed newborn, close follow-up of pregnancy is recommended. However, these results must be taken with caution being a case series with small sample size

Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice. Objectives: To present clinical and pharmacokinetic data of nine mother-infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006-2018). Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother-infant pairs at delivery, and at days 1-5, 7-11, 30, and 60 postpartum, and monthly until 6-months. Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02-1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum. Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair

Five-year diagnostic stability among adolescents in an inpatient psychiatric unit

Introduction: In childhood, diagnoses made at the first admission to a psychiatric unit are frequently unstable and temporary. In this study, we examined the stability of DSM-IV-TR disorders and groups of disorders among adolescents followed-up for 5 years after hospitalization. Method: All inpatients admitted for the first time between 2007 and 2008 were included and contacted after 5 years for re-evaluation. The final sample comprised 72 patients. At admission, diagnoses were based on the DSM-IV-TR criteria, Fourth Edition. At five years, diagnoses were made using structured clinical interviews for DSM-IV axis I Disorders and for axis II (SCID-I and SCID-II) as well as the Personality Diagnostic Questionnaire, Fourth Edition (PDQ-4). We also evaluated and collected information on the global assessment of functioning using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) instrument. Depending on the distribution of variables, we used the chi-squared and Fisher exact tests or the Student t and McNemar tests for statistical analyses. Results: The most stable diagnoses were schizophrenia spectrum disorders, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, Tourette syndrome, and pervasive developmental disorder. The most unstable diagnoses were disruptive disorders. Participants were satisfied with their quality of life and the global outcomes of the sample were positive. Conclusion: Major psychiatric disorders, including mood and schizophrenia spectrum disorders, were significantly more stable than other diagnoses and tended to continue into adulthood. In the case of study participants, suffering a mental disorder during adolescence did not appear to affect global functioning outcomes

Psychometric properties of the Spanish version of the Frost Multidimensional Perfectionism Scale in women

This instrumental study was designed to analyze the psychometric properties of the Spanish version of the Frost Multidimensional Perfectionism Scale (FMPS). The total sample was made up of 582 female college students, with a mean age of 21.68 (SD= 4.45). The results of confirmatory factor analysis identified the six-factor solution proposed by the original authors as the best factor structure, with acceptable fit indices. Cronbach's alpha coefficient was .93 for the FMPS total score and ranged from .74 to .91 for the subscales. Test-retest reliability suggested a good temporal stability of the FMPS total score [ICC= .89 (95% CI= .80-.94)] and its subscales. Results showed moderate to high associations between the Spanish version of the FMPS and other measures of perfectionism. The Spanish version of FMPS has shown satisfactory psychometric properties to be used in women. Future research should replicate these findings in broader samples, in clinical populations, and use longitudinal designs to determine whether perfectionism is a risk factor for psychopathology in womenEste estudio instrumental se diseñó para estudiar las propiedades psicométricas de la versión española de la Escala Multidimensional de Perfeccionismo de Frost (FMPS). La muestra total fue de 582 mujeres, estudiantes universitarias, con una edad media de 21,68 años (DT= 4,45). Los resultados del análisis factorial confirmatorio identificaron los seis factores propuestos por Frost et al. (1990) como la mejor estructura factorial, con índices de ajuste aceptables. El coeficiente alfa de Cronbach fue de ,93 para la puntuación total del FMPS, y entre ,71 y ,91 para las diferentes subescalas. La fiabilidad test-retest sugirió una buena estabilidad temporal de la puntuación total del FMPS [CCI= 0.89 (95% IC= ,80-,94)] y de sus subescalas. Se observaron asociaciones de moderadas a fuertes entre la versión española del FMPS y otras medidas de perfeccionismo. La versión española del FMPS ha mostrado buenas propiedades psicométricas para ser aplicada en mujeres. Futuras investigaciones deberían replicar estos hallazgos en muestras más amplias, en población clínica y utilizar diseños longitudinales para determinar si el perfeccionismo es un factor de riesgo para la psicopatología en las mujere

Enzyme replacement therapy for the treatment of Hunter disease: A systematic review with narrative synthesis and meta-analysis

Background: In the last 10 years enzyme replacement therapy (ERT) has become an alternative for the treatment of patients with Hunter disease (HD). Nevertheless, the information regarding efficacy and safety is scarce and mainly based on the pivotal trials. This scarcity is especially evident for adults and severe forms of HD. Methods: A systematic review of publications in the electronic databases PUBMED, EMBASE and Cochrane Central was undertaken. Clinical trials and observational studies were included. The data about efficacy and security were retrieved and analysed with Review Manager version 5.3. Results: 677 records were found, 559 remaining after the removal of duplicates. By title and abstract review, 427 were excluded. Full reading of the rest was made (122 publications) and 42 were finally included. It was not possible to perform meta-analysis of all the endpoints due to high heterogeneity in the reporting and measuring of variables in each publication. Eight clinical trials were included, 6 with high risk of bias. The quality of the other studies was low in 12%, average in 68% and good in 21%. Main findings were: a reduction in the elimination of glycosaminoglycans (GAG) in urine in all the studies (26/26), decrease in liver and spleen size (18/18), increase of 52.59 m (95% CI, 36, 42-68.76, p < .001) in the 6-min walk test (TM6M), increase in forced vital capacity (FVC) of 9.59% (95% CI 4.77-14.51, p < .001), reduction of the left ventricular mass index of 3.57% (95% CI 1.2-5.93) and reduction in mortality (OR) of 0.44 (0.27-0.71). Discussion: The data suggests a clear and consistent effect of ERT in HD reducing the accumulation of GAGs in the body, demonstrated by the reduction of its urinary excretion, as well as by the reduction of its deposits (spleen, liver and heart). Likewise, there is an improvement in physical and respiratory function. In addition, a reduction in mortality has been observed. Lack of studies, small size of the samples, and methodological deficiencies are the main limitations to establish definite conclusions. Conclusions: The data suggests that ERT is effective and safe in the treatment of HD. There is a need to evaluate patient-centred outcomes and the impact on quality of life

PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction

Dyslipidaemia in HIV-infected women on antiretroviral therapy. Analysis of 922 patients from the Spanish VACH cohort

Background: Information concerning lipid disturbances in HIV-infected women on antiretroviral therapy (ART) is scarce. The objective of the study is to describe the lipid profile in a large cohort of HIV-infected women on contemporary ART and analyse differences between regimes and patient's characteristics. Methods: Observational, multicentre, cross-sectional study from the Spanish VACH Cohort. 922 women on stable ART without lipid-lowering treatment were included. Results: Median age was 42 years, median CD4 lymphocyte count was 544 cells/mm3, and 85.6% presented undetectable HIV-1 viral load. Median total cholesterol (TC) was 189 mg/dL (interquartile range, IQR, 165-221), HDL cholesterol 53 mg/dL (IQR, 44-64), LDL cholesterol 108 mg/dL (IQR, 86-134), and triglycerides 116 mg/dL (IQR, 85-163). Mean accumulated time on ART was 116 months; 47.4% were on NNRTI-based regimes, 44.7% on PI, and 6.7% on only-NRTI therapy. 43.8% were also hepatitis C (HCV) coinfected. Patients on PI treatment presented higher TC/HDL ratio than those on NNRTI (p < 0.001). Significantly higher HDL values were observed in NNRTI-treated patients. HCV-coinfected patients presented lower TC/HDL ratio than the non HCV-coinfected. In multivariate analysis, factors independently associated with TC/HDL ratio were age, triglyceride levels and HCV co-infection. PI treatment presented a non-significant association with higher TC/HDL ratio. Conclusions: In HIV-infected women, the NNRTI-based ART is associated with a better lipid profile than the PI-based. Factors unrelated to ART selection may also exert an independent, significant influence on lipids; in particular, age, and triglyceride levels are associated with an increased TC/HDL ratio while HCV co-infection is associated with a reduced TC/HDL ratio

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents

This is the peer reviewed version of the following article: Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. Journal of Gastroenterology and Hepatology (2020): 29 April, which has been published in final form at https://doi.org/10.1111/jgh.15084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsBiological therapies may be changing the natural history of inflammatory bowel diseases, reducing the need for surgical intervention. We aimed to assess whether the availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). Methods Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990‐1995 and 2007‐2012 for CD; 1995‐2000 and 2007‐2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts. Results A total of 7,370 CD patients (2,022 in Cohort 1 and 5,348 in Cohort 2) and 8,069 UC patients (2,938 in Cohort 1 and 5,131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3 and 5 years, respectively p<0.0001), though not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3 and 5 years, respectively; p=0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high‐volume IBD centres (in both CD and UC) and immunosuppressant use (in CD) were protective factors. Conclusions Anti‐TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in U

Post-Hospital Syndrome and Hyponatremia

Introduction: Post-hospital syndrome (PHS) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the most frequent hydroelectrolytic disorder in hospitalized patients and may be related to the appearance of PHS. Objective: The objective is to estimate the prevalence of PHS that is assessed as the rate of readmissions in the first 30 days after discharge, in patients with hyponatremia. Material and Methods: It is a descriptive observational study of patients with hyponatremia who were discharged from 1 September 2010 to 2 February 2020 at the Internal Medicine Service of the Hospital University of San Juan (Alicante, Spain). Results: Of the 25 included patients, 5 (20%) were readmitted within a month of discharge, after a mean of 11.4 days (standard deviation [SD] 5.1). The overall mortality of the study was 20% (n = 5), with one case of death in the first 30 days post-hospitalization (4%). In 12 patients (48%) the origin of the hyponatremia was undetermined. The most frequently recorded etiology for the condition was pharmacological (n = 7, 28%), and there was pronounced variability in its clinical and laboratory study. The most widely used corrective measure was drug withdrawal, in 16 patients (64%). Water intake restriction was the most common treatment after discharge (5 patients, 20%), followed by urea (2 patients, 8%), while tolvaptan was not used. Conclusion: Hyponatremia may be the cause of PHS, which could increase the rate of early readmission. Hyponatremia is an underdiagnosed and undertreated entity, so it is necessary to apply an appropriate system to optimize its management and, in future studies, to assess its impact on PHS