Remediation of pesticides in commercial farm soils by solarization and ozonation techniques.

Soil contamination by pesticides is a growing environmental problem. Even though nowadays numerous soil remediation technologies are available, most of them have not been tested at field scale. This study attempts to demonstrate the efficiency of solarization-ozonation techniques for the removal of twelve pesticides at full scale. Initial solarization and ozonation trials were conducted in plots located in a greenhouse using freshly and aged contaminated soils under controlled pilot conditions. The combination of solarization and ozonation treatment was efficient for all the studied pesticides both in freshly and in aged contaminated soils, being the lower degradation values found for the second type. This low removal suggests that the increase of pesticides' adsorption on soil resulting from ageing decreases their availability. Once the essays were carried out at pilot scale, the solarization-ozonation applicability was evaluated in a commercial farm soil. This trial was carried out in a greenhouse whose soil had previously been contaminated with some of the pesticides studied. A significant degradation (53.8%) was observed after 40 days of treatment. Pesticides' main metabolites were identified during the different remediation experiments. In addition, the cost of the combined solarization and ozonation technology was evaluated. Finally, our results suggest that this combination of techniques could be considered a promising technology to degrade pesticides in soil.

MicroRNAs and their role in the malignant transformation of oral leukoplakia: a scoping review.

BACKGROUND: MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral epithelial precursor lesions such as oral leukoplakia. The aim was to perform a scoping review of the contemporary literature about the different roles of miRNAs during the malignant transformation of oral leukoplakia. MATERIAL AND METHODS: We conducted a systematic search with the following MeSH terms: 'oral leukoplakia', 'carcinoma in situ', 'microRNAs', 'mouth neoplasms' and 'epithelial-mesenchymal transition' in PubMed/MEDLINE, EMBASE and SpringerLink. RESULTS: Fifteen articles were included for analysis, among which in vivo and in vitro articles were included. A total of 21 different miRNAs were found to be involved in the malignant transformation process of oral leukoplakia. Regarding their possible effects, 6 miRNAs were classified as oncogenic, 5 as tumour suppressors and 10 were related to epithelial-mesenchymal transition, invasion and migration. CONCLUSIONS: Based on the current review, we concluded that miRNAs-21, 345, 181-b and 31* seem to be potential markers of malignant transformation of oral leukoplakia. However, further clinical prospective studies are needed in order to validate their utility as prognostic biomarkers.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

Personalized medicine begins with the phenotype: identifying antipsychotic response phenotypes in a first-episode psychosis cohort.

AIMS: Here, we present a clustering strategy to identify phenotypes of antipsychotic (AP) response by using longitudinal data from patients presenting first-episode psychosis (FEP). METHOD: One hundred and ninety FEP with complete data were selected from the PEPs project. The efficacy was assessed using total PANSS, and adverse effects using total UKU, during one-year follow-up. We used the Klm3D method to cluster longitudinal data. RESULTS: We identified four clusters: cluster A, drug not toxic and beneficial; cluster B, drug beneficial but toxic; cluster C, drug neither toxic nor beneficial; and cluster D, drug toxic and not beneficial. These groups significantly differ in baseline demographics, clinical, and neuropsychological characteristics (PAS, total PANSS, DUP, insight, pIQ, age of onset, cocaine use and family history of mental illness). CONCLUSIONS: The results presented here allow the identification of phenotypes of AP response that differ in well-known simple and classic clinical variables opening the door to clinical prediction and application of personalized medicine.

Understanding gold toxicity in aerobically-grown Escherichia coli.

BACKGROUND: There is an emerging field to put into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.

The associations between menopausal symptoms and sleep quality in Spanish postmenopausal women.

Objectives: Around the menopause, sleep disturbances frequently occur or worsen and are associated with decreased health quality and physical and psychological problems. The aim of this study was to analyze sleep quality and its association with the impact of menopausal symptoms in Spanish postmenopausal women. Methods: A total of 278 postmenopausal women (age 60.95 ± 8.01 years) participated in this cross-sectional study. The Medical Outcomes Study Sleep Scale (MOS-SS) and the Menopause Rating Scale (MRS) were used to analyze sleep quality and severity of menopausal symptoms, respectively. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Results: The linear regression showed that a greater impact of menopausal symptoms (MRS total score) was associated with worse scores regarding sleep adequacy (p < 0.001, R2 = 0.056), snoring (p = 0.020, R2 = 0.036), awaken short of breath (p < 0.001, R2 = 0.089), and quantity of sleep (p < 0.001, R2 = 0.075) domains. Anxiety (p < 0.001) and worse somatic symptoms (p = 0.001) were related to greater sleep disturbances (R2 = 0.164). We also found relationships of heightened psychological symptoms (p < 0.001) and low physical activity level (p = 0.003) with increased daytime somnolence (R2 = 0.064). Finally, higher MRS total score and anxiety levels were associated with worse sleep quality assessed by MOS-SS Sleep Problems Index I (R2 = 0.179, p < 0.001 and p = 0.001, respectively) and Sleep Problems Index II (R2 = 0.146, p < 0.001 and p = 0.011, respectively). Conclusions: Anxiety and severity of menopausal symptoms were associated with poorer sleep quality. Furthermore, low physical activity level and worse psychological symptoms in menopause were predictors for increased somnolence. Therefore, screening for these factors in postmenopausal women is important, since they may be susceptible for intervention.

Cognitive reserve as an outcome predictor: first-episode affective versus non-affective psychosis.

OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education-occupation; leisure activities). The groups were divided into high and low CR. RESULTS: In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CONCLUSION: CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.

Molecular recognition of a single sphingolipid species by a protein's transmembrane domain.

Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.

Individual trajectories of cognitive performance in first episode psychosis: a 2-year follow-up study.

Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profiles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profiles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the first 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specific interventions.

Psychometric assessment of the cultural capacity scale Spanish version in Chilean nursing students.

AIM: To assess the psychometric properties of the Cultural Capacity Scale Spanish version in Chilean nursing students. BACKGROUND: The increased diversity in healthcare facilities and the current shortage of local nursing workforce in Chile present a significant challenge to the nursing education to train future competent local nurses. To facilitate cultural competence development among Chilean nursing students, it is necessary to regularly assess their cultural competence, which necessitates a culturally adapted valid and reliable tool. METHODS: A convenience sample of 502 Chilean nursing students was surveyed in this cross-sectional study using the culturally adapted scale. Reliability of the instrument was established by internal consistency and stability reliability, while validity was established by content and construct. RESULTS: The Cronbach's α value of the entire scale was 0.95, and the test-retest reliability was 0.85. The Corrected Item-Total Correlations ranged from 0.45 to 0.78. The tool manifested an excellent content and construct validity. The exploratory factor analysis confirmed a single factor of the scale. DISCUSSION: The tool demonstrated evidence of internal consistency, stability reliability, content validity and construct validity. The study provided cross-cultural evidence for the potential application of this scale in Chile and other Spanish-speaking countries. CONCLUSION: The Cultural Capacity Scale Spanish version demonstrated sound psychometric properties for assessing the cultural competence of Chilean nursing students. LIMITATIONS: The sample was restricted to one university, and the tool was only used in Chilean nursing students. IMPLICATIONS FOR NURSING POLICY: The establishment of the Spanish version of the tool will facilitate accurate and timely monitoring of the cultural competence among Chilean nursing students and other Spanish-speaking nursing students and nurses, which can inform the creation of nursing policies aimed at ensuring cultural competence development.

C8-glycosphingolipids preferentially insert into tumor cell membranes and promote chemotherapeutic drug uptake.

Insufficient drug delivery into tumor cells limits the therapeutic efficacy of chemotherapy. Co-delivery of liposome-encapsulated drug and synthetic short-chain glycosphingolipids (SC-GSLs) significantly improved drug bioavailability by enhancing intracellular drug uptake. Investigating the mechanisms underlying this SC-GSL-mediated drug uptake enhancement is the aim of this study. Fluorescence microscopy was used to visualize the cell membrane lipid transfer intracellular fate of fluorescently labeled C6-NBD-GalCer incorporated in liposomes in tumor and non-tumor cells. Additionally click chemistry was applied to image and quantify native SC-GSLs in tumor and non-tumor cell membranes. SC-GSL-mediated flip-flop was investigated in model membranes to confirm membrane-incorporation of SC-GSL and its effect on membrane remodeling. SC-GSL enriched liposomes containing doxorubicin (Dox) were incubated at 4°C and 37°C and intracellular drug uptake was studied in comparison to standard liposomes and free Dox. SC-GSL transfer to the cell membrane was independent of liposomal uptake and the majority of the transferred lipid remained in the plasma membrane. The transfer of SC-GSL was tumor cell-specific and induced membrane rearrangement as evidenced by a transbilayer flip-flop of pyrene-SM. However, pore formation was measured, as leakage of hydrophilic fluorescent probes was not observed. Moreover, drug uptake appeared to be mediated by SC-GSLs. SC-GSLs enhanced the interaction of doxorubicin (Dox) with the outer leaflet of the plasma membrane of tumor cells at 4°C. Our results demonstrate that SC-GSLs preferentially insert into tumor cell plasma membranes enhancing cell intrinsic capacity to translocate amphiphilic drugs such as Dox across the membrane via a biophysical process.

Fall prevention in postmenopausal women: the role of Pilates exercise training.

Falls and fall-related injuries are a major public health concern for postmenopausal women. Fear of falling, impairments in gait and postural control, and changes in body composition have been identified as important risk factors for falling. Physical exercise is an important tool in fall prevention and management. The Pilates method is a non-impact activity that can be adapted to different physical conditions and health status and is recommended for various populations. In postmenopausal women, it has been deemed an effective way to improve some fall-related physical and psychological aspects, such as postural and dynamic balance. In addition, some physical capacities, such as flexibility, personal autonomy, mobility, and functional ability have also shown to benefit from Pilates interventions involving women in their second half of life, as well as certain psychological aspects including fear of falling, depressive status, and quality of life. Pilates exercise has shown effectively to prevent falls in postmenopausal women by improving their balance, physical and psychological functioning, and independence. Nevertheless, further studies are needed to demonstrate its validity in different clinical situations.

Sialyllactose in viral membrane gangliosides is a novel molecular recognition pattern for mature dendritic cell capture of HIV-1.

HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1.

Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.

Effects of 6 Weeks of Balance Training on Chronic Ankle Instability in Athletes: A Randomized Controlled Trial.

The objective of the present study was to determine the effectiveness of a 6-week balance training program on patients with Chronic Ankle Instability (CAI) in relation to the results obtained in Dynamic Balance, subjective feeling of instability and pain using a single-blind randomized controlled trial. 70 athletes were randomly assigned to control or intervention group. The control group performed their usual training, and the intervention group was administered the same usual activity in addition to a balance program. The paired t-test was performed to evaluate the change scores in each group. The t-test for independent samples was performed to evaluate between-group differences in change scores. Significance level was assigned for p-values less than 0.05 for all analyses. There were significant differences between groups in change scores in CAIT and all of the SEBTs reach distances (p<0.001) but not in Pain (p=0.586). The effect sizes were larger for the outcomes measures that showed significant differences. In the within-group change, the experimental groups showed larger effect sizes in CAIT, SEBT posteromedial and SEBT posterolateral, and moderate effect sizes in SEBT anterior. Exercise therapy training based on multi-station balance tasks led to significant improvements in dynamic balance and self-reported sensation of instability in patients with CAI.

A cholesterol recognition motif in human phospholipid scramblase 1.

Human phospholipid scramblase 1 (SCR) catalyzes phospholipid transmembrane (flip-flop) motion. This protein is assumed to bind the membrane hydrophobic core through a transmembrane domain (TMD) as well as via covalently bound palmitoyl residues. Here, we explore the possible interaction of the SCR TMD with cholesterol by using a variety of experimental and computational biophysical approaches. Our findings indicate that SCR contains an amino acid segment at the C-terminal region that shows a remarkable affinity for cholesterol, although it lacks the CRAC sequence. Other 3-OH sterols, but not steroids lacking the 3-OH group, also bind this region of the protein. The newly identified cholesterol-binding region is located partly at the C-terminal portion of the TMD and partly in the first amino acid residues in the SCR C-terminal extracellular coil. This finding could be related to the previously described affinity of SCR for cholesterol-rich domains in membranes.

The C-terminal transmembrane domain of human phospholipid scramblase 1 is essential for the protein flip-flop activity and Ca²âº-binding.

Human phospholipid scramblase 1 (SCR) is a 318 amino acid protein that was originally described as catalyzing phospholipid transbilayer (flip-flop) motion in plasma membranes in a Ca²âº-dependent, ATP-independent way. Further studies have suggested an intranuclear role for this protein in addition. A putative transmembrane domain located at the C terminus (aa 291-309) has been related to the flip-flop catalysis. In order to clarify the role of the C-terminal region of SCR, a mutant was produced (SCRΔ) in which the last 28 amino acid residues were lacking, including the α-helix. SCRΔ had lost the scramblase activity and its affinity for Ca²âº was decreased by one order of magnitude. Fluorescence and IR spectroscopic studies revealed that the C-terminal region of SCR was essential for the proper folding of the protein. Moreover, it was found that Ca²âº exerted an overall destabilizing effect on SCR, which might facilitate its binding to membranes.

In vitro leishmanicidal activity of pyrazole-containing polyamine macrocycles which inhibit the Fe-SOD enzyme of Leishmania infantum and Leishmania braziliensis species.

The in vitro leishmanicidal activity and cytotoxicity of pyrazole-containing macrocyclic polyamines 1-4 was assayed on Leishmania infantum and Leishmania braziliensis species. Compounds 1-4 were more active and less toxic than glucantime and both infection rates and ultrastructural alterations confirmed that 1 and 2 were highly leishmanicidal and induced extensive parasite cell damage. Modifications in the excretion products of parasites treated with 1-3 were also consistent with substantial cytoplasm alterations. Compound 2 was highlighted as a potent inhibitor of Fe-SOD in both species, whereas its effect on human CuZn-SOD was poor. Molecular modelling suggested that 2 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the enzyme`s antioxidant features.

Management of pudendal neuralgia.

Pelvic pain is a frequent complaint in women during both reproductive and post-reproductive years. Vulvodynia includes different manifestations of chronic vulvar pain with no known cause. Many women do not receive a diagnosis and appropriate treatment. Pudendal neuralgia is a painful condition caused by inflammation, compression or entrapment of the pudendal nerve; it may be related to or be secondary to childbirth, pelvic surgery, intense cycling, sacroiliac skeletal abnormalities or age-related changes. Clinical characteristics include pelvic pain with sitting which increases throughout the day and decreases with standing or lying down, sexual dysfunction and difficult with urination and/or defecation. To confirm pudendal neuralgia, the Nantes criteria are recommended. Treatment includes behavioral modifications, physiotherapy, analgesics and nerve block, surgical pudendal nerve decompression, radiofrequency and spinal cord stimulation.

Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training.

We aimed to test exercise-induced adaptations on skeletal muscle when quercetin is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin exercised, placebo sedentary, and placebo exercised. Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups were supplemented with quercetin, via gavage, on alternate days throughout the experimental period. Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α mRNA levels, mitochondrial DNA (mtDNA) content, and citrate synthase (CS) activity were measured on quadriceps muscle. Redox status was also quantified by measuring muscle antioxidant enzymatic activity and oxidative damage product, such as protein carbonyl content (PCC). Quercetin supplementation increased oxidative damage in both exercised and sedentary rats by inducing higher amounts of PCC (P < 0.001). Quercetin supplementation caused higher catalase (P < 0.001) and superoxide dismutase (P < 0.05) activity in the non-exercised animals, but not when quercetin is supplemented during exercise. Quercetin supplementation increased SIRT1 expression, but when quercetin is supplemented during exercise, this effect is abolished (P < 0.001). The combination of exercise and quercetin supplementation caused lower (P < 0.05) mtDNA content and CS activity when compared with exercise alone. Quercetin supplementation during exercise provides a disadvantage to exercise-induced muscle adaptations.