Content Validity of the Spanish Adaptation of the Premature Infant Pain Profile Revised.

BACKGROUND: To the best of our knowledge, there are no validated neonatal pain assessment scales in Spanish. Given the need for such a scale, a study was undertaken to adapt and validate the Premature Infant Pain Profile-Revised (PIPP-R) scale. After translation and back-translation, content validity was addressed, a crucial phase in validation studies, in which researchers examine whether the items that make up the scale represent the content that the scale is intended to assess. AIMS: The aim was to provide evidence for the content validity of the Spanish adaptation of the PIPP-R scale. METHOD: The study used the Delphi technique with 10 experts. Data collection was anonymous and was conducted through an online platform. It was an ad hoc survey consisting of four questions, with a five-point Likert scale for each item on the scale and for the instruction table. An item-content validity index (I-CVI) and a scale-content validity index (S-CVI) were calculated for the analysis. RESULTS: After two rounds of the survey, all items exceeded an I-CVI of 0.9. The S-CVI value was 0.98 (±0.03) for the scale, and 1 for its instruction table. The kappa index yielded values indicating an excellent degree of agreement. CONCLUSIONS: The Spanish version of the PIPP-R obtained a high degree of content validity according to the expert group and the Delphi technique.

NANDA-I and NOC Linkages for Six Psychosocial Nursing Diagnoses: A Validation Study.

The aim of this study was to validate the diagnostic content and the NANDA-I and NOC linkages for six psychosocial nursing diagnoses. This multicentre, descriptive, cross-sectional validation study followed Fehring's model. Expert nurses in nursing methodology and standardised nursing languages in Spain participated, with expertise criteria based on academic level and clinical, teaching, and research experience in the fields of nursing methodology and standardised nursing languages. This study adhered to the STROBE guidelines for cross-sectional studies. Eighty-seven professionals participated in the diagnostic content validation phase, and 57 in the NANDA-I and NOC linkages validation phase. The content validity indices of the six diagnoses ranged from 0.74 to 0.84, all considered valid. All 84 proposed defining characteristics were valid, with 42 scoring ≥0.8. Thirty-two linkages between diagnoses and NOC outcomes were proposed, all valid, with mean scores between 0.73 and 0.98. Each diagnosis was linked to 5-6 NOC outcomes, comprising 26 main outcomes and 6 supplementary outcomes. Overall coverage rates for each diagnosis ranged from 68.42% to 100%. All linkages between defining characteristics and NOC outcome indicators were validated. The six selected psychosocial diagnoses, their defining characteristics, and the proposed linkages between diagnoses and outcomes have been validated. The validation of linkages between NOC indicators and nearly all major defining characteristics of these six psychosocial diagnoses will make it possible to enhance diagnostic accuracy and enable continuous assessment of the effects of nursing interventions on the clinical progression of these diagnoses.

Suicide, neuroinflammation and other physiological alterations.

Suicide is considered one of the major public health problems worldwide, being the second leading cause of death in the 15-29 age group. It is estimated that every 40s someone in the world commits suicide. The social taboo surrounding this phenomenon as well as the fact that suicide prevention measures currently fail to avoid deaths from this cause, means that more research is needed to understand its mechanisms. The present narrative review on suicide tries to point out several important aspects, such as risk factors or the dynamics of suicide, as well as the current findings in the field of physiology that could offer advances in the understanding of suicide. Subjective measures of risk such as scales and questionnaires are not effective alone, whereas the objective measures can be addressed from physiology. Thus, an increased neuroinflammation in people who take their own lives has been found, with an increase in inflammatory markers such as interleukin-6 and other cytokines in plasma or cerebrospinal fluid. Also, the hyperactivity of the hypothalamic-pituitary-adrenal axis and a decrease in serotonin or in vitamin D levels seems to also be involved. In conclusion, this review could help to understand which factors can trigger an increased risk of dying by suicide, as well as pointing out those alterations that occur in the body when someone attempt to commit suicide or succeeds in taking their own life. There is a need for more multidisciplinary approaches that address suicide to help to raise awareness of the relevance of this problem that causes the death of thousands of people every year.

Moderate Beer Consumption Modifies Tumoral Growth Parameters and Pyrrolidone Carboxypeptidase Type-I and Type-II Specific Activities in the Hypothalamus-Pituitary-Mammary Gland Axis in an Animal Model of Breast Cancer.

AIMS: To determine the effect of moderate alcoholic and nonalcoholic beer consumption on tumoral growth parameters, the histopathology, pyrrolidone carboxypeptidase type I (Pcp I), and type II (Pcp II) specific activities in the hypothalamus-pituitary-mammary gland axis, and the circulating levels of estradiol (E2) and progesterone (P4) in rats with N-methyl-N-nitrosourea (NMU) induced mammary tumors. MATERIAL AND METHODS: Food and drink intake, weight gain and tumor growth parameters were collected. The malignant phenotype of the tumor was performed using the Scarff-Bloom-Richardson grading method. Pcp specific activities were fluorometrically analyzed using pyroglutamyl-ß-naphthylamide as substrate. Circulating steroid hormones were determined. RESULTS: Differences were found in tumoral parameters, depending on the drink. Animals that were given alcohol-containing beer (A/C) beer to drink showed the lowest values of hypothalamic Pcp I, in association with the lowest levels of circulating E2. The significant decrease in Pcp I activity in all NMU-treated groups suggest a clear role of the Pcp I in the tumoral process, and A/C beer interferes with it. DISCUSSION: Moderate consumption of alcoholic beer would have beneficial effects against mammary tumors through the modification of the endocrine status mediated by GnRH due to changes on Pcp I and II activities at different levels.

Neoadjuvant chemotherapy modifies serum pyrrolidone carboxypeptidase specific activity in women with breast cancer and influences circulating levels of GnRH and gonadotropins.

PURPOSE: Functional studies have demonstrated that gonadotropin-releasing hormone (GnRH) regulates cell proliferation, apoptosis, and tissue remodeling. GnRH is metabolized by the proteolytic regulatory enzyme pyrrolidone carboxypeptidase (Pcp) (E.C. 3.4.19.3), which is an omega peptidase widely distributed in fluids and tissues. We previously reported a decrease in both rat and human Pcp activity in breast cancer, suggesting that GnRH may be an important local hormonal factor in the pathogenesis of breast cancer. Recently, we have described that postmenopausal women with breast cancer show lower levels of serum Pcp activity than control postmenopausal women. To determine the effect of neoadjuvant chemotherapy (NACT) on serum Pcp specific activity and circulating levels of GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and steroid hormones 17-ß-estradiol and progesterone in pre- and postmenopausal women diagnosed with infiltrating ductal carcinoma. METHODS: Serum Pcp activity was measured fluorometrically using pyroglutamyl-ß-naphthylamide. Circulating GnRH levels were dosed using a commercial RIA kit. Circulating LH and FSH levels were measured by enzyme immunoassays. Levels of steroid hormones were measured in serum samples by dissociation-enhanced lanthanide fluorescence immunoassay. RESULTS AND CONCLUSION: Our results show the effect of NACT on the hypothalamic-pituitary axis, with the consequent alteration of circulating gonadotropins in premenopausal women with breast cancer. However, the results obtained in postmenopausal women with breast cancer treated with NACT, that is, the significant decrease in the concentration of GnRH and FSH compared to control postmenopausal women, differ from those obtained for premenopausal women. The only difference between pre- and postmenopausal women is their hormonal profile at the beginning of the study, that is, the presence of menopause and the consequent alteration of the hypothalamic-pituitary-gonadal axis.

Statins Directly Regulate Pituitary Cell Function and Exert Antitumor Effects in Pituitary Tumors.

INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs), the most abundant of all intracranial tumors, entail severe comorbidities. First-line therapy is transsphenoidal surgery, but subsequent pharmacological therapy is often required. Unfortunately, many patients are/become unresponsive to available drugs (somatostatin analogues [SSAs]/dopamine agonists), underscoring the need for new therapies. Statins are well-known drugs commonly prescribed to treat hyperlipidemia/cardiovascular diseases, but can convey additional beneficial effects, including antitumor actions. The direct effects of statins on normal human pituitary or PitNETs are poorly known. Thus, we aimed to explore the direct effects of statins, especially simvastatin, on key functional parameters in normal and tumoral pituitary cells, and to evaluate the combined effects of simvastatin with metformin (MF) or SSAs. METHODS: Effects of statins in cell proliferation/viability, hormone secretion, and signaling pathways were evaluated in normal pituitary cells from a primate model (Papio anubis), tumor cells from corticotropinomas, somatotropinomas, nonfunctioning pituitary tumors, and PitNET cell-lines (AtT20/GH3-cells). RESULTS: All statins decreased AtT20-cell proliferation, simvastatin showing stronger effects. Indeed, simvastatin reduced cell viability and/or hormone secretion in all PitNETs subtypes and cell-lines, and ACTH/GH/PRL/FSH/LH secretion (but not expression), in primate cell cultures, by modulating MAPK/PI3K/mTOR pathways and expression of key receptors (GH-releasing hormone-receptor/ghrelin-R/Kiss1-R) regulating pituitary function. Addition of MF or SSAs did not enhance simvastatin antitumor effects. CONCLUSION: Our data reveal direct antitumor effects of simvastatin on PitNET-cells, paving the way to explore these compounds as a possible tool to treat PitNETs.

Effects of gonadotrophins and insulin on glucose uptake in the porcine cumulus-oocyte complex during IVM.

The combination of gonadotrophins (LH and FSH) and insulin is frequently used in porcine oocyte IVM, but the individual effects of gonadotrophins and insulin have not been completely studied. The aim of this study was to investigate the mechanisms involved in glucose metabolism in the swine cumulus-oocyte complex (COC), analysing the effects of gonadotrophins (10IUmL-1 LH+10IUmL-1 FSH) and 0.4µUmL-1 insulin, during 44h of IVM, on glucose transport and consumption, as well as on nuclear maturation and sperm penetration. We evaluated the effects of gonadotrophins and insulin separately or in combination on glucose consumption, membrane permeability to the glucose fluorescent analogue 6-(N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-deoxyglucose (6-NBDG), the presence of GLUT-4 and oocyte maturation rates, after 44h of IVM. Nuclear maturation percentages increased significantly following the addition of gonadotrophins alone or in combination with insulin to the culture medium (P P P <0.0001). Although gonadotrophins and insulin increased GLUT-4 expression, neither modified 6-NBDG incorporation. In conclusion, gonadotrophins and insulin had different effects during IVM; although gonadotrophins increased maturation rates and glucose consumption, they had no effect on glucose transport, and insulin improved sperm penetration without affecting the parameters related to glucose utilisation. Therefore, glucose metabolism is likely to be primarily regulated by its consumption in metabolic pathways rather than by changes in membrane permeability.

Reliability and Repeatability of the Instrument for the Assessment of Stress in Nursing Students (ASNS).

Background and objectives: Stress in nursing students is a very common experience, especially when they face clinical practice. The aims of this study were to perform a transcultural adaptation and to examine the reliability and repeatability of the Instrument for the Assessment of Stress in Nursing Students for a Spanish population. Methods: A test-retest analysis was carried out in two face-to-face sessions with the students with a lapse of 10 days between the two sessions. A cross-sectional descriptive study was carried out between the months of May and June 2018. Sixty-four nursing students were recruited with a consecutive sampling method that targeted individuals in the freshman class. Results: A good internal consistency was shown for the total score (α = 0.8861) and for each of the six domains. The test-retest reliability, using the Wilcoxon paired test, was not significant, indicating no differences between the total scores or the domain scores (p ≥ 0.05). Finally, Bland and Altman plots of visual distributions did not show differences between the total scores and the domain scores. Conclusion: The Instrument for the Assessment of Stress in Nursing Students was shown to be a reliable tool for measuring stress factors among Spanish nursing students.

Intensity-modulated radiation therapy and volumetric modulated arc therapy versus conventional conformal techniques at high energy: Dose assessment and impact on second primary cancer in the out-of-field region.

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+).

UNLABELLED: Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naïve (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment-related serious AEs. CONCLUSION: The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience.

Real-world experience with daclatasvir plus sofosbuvir ± ribavirin for post-liver transplant HCV recurrence and severe liver disease.

Optimizing therapy of post-transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post-liver transplant recurrence in a real-world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians' discretion. Patients (N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post-treatment week 12 (SVR12) was 94% (80/85) in a modified intention-to-treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as-observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events (AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow-up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug-drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post-transplant HCV recurrence, including patients with severe liver disease.

Variations in diabetes remission rates after bariatric surgery in Spanish adults according to the use of different diagnostic criteria for diabetes.

BACKGROUND: There are multiple criteria to define remission of type 2 diabetes (DM2) after bariatric surgery but there is not a specific one widely accepted. Our objectives were to compare diagnostic criteria for DM2 remission after bariatric surgery: Criteria from Spanish scientific associations (SEEN/SEEDO/SED) and from the American Diabetes Association (ADA). We also aim to analyse the degree of correlation between these sets of criteria. METHODS: Retrospective observational study in 127 patients undergoing bariatric surgery in a single centre (Hospital Universitario Reina Sofía, Córdoba, Spain) between January 2001 and December 2009. We analysed DM2 remission following bariatric surgery comparing DM2 diagnostic criteria approved by Spanish scientific associations and ADA criteria. RESULTS: In total, 62.2% of patients were women; mean age was 47.1 years. Following surgery, 52% achieved complete remission according to ADA criteria, and 63.8% following the criteria approved by Spanish associations (p = 0.001);18.9 and 8.7%, respectively, showed partial remission (p = 0.007), and 29.1 and 27.6% no remission, according to the criteria approved by each association (p = 0.003). There was good correlation between both sets of criteria (Rho 0.781; p < 0.001). CONCLUSIONS: In our series, using more stringent criteria for defining DM2 remission (ADA criteria) results in a lower rate of remission, although we found a a high degree of correlation between both sets of criteria.

Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort.

OBJECTIVE: We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease. DESIGN: Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). RESULTS: Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child-Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI -2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related. CONCLUSIONS: DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease. TRIAL REGISTRATION NUMBER: NCT02097966.

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

BACKGROUND: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. OBJECTIVE: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. METHODS: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. RESULTS: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. CONCLUSIONS: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

A PCR-RFLP method for detection of the LNPEP encoding human insulin-regulated aminopeptidase (IRAP) rs4869317 polymorphism.

BACKGROUND & OBJECTIVES: Insulin regulated aminopeptidase (IRAP) has been related to certain pathologies such as breast cancer, Alzheimer΄s disease and septic shock. IRAP is encoded by the leucyl/cystinyl aminopeptidase (LNPEP) gene. The genetic variation in the LNPEP gene has been analyzed in relation with the mortality and vasopressin clearance in septic shock. The LNPEP rs4869317 SNP (single nucleotide polymorphism) was the most significantly associated SNP with vasopressinase activity, being TT genotype associated with increased mortality. The objective of the present study was to develop a simple method to allow a quick and affordable genotyping for the rs4869317 SNP of LNPEP gene. METHODS: Blood DNA samples were obtained from randomly selected healthy volunteers (n=28). A pair of primers was designed to amplify an 834 bp region of the LNPEP gene containing the rs4869317 SNP. The two alleles (T or A) were detected by digestion of the PCR products with the PacI restriction endonuclease. This enzyme only cuts the PCR products when the adenine is present in the SNP. RESULTS: All individuals showed RFPL (restriction fragment length polymorphism) fragments for the expected genotypes (TT, TA or AA). The methodology was validated by sequencing of the amplified DNAs from several 'T/T' and 'A/A' homozygotes and 'T/A' heterozygotes. The results from both methods showed agreement. INTERPRETATION & CONCLUSIONS: The PCR-RFLP is a simple and reliable method that allows a quick genotyping for the rs4869317 SNP of LNPEP gene. The study of this polymorphism could be useful in future investigations to analyze the role of genetic variants of IRAP in several physiological/pathological conditions.

Fibromyalgia: A Review of the Pathophysiological Mechanisms and Multidisciplinary Treatment Strategies.

Fibromyalgia is a syndrome characterized by chronic widespread musculoskeletal pain, which may or may not be associated with muscle or joint stiffness, accompanied by other symptoms such as fatigue, sleep disturbances, anxiety, and depression. It is a highly prevalent condition globally, being considered the third most common musculoskeletal disorder, following lower back pain and osteoarthritis. It is more prevalent in women than in men, and although it can occur at any age, it is more common between the ages of thirty and thirty-five. Although the pathophysiology and etiopathogenesis remain largely unknown, three underlying processes in fibromyalgia have been investigated. These include central sensitization, associated with an increase in the release of both excitatory and inhibitory neurotransmitters; peripheral sensitization, involving alterations in peripheral nociceptor signaling; and inflammatory and immune mechanisms that develop concurrently with the aforementioned processes. Furthermore, it has been determined that genetic, endocrine, psychological, and sleep disorders may influence the development of this pathology. The accurate diagnosis of fibromyalgia remains challenging as it lacks specific diagnostic biomarkers, which are still under investigation. Nonetheless, diagnostic approaches to the condition have evolved based on the use of scales and questionnaires for pain identification. The complexity associated with this pathology makes it difficult to establish a single effective treatment. Therefore, treatment is multidisciplinary, involving both pharmacological and non-pharmacological interventions aimed at alleviating symptoms. The non-pharmacological treatments outlined in this review are primarily related to physiotherapy interventions. The effectiveness of physical exercise, both on land and in water, as well as the application of electrotherapy combined with transcranial therapy and manual therapy has been highlighted. All of these interventions aim to improve the quality of life of patients highly affected by fibromyalgia.

Predictive Ability of Serum Amino Acid Levels to Differentiate Fibromyalgia Patients from Healthy Subjects.

BACKGROUND: Fibromyalgia is a complex illness to diagnose and treat. OBJECTIVES: To evaluate a broad range of circulating free amino acid (AA) levels in fibromyalgia patients as well as the ability of the AAs to differentiate fibromyalgia patients from healthy subjects. DESIGN: We carried out a case-control study to evaluate AA levels in 62 patients with fibromyalgia and 78 healthy subjects. This study adheres to the STROBE guidelines. METHODS: AAs content was assayed by HPLC in serum samples. The predictive value of AA levels in fibromyalgia was determined by receiver operating characteristic (ROC) curve and forward binary logistic regression analyses. RESULTS: Fibromyalgia patients showed higher serum levels of aspartic acid, glutamic acid, aminoadipic acid, asparagine, histidine, 3-methyl-histidine, 5-methyl-histidine, glycine, threonine, taurine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, ornithine, lysine, branched chain AAs (BCAAs), large neutral AAs, essential AAs (EAAs), non-essential AAs (NEAAs), basic AAs, EAAs/NEAAs ratio, phenylalanine/tyrosine ratio, and global arginine bioavailability ratio than the controls. Serum alanine levels were lower in patients than in controls. According to ROC analysis, most of these AAs may be good markers for differentiating individuals with fibromyalgia from healthy subjects. Results of logistic regression showed that the combination of glutamic acid, histidine, and alanine had the greatest predictive ability to diagnose fibromyalgia. CONCLUSIONS: Our results show an imbalance in serum levels of most AAs in patients with fibromyalgia, which suggest a metabolic disturbance. The determination of serum levels of these AAs may aid in the diagnosis of fibromyalgia, in combination with clinical data of the patient.

Mapping the Evidence on the Impact of mHealth Interventions on Patient-Reported Outcomes in Patients With Breast Cancer: A Systematic Review.

PURPOSE: To comprehensively synthesize the existing evidence concerning mHealth interventions for patients with breast cancer (BC). DESIGN: On July 30, 2023, we searched PubMed, PsycINFO, and Google Scholar for articles using the following inclusion criteria: evaluation of mHealth interventions in patients with cancer, at least 30 participants with BC, randomized control trials or prospective pre-post studies, determinants of health (patient-reported outcomes [PROs] and quality of life [QoL]) as primary outcomes, interventions lasting at least 8 weeks, publication after January 2015. Publications were excluded if they evaluated telehealth or used web-based software for desktop devices only. The quality of the included studies was analyzed with the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies. RESULTS: We included 30 studies (20 focused on BC), encompassing 5,691 patients with cancer (median 113, IQR, 135.5). Among these, 3,606 had BC (median 99, IQR, 75). All studies contained multiple interventions, including physical activity, tailored information for self-management of the disease, and symptom tracker. Interventions showed better results on self-efficacy (3/3), QoL (10/14), and physical activity (5/7). Lifestyle programs (3/3), expert consulting (4/4), and tailored information (10/11) yielded the best results. Apps with interactive support had a higher rate of positive findings, while interventions targeted to survivors showed worse results. mHealth tools were not available to the public in most of the studies (17/30). CONCLUSION: mHealth interventions yielded heterogeneous results on different outcomes. Identifying lack of evidence on clinical scenarios (eg, patients undergoing systemic therapy other than chemotherapy) could aid in refining strategic planning for forthcoming research endeavors within this field.

Psychological distance and reaction time in a Stroop task.

Several sources of interference may simultaneously affect the onset of the well-known "Stroop effect." Among them is the semantic component, which is reflected in the gradient or semantic effect. This effect consists of an increase in the amount of interference as the semantic distance between the word and the color concept decreases. Shepard (Science 237:1317-1323, 1987) relates psychological space, measured through multidimensional scaling, to mean response times. The present investigation aims to study the function relating the semantic gradient with the psychological distance between the word and the color in a Stroop task. After measuring the gradient, we obtained the subjective rating of the degree of dissimilarity of the gradient words with the concept of "color." In our work, we show that the amount of interference in a Stroop task increases when the semantic distance from the word to the color concept decreases, and it does so exponentially. We replicated the study with different stimuli to test the robustness of the results.

Divergent approach to nanoscale glycomicelles and photo-responsive supramolecular glycogels. Implications for drug delivery and photoswitching lectin affinity.

The field of stimuli-responsive supramolecular biomaterials has rapidly advanced in recent years, with potential applications in diverse areas such as cancer theranostics, tissue engineering, and catalysis. However, designing molecular materials that exhibit predetermined hierarchical self-assembly to control the size, morphology, surface chemistry, and responsiveness of the final nanostructures remains a significant challenge. In this study, we present a divergent synthetic approach for the fabrication of spherical micelles and functional 1D-glyconanotube-based photoresponsive gels from structurally related diazobenzene/diacetylene glycolipids. The resulting nanostructures were characterized using NMR, TEM, and SEM, confirming the formation of spherical and tubular nanostructures in both the gel and solution states. Upon UV irradiation, a reversible gel-sol transition was observed, resulting from the photoswitching of the azobenzene unit from the stretched trans form to the compact, metastable cis form. Our gels were shown to enable spatio-temporal control of the adhesion and release of the lectin Concanavalin A, demonstrating potential use as regenerable biomaterials to fight against infections with toxins and pathogens. Additionally, our micelles and gels were evaluated as nanocontainers for loading and controlled release of hydrophobic dyes and antitumoural agents, suggesting their possible use as smart theranostic drug delivery systems.