The analysis of fatty acids and their derivatives in the liver of C57BL/6 mice with long-term caloric restrictions.

Caloric restriction (CR) is a dietetic intervention based on the reduction of daily calorie intake by 10-30 %. When subjected to CR, the organism adjusts its metabolism to the changing availability of key nutrients. However, fatty acids' content in organisms subjected to long-term CR has not been evaluated. The aim of the research was to analyze the influence of long-term CR on the contents of medium- and long-chain fatty acids, as well as on the contents of fatty acid derivatives in liver. The study was performed on C57BL female (n = 12) and male (n = 12) mice subjected to lifelong 30 % calorie restriction. Fatty acids were analyzed using gas chromatography, while fatty acid derivatives were analyzed with liquid chromatography. The dynamics of change of the lipid profile of the labeled fatty acids observed in the liver tissue confirms that lipolysis actively takes place in this organ when hungry. Moreover, it is highly possible that de novo synthesis of acids takes place, with the aim to ensure energy substrates to the body. Moreover, an increase of concentration was observed for fatty acid derivatives, those with anti-inflammatory properties (resolvin, LTX A4). However, there was no increase in the concentration of pro-inflammatory eicosanoids. The results suggest that it is important to take into consideration the introduction of appropriate supplements when using CR.

Microbiota-derived metabolites in colorectal cancer patients in preoperative period.

OBJECTIVE: Short-chain fatty acids (SCFAs) are microbial derived metabolites, which have multiple beneficial properties. The amount of SCFAs depends on several factors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In colorectal cancer (CRC) patients, microbiota alterations have been shown. Consequently, metabolome within the gut might change to a large extent. Therefore, the aim of this study was to analyse the content of SCFAs and the proportion between SCFAs in the stool obtained from CRC patients in preoperative period. PATIENTS AND METHODS: This study included 15 patients with CRC in preoperative period. The stool samples were taken and stored at -80°C in the Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Poland. The analysis of SCFAs from stool samples was conducted by means of gas chromatography. RESULTS: This study included mainly males (66.67%, n=10). In all patients, there was abnormal proportion between SCFAs. The extremely higher concentration of butyrate was noted in 2 samples (13.33%) compared to the rest of patients. However, based on normal proportion between SCFAs, the results <1 for butyrate were noted in 93.33% of patients. CONCLUSIONS: SCFAs pool is altered in CRC patients, among others characterized by low level of butyrate. It should be considered to administer butyrate supplementation to CRC patients especially prior to surgery to support an appropriate preparation to this treatment.

Internalized homophobia and sexual risk behavior in men who have sex with men: The mediational role of sexual self-concept.

Men who have sex with men (MSM) are one of the populations most likely to be infected with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) worldwide. Sexual risk behaviors (SRB) are the main route of HIV transmission. Among the factors associated with SRB, internalized homophobia (rejection of one's sexuality) is a risk factor unique for MSM. However, how this factor influences SRB is not clear. Therefore, the present study attempts to clarify the mechanism of action of the relationship between internalized homophobia on SRB based on the mediating effects of sexual self-concept. A study was conducted with 124 MSM living in Chile over 18 years of age (M = 24.4 and SD = 4.19). Through path analysis, it was observed that internalized homophobia has slight inverse effects on SRBs (multiple sexual partners and sexual activity under the influence of alcohol or drugs) when the sexual self-efficacy dimension acts as a mediating variable. These findings suggest that developing sexually transmitted infections (STIs) and HIV/AIDS prevention campaigns focused on MSM must highlight the development of a healthy sexual self-concept and address self-stigma.

Effect of nonuniform perpendicular anisotropy in ferromagnetic resonance spectra in magnetic nanorings.

The high frequency dynamic behaviors of magnetic nanorings with variable anisotropy along their radius have been studied using micromagnetic simulations. The dynamic susceptibility spectrum and spatial localization of the ferromagnetic resonance modes are investigated by varying anisotropy gradients in nanorings of 200 nm of external radius, with different internal radii. Both the resonant frequencies and the number of peaks depend on the lower energy magnetization configuration which in turn is a function of anisotropy gradients. Besides, it is shown that the effects of the anisotropy gradient are relevant even for the narrowest ring of 10 nm wide. The idea of controlling frequencies by modifying the anisotropy gradients of the system suggests the possibility of using these nanostructures in potential magnetic controllable frequency devices.

Desarrollo y evidencia de validez de una escala multidimensional de riesgo de suicidio y factores protectores en un contexto chileno / Development and evidence of validity of a multidimensional scale of suicide risk and protective factors in a Chilean context

Resumen: El Suicidio es un grave problema de salud pública, por lo que evaluar su riesgo es fundamental para su prevención. Si bien existen múltiples factores relacionados, se cuentan con pocos instrumentos psicométricos para la medición conjunta de factores protectores y de riesgo, dificultando una comprensión multidimensional del comportamiento suicida. Sobre esta base, el presente estudio tiene como objetivo desarrollar una propuesta de evaluación multidimensional, de rápida aplicación, que permita evaluar tanto factores de riesgo como protectores. Se utilizó un diseño transversal, de tipo instrumental, junto a un muestreo no probabilístico, por disponibilidad, con dos muestras, de adultos jóvenes mayores de 18 años (n= 405 y n=117). El instrumento final se compone de 25 ítems y 5 dimensiones (i.e. ideación suicida, estrategias de afrontamiento enfocadas en la emoción, autoestima, apoyo social percibido y expectativas hacia el futuro). Los resultados indican buen ajuste del modelo, utilizando ESEM , adecuados niveles de fiabilidad (ω> .8) (α > 0.7). Además, se contó con evidencia de validez basada en la relación con otras variables e invarianza métrica entre hombres y mujeres. Los resultados obtenidos, sugieren que las puntuaciones son fiables y presentan evidencias de validez para su interpretación en población equivalente.

Abstract: Suicide is a major public health concern, making risk assessment essential for its prevention. Although there are multiple related factors, there are few psychometric tools for the joint measurement of both protective and risk factors, making a multidimensional understanding of suicidal behaviour difficult. On this basis, the present study aims to develop a quickly applicable, multidimensional assessment approach to evaluate both risk and protective factors. A cross-sectional, instrumental design was used, together with a non-probabilistic, availability sampling, with two samples of young adults over 18 years of age (n=405 and n=117). The final measure is composed by 25 items and 5 dimensions (i.e. suicidal ideation, emotion-focused coping strategies, self-esteem, perceived social support and expectations towards the future). Results show good model fit, using ESEM, adequate levels of reliability (ω> .8) (α > 0.7). In addition, there was evidence of validity based on the relationship with other variables and metric invariance between men and women. Results suggest that the scores are reliable and present evidence of validity for their interpretation in equivalent populations.

Effects of probiotics supplementation on the hormone and body mass index in perimenopausal and postmenopausal women using the standardized diet. A 5-week double-blind, placebo-controlled, and randomized clinical study.

OBJECTIVE: The results of pioneering studies indicate that probiotics can alleviate menopausal symptoms (including cardiometabolic dysfunctions) and improve the quality of life of perimenopausal/postmenopausal women. However, the results of randomized control trials are scarce to evaluate whether the administration of probiotics could affect the balance of sex hormones during the menopause period. PATIENTS AND METHODS: In this randomized, double-blind, and placebo-controlled study, 48 perimenopausal and postmenopausal women received multispecies probiotic Sanprobi Barrier in a dose of 2.5 × 109 (CFU) for five weeks. Dietary guidelines were introduced in both groups simultaneously (~1800 kcal/per day, whole grain, no-wheat meals). The study aimed to assess the variations in follicle-stimulating hormone (FSH), estradiol (E2), cortisol (as the hypothalamic-pituitary-ovarian axis hormone), and the body mass during the intervention. RESULTS: At the endpoint, FSH level has increased significantly concerning the baseline after the probiotic intake (31.91 vs. 42.00 mIU/ml; p < 0.009). Also, in the placebo group, a strong trend to elevate FSH was observed (22.31 vs. 41.99 mIU/ml; p = 0.055). Body mass has crucially decreased in reference to the baseline in both groups (PRO: 27.90 vs. 26.30 kg/m2, p<0.001; PBO: 25.90 to 24.60 kg/m2, p<0.001). CONCLUSIONS: Probiotics affect FSH levels in perimenopausal women while simultaneously representing a non-invasive strategy to impact hormonal homeostasis. They could potentially have an impact on cardiometabolic health.

Influence of the simultaneous calibration of multiple ring dosimeters on the individual absorbed dose.

Ring dosimeters for personal dosimetry are calibrated in accredited laboratories following ISO 4037-3 guidelines. The simultaneous irradiation of multiple dosimeters would save time, but has to be carefully studied, since the scattering conditions could change and influence the absorbed dose in nearby dosimeters. Monte Carlo simulations using PENELOPE-2014 were performed to explore the need to increase the uncertainty ofHp0.07in the simultaneous irradiation of three and five DXT-RAD 707H-2 (Thermo Scientific) ring dosimeters with beam qualities: N-30, N-80 and N-300. Results show that the absorbed dose in each dosimeter is compatible with each of the others and with the reference simulation (a single dosimeter), with a coverage probability of 95% (k= 2). Comparison with experimental data yielded consistent results with the same coverage probability. Therefore, five ring dosimeters can be simultaneously irradiated with beam qualities ranging, at least, between N-30 and N-300 with a negligible impact on the uncertainty ofHp0.07.

Dynamic and static properties of stadium-shaped antidot arrays.

In this work we performed a detailed numerical analysis on the static and dynamic properties of magnetic antidot arrays as a function of their geometry. In particular, we explored how by varying the shape of these antidot arrays from circular holes to stadium-shaped holes, we can effectively control the magnetic properties of the array. Using micromagnetic simulations we evidenced that coercivity is very sensitive to the shape of antidots, while the remanence is more robust to these changes. Furthermore, we studied the dynamic susceptibility of these systems, finding that it is possible to control both the position and the number of resonance peaks simply by changing the geometry of the holes. Thus, this work provides useful insights on the behavior of antidot arrays for different geometries, opening routes for the design and improvement of two-dimensional technologies.

Lipoxin (LTX A4 5S, 6R, 15R) levels drastically decrease after 5 years of hemodialysis treatment.

The increased risk of atherosclerosis in patients with chronic kidney disease (CKD) is associated with the increased concentration of fatty acids from the omega-6 family. Products of arachidonic acid oxidation, including prostaglandins, thromboxanes, hydroxyleicosa-tetraenoic acids (HETES) and hydroxyoctadecadienoic acids (HODES) are involved in the pathogenesis of cancer and cardiovascular diseases due to increased oxidative stress. The aim of our study was to determine the relations resulting from the duration of CKD treatment. One of our main concerns is, whether and when the cascade of synthesis of inflammatory mediators may be insufficient in patients with CKD during many years of treatment. The study involved 121 patients with CKD and 87 healthy volunteers. Eicosanoid profiles 9(S)-HODE, 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R)-lipoxinA4, 5(S),6(R),15(R)-lipoxinA4 were extracted in plasma. The HPLC separations were performed by means of 1260 liquid chromatography. Patients with CKD have a significantly higher concentration of the following inflammatory mediators: 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R), 15(R)-lipoxinA4 relative to the control group. However, the concentrations of 9(S)-HODE were lower in the CKD group. The comparison of sexes did not show significant differences in terms of CKD. A tendency for lower concentrations of HETE and HODE were observed in the group of men. 15LOX, 12LOX and 5LOX pathways in chronic kidney disease are increased, while COX are suppressed (9-HODE). The analysis of the treatment time of patients with CKD shows that incorrect levels of 5(S), 6(R) and 15(R)-lipoxinA4 are developed. We present a new evidence of possible concepts and future clinical interventions in patients suffering from chronic kidney disease for many years. These data for the first time demonstrate that lipoxin levels drastically decrease in the course of CKD. Therefore, synthetic LXA4 analogues may be used as an antioxidant therapy in CKD, which requires further research.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Convergent Validity of a Novel Clinical Reasoning Tool in Clerkship Medical Students: Pilot Study.

Medical student educators have limited tools for standardized clinical reasoning assessment. The clinical reasoning task (CRT) checklist has been shown to identify specific tasks in the diagnostic process among residents and faculty. Authors assessed a novel student think aloud protocol strategy, the CRT, compared with the validated clinical data interpretation (CDI) test in six third-year medical students. The CRT was scored by two independent reviewers (kappa = 0.88). CRT and CDI scores were strongly positively correlated (r = 0.768, p = 0.074, df = 4). CRT provides both a global assessment of clinical reasoning and specific clinical reasoning deficits.

A forty year journey: The generation and roles of NO in plants.

In this year there is the 40th anniversary of the first publication of plant nitric oxide (NO) emission by Lowell Klepper. In the decades since then numerous milestone discoveries have revealed that NO is a multifunctional molecule in plant cells regulating both plant development and stress responses. Apropos of the anniversary, these authors aim to review and discuss the developments of past concepts in plant NO research related to NO metabolism, NO signaling, NO's action in plant growth and in stress responses and NO's interactions with other reactive compounds. Despite the long-lasting research efforts and the accumulating experimental evidences numerous questions are still needed to be answered, thus future challenges and research directions have also been drawn up.

Three-dimensional photographic analysis of the face in European adults from southern Spain with normal occlusion: reference anthropometric measurements.

BACKGROUND: Recent non-invasive 3D photography method has been applied to facial analysis, offering numerous advantages in orthodontic. The purpose of this study was to analyze the faces of a sample of healthy European adults from southern Spain with normal occlusion in order to establish reference facial soft tissue anthropometric parameters in this specific geographic-ethnic population, as well as to analyze sexual dimorphism. METHODS: A sample of 100 healthy adult volunteers consisting of 50 women (mean age, 22.92 ± 1.56 years) and 50 men (mean age, 22.37 ± 2.12 years) were enrolled in this study. All participants had normal occlusion, skeletal Class I, mesofacial pattern, and healthy body mass index. Three-dimensional photographs of the faces were captured non-invasively using Planmeca ProMax 3D ProFace®. Thirty landmarks related to the face, eyes, nose, and orolabial and chin areas were identified. RESULTS: Male displayed higher values in all vertical and transversal dimensions, with the exception of the lower lip height. Larger differences between sexes were observed in face, mandible, and nose. Male also had higher values in the angular measurements which referred to the nose. No sex differences were found in transverse upper lip prominence or transverse mandibular prominence. No differences were found in the ratio measurements, with the exception of intercantal width/nasal width, which was higher in women than in men. CONCLUSIONS: Reference anthropometric measurements of facial soft tissues have been established in European adults from southern Spain with normal occlusion. Significant sexual dimorphism was found, with remarkable differences in size between sexes.

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

[Klinefelter'syndrome: A predisposition to sexual crime?] / Le syndrome de Klinefelter : une prédisposition au crime sexuel ?

BACKGROUND: Several studies have reported over-representation of psychiatric disorders among patients with Klinefelter' Syndrome (KS), with forensic complications. OBJECTIVE: Consider determinants of sexual assault in patient with KS. REVIEW: In this work, we present the case of Jules, 23 years old, with KS, benefiting from steroid replacement therapy, convicted of rape of a minor and evaluated in this context. We question here the role of his genetic pathology and of his hormonal treatment in this sexual assault. FINDINGS: According to evidence from the literature, it is not possible to determine with certainty the fair value of each factor and their impact on the occurrence of the sexual criminal act. Indeed, although the crime rate among KS subjects is higher than in the general population, the majority of them have never been in trouble with the law; moreover, these subjects were no more likely to commit violent sexual acts than were criminals without KS. As for hormonal treatment, it seems that testosterone is better viewed as a facilitator of initiating an aggressive response than as a primary inductor. CONCLUSION: In conclusion, the onset of sexual violence that accompanied the introduction of hormonal treatment into a patient with KS suggests an effective involvement of steroid replacement therapy, even small, in the criminal act. This must incite clinicians to extreme prudence and to take account of multidisciplinary expertise (psychiatrist, endocrinologist) in order to reconsider the continuation of the treatment in this particular forensic context. Finally, we discuss other factors that can precipitate such a violent act.

Clinical Reasoning and Knowledge Organization: Bridging the Gap Between Medical Education and Neurocognitive Science.

PURPOSE: The purpose of this pilot study was 2-fold. The first was to investigate the conceptual relationship between previously validated methodologies. The second was to establish a linkage between medical education research and current neurocognitive science that accounts for knowledge organization during the clinical reasoning process. METHODS: Transcripts of Think Aloud interviews conducted after an objective structured clinical examination (n = 12) were coded and analyzed into 3 clinical reasoning competencies (semantic, diagnostic, and knowledge network organization). Correlational analyses were conducted to establish relationships between the 2 methodologies. Analyses of variance examined group differences. RESULTS: Significant correlations with large effect sizes were found between semantic, diagnostic, and knowledge network organization variables. Analysis of variance results approach significant difference in the knowledge network organization between weak versus strong diagnosticians. CONCLUSIONS: Knowledge network organization measurement can be used to discern differences in clinical reasoning and may offer explanations for the variation in health professionals' diagnostic performance.