Minimal Clinically Important Differences in Hand Pain Intensity (Numerical Pain Rate Scale) and Related-Function (Boston Carpal Tunnel Questionnaire) in Women With Carpal Tunnel Syndrome.

OBJECTIVE: To calculate the minimal clinically important differences (MCIDs) for hand pain intensity and the Boston Carpal Tunnel Questionnaire (BCTQ) in a sample of women with carpal tunnel syndrome (CTS). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: A Hospital Rehabilitation Unit. PARTICIPANTS: One hundred twenty women with clinical and electromyographic diagnosis of CTS who were randomly assigned into 2 groups (N=120). INTERVENTIONS: One group received 3 sessions of manual physical therapy (n=60) and the other group received surgery (n=60). MAIN OUTCOME MEASURES: Mean and the worst pain intensity (numerical pain rate scale, 0-10 points) and functional status and symptoms' severity subscales of the BCTQ questionnaire were assessed before and 1 month after treatment. The Global Rating of Change (GROC) was used as the anchor variable for determining the MCID. RESULTS: A change of 1.5 and 2.5 points in mean and the worst pain intensity represents the MCID for Numerical Pain Rating Scale, whereas a change of 0.23 and 0.64 points in functional status and symptoms' severity represents the MCID for each subscale of the BCTQ. All variables showed acceptable discrimination between patients classified as "improved" and those classified as "stable/not improved" (area under the curve≥0.72). Mean pain intensity (Youden index, 0.53; sensitivity: 73.3%; specificity: 80%) and symptoms' severity (Youden index, 0.69; sensitivity: 90%; specificity: 77.8%) showed the best discriminative ability expressed as a percentage of prediction. Participants classified as "improved" had significantly greater improvements in pain intensity, functional status, and symptoms' severity compared with those classified as "stable/not improved". CONCLUSION: A change of 1.5 and 2.5 points in mean and the worst pain and a change of 0.23 and 0.64 points in functional status and symptoms' severity represents the MCID for pain intensity and BCTQ in women with CTS 1 month after treatment.

JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms.

Background: Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway. Objective: This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms. Methods: The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Results: The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Conclusion: Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Antecedentes: Entre las neoplasias mieloproliferativas crónicas no asociadas con mutaciones BCR-ABL se encuentran la policitemia vera, la mielofibrosis primaria y la trombocitemia esencial. Estas enfermedades están causadas por mutaciones en genes, como los genes JAK2, MPL y CALR, que participan en la regulación de la vía de señalización JAK-STAT. Objetivo: Establecer las frecuencias de mutaciones en los genes JAK2, MPL y CALR en un grupo de pacientes colombianos con diagnóstico clínico negativo de NMP BCR-ABL. Metodos: Se analizaron las mutaciones y deleciones o inserciones JAK2 V617F y MPL W515K en el exón 9 del gen CALR en 52 pacientes colombianos con policitemia vera, mielofibrosis primaria y trombocitemia esencial. Resultados: La mutación JAK2V617F la portaban el 51.9% de los pacientes, la mutación CALR el 23.0% y la mutación MPL el 3.8%; El 23.0% fueron triple negativos para las mutaciones analizadas. En estas neoplasias se identificaron seis tipos de mutación en CALR, uno de los cuales no ha sido reportado previamente. Además, un paciente presentó una doble mutación tanto en el gen CALR como en el JAK2. En cuanto a los resultados hematológicos para las mutaciones, se encontraron diferencias significativas en el nivel de hemoglobina, el nivel de hematocrito y el recuento de plaquetas entre las tres neoplasias. Conclusiones: Así, este estudio demuestra la importancia de la caracterización molecular de las mutaciones JAK2, CALR y MPL en pacientes colombianos (cuyo contexto genético aún no está claro en las neoplasias antes mencionadas) para lograr un diagnóstico certero, un buen pronóstico, un manejo adecuado y una mejoría del paciente. supervivencia.

Prognostic Factors for Postoperative Chronic Pain after Knee or Hip Replacement in Patients with Knee or Hip Osteoarthritis: An Umbrella Review.

Knee and hip osteoarthritis are highly prevalent in the older population. Management of osteoarthritis-related pain includes conservative or surgical treatment. Although knee or hip joint replacement is associated with positive outcomes, up to 30% of patients report postoperative pain in the first two years. This study aimed to synthesize current evidence on prognostic factors for predicting postoperative pain after knee or hip replacement. An umbrella review of systematic reviews was conducted to summarize the magnitude and quality of the evidence for prognostic preoperative factors predictive of postoperative chronic pain (>6 months after surgery) in patients who had received knee or hip replacement. Searches were conducted in MEDLINE, CINAHL, PubMed, PEDro, SCOPUS, Cochrane Library, and Web of Science databases from inception up to 5 August 2022 for reviews published in the English language. A narrative synthesis, a risk of bias assessment, and an evaluation of the evidence confidence were performed. Eighteen reviews (nine on knee surgery, four on hip replacement, and seven on both hip/knee replacement) were included. From 44 potential preoperative prognostic factors, just 20 were judged as having high or moderate confidence for robust findings. Race, opioid use, preoperative function, neuropathic pain symptoms, pain catastrophizing, anxiety, other pain sites, fear of movement, social support, preoperative pain, mental health, coping strategies, central sensitization-associated symptoms, and depression had high/moderate confidence for an association with postoperative chronic pain. Some comorbidities such as heart disease, stroke, lung disease, nervous system disorders, and poor circulation had high/moderate confidence for no association with postoperative chronic pain. This review has identified multiple preoperative factors (i.e., sociodemographic, clinical, psychological, cognitive) associated with postoperative chronic pain after knee or hip replacement. These factors may be used for identifying individuals at a risk of developing postoperative chronic pain. Further research can investigate the impact of using such prognostic data on treatment decisions and patient outcomes.

JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms

Background: Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway. Objective: This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms. Methods: The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Results: The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Conclusion: Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Antecedentes: Entre las neoplasias mieloproliferativas crónicas no asociadas con mutaciones BCR-ABL se encuentran la policitemia vera, la mielofibrosis primaria y la trombocitemia esencial. Estas enfermedades están causadas por mutaciones en genes, como los genes JAK2, MPL y CALR, que participan en la regulación de la vía de señalización JAK-STAT. Objetivo: Establecer las frecuencias de mutaciones en los genes JAK2, MPL y CALR en un grupo de pacientes colombianos con diagnóstico clínico negativo de NMP BCR-ABL. Metodos: Se analizaron las mutaciones y deleciones o inserciones JAK2 V617F y MPL W515K en el exón 9 del gen CALR en 52 pacientes colombianos con policitemia vera, mielofibrosis primaria y trombocitemia esencial. Resultados: La mutación JAK2V617F la portaban el 51.9% de los pacientes, la mutación CALR el 23.0% y la mutación MPL el 3.8%; El 23.0% fueron triple negativos para las mutaciones analizadas. En estas neoplasias se identificaron seis tipos de mutación en CALR, uno de los cuales no ha sido reportado previamente. Además, un paciente presentó una doble mutación tanto en el gen CALR como en el JAK2. En cuanto a los resultados hematológicos para las mutaciones, se encontraron diferencias significativas en el nivel de hemoglobina, el nivel de hematocrito y el recuento de plaquetas entre las tres neoplasias. Conclusiones: Así, este estudio demuestra la importancia de la caracterización molecular de las mutaciones JAK2, CALR y MPL en pacientes colombianos (cuyo contexto genético aún no está claro en las neoplasias antes mencionadas) para lograr un diagnóstico certero, un buen pronóstico, un manejo adecuado y una mejoría del paciente. supervivencia.

Quality of Life after Radical Prostatectomy: A Longitudinal Study.

BACKGROUND: Men with prostate cancer who undergo radical prostatectomy experience a decrease in quality of life, often related to sexual disfunction and urinary incontinence. Knowing and measuring the impact of radical prostatectomy on the individual's social, emotional, and family quality of life could help to plan and develop an appropriate, patient-centred therapeutic approach. AIM: In this study, we aimed to evaluate changes in quality of life of patients with prostate cancer before and after radical prostatectomy. METHODS: A longitudinal, observational study of 114 participants was conducted using the method of test-retest. Quality of life before and after radical prostatectomy was measured through the following self-administered questionnaires: (1) The EORTC QLQ-C30 in its Spanish version was used to assess the generic quality of life the participants; (2) the EORTC QLQ-PR25 in its Spanish version was used to assess the specific, health-related quality of life of prostate cancer patients. RESULTS: A total of 114 men took part in this study. The results from the QLQ-C30 questionnaire indicated an improvement in the dimensions of emotional role and cognitive function, as well as in the symptoms of fatigue, pain, nausea and vomiting, insomnia, and loss of appetite, after surgery. Patients scored lower in the dimensions of role functioning, social function, and economic impact after radical prostatectomy. According to the results from the QLQ-PR25 questionnaire, 61.40% of the participants experienced sexual impotence and 26.31% suffered urinary incontinence after surgery. There were significant differences in some postsurgical outcomes between patients who had neurovascular bundles preserved and those who had not. CONCLUSIONS: In-depth knowledge of, and measurement of changes in, quality of life after radical prostatectomy should allow for comprehensive, multidisciplinary, patient-centred care planning. Psychosocial assessment, both before and after surgery, is crucial in patients with prostate cancer. This study was prospectively registered with the CEIC-A on 2012-06-27, with registration number C.P.-C.I. PI12/0088.

Polimorfismos en genes candidatos a la composición de ácidos grasos y su efecto en carne Wagyu-Cross

RESUMEN Objetivo. Comparar la composición de ácidos grasos (FA) en la carne Wagyu y sus cruzas con Angus, Beefmaster, Brangus y Hereford, y analizar su relación con marcadores genéticos del metabolismo lipídico. Materiales y métodos. Se colectaron 111 muestras de Longissimus dorsi, las cuales se agruparon por grupo genético, se cuantificaron los FA (cromatografía de gases líquidos) y se tipificaron marcadores de ADN asociados teóricamente a FA. Se examinó el equilibrio de Hardy-Weinberg y desequilibrio de ligamiento de los marcadores y se estimó el efecto de las cruzas y el efecto de los genotipos. Resultados. Las cruzas no mostraron diferencias substanciales en la composición de FA con respecto a Wagyu. Nueve SNPs mostraron asociación con la composición de FA, y se encontró un efecto importante en el marcador SLC2A4 ss62538460, el cual influyó sobre SFA, MUFA y MUFA/SFA. Los marcadores, PLTP ss77832104 y IGF2R ss77831885 influyeron sobre C16:0, MYOZ1 ss77832104 sobre C17:1 y PPARGC1A c.1892+19 sobre C18:2. Además, se comprobaron efectos previamente descritos de MEF2C ss38329156 y SCD c.878. Conclusiones. Los presentes resultados representan una de las primeras evidencias sobre la deposición de FA en ganado Wagyu y sus cruzas y propone algunos loci en genes candidatos con posibilidad de implementación en estrategias de mejoramiento asistido.

ABSTRACT Objective. To assess the fatty acids composition (FA) in Wagyu beef and its crosses with Angus, Beefmaster, Brangus and Hereford, and to analyze its relationship with genetic markers related to lipid metabolism. Materials and methods. 111 Longissimus dorsi samples were collected and grouped by genetic group. FA were extracted and quantified in a gas-liquid chromatography and DNA markers theoretically associated to FA were typed. Hardy-Weinberg equilibrium and linkage disequilibrium were examined, the effect of crosses and the effect of genotypes were estimated. Results. The crosses did not show substantial differences in FA composition. Nine SNPs showed association with FA composition, and a significant effect was found in the SLC2A4 marker ss62538460 which influenced SFA, MUFA and MUFA/SFA; PLTP ss77832104 and IGF2R ss77831885 markers, influenced C16:0, MYOZ1 ss77832104 on C17:1 and PPARGC1A c.1892+19 on C18:2. In addition, previously described effects of MEF2C ss38329156 and SCD c.878 were supported. Conclusions. These results are first evidence on FA deposition in Wagyu cattle and their crosses, and proposes some loci in candidate genes with the possibility of implementation in assisted selection strategies.

Factors related with nursing students' health literacy: a cross sectional study.

Background: Nursing professionals have a crucial role in promoting health literacy in health services, so it is necessary to ensure health literacy skills in future health professionals. Objective: The objective of the study was to examine the health literacy of nursing students and its associated factors. Methods: A cross-sectional descriptive study was carried out on 460 nursing students. For data collection, a semi-structured questionnaire was obtained on sociodemographic characteristics, perception and health care, use of the health system and lifestyles. In addition, health literacy was assessed using the European Health Literacy Questionnaire. Results: 6.1% of the participants had an inadequate level of health literacy and 36.5% problematic. The probability of having sufficient health literacy is directly associated with age; and inversely with smoking, prolonged screen time and living alone (p < 0.05). Conclusion: A large percentage of nursing students need to improve their health literacy skills. It is necessary to integrate a greater number of contents in health literacy in the curriculum of nursing students.

Ultrasound-guided percutaneous electrical nerve stimulation versus surgery for women with unilateral carpal tunnel syndrome: A randomized parallel-group trial.

OBJECTIVE: The aim of this clinical trial was to compare the outcomes of the application of ultrasound-guided percutaneous nerve stimulation (PENS) targeting the median nerve versus surgery for improving pain and function in women with CTS. METHODS: In this randomized parallel-group trial (ClinicalTrials.gov, NCT04246216), 70 women with CTS were randomly allocated to either PENS (n = 35) or surgery (n = 35) group. Hand pain intensity (mean pain and the worst pain experienced) was the primary outcome. Functional status and symptoms severity (Boston Carpal Tunnel Questionnaire, BCTQ) and self-perceived improvement (Global Rating of Change, GROC) were the secondary outcomes. Outcomes were assessed at baseline and 1, 3, 6 and 12 months after each intervention. Analysis was performed with intention to treat with mixed ANCOVAs adjusted for baseline outcomes. RESULTS: Analyses showed an adjusted advantage for PENS at 1 (Δ -2.0, 95% CI -2.9 to -1.1) and 3 (Δ -1.4, 95% CI -2.3 to -0.5) months for mean pain, at 1 (Δ -2.2, 95% CI -3.3 to -1.1), 3 (Δ -1.75, 95% CI -2.9 to -0.6) and 6 (Δ -1.7, 95% CI -2.8 to -0.6) months in the worst pain intensity, and at 1 (Δ -0.95, 95% CI -1.1 to -0.8), 3 (Δ -0.55, 95% CI -0.8 to -0.3) and 6 (Δ -0.4, 95% CI -0.6 to -0.8) months in function. Both groups exhibited similar changes in symptom severity. Both groups reported similar improvement at 12 months in all outcomes. Symptoms and function improved in both groups, with PENS leading to better short-term outcomes than surgery. CONCLUSION: This clinical trial confirms that PENS applied with current understanding of pain mechanisms in CTS is as useful as surgery in women with CTS without denervation. The potential placebo effect of both interventions should not be ignored. SIGNIFICANCE: The application of percutaneous nerve stimulation was more effective at short-term, but similar effective at mid and long-term, than surgery in women with carpal tunnel syndrome.

Multidimensional evaluation of the pain profile as prognostic factor in individuals with hip or knee osteoarthritis receiving total joint replacement: protocol of a 2-year longitudinal prognostic cohort study.

INTRODUCTION: Knee and hip osteoarthritis are two highly prevalent musculoskeletal pain conditions. Unsuccessful rates after hip/knee replacement range from 10% to 20%. Subjects with sensitisation manifestations are vulnerable to worse clinical outcomes. Most studies have analysed outcomes up to 1 year after surgery. The aim of this 2-year longitudinal study will be to evaluate sensory-related, psychological and psychophysical pain sensitisation manifestations and a potential epigenetic biomarker as prognostic clinical outcomes for the development of chronic postoperative pain after knee or hip replacement. METHODS AND ANALYSIS: A prospective longitudinal study with a 2-year follow-up period will be conducted. The prognostic variables will include pain, function, related-disability, anxiety, depression, quality of life, sensitisation-associated symptoms, kinesiophobia, neuropathic pain and catastrophising, and expectative of the intervention will be assessed before surgery. We will also evaluate the presence of the Val158Met polymorphism as a possible epigenetic marker. Clinical outcomes including pain, related-disability and self-perceived satisfaction, sensitisation-associated symptoms and neuropathic pain will be assessed 3, 6, 12, 18 and 24 months after surgery. These variables will be used to construct three prediction models: (1) pain and function, (2) sensitisation-associated symptomatology and (3) neuropathic pain features classifying those patients in responders and non-responders. Data from knee or hip osteoarthritis will be analysed separately. Statistical analyses will be conducted with logistic regressions. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of both institutions involved (Hospital Universitario Fundación Alcorcón (HUFA) 19-141 and Universidad Rey Juan Carlos (URJC) 0312201917319). Participants will sign the written informed consent before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.

Health-related behaviors and symptoms of anxiety and depression in Spanish nursing students: an observational study.

Background: Symptoms of anxiety and depression are prevalent among young adults and are a significant public health issue. College students are at a higher risk of experiencing poor mental health than other young people due to several factors, including moving away from home, financial pressures, heavy workload, poor time management skills, competitivity, new processes of socialization and insufficient coping mechanisms, among others. In addition, nursing students' mental and physical health may also be affected by unhealthy lifestyle habits and health-related behaviors. Aim: To determine the prevalence of symptoms of depression and anxiety, and the association between these symptoms and health-related behaviors, in a population of Spanish student nurses. Methods: Cross-sectional study on a sample of 339 nursing students. We used the Hospital Anxiety and Depression Scale, the International Physical Activity Questionnaire-Short form, the Spanish Healthy Eating Index and an "ad hoc" questionnaire for sociodemographic variables. The association between psychological symptoms and health-related behaviors was analyzed through binary logistic regression models. Results: The prevalence of symptoms of depression and anxiety was 3.8% and 24.5%, respectively. Negative health-related behaviors were frequent, namely tobacco and alcohol consumption, suboptimal physical activity and diet. Moderate physical activity was associated with a lower probability of experiencing depressive symptoms. Symptoms of anxiety were related to a low level of physical activity, an unhealthy diet and alcohol consumption ≥2 times a week. Conclusion: Student nurses could benefit from the implementation of both physical and mental health promotion initiatives.

Predictors of the Quality of Life of University Students: A Cross-Sectional Study.

Quality of life (QOL) is a complex and multifaceted concept that has been used to study different aspects of people's lives, including physical and psychological wellbeing, financial independence, social relationships, personal beliefs and living situation. In this study, we aimed to assess the QOL of a group of Spanish university students and identify associated factors. METHOD: We completed a cross-sectional study of the QOL of 868 university students using the WHOQOL-BREF questionnaire. In addition, data regarding sociodemographic information and self-esteem (Rosenberg Self-Esteem Scale), physical activity (International Physical Activity Questionnaire-Short version), diet (Spanish Index of Healthy Eating), alcohol consumption (CAGE questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) were collected. RESULTS: A total of 66.2% of participants assessed their QOL positively, while 58.8% favorably evaluated their overall health. Students reported the highest scores for the physical health domain of QOL, whereas they gave the lowest scores for the psychological health domain. Age was inversely associated with QOL. Higher self-esteem and satisfaction with academic performance, as well as sleep and diet quality, were directly associated with higher QOL. The physical health domain of QOL was scored more highly by participants who had a healthy body weight or those who reported moderate levels of physical activity. Higher scores in the social relationships domain of QOL were directly linked to alcohol intake, smoking and low body weight in addition to being inversely associated with screen time. The psychological domain of QOL was lower for those who were overweight or lived alone. CONCLUSION: Many sociodemographic, academic and behavioral variables are associated with university students' QOL. The present findings underscore the need to direct further initiatives toward identifying and overcoming barriers to increased QOL for university students.

Do Short-Term Effects Predict Long-Term Improvements in Women Who Receive Manual Therapy or Surgery for Carpal Tunnel Syndrome? A Bayesian Network Analysis of a Randomized Clinical Trial.

OBJECTIVE: The purpose of this study was to develop a data-driven Bayesian network approach to understand the potential multivariate pathways of the effect of manual physical therapy in women with carpal tunnel syndrome (CTS). METHODS: Data from a randomized clinical trial (n = 104) were analyzed comparing manual therapy including desensitization maneuvers of the central nervous system versus surgery in women with CTS. All variables included in the original trial were included in a Bayesian network to explore its multivariate relationship. The model was used to quantify the direct and indirect pathways of the effect of physical therapy and surgery on short-term, mid-term, and long-term changes in the clinical variables of pain, related function, and symptom severity. RESULTS: Manual physical therapy improved function in women with CTS (between-groups difference: 0.09; 95% CI = 0.07 to 0.11). The Bayesian network showed that early improvements (at 1 month) in function and symptom severity led to long-term (at 12 months) changes in related disability both directly and via complex pathways involving baseline pain intensity and depression levels. Additionally, women with moderate CTS had 0.14-point (95% CI = 0.11 to 0.17 point) poorer function at 12 months than those with mild CTS and 0.12-point (95% CI = 0.09 to 0.15 point) poorer function at 12 months than those with severe CTS. CONCLUSION: Current findings suggest that short-term benefits in function and symptom severity observed after manual therapy/surgery were associated with long-term improvements in function, but mechanisms driving these effects interact with depression levels and severity as assessed using electromyography. Nevertheless, it should be noted that between-group differences depending on severity determined using electromyography were small, and the clinical relevance is elusive. Further data-driven analyses involving a broad range of biopsychosocial variables are recommended to fully understand the pathways underpinning CTS treatment effects. IMPACT: Short-term effects of physical manual therapy seem to be clinically relevant for obtaining long-term effects in women with CTS.

Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health.

The EFSA has updated the Guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain, human and animal health. It covers the application areas within EFSA's remit, including novel foods, food contact materials, food/feed additives and pesticides. The updated guidance, now Scientific Committee Guidance on nano risk assessment (SC Guidance on Nano-RA), has taken account of relevant scientific studies that provide insights to physico-chemical properties, exposure assessment and hazard characterisation of nanomaterials and areas of applicability. Together with the accompanying Guidance on Technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles (Guidance on Particle-TR), the SC Guidance on Nano-RA specifically elaborates on physico-chemical characterisation, key parameters that should be measured, methods and techniques that can be used for characterisation of nanomaterials and their determination in complex matrices. The SC Guidance on Nano-RA also details aspects relating to exposure assessment and hazard identification and characterisation. In particular, nanospecific considerations relating to in vitro/in vivo toxicological studies are discussed and a tiered framework for toxicological testing is outlined. Furthermore, in vitro degradation, toxicokinetics, genotoxicity, local and systemic toxicity as well as general issues relating to testing of nanomaterials are described. Depending on the initial tier results, additional studies may be needed to investigate reproductive and developmental toxicity, chronic toxicity and carcinogenicity, immunotoxicity and allergenicity, neurotoxicity, effects on gut microbiome and endocrine activity. The possible use of read-across to fill data gaps as well as the potential use of integrated testing strategies and the knowledge of modes or mechanisms of action are also discussed. The Guidance proposes approaches to risk characterisation and uncertainty analysis.

Safety assessment of titanium dioxide (E171) as a food additive.

The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

Re-evaluation of polydextrose (E 1200) as a food additive.

This opinion deals with the re-evaluation of polydextrose (E 1200) when used as a food additive. The Panel followed the conceptual framework for the risk assessment of certain additives and considered that: adequate exposure estimates were available; the margin of safety (MOS)/margin of exposure (MOE) for arsenic was between 0.5-14 and 8.5 for lead; the exhaustions of the tolerable weekly intake (TWI) for cadmium would be 165%, 10% for mercury, whereas the exhaustion of the tolerable daily intake (TDI) for nickel would be 9%; the absorption is limited and part of polydextrose is fermented in the large intestine into short-chain fatty acids (SCFA); adequate toxicity data were available; there is no concern with respect to genotoxicity; no adverse effects were reported in subchronic studies in rats, dogs or monkeys nor in chronic or carcinogenicity studies in mice and rats at the highest doses tested of up 12,500 mg/kg body weight (bw) per day and 15,000 mg/kg bw per day, respectively; the nephrocalcinosis in dogs given high doses of polydextrose was considered to be a treatment-related but a secondary effect related to diarrhoea, and hence not relevant for the risk assessment; no adverse effects were reported in reproductive or developmental toxicity studies in rats administered up to 10,000 mg polydextrose/kg bw per day, or in a developmental toxicity study in rabbits up to 1,818 mg/kg bw per day (the highest dose tested). Therefore, the Panel concluded that there is no need for numerical acceptable daily intake (ADI) for polydextrose (E 1200), and that there is no safety concern for the reported uses and use levels of polydextrose as a food additive. The Panel recommended that European Commission considers to lower the maximum limit for lead and to introduce limits for arsenic, cadmium and mercury in the EU specifications for polydextrose (E 1200), and to verify that polydextrose-N as a food additive (E 1200) is no longer marketed in the EU.

Re-evaluation of l(+)-tartaric acid (E 334), sodium tartrates (E 335), potassium tartrates (E 336), potassium sodium tartrate (E 337) and calcium tartrate (E 354) as food additives.

The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on tartaric acid-tartrates (E 334-337, 354) when used as food additives. The Scientific Committee for Food (SCF) in 1990 established an acceptable daily intake (ADI) of 30 mg/kg body weight (bw) per day, for l(+)-tartaric acid and its potassium and sodium salts. The metabolism of l(+)-tartaric acid and its potassium sodium salt was shown to be species dependent, with a greater absorption in rats than in humans. No toxic effects, including nephrotoxicity, were observed in toxicological studies in which the l(+)-form was tested. There was no indication for a genotoxic potential of tartaric acid and its sodium and potassium salts. In a chronic study in rats, no indication for carcinogenicity of monosodium l(+)-tartrate was reported at the highest dose tested (3,100 mg/kg bw per day). The available studies for maternal or developmental toxicity did not report any relevant effects; no studies for reproductive toxicity were available; however, no effects on reproductive organs were observed in the chronic toxicity study. The Panel concluded that the data on systemic availability were robust enough to derive a chemical-specific uncertainty factor instead of the usual default uncertainty factor of 100. A total uncertainty factor of 10 was derived by applying a total interspecies uncertainty factor of 1 instead of 10, based on data showing lower internal exposure in humans compared to rats. The Panel established a group ADI for l(+)-tartaric acid-tartrates (E 334-337 and E 354) of 240 mg/kg bw per day, expressed as tartaric acid, by applying the total uncertainty factor of 10 to the reference point of 3,100 mg sodium tartrate/kg bw per day, approximately to 2,440 mg tartaric acid/kg bw per day. The exposure estimates for the different population groups for the refined non-brand-loyal exposure scenario did not exceed the group ADI of 240 mg/kg bw per day, expressed as tartaric acid. Some recommendations were made by the Panel.

Re-evaluation of polyvinylpyrrolidone (E 1201) and polyvinylpolypyrrolidone (E 1202) as food additives and extension of use of polyvinylpyrrolidone (E 1201).

The present opinion deals with the re-evaluation of polyvinylpyrrolidone (E 1201, PVP) and polyvinylpolypyrrolidone (E 1202, PVPP) when used as food additives. One request for extension of use of PVP (E 1201) in foods for special medical purposes was also considered in this assessment. The Panel followed the conceptual framework under Commission Regulation (EU) No 257/2010 and considered that: the exposure assessment was based on the reported use and use levels (one food category out of the two food categories in which PVP and PVPP are authorised); the 95th percentile of exposure to PVP and PVPP of maximally 23.7 and 25 mg/kg body weight (bw) per day in children, respectively, was overestimated, because it was assumed that 100% of the food supplements consumed contained PVP or PVPP at the maximum reported use levels; the extension of use of PVP (E 1201) to foods for special medical purposes (FC 13.2) would result in an exposure of PVP of 4.3 mg/kg bw per day for children; the absorption of PVP and PVPP is very low; sufficient toxicity data were available for PVP; there is no concern with respect to the genotoxicity of PVP and PVPP; no carcinogenic effects were reported in carcinogenicity studies in rats at a dose of 2,500 mg PVP/kg bw per day, the highest dose tested; there is no need for chronic toxicity/carcinogenicity data for PVPP for the safety assessment of PVPP given the chemical similarity between PVP and PVPP, and the lack of adverse effects in the available repeated dose toxicity studies. Therefore, the Panel concluded that there is no need for numerical acceptable daily intakes (ADIs) for PVP and PVPP, and that there is no safety concern for the reported uses and use levels of PVP and PVPP as food additives. The Panel further concluded that the proposed extension of use is not expected to be of safety concern at the proposed maximum permitted level (MPL) and recommended consumption level.

Novel genes involved in the genetic architecture of temperament in Brahman cattle.

Cattle temperament is a complex and economically relevant trait. The objective of this study was to identify genomic regions and genes associated with cattle temperament. From a Brahman cattle population of 1,370 animals evaluated for temperament traits (Exit velocity-EV, Pen Score-PS, Temperament Score-TS), two groups of temperament-contrasting animals were identified based on their EV-average values ±1/2 standard deviation (SD). To be considered in the calm group, the EV of females ranged between 0.16-1.82 m/s (n = 50) and the EV of males ranged between 0.4-1.56 m/s (n = 48). Females were classified as temperamental if their EV ranged between 3.13-7.66 m/s (n = 46) and males were classified as temperamental if their EV ranged between 3.05-10.83 m/s (n = 45). Selected animals were genotyped using a total of 139,376 SNPs (GGP-HD-150K), evaluated for their association with EV. The Genome-Wide Association analysis (GWAS) identified fourteen SNPs: rs135340276, rs134895560, rs110190635, rs42949831, rs135982573, rs109393235, rs109531929, rs135087545, rs41839733, rs42486577, rs136661522, rs110882543, rs110864071, rs109722627, (P<8.1E-05), nine of them were located on intergenic regions, harboring seventeen genes, of which only ACER3, VRK2, FANCL and SLCO3A1 were considered candidate associated with bovine temperament due to their reported biological functions. Five SNPs were located at introns of the NRXN3, EXOC4, CACNG4 and SLC9A4 genes. The indicated candidate genes are implicated in a wide range of behavioural phenotypes and complex cognitive functions. The association of the fourteen SNPs on bovine temperament traits (EV, PS and TS) was evaluated; all these SNPs were significant for EV; only some were associated with PS and TS. Fourteen SNPs were associated with EV which allowed the identification of twenty-one candidate genes for Brahman temperament. From a functional point of view, the five intronic SNPs identified in this study, are candidates to address control of bovine temperament, further investigation will probe their role in expression of this trait.

Understanding central sensitization for advances in management of carpal tunnel syndrome.

Carpal tunnel syndrome is the most common nerve compression disorder of the upper extremity, and it is traditionally considered a peripheral neuropathy associated with a localized compression of the median nerve just at the level of the carpal tunnel. Surgery and physiotherapy are treatment approaches commonly used for this condition; however, conflicting clinical outcomes suggest that carpal tunnel syndrome may be more complex. There is evidence supporting the role of peripheral nociception from the median nerve in carpal tunnel syndrome; however, emerging evidence also suggests a potential role of central sensitization. The presence of spreading pain symptoms (e.g. proximal pain), widespread sensory changes, or bilateral motor control impairments in people presenting with strictly unilateral sensory symptoms supports the presence of spinal cord changes. Interestingly, bilateral sensory and motor changes are not directly associated with electrodiagnostic findings. Other studies have also reported that patients presenting with carpal tunnel syndrome exhibit neuroplastic brainstem change supporting central sensitization. Current data would support the presence of a central sensitization process, mediated by the peripheral drive originating in the compression of the median nerve, in people with carpal tunnel syndrome. The presence of altered nociceptive gain processing should be considered in the treatment of carpal tunnel syndrome by integrating therapeutic approaches aiming to modulate long-lasting nociceptive barrage into the central nervous system (peripheral drive) and strategies aiming to activate endogenous pain networks (central drive).

Influence of Clinical, Psychological, and Psychophysical Variables on Long-term Treatment Outcomes in Carpal Tunnel Syndrome: Evidence From a Randomized Clinical Trial.

OBJECTIVE: To assess the influence of clinical, psychological, and psychophysical variables on long-term clinical outcomes after the application of either physical therapy or surgery in women presenting with carpal tunnel syndrome (CTS). METHODS: A secondary analysis of a randomized trial investigating the efficacy of manual therapy including desensitization maneuvers of the central nervous system against surgery in 120 women with CTS was performed. Clinical outcomes including pain intensity, function, or symptom severity were assessed at 6 and 12 months post-intervention. Participants completed at baseline several clinical (pain intensity, function, and symptom severity), psychological (depression), and psychophysical (pressure pain thresholds and pain extent) variables, which were included as predictors. Multiple regression analyses were conducted to assess the relationship between baseline variables and clinical outcomes at 6 and 12 months post-intervention. RESULTS: The regression models indicated that higher scores of each clinical outcome (ie, intensity of pain or symptom severity) at baseline predicted better outcomes at 6 and 12 months post-intervention (from 15% to 65% of variance) in both groups. Lower pressure pain thresholds over the carpal tunnel at baseline predicted poorer clinical outcomes at 6 and 12 months post-intervention (from 5% to 20% of variance) in the physical therapy group, whereas higher depressive symptoms at baseline contributed to poorer outcomes at 6 and 12 months post-intervention (from 5% to 15% of the variance) within the surgery group. CONCLUSION: This study found that baseline localized pressure pain sensitivity and depression were predictive of long-term clinical outcomes in women with CTS following physical therapy or surgery, respectively.