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This scientific commentary refers to ‘Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer’s disease’ by Spotorno et al. (https://doi.org/10.1093/brain/awad428)., E.R.-V. is supported by research grants from the Stockholm County Council-Karolinska Institutet regional agreement on medical training and clinical research (ALF grants FoUI-960437, FoUI-975492), Neuroförbundet (F2022-0036, F2023-0049), Demensfonden, Alzheimerfonden (AF-939647, AF-968569), Åhlén foundation, Stiftelsen för Gamla Tjänarinnor, Gun and Bertil Stohnes Foundation, and Karolinska Institutet (KI Fonder). V.M. received funding from a Juan de la Cierva fellowship (JDC2022-048492-I) from the Ministry of Science of the Spanish Government. C.G. received funding from the Swedish FTD Initiative-Schörling Foundation; Swedish Research Council Dnr 529-2014-7504, 2019-0224, 2015-02926, 2018-02754; Alzheimerfonden; Hjärnfonden; Demensfonden and Region Stockholm ALF-project., Peer Reviewed, Postprint (author's final draft)

Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimi

Success in extreme environments comes with a cost of subtle performance decrements that if not mitigated properly can lead to lifethreatening consequences. Identification and prediction of performance decline could alleviate deleterious consequences and enhance success in challenging and high-risk operations. The Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH) project was designed to examine the cognitive, physiological, and biological markers of performance decline in the extreme environment of the Grand Canyon Rim-to-Rim (R2R) hike. The study utilized commercial off-the-shelf cognitive and physiological monitoring techniques, along with subjective self-assessments and hematologic measurements to determine subject performance and changes across the hike. The multiyear effort collected these multiple data streams in parallel on a large sample of participants hiking the R2R, leading to a rich and complex data set. This article describes the methodology and its evolution as devices and measurements were assessed after each data collection event. It also highlights a subset of the patterns of results found across the data streams. Subsequent work will draw on this data set to focus on building more sophisticated, predictive statistical models and dive deeper into specific analyses (such as the physiological and biological profiles of hikers who were left behind by their hiking partners).

Success in extreme environments comes with a cost of subtle performance decrements that if not mitigated properly can lead to lifethreatening consequences. Identification and prediction of performance decline could alleviate deleterious consequences and enhance success in challenging and high-risk operations. The Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH) project was designed to examine the cognitive, physiological, and biological markers of performance decline in the extreme environment of the Grand Canyon Rim-to-Rim (R2R) hike. The study utilized commercial off-the-shelf cognitive and physiological monitoring techniques, along with subjective self-assessments and hematologic measurements to determine subject performance and changes across the hike. The multiyear effort collected these multiple data streams in parallel on a large sample of participants hiking the R2R, leading to a rich and complex data set. This article describes the methodology and its evolution as devices and measurements were assessed after each data collection event. It also highlights a subset of the patterns of results found across the data streams. Subsequent work will draw on this data set to focus on building more sophisticated, predictive statistical models and dive deeper into specific analyses (such as the physiological and biological profiles of hikers who were left behind by their hiking partners).

ObjectiveThe aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials.MethodsA systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included.ResultsA total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis."ConclusionsThere is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.

Success in extreme environments comes with a cost of subtle performance decrements that if not mitigated properly can lead to lifethreatening consequences. Identification and prediction of performance decline could alleviate deleterious consequences and enhance success in challenging and high-risk operations. The Rim-to-Rim Wearables at the Canyon for Health (R2R WATCH) project was designed to examine the cognitive, physiological, and biological markers of performance decline in the extreme environment of the Grand Canyon Rim-to-Rim (R2R) hike. The study utilized commercial off-the-shelf cognitive and physiological monitoring techniques, along with subjective self-assessments and hematologic measurements to determine subject performance and changes across the hike. The multiyear effort collected these multiple data streams in parallel on a large sample of participants hiking the R2R, leading to a rich and complex data set. This article describes the methodology and its evolution as devices and measurements were assessed after each data collection event. It also highlights a subset of the patterns of results found across the data streams. Subsequent work will draw on this data set to focus on building more sophisticated, predictive statistical models and dive deeper into specific analyses (such as the physiological and biological profiles of hikers who were left behind by their hiking partners).

OBJECTIVE: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma. METHODS: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment. RESULTS: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms. CONCLUSIONS: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

Background: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management. Objective: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED. Methods: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional troponin not due to acute coronary syndrome (ACS) were included. Our primary outcome was a composite endpoint: time to 30-day cardiovascular death and/or heart failure-related events. Results: Of the 491 subjects included in the GUIDED-HF trial, 418 had troponin measured during the ED evaluation and 66 (16%) had troponin values above the 99th percentile. Median age was 63 years (interquartile range, 54-70), 62% (n = 261) were male, 63% (n = 265) were Black, and 16% (n = 67) experienced our primary outcome. There were no differences in our primary outcome between those with and without troponin elevation (12/66, 18.1% vs 55/352, 15.6%; P = 0.60). This effect was maintained regardless of assignment to usual care or the intervention arm. In multivariable regression analysis, there was no association between our primary outcome and elevated troponin (hazard ratio, 1.00; 95% confidence interval, 0.49-2.01, P = 0.994). Conclusion: If confirmed in a larger cohort, these findings may facilitate safe ED discharge for a group of patients with AHF without ACS when an elevated troponin is the primary reason for admission.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

The violence exercised on any human being can expose them to suffer negative effects on their physical and mental health, in the case of women, the consequences of suffering this scourge not only influence their person, but, in case of being in a state of pregnancy can increase the risk of suffering pathological conditions of the mother and child. There are some biological markers that can guide the diagnostic confirmation of such effects on health, the objective is to study the levels of plasma cortisol in women victims of gender violence. Bibliographic resources will be applied to theoretically orient the hypothesis proposed through qualitative research of academic and scientific production of the variables. It is expected to demonstrate the positive and direct relationship between violence and its severity with the plasma level of cortisol in women., La violencia ejercida sobre cualquier ser humano puede exponerlos a padecer efectos negativos sobre su salud física y mental, en el caso de las mujeres, las consecuencias de padecer este flagelo no solo influyen en su persona, sino que, en caso de estar en estado de gravidez puede aumentar el riesgo de padecer condiciones patológicas propias de la madre y el niño. Existen algunos marcadores biológicos que pueden orientar la confirmación diagnóstica de tales efectos en la salud, el objetivo es estudiar los niveles de cortisol plasmático en mujeres víctimas de violencia de género. Se aplicarán los recursos bibliográficos para orientar teóricamente la hipótesis planteada a través de la investigación cualitativa de producción académica y científica de las variables. Se espera demostrar la relación positiva y directa que hay entre la violencia y su severidad con el nivel plasmático de cortisol en mujeres.

Breast cancer treatment can induce alterations in blood-and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors.This systematic review summarized studies of the last decade, using the PubMed database, evaluating blood markers, and the association between blood-or structural neuroimaging markers and cognition across the chemotherapy trajectory for primary breast cancer, following PRISMA guidelines.Forty-four studies were included. Differences were observed in all blood marker categories, from on-therapy until years post-chemotherapy. Associations were found between cognitive functioning and (1) blood markers (mainly inflammation-related) during, shortly-, or years post-chemotherapy and (2) white and gray matter metrics in frontal, temporal and parietal brain regions months up until years post-chemotherapy. Preliminary evidence exists for epigenetic and metabolic changes being associated with cognition, only after chemotherapy.This review demonstrated time-dependent associations between specific blood-based and structural neuroimaging markers with cognitive impairment in patients with breast cancer. Future studies are encouraged to include both neuroimaging-and blood markers (e.g. of neuronal integrity, epigenetics and metabolism) to predict long-term cognitive effects of chemotherapy.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed. Materials and Methods: Here, the relation between cortical thickness and clinical response (17-item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham-controlled, double-blinded, cross-over aiTBS design (NCT01832805). Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses. Conclusion: Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC.

Background: Occupational exposure to pesticides has been reported among general population worldwide. However, little is known about the associations between non-occupational exposure to pesticides, and biological markers of health and their response by sex. Objectives: We aimed to assess the associations between non-occupational overall pesticide exposure, length of exposure and specific pesticides reported with 35 biological markers of health representing cardiometabolic, haematological, lung function, sex hormones, liver and kidney function profiles, and vitamin D in Finnish cohort. Methods: 31-year cross-sectional examination of the Northern Finland Birth Cohort 1966 provided blood samples for biomarker measurements in 1997–1998. Number of subjects varied between 2361 and 5037 for given exposures and certain outcome associations. Multivariable regression analyses were performed to examine associations between overall pesticide exposure (OPE), length of pesticide exposure in months (PEM), in years (PEY), and specific pesticides use (PEU) or not with cardiometabolic [SBP, DBP, TC, LDL, HDL, triglycerides, fasting glucose, insulin, HOMA-IR, HOMA-B, HOMA-S, hs-CRP], hematological [WBC, RBC, Hb, HCT, MCV, MCH, MCHC, platelets], lung function (FVC, FEV1), sex hormones [luteinizing hormone (LH), testosterone (TT), sex-hormone binding globulin (SHBG)], liver and kidney function profiles [total protein, albumin, globulin, ALP, ALT, GGT, urea, creatinine], and vitamin D adjusting for sex, BMI, socioeconomic position (SEP) and season of pesticide use. Results: This cohort study on up to 5037 adults with non-occupational OPE, PEM, PEY and PEU differed by sex and SEP. In regression analyses, all the exposures were positively associated with total cholesterol and low-density lipoprotein cholesterol, and PEU was negatively associated with high-density lipoprotein cholesterol in females. OPE and PEM were positively associated with haematocrit in females and PEU with pl

Purpose: To investigate inter- and intra-individual variation in the levels and outputs (concentration multiplied by salivary flow rate) of salivary metabolites in patients with primary Sjögren’s syndrome (pSS). Methods: A total of 56 samples of stimulated saliva were collected from 14 female pSS patients during four laboratory visits within 20 weeks and analyzed using proton nuclear magnetic resonance spectroscopy. Single saliva samples from each of 15 controls were also analyzed. Results: Among 21 quantified metabolites, choline was significantly elevated in the pSS patients at each time point (P ≤ 0.015), taurine at the last three time points (P ≤ 0.013), alanine at the last two time points (P ≤ 0.007) and glycine at the last time point (P = 0.005). Inter-individual variation in metabolite concentrations was generally larger among the patients than among the controls, and significantly large variations were observed for glycine (P ≤ 0.007, all time points), choline (P ≤ 0.033, three last time points) and alanine (P = 0.028, baseline). Metabolite output analysis showed that choline had the lowest intra-patient variation. Conclusions: In spite of considerable intra- and inter-individual variation, levels and outputs of specific metabolites in patients with pSS differ from those in controls, and may be potentially applicable as new biological markers for monitoring of the response to treatment.

Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed. Materials and Methods: Here, the relation between cortical thickness and clinical response (17-item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham-controlled, double-blinded, cross-over aiTBS design (NCT01832805). Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses. Conclusion: Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC.

Background Occupational exposure to pesticides has been reported among general population worldwide. However, little is known about the associations between non-occupational exposure to pesticides, and biological markers of health and their response by sex. Objectives We aimed to assess the associations between non-occupational overall pesticide exposure, length of exposure and specific pesticides reported with 35 biological markers of health representing cardiometabolic, haematological, lung function, sex hormones, liver and kidney function profiles, and vitamin D in Finnish cohort. Methods 31-year cross-sectional examination of the Northern Finland Birth Cohort 1966 provided blood samples for biomarker measurements in 1997–1998. Number of subjects varied between 2361 and 5037 for given exposures and certain outcome associations. Multivariable regression analyses were performed to examine associations between overall pesticide exposure (OPE), length of pesticide exposure in months (PEM), in years (PEY), and specific pesticides use (PEU) or not with cardiometabolic [SBP, DBP, TC, LDL, HDL, triglycerides, fasting glucose, insulin, HOMA-IR, HOMA-B, HOMA-S, hs-CRP], hematological [WBC, RBC, Hb, HCT, MCV, MCH, MCHC, platelets], lung function (FVC, FEV1), sex hormones [luteinizing hormone (LH), testosterone (TT), sex-hormone binding globulin (SHBG)], liver and kidney function profiles [total protein, albumin, globulin, ALP, ALT, GGT, urea, creatinine], and vitamin D adjusting for sex, BMI, socioeconomic position (SEP) and season of pesticide use. Results This cohort study on up to 5037 adults with non-occupational OPE, PEM, PEY and PEU differed by sex and SEP. In regression analyses, all the exposures were positively associated with total cholesterol and low-density lipoprotein cholesterol, and PEU was negatively associated with high-density lipoprotein cholesterol in females. OPE and PEM were positively associated with haematocrit in females and PEU with platelets in ma

Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

Objetivo: avaliar sintomas osteomusculares e comportamento de biomarcadores em professores do ensino médio da rede pública no município de Caxias - MA. Metodologia: A pesquisa foi realizada nos colégios Centro de Ensino Inácio Passarinho e Centro de Ensino Aluízio de Azevedo. Foram incluídos no estudo, todos os professores efetivos e em atividade em salas de aula no período da coleta de dados. A coleta de dados foi feita com a aplicação de um questionário sócio econômico e coleta de sangue periférico para avaliação dos marcadores musculares. Resultados: os resultados que apontam os docentes como grupo de risco para problemas osteomusculares, os comprometimentos da qualidade de vida desses professores não refletem somente na vida pessoal destes trabalhadores, como também, influenciam diretamente no ensino dos alunos. Conclusão: Tais docentes estão em condições propicias ao surgimento das Lesões por Esforços Repetitivos (LER) e Os Distúrbios Osteomusculares Relacionados ao Trabalho (DORT) e em sua maioria apresentaram desgaste físico e mental.

Changes to the DSM-5's conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal dysregulation. While the relationship between PTSD and threat sensitivity is well defined, how they relate to impulsivity remains understudied. We examined the relationship between PTSD symptom severity, threat sensitivity, and impulsivity. 124 participants completed the PTSD Checklist (PCL-C) and the Barratt Impulsiveness Scale 11th ed (BIS-11). BIS-11 items were separated to define cognitive and behavioral impulsivity subdomains. A trauma-exposed subsample of 39 participants were also exposed to no, ambiguous, and high threat conditions in a threat-enhanced acoustic startle paradigm with psychophysiological response as the outcome variable. PTSD severity was significantly associated with greater overall impulsivity and behavioral impulsivity. Greater overall impulsivity and both cognitive and behavioral impulsivity subdomains were significantly associated with psychophysiological magnitudes across threat conditions in the traumatized subsample. Our results suggest PTSD severity may linked to behavioral impulsivity and both cognitive and behavioral impulsivity are associated with threat sensitivity and hyperarousal. Assessing impulsivity within the context of PTSD, particularly in terms of its cognitive and behavioral subdomains, may provide important, clinically relevant information.

ObjectivesAdult patients with epilepsy have an increased prevalence of major depressive disorder (MDD). Intracranial EEG (iEEG) captured during extended inpatient monitoring of patients with treatment-resistant epilepsy offers a particularly promising method to study MDD networks in epilepsy.MethodsThe authors used 24 hours of resting-state iEEG to examine the neural activity patterns within corticolimbic structures that reflected the presence of depressive symptoms in 13 adults with medication-refractory epilepsy. Principal component analysis was performed on the z-scored mean relative power in five standard frequency bands averaged across electrodes within a region.ResultsPrincipal component 3 was a statistically significant predictor of the presence of depressive symptoms (R2=0.35, p=0.014). A balanced logistic classifier model using principal component 3 alone correctly classified 78% of patients as belonging to the group with a high burden of depressive symptoms or a control group with minimal depressive symptoms (sensitivity, 75%; specificity, 80%; area under the curve=0.8, leave-one-out cross validation). Classification was dependent on beta power throughout the corticolimbic network and low-frequency cingulate power.ConclusionsThese finding suggest, for the first time, that neural features across circuits involved in epilepsy may distinguish patients who have depressive symptoms from those who do not. Larger studies are required to validate these findings and to assess their diagnostic utility in MDD.

Objetivo: evaluar los síntomas musculoesqueléticos y el comportamiento de los biomarcadores en maestros de escuelas públicas en Caxias - MA. Metodología: La investigación se realizó en el Centro Docente Inácio Passarinho y en el Centro Docente Aluízio de Azevedo. El estudio incluyó a todos los maestros efectivos y de aula durante el período de recopilación de datos. La recolección de datos se realizó mediante la aplicación de un cuestionario socioeconómico y la recolección de sangre periférica para evaluar los marcadores musculares. Resultados: los resultados que señalan a los maestros como un grupo de riesgo para problemas musculoesqueléticos, la calidad de vida de estos maestros no solo se refleja en la vida personal de estos trabajadores, sino que también influye directamente en la enseñanza de los estudiantes. Conclusión: estos maestros están en una condición favorable para la aparición de lesiones por esfuerzo repetitivo (RSI) y trastornos musculoesqueléticos relacionados con el trabajo (WRMSD) y la mayoría de ellos presentaban angustia física y mental., Objective: to evaluate musculoskeletal symptoms and behavior of biomarkers in public high school teachers in Caxias - MA. Methodology: The research was carried out at Inácio Passarinho Teaching Center and Aluízio de Azevedo Teaching Center. The study included all effective and classroom teachers during the data collection period. Data collection was performed by applying a socioeconomic questionnaire and peripheral blood collection to evaluate muscle markers. Results: the results that point teachers as a risk group for musculoskeletal problems, the quality of life impairments of these teachers not only reflect on the personal life of these workers, but also directly influence the teaching of students. Conclusion: these teachers are in a favorable condition for the onset of Repetitive Strain Injury (RSI) and Work-Related Musculoskeletal Disorders (WRMSD) and most of them presented physical and mental distress., Objetivo: avaliar sintomas osteomusculares e comportamento de biomarcadores em professores do ensino médio da rede pública no município de Caxias - MA. Metodologia: A pesquisa foi realizada nos colégios Centro de Ensino Inácio Passarinho e Centro de Ensino Aluízio de Azevedo. Foram incluídos no estudo, todos os professores efetivos e em atividade em salas de aula no período da coleta de dados. A coleta de dados foi feita com a aplicação de um questionário sócio econômico e coleta de sangue periférico para avaliação dos marcadores musculares. Resultados: os resultados que apontam os docentes como grupo de risco para problemas osteomusculares, os comprometimentos da qualidade de vida desses professores não refletem somente na vida pessoal destes trabalhadores, como também, influenciam diretamente no ensino dos alunos. Conclusão: Tais docentes estão em condições propicias ao surgimento das Lesões por Esforços Repetitivos (LER) e Os Distúrbios Osteomusculares Relacionados ao Trabalho (DORT) e em sua maioria apresentaram desgaste físico e mental.

Objetivo: avaliar sintomas osteomusculares e comportamento de biomarcadores em professores do ensino médio da rede pública no município de Caxias - MA. Metodologia: A pesquisa foi realizada nos colégios Centro de Ensino Inácio Passarinho e Centro de Ensino Aluízio de Azevedo. Foram incluídos no estudo, todos os professores efetivos e em atividade em salas de aula no período da coleta de dados. A coleta de dados foi feita com a aplicação de um questionário sócio econômico e coleta de sangue periférico para avaliação dos marcadores musculares. Resultados: os resultados que apontam os docentes como grupo de risco para problemas osteomusculares, os comprometimentos da qualidade de vida desses professores não refletem somente na vida pessoal destes trabalhadores, como também, influenciam diretamente no ensino dos alunos. Conclusão: Tais docentes estão em condições propicias ao surgimento das Lesões por Esforços Repetitivos (LER) e Os Distúrbios Osteomusculares Relacionados ao Trabalho (DORT) e em sua maioria apresentaram desgaste físico e mental.

Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

Objetivo: avaliar sintomas osteomusculares e comportamento de biomarcadores em professores do ensino médio da rede pública no município de Caxias - MA. Metodologia: A pesquisa foi realizada nos colégios Centro de Ensino Inácio Passarinho e Centro de Ensino Aluízio de Azevedo. Foram incluídos no estudo, todos os professores efetivos e em atividade em salas de aula no período da coleta de dados. A coleta de dados foi feita com a aplicação de um questionário sócio econômico e coleta de sangue periférico para avaliação dos marcadores musculares. Resultados: os resultados que apontam os docentes como grupo de risco para problemas osteomusculares, os comprometimentos da qualidade de vida desses professores não refletem somente na vida pessoal destes trabalhadores, como também, influenciam diretamente no ensino dos alunos. Conclusão: Tais docentes estão em condições propicias ao surgimento das Lesões por Esforços Repetitivos (LER) e Os Distúrbios Osteomusculares Relacionados ao Trabalho (DORT) e em sua maioria apresentaram desgaste físico e mental.

Background: There remains a lack of large-scale clinical studies of cognitive impairment that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings. The MemClin project will amass large quantities of cross-disciplinary data allowing for the construction of robust models to improve diagnostic accuracy, expand our knowledge on differential diagnostics, strengthen longitudinal prognosis, and harmonise examination protocols across centres. The current article describes the Memory Clinic (MemClin) project's study-design, materials and methods, and patient characteristics. In addition, we present preliminary descriptive data from the ongoing data collection. Methods: Nine out of ten memory clinics in the greater Stockholm area, which largely use the same examination methods, are included. The data collection of patients with different stages of cognitive impairment and dementia is coordinated centrally allowing for efficient and secure large-scale database construction. The MemClin project rest directly on the memory clinics examinations with cognitive measures, health parameters, and biomarkers. Results: Currently, the MemClin project has informed consent from 1543 patients. Herein, we present preliminary data from 835 patients with confirmed cognitive diagnosis and neuropsychological test data available. Of those, 239 had dementia, 487 mild cognitive impairment (MCI), and 104 subjective cognitive impairment (SCI). In addition, we present descriptive data on visual ratings of brain atrophy and cerebrospinal fluid markers. Conclusions: Based on our current progress and preliminary data, the MemClin project has a high potential to provide a large-scale database of 1200-1500 new patients annually. This coordinated data collection will allow for the construction of improved diagnostic and prognostic models for neurodegenerative disorders and other cognitive conditions in their naturalistic setting.

BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values. METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent. RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times. CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.

Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear. Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association. Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders. Results: The mean LTL was 1.56 +/- 0.25 in controls, 1.44 +/- 0.23 in MCI, and 1.28 +/- 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101-0.597) and AD (OR 0.123; 95% CI 0.044-0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

Many caregivers of geriatric patients are spouses who are old themselves. In many aspects, their mental, social and physical health may be at the core of successful caregiving. If the caregiver faces any health issue, this could lead to undesired care breakdown. In this context, this thesis aimed at assessing the health of older spousal caregivers with clinical and biological markers. In summary, our clinical and laboratory based investigations showed a relatively good health among these older caregivers. They are at an increased risk of being frail but few of them are frail, consistent with the idea that you have to be in good health to remain caregiver. The difficulties encountered by the spousal caregivers involved primarily disruption of their activities and feeling of social isolation. However, a large majority of the older spousal caregivers found caregiving as a source of self-fulfilment. This dimension takes into account the desire and the pleasure to give care. This thesis has also supported the role of protective factors against the caregiver’s burden., (SP - Sciences de la santé publique) -- UCL, 2019

ObjectiveSensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches.MethodsFunctional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined.ResultsAcross repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure.ConclusionsThe results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.

ObjectiveAnxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions. Because of the early onset of anxiety disorders and the increased incidence in anxiety disorders in females during their reproductive years, it is important to understand whether the reduction in uncinate fasciculus FA exists in children with anxiety disorders and the extent to which this alteration is sex related. To address these issues, the authors assessed FA in the uncinate fasciculus in unmedicated boys and girls with anxiety disorders.MethodsFA measures were derived from diffusion tensor images that were acquired from 98 unmedicated children (ages 8-12); 52 met criteria for generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, or anxiety disorder not otherwise specified, and 46 were matched control subjects.ResultsTract-based results demonstrated that children with anxiety disorders have significant reductions in uncinate fasciculus FA. A significant sex-by-group interaction and post hoc testing revealed that this effect was evident only in boys. No other main effects or sex-by-group interactions were found for other white matter tracts.ConclusionsThese findings provide evidence of uncinate fasciculus white matter alterations in boys with anxiety disorders. The data demonstrate that anxiety disorder-related alterations in prefrontal-limbic structural connectivity are present early in life, are not related to psychotropic medication exposure, and are sex specific. Building on these findings, future research has the potential to provide insights into the genesis a

[Introduction] Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening., [Study method] A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010–2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained., [Results] A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms., [Conclusions] The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.

[ES] La enfermedad pulmonar obstructiva crónica (EPOC) es una entidad de presentación heterogénea. Por ello, se han intentado perfilar diferentes fenotipos y endotipos, que permitirían un manejo más diferenciado. El objetivo del proyecto Biomarcadores en la EPOC (BIOMEPOC) es identificar biomarcadores sanguíneos útiles para tipificar mejor a los enfermos. Se analizarán datos clínicos y muestras sanguíneas en un grupo de pacientes y controles sanos. El proyecto constará de fases de prospección y de validación. Se realizarán determinaciones analíticas sanguíneas con técnicas convencionales y de diversas ciencias «ómicas» (transcriptómica, proteómica y metabolómica). Las primeras se realizarán orientadas por hipótesis, mientras que con las segundas se realizará una exploración sin dicho condicionante. Finalmente se realizará un análisis multinivel. En el momento actual se han reclutado 269 pacientes y 83 controles, y se está iniciando el procesamiento de muestras. Con los resultados obtenidos se espera identificar nuevos biomarcadores que, en solitario o combinados, permitan una mejor tipificación de los pacientes., [EN] Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain ‘omics’ (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

Nowadays in biosensing, development of analytical techniques is focused on improvement for monitoring biologically active species in living organisms, especially in real-time analysis. This article provides an overview of applications of electrochemical tyrosinase biosensors in the analysis of medicinally significant substances, also known as biomarkers. At the beginning, special attention is paid to characterisation of the tyrosinase enzyme, explanation of reaction mechanisms of tyrosinase with various types of electrochemical transducers and techniques needed for stable immobilization of this biocatalyst on the transducer surface used. In this case, amperometric transducers represent the most frequently used type of electrochemical sensing because they usually provide sensitive current response to the presence of analyte in the sample. Many scientific works suggest that these very selective bioanalytical devices could find application in the clinical diagnosis of various serious diseases because they represent the effective analytical tools for diagnosis of neurodegenerative disorders, detection of microbial pathogens responsible for foodborne illness and diagnosis of cytopathology, especially melanoma cancer. Additionally, various kinds of electrochemical tyrosinase biosensors are presented which were developed to determine the catalytic activity of other enzymes significant for human metabolism, medicaments and their metabolic products, several hormones, amino acids and proteins. Despite all of their advantages, it is necessary to state that tyrosinase biosensors are still not used in the routine laboratory practice due to their relatively short service life which is not longer than one month unfortunately. Never-ending development of catalytic polymers imitating the tyrosinase active site could be one of ways to solve this serious drawback., V současné době je vývoj biosenzorů zaměřen na zlepšení sledování biologicky aktivních látek v živých organismech, zejména v analýzách v reálném čase. Tento článek poskytuje přehled o aplikacích elektrochemických tyrosinázových biosenzorů v analýze klinicky významných látek, také známých jako biomarkery. Ze začátku je zvláští pozornost věnována charakterizaci enzymu tyrosinázy, vysvětlení reakčních mechanismů tyrosinázy s různými typy elektrochemických snímačů a technikám potřebných pro stabilní zakotvení tohoto biokatalyzátoru na povrch použitého snímače. V tomto případě představují amperometrická zařízení nejčastěji používaný typ elektrochemického snímání, protože obvykle poskytují citlivou proudovou odezvu na přítomnost analytu ve vzorku. Mnoho vědeckých prací naznačuje, že tato velmi selektivní bioanalytická zařízení mohou nalézt uplatnění v klinické diagnostice různých závažných onemocnění, protože představují efektivní analytické nástroje pro diagnostiku neurodegenerativních poruch, detekci mikrobiálních patogenů odpovědných za choroby přenášené potravinami a diagnostiku cytopathologie, zejména rakoviny melanomu. Navíc jsou zde prezentovány různé druhy elektrochemických tyrosinázových biosenzorů, které byly vyvinuty pro stanovení katalytické aktivity dalších enzymů významných pro lidský metabolismus, léků a jejich metabolických produktů, několika hormonů, aminokyselin a bílkovin. Navzdory všem jejich výhodám je třeba uvést, že tyrosinázové biosenzory se stále ještě nepoužívají v běžné laboratorní praxi kvůli jejich poměrně krátké životnosti, která bohužel není delší než jeden měsíc. Nekončící vývoj katalytických polymerů napodobujících tyrosinázové aktivní místo může být jedním ze způsobů, jak tuto vážnou nevýhodu řešit.

Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.

terapiji lokalno odmaklog karcinoma dojke (LOKD) preoperativna radioterapija (PRT) je u današnje vreme indikovana nakon primarne (neoadjuvantne) hemioterapije (PHT) u slučaju da nije postignuta resektabilnost tumora. Pre uvodjenja neoadjuvantne hemioterapije, PRT se mnogo češće koristila kao jedini neoadjuvantni pristup za inicijalno inoperabilne tumore, u cilju smanjenja tumorskog volumena i omogućavanja radikalne hirurgije. Cilj ove analize je evaluacija tumorskog odgovora i dugoročnog ishoda bolesti kod pacijenata tretiranih samo PRT, bez uticaja sistemske terapije, i procena povezanosti bioloških markera sa odgovorom na PRT. Metod: U periodu od 1997-2000.godine 134 bolesnica sa neinflamatornim LOKD stadijuma IIIA i IIIB tretirano je preoperativnom RT. Tumorska doza je bila 45 Gy u 15 frakcija (3 Gy po frakciji) naizmenično svakog drugog dana na regiju dojke i regionalnih limfatika u toku 6 nedelja. Šest nedelja po završenoj RT, učinjena je radikalna mastektomija kod svih bolesnica i potom primenjena adjuvantna terapija (hemioterapija i/ili hormonska terapija) po tadašnjem protokolu. Ishod bolesti je procenjivan na osnovu ukupnog preživljavanja (OS) i preživljavanja bez znakova bolesti (DFS). Krive preživljavanja (OS i DFS) su procenjivane korišćenjem Kaplan-Meier metode i univarijantne statističke analize korišćenjem Log-Rank testa u cilju procene razlike izmedju analiziranih grupa. Status hormonskih receptora ER i PgR, HER-2 status i Ki-67 su analizirani imunohistohemijskim metodama na uzorku biopsiranog tumora i uzorku na mastektomiji. Merenje genske ekspresije vršeno je iz parafinskih uzoraka tumorskog tkiva Microarray analizom. Rezultati: Medijana praćenja iznosila je 74 meseca (ranga 4-216). Klinički odgovor tumora na PRT zabeležen je kod 77.6% bolesnica. Klinički kompletan odgovor tumora (cCR) postignut je kod 21.6% bolesnica, dok je patohistološki kompletan odgovor (pCR) u dojci registrovan kod 15% bolesnica. Od toga 10/134 (7.5%) je ostvario totalni pCR, In the treatment of locally advanced breast cancer (LABC) preoperative radiotherapy (PRT) today is indicated after primary (neoadjuvant) chemotherapy (PCT) if resectability of tumor was not achieved. Before the introduction of PCT in treatment strategy, PRT was more frequently used as the sole neoadjuvant approach for initially inoperable tumors, in order to reduce tumor volume and reach radical surgery. The purpose of this analysis was to evaluate the tumor response and long-term outcome at patients treated with only PRT, without influence of systemic therapy, and to assess the relationship of biological markers with response to PRT. Method: Between 1997 and 2000, 134 patients with non-inflammatory LABC stage IIIA and IIIB were treated with PRT. The tumor dose was 45 Gy in 15 fractions (3 Gy per fraction) every second day to the breast and to regional lymph nodes over 6 weeks. Radical mastectomy was performed 6 weeks after PRT to all patients and adjuvant systemic therapy was administered as per protocol. The measure of disease outcome were overall survival (OS) and disease-free survival (DFS). Survival and DFS curves were estimated using the Kaplan-Meier method and univariate statistical analysis by Log rank test was used to assess the difference in time to event (OS/DFS) between the analyzed groups. The hormone receptor status of ER and PgR, HER-2 status and Ki-67 were assessed by immunohistochemistry on the biopsy and mastectomy specimens. Gene expression profiles were established using micro-array analysis in a formalin-fixed paraffin-embedded (FFPE) tumor samples. Results: Median follow-up was 74 months (range 4-216 months). An objective clinical tumor response after preoperative RT was observed in 77.6% of patients. Clinical complete tumor response (cCR) was achieved in 21.6% of patients. Pathological CR in the breast was achieved in 15% of patients. Among them 10/134 (7.5%) had total pCR (no invasive tumor in breast associated with no involved regional axill

Some studies document racial disparities in self-reported health associated with alcohol use and abuse. However, few studies examined biomarkers that underlie the onset of alcohol-related chronic diseases. We investigated whether the association between alcohol abuse and five biomarkers of inflammation (CRP, IL-6, fibrinogen, E-selectin, sICAM-1) vary between Black and White Americans aged 35 to 84 (n = 1173) from the Midlife in the United States Biomarker Study. Multivariable Ordinary Least Squares regressions were used to assess Black-White differences in the association between alcohol abuse and the biomarkers. Race moderated the association between alcohol abuse and CRP (b = 0.56, SE = 0.28, p = 0.048), IL-6 (b = 0.65, SE = 0.22, p = 0.004), and a composite inflammation score (b = 0.014, SE = 0.07, p = 0.041). These findings potentially shed light for why alcohol has a stronger negative association with poorer health for Blacks compared to Whites. Analysis should be replicated in larger prospective cohorts.

OBJECTIVE:The authors sought to assess associations among early-life exposure to adversity, the development and maturation of neurons and brain circuits, and neurodevelopmental outcomes. Specifically, they examined whether fetal exposure to placental corticotropin-releasing hormone (CRH), a molecule conveying maternal signals to the fetus, predicts brain growth and neuropsychiatric outcomes in school-age children. METHOD:In a large, well-characterized prospective cohort, concentrations of placental CRH (pCRH) in maternal plasma were determined during five intervals during gestation. When the children reached school age, their brain structures were examined using MRI, and emotional and cognitive tests assessing internalizing and externalizing behaviors and attention were administered (N=97, 49 of them girls). RESULTS:Levels of pCRH during gestation predicted structural and functional brain outcomes in children. Specifically, fetal exposure to elevated pCRH levels was associated with thinning of selective cortical regions and with commensurate cognitive and emotional deficits. The relations among fetal exposure to pCRH, cortical thinning, and childhood function were sex specific. CONCLUSIONS:In view of the established effects of CRH on maturation and arborization of cortical neurons, and the major contribution of dendrites to cortical volume, these findings position pCRH as an important mediator of the consequences of early-life adversity on neuropsychiatric outcomes.

Background Methods Anxiety is characterized by prolonged preparation for real or perceived threat. This may manifest both as psychological and physiological activation, ultimately leading to greater risk for poor health. Chronic inflammation may play an integral role in this relationship, given the influential role that it has in chronic illness. The aim of this meta-analysis is to examine levels of chronic inflammation, measured by inflammatory cytokines and C-reactive protein, in people with anxiety disorders, PTSD (posttraumatic stress disorder), or obsessive-compulsive disorder compared to healthy controls. Several moderating variables, including specific diagnosis and depression comorbidity, were also assessed. Seventy six full-text articles were screened for eligibility with 41 studies ultimately included in analysis. Results Conclusions Results demonstrated a significant overall difference between healthy controls (HCs) and people with anxiety disorders in pro-inflammatory cytokines (P = 0.013, Hedge's g = -0.39), which appears to be largely driven by interleukin-1 beta (IL-1 beta; P = 0.009, Hedge's g = -0.50), IL-6 (P < 0.001, Hedge's g = -0.93), and tumor necrosis factor-alpha (P = 0.030, Hedge's g = -0.56). Moderation analyses revealed a moderating effect of diagnosis (P = 0.050), as only individuals with PTSD demonstrated differences in inflammation between HCs (P = 0.004, Hedge's g = -0.68). These data demonstrate the association between inflammatory dysregulation and diagnoses associated with chronic, impactful, and severe anxiety and provides insight into the way that anxiety, and in particular PTSD, is related to certain inflammatory markers. In doing so, these findings may provide an initial step in disentangling the relationship between anxiety and basic health processes.