Dietary Fiber, Insulin and Breast Tissue Composition at Age 15-18: A Cross-Sectional Study.

BACKGROUND: Risk of breast cancer in adult life is influenced by body size and height in childhood, but the mechanisms responsible for these associations are currently unknown. We carried out research to determine if, at age 15-18, measures of dietary intake were associated with body size, hormones, and with variations in breast tissue composition that in adult life are associated with risk of breast cancer. METHODS: In a cross-sectional study of 766 healthy Caucasian women aged 15-18, we measured percent breast water (PBW), total breast water and fat by magnetic resonance (MR), and assessed dietary intake using a validated food frequency questionnaire. We also measured height, weight, skin-fold thicknesses and waist-to-hip ratio, and in fasting blood assayed glucose and insulin. RESULTS: After adjustment for age, measures of body size, and energy intake, dietary fiber (insoluble and total fiber) and insulin were associated positively and significantly with PBW. CONCLUSIONS: Dietary fiber and fasting insulin were associated with breast tissue measures. These data suggest a potential approach to breast cancer prevention.

Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies.

(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (1H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using 1H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the 'fear neurocircuitry' in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.

Does laparoscopic reoperation yield symptomatic improvements similar to those of primary laparoscopic Heller myotomy in achalasia patients?

BACKGROUND: Laparoscopic Heller myotomy fails in approximately 3.5% to 15% of patients. Evidence of successful laparoscopic reoperation is limited to a few studies. METHODS: This case-control study was conducted in patients who underwent laparoscopic Heller myotomy reoperation (LHM-R) from 2008 to 2016. The operative outcomes, preoperative and last follow-up manometric parameters, and symptom questionnaire results, including the Eckardt, Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) and eating assessment tool (EAT-10) scores, were obtained. The data were compared with those of patients who underwent primary laparoscopic Heller myotomy (LHM-1). RESULTS: Thirty-five patients who underwent LHM-R and 35 patients who underwent LHM-1 were included. The reasons for failure in the LHM-R patient group included incomplete myotomy (71.4%), myotomy fibrosis (25.7%) and structural alterations in fundoplication (2.9%). The follow-up duration was 34 months for the LHM-R group and 24 months for the LHM-1 group (p = 0.557). The procedure was performed by laparoscopy in 100% of the patients in the two groups. No differences were found regarding surgical morbidity (11.4% LHM-R vs. 2.9% LHM-1, p = 0.164). The symptomatic outcomes were equivalent between groups (Eckardt p = 0.063, EAT-10 p = 0.166, GERD-HRQL p = 0.075). An IRP < 15 mmHg was achieved in 100% of the LHM-R and LHM-1 patients. At the last follow-up, 82.1% of the LHM-R patients and 91.4% of the LHM-1 patients were in symptomatic remission (p = 0.271). CONCLUSION: The results achieved with LHM-R are similar to those achieved with LHM-1. Laparoscopic reoperation should be considered an effective and safe treatment after a failed Heller myotomy.

Manual segmentation of the fornix, fimbria, and alveus on high-resolution 3T MRI: Application via fully-automated mapping of the human memory circuit white and grey matter in healthy and pathological aging.

Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the alveus and cornu ammonis (CA) 1 were well preserved (all p's<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required.

The origins of breast cancer associated with mammographic density: a testable biological hypothesis.

BACKGROUND: Our purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density (PMD), and to reconcile the apparent paradox that although PMD decreases with increasing age, breast cancer incidence increases. METHODS: We used the Moolgavkar model of carcinogenesis as a framework to examine the known biological properties of the breast tissue components associated with PMD that includes epithelium and stroma, in relation to the development of breast cancer. In this model, normal epithelial cells undergo a mutation to become intermediate cells, which, after further mutation, become malignant cells. A clone of such cells grows to become a tumor. The model also incorporates changes with age in the number of susceptible epithelial cells associated with menarche, parity, and menopause. We used measurements of the radiological properties of breast tissue in 4454 healthy subjects aged from 15 to 80+ years to estimate cumulative exposure to PMD (CBD) in the population, and we examined the association of CBD with the age-incidence curve of breast cancer in the population. RESULTS: Extensive PMD is associated with a greater number of breast epithelial cells, lobules, and fibroblasts, and greater amounts of collagen and extracellular matrix. The known biological properties of these tissue components may, singly or in combination, promote the acquisition of mutations by breast epithelial cells specified by the Moolgavkar model, and the subsequent growth of a clone of malignant cells to form a tumor. We also show that estimated CBD in the population from ages 15 to 80+ years is closely associated with the age-incidence curve of breast cancer in the population. CONCLUSIONS: These findings are consistent with the hypothesis that the biological properties of the breast tissue components associated with PMD increase the probability of the transition of normal epithelium to malignant cells, and that the accumulation of mutations with CBD may influence the age-incidence curve of breast cancer. This hypothesis gives rise to several testable predictions.

Integration of routine QA data into mega-analysis may improve quality and sensitivity of multisite diffusion tensor imaging studies.

A novel mega-analytical approach that reduced methodological variance was evaluated using a multisite diffusion tensor imaging (DTI) fractional anisotropy (FA) data by comparing white matter integrity in people with schizophrenia to controls. Methodological variance was reduced through regression of variance captured from quality assurance (QA) and by using Marchenko-Pastur Principal Component Analysis (MP-PCA) denoising. N = 192 (119 patients/73 controls) data sets were collected at three sites equipped with 3T MRI systems: GE MR750, GE HDx, and Siemens Trio. DTI protocol included five b = 0 and 60 diffusion-sensitized gradient directions (b = 1,000 s/mm2 ). In-house DTI QA protocol data was acquired weekly using a uniform phantom; factor analysis was used to distil into two orthogonal QA factors related to: SNR and FA. They were used as site-specific covariates to perform mega-analytic data aggregation. The effect size of patient-control differences was compared to these reported by the enhancing neuro imaging genetics meta-analysis (ENIGMA) consortium before and after regressing QA variance. Impact of MP-PCA filtering was evaluated likewise. QA-factors explained ∼3-4% variance in the whole-brain average FA values per site. Regression of QA factors improved the effect size of schizophrenia on whole brain average FA values-from Cohen's d = .53 to .57-and improved the agreement between the regional pattern of FA differences observed in this study versus ENIGMA from r = .54 to .70. Application of MP-PCA-denoising further improved the agreement to r = .81. Regression of methodological variances captured by routine QA and advanced denoising that led to a better agreement with a large mega-analytic study.

Chemical exchange saturation transfer for predicting response to stereotactic radiosurgery in human brain metastasis.

PURPOSE: The purpose of this work was to determine the predictive value of chemical exchange saturation transfer (CEST) metrics in brain metastases treated with stereotactic radiosurgery (SRS). METHODS: CEST spectra at a radiofrequency power of 0.52 µT were collected on a 3 Tesla (T) magnetic resonance imaging from 25 patients at three time points: pretreatment, 1 week, and 1 month post-treatment. Amide proton transfer-weighted images and maps of the amplitude and width of Lorentzian-shaped CEST peaks and the relaxation-compensated AREX metric were constructed at the offset frequencies of amide, amine, and relayed nuclear Overhauser effect (NOE) from aliphatic groups as well as the broad magnetization transfer effect. Pretreatment CEST metrics, as well as CEST metric changes at 1 week post-treatment, were compared to changes in tumor volume at 1 month. RESULTS: Significant (P < 0.05) 1-week predictive metrics included NOE peak amplitude (R = 0.69) in normal-appearing white matter (NAWM) and width (R = -0.55) in tumor. Baseline NOE in contralateral NAWM was negatively correlated (R = -0.69) with volume changes at 1 month. Metrics-defined outside tumor margins had higher correlation with volume changes than tumor regions of interest. CONCLUSION: CEST metrics, in particular, the NOE peak amplitude, can predict volume changes 1 month post-SRS. Magn Reson Med 78:1110-1120, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Derivation of high-resolution MRI atlases of the human cerebellum at 3T and segmentation using multiple automatically generated templates.

The cerebellum has classically been linked to motor learning and coordination. However, there is renewed interest in the role of the cerebellum in non-motor functions such as cognition and in the context of different neuropsychiatric disorders. The contribution of neuroimaging studies to advancing understanding of cerebellar structure and function has been limited, partly due to the cerebellum being understudied as a result of contrast and resolution limitations of standard structural magnetic resonance images (MRI). These limitations inhibit proper visualization of the highly compact and detailed cerebellar foliations. In addition, there is a lack of robust algorithms that automatically and reliably identify the cerebellum and its subregions, further complicating the design of large-scale studies of the cerebellum. As such, automated segmentation of the cerebellar lobules would allow detailed population studies of the cerebellum and its subregions. In this manuscript, we describe a novel set of high-resolution in vivo atlases of the cerebellum developed by pairing MR imaging with a carefully validated manual segmentation protocol. Using these cerebellar atlases as inputs, we validate a novel automated segmentation algorithm that takes advantage of the neuroanatomical variability that exists in a given population under study in order to automatically identify the cerebellum, and its lobules. Our automatic segmentation results demonstrate good accuracy in the identification of all lobules (mean Kappa [κ]=0.731; range 0.40-0.89), and the entire cerebellum (mean κ=0.925; range 0.90-0.94) when compared to "gold-standard" manual segmentations. These results compare favorably in comparison to other publically available methods for automatic segmentation of the cerebellum. The completed cerebellar atlases are available freely online (http://imaging-genetics.camh.ca/cerebellum) and can be customized to the unique neuroanatomy of different subjects using the proposed segmentation pipeline (https://github.com/pipitone/MAGeTbrain).

Comparing average breast fat content results from two different protocols at 1.5T and 3T: can the data be pooled?

PURPOSE: To compare the total breast fat content computed from two separate studies, performed on different scanners and with different protocols, with the goal of defining a relationship to allow pooling the data. MATERIALS AND METHODS: Twelve healthy volunteer women were scanned with two different protocols on the same day. The protocols differed in four important aspects: vendors (GE vs. Philips), scanner main magnetic field strengths (1.5T vs. 3T), pulse sequences (2D fast spin-echo vs. 3D spoiled gradient-echo), and water/fat separation techniques. The resulting water and fat maps were processed with in-house software to extract breast tissue slice-wise. Percent fat content was calculated for each breast, per subject. RESULTS: Total percent fat contents (averaged across both breasts) resulting from both protocols were plotted against each other, on a subject-by-subject basis, revealing a strong correlation (R(2) > 0.99), with an overestimation of the fat content from Protocol 1 relative to Protocol 2. The proposed T2 TE-correction for Protocol 1 improves the correlation while decreasing the discrepancy between protocols. CONCLUSION: Total breast fat content of healthy women resulting from the two protocols can be pooled using a linear relationship. The proposed T2 TE-corrected Protocol 1 is expected to yield accurate fat content.

White matter microstructure in transmasculine and cisgender adolescents: A multiparametric and multivariate study.

Adolescence is a sensitive developmental period for neural sex/gender differentiation. The present study used multiparametric mapping to better characterize adolescent white matter (WM) microstructure. WM microstructure was investigated using diffusion tensor indices (fractional anisotropy; mean, radial, and axial diffusivity [AD]) and quantitative T1 relaxometry (T1) in hormone therapy naïve adolescent cisgender girls, cisgender boys, and transgender boys (i.e., assigned female at birth and diagnosed with gender dysphoria). Diffusion indices were first analyzed for group differences using tract-based spatial statistics, which revealed a group difference in AD. Thus, two multiparametric and multivariate analyses assessed AD in conjunction with T1 relaxation time, and with respect to developmental proxy variables (i.e., age, serum estradiol, pubertal development, sexual attraction) thought to be relevant to adolescent brain development. The multivariate analyses showed a shared pattern between AD and T1 such that higher AD was associated with longer T1, and AD and T1 strongly related to all five developmental variables in cisgender boys (10 significant correlations, r range: 0.21-0.73). There were fewer significant correlations between the brain and developmental variables in cisgender girls (three correlations, r range: -0.54-0.54) and transgender boys (two correlations, r range: -0.59-0.77). Specifically, AD related to direction of sexual attraction (i.e., gynephilia, androphilia) in all groups, and T1 related to estradiol inversely in cisgender boys compared with transgender boys. These brain patterns may be indicative of less myelination and tissue density in cisgender boys, which corroborates other reports of protracted WM development in cisgender boys. Further, these findings highlight the importance of considering developmental trajectory when assessing the subtleties of neural structure associated with variations in sex, gender, and sexual attraction.

Pirfenidone use in fibrotic diseases: What do we know so far?

BACKGROUND: Pirfenidone has demonstrated significant anti-inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti-inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro-inflammatory cytokines, apoptosis, and fibroblast activation. OBJECTIVE: To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. FINDINGS: Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. CONCLUSION: Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

A novel in vivo atlas of human hippocampal subfields using high-resolution 3 T magnetic resonance imaging.

The hippocampus is a neuroanatomical structure that has been widely studied in the context of learning, memory, stress, and neurodegeneration. Neuroanatomically, the hippocampus is subdivided into several subfields with intricate morphologies and complex three-dimensional relationships. Recent studies have demonstrated that the identification of different subfields is possible with high-resolution and -contrast image volumes acquired using ex vivo specimens in a small bore 9.4 T scanner and, more recently, in vivo, at 7 T. In these studies, the neuroanatomical definitions of boundaries between subfields are based upon salient differences in image contrast. Typically, the definition of subfields has not been possible using commonly available magnetic resonance (MR) scanners (i.e.: 1.5 or 3T) due to resolution and contrast limitations. To overcome the limited availability of post-mortem specimens and expertise in state-of-the-art high-field imaging, we propose a coupling of MR acquisition and detailed segmentation techniques that allow for the reliable identification of hippocampal anatomy (including subfields). High-resolution and -contrast T1- and T2-weighted image volumes were acquired from 5 volunteers (2 male; 3 female; age range: 29-57, avg. 37) using a clinical research-grade 3T scanner and have final super-sampled isotropic voxel dimensions of 0.3mm. We demonstrate that by using these acquisition techniques, our data results in contrast-to-noise ratios that compare well with high-resolution images acquired with long scan times using post-mortem data at higher field strengths. For the subfields, the cornus ammonis (CA) 1, CA2/CA3, CA4/dentate gyrus, stratum radiatum/stratum lacunosum/stratum moleculare, and subiculum were all labeled as separate structures. Hippocampal volumes are reported for each of the substructures and the hippocampus as a whole (range for hippocampus: 2456.72-3325.02 mm(3)). Intra-rater reliability of our manual segmentation protocol demonstrates high reliability for the whole hippocampus (mean Dice Kappa of 0.91; range 0.90-0.92) and for each of the subfields (range of Dice Kappas: 0.64-0.83). We demonstrate that our reliability is better than the Dice Kappas produced by simulating the following errors: a translation by a single voxel in all cardinal directions and 1% volumetric shrinkage and expansion. The completed hippocampal atlases are available freely online (info2.camh.net/kf-tigr/index.php/Hippocampus) and can be coupled with novel computational neuroanatomy techniques that will allow for them to be customized to the unique neuroanatomy of different subjects, and ultimately be utilized in different analysis pipelines.

Diurnal oscillations of MRI metrics in the brains of male participants.

Regulation of biological processes according to a 24-hr rhythm is essential for the normal functioning of an organism. Temporal variation in brain MRI data has often been attributed to circadian or diurnal oscillations; however, it is not clear if such oscillations exist. Here, we provide evidence that diurnal oscillations indeed govern multiple MRI metrics. We recorded cerebral blood flow, diffusion-tensor metrics, T1 relaxation, and cortical structural features every three hours over a 24-hr period in each of 16 adult male controls and eight adult male participants with bipolar disorder. Diurnal oscillations are detected in numerous MRI metrics at the whole-brain level, and regionally. Rhythmicity parameters in the participants with bipolar disorder are similar to the controls for most metrics, except for a larger phase variation in cerebral blood flow. The ubiquitous nature of diurnal oscillations has broad implications for neuroimaging studies and furthers our understanding of the dynamic nature of the human brain.

Exploring brain glutathione and peripheral blood markers in posttraumatic stress disorder: a combined [1H]MRS and peripheral blood study.

Introduction: Oxidative stress has been implicated in psychiatric disorders, including posttraumatic stress disorder (PTSD). Currently, the status of glutathione (GSH), the brain's most abundant antioxidant, in PTSD remains uncertain. Therefore, the current study investigated brain concentrations of GSH and peripheral concentrations of blood markers in individuals with PTSD vs. Healthy Controls (HC). Methods: GSH spectra was acquired in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) using MEGA-PRESS, a J-difference-editing acquisition method. Peripheral blood samples were analyzed for concentrations of metalloproteinase (MMP)-9, tissue inhibitors of MMP (TIMP)-1,2, and myeloperoxidase (MPO). Results: There was no difference in GSH between PTSD and HC in the ACC (n = 30 PTSD, n = 20 HC) or DLPFC (n = 14 PTSD, n = 18 HC). There were no group differences between peripheral blood markers (P > 0.3) except for (non-significantly) lower TIMP-2 in PTSD. Additionally, TIMP-2 and GSH in the ACC were positively related in those with PTSD. Finally, MPO and MMP-9 were negatively associated with duration of PTSD. Conclusions: We do not report altered GSH concentrations in the ACC or DLPFC in PTSD, however, systemic MMPs and MPO might be implicated in central processes and progression of PTSD. Future research should investigate these relationships in larger sample sizes.

A Higher Manometric Esophageal Length to Height Ratio in Achalasia Explains the Lower Prevalence of Hiatal Hernia.

Background/Aims: The evidence suggests that a shorter esophageal length (EL) in gastroesophageal reflux disease (GERD) patients is associated with the presence of hiatal hernia (HH). However, there are no reports of this association in patients with achalasia. The aim is to (1) determine the prevalence of hiatal hernia in achalasia patients, (2) compare achalasia EL with GERD patients and healthy volunteers (HV), (3) measure achalasia manometric esophageal length to height (MELH) ratio, and (4) determine if there are differences in symptoms between patients with and without hiatal hernia. Methods: This retrospective and cross-sectional study consist of 87 pre-surgical achalasia patients, 22 GERD patients, and 30 HV. High-resolution manometry (HRM), barium swallow, and upper endoscopy were performed to diagnose HH. The EL and MELH ratio were measured by HRM. Symptoms were assessed with Eckardt, Eating Assessment Tool, and GERD-health-related quality of life questionnaires. Results: The HH in GERD's prevalence was 73% vs 3% in achalasia patients (P < 0.001). Achalasia patients had a longer esophagus and a higher MELH ratio than HV and GERD patients (P < 0.001). GERD patients had a lower MELH ratio than HV (P < 0.05). EAT-10 (P < 0.0001) and Eckardt (P < 0.05) scores were higher in achalasia without HH vs HH. Conclusions: The prevalence of HH in achalasia is significantly lower than in GERD. The longer EL and the higher MELH ratio in achalasia could explain the lower prevalence of HH. Despite the low prevalence of HH in achalasia patients, the surgeon should be encouraged not to rule out HH since the risk of postoperative reflux may increase if this condition is not identified and corrected.

A novel method for simultaneous 3D B(1) and T(1) mapping: the method of slopes (MoS).

A novel three-dimensional simultaneous B(1) and T(1) mapping method is introduced: the method of slopes (MoS). The linearity of the spoiled gradient recalled echo (SPGR) signal vs flip angle relation is exploited: B(1) mapping is achieved by a two-point extrapolation to signal null with a correction scheme while T(1) mapping uses the slopes of the SPGR signal vs flip angle curves near the origin and near the signal null. This new method improves upon the existing variable flip angle (VFA) T(1)-mapping method in that (i) consistency between B(1) and T(1) maps is ensured (ii) the sampling scheme is T(1)-independent (iii) the noise bias and singularity, associated with using a linear form for the SPGR signal equation, is eliminated by using the full equation. The method is shown to yield accurate and robust results via simulations. Initial estimates of B(1) and T(1) values are obtained from three data points via simple computations and straight line approximations. Initial estimates of B(1) values, for a range of values, are shown to be accurate due to the proposed B(1) correction scheme. The accuracy and robustness of T(1) values is achieved via a non-linear fitting algorithm which includes a fourth data point sampled at high SNR. The MoS was validated by comparing resulting B(1) and T(1) maps with those obtained using other standard methods. Finally, the ability to obtain brain B(1) and T(1) maps using the MoS was demonstrated by in vivo experiments. The MoS is expected to perform well on other motion-free anatomical regions as well.

Quantifying GABA in Addiction: A Review of Proton Magnetic Resonance Spectroscopy Studies.

Gamma-aminobutyric acid (GABA) signaling plays a crucial role in drug reward and the development of addiction. Historically, GABA neurochemistry in humans has been difficult to study due to methodological limitations. In recent years, proton magnetic resonance spectroscopy (1H-MRS, MRS) has emerged as a non-invasive imaging technique that can detect and quantify human brain metabolites in vivo. Novel sequencing and spectral editing methods have since been developed to allow for quantification of GABA. This review outlines the clinical research utilization of 1H-MRS in understanding GABA neurochemistry in addiction and summarizes current literature that reports GABA measurements by MRS in addiction. Research on alcohol, nicotine, cocaine, and cannabis addiction all suggest medications that modulate GABA signaling may be effective in reducing withdrawal, craving, and other addictive behaviors. Thus, we discuss how improvements in current MRS techniques and design can optimize GABA quantification in future studies and explore how monitoring changes to brain GABA could help identify risk factors, improve treatment efficacy, further characterize the nature of addiction, and provide crucial insights for future pharmacological development.

[Functional recovery at discharge and at three months after a multicomponent physical exercise intervention in elderly subjects hospitalized in an Acute Geriatric Unit]. / Recuperación funcional al alta y a tres meses tras una intervención multicomponente de ejercicio físico en ancianos hospitalizados en una unidad de agudos de geriatría.

INTRODUCTION: Hospitalization in the elderly, even in short stays, is associated with functional impairment. Once the acute illness is reversed, the evolution of this hospital-generated impairment can be variable, and a year after hospitalization more than half of the elderly patients remain impaired. This impairment is associated with a higher risk of institutionalization, of mortality at discharge and of 30-day mortality. Previous studies have shown how interdisciplinary physical exercise programs can improve functionality at discharge and decrease mortality rate, hospital stay and institutionalization. STUDY DESIGN AND OBJECTIVES: In the Acute Geriatric Unit of the Gregorio Marañon University hospital a randomized controlled trial was carried out to assess the effectiveness of an exercise and health education program to prevent functional decline during hospitalization and at three months after discharge in elderly subjects aged 74 years or older. Patients were excluded if at least one of the following exclusion criteria was met: baseline Barthel Index (15-days prior hospitalization) below 20, severe cognitive impairment or inability to walk. The intervention consisted on a physical exercise program (that included squats, balance, gait stimulation, elastic bands, and inspiratory muscle training) and health education program. The control group received usual care.

Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain's intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.