Table_1_Gastrointestinal Talaromyces marneffei infection in a patient with AIDS: A case report and systematic review.docx

Talaromyces marneffei is a thermally dimorphic fungus that affects multiple organs and frequently invades immunocompromised individuals. However, only a few studies have reported the presence of intestinal infection associated with T. marneffei. Herein, we reported a case of intestinal T. marneffei infection in a man who complained of a 1-month history of intermittent fever, abdominal pain, and diarrhea. The result of the human immunodeficiency virus antibody test was positive. Periodic acid-Schiff and Gomorrah’s methylamine silver staining of the intestinal biopsy tissue revealed T. marneffei infection. Fortunately, the patient’s symptoms rapidly resolved with prompt antifungal treatment. In addition, we summarized and described the clinical characteristics, management, and outcomes of patients with intestinal T. marneffei infection. A total of 29 patients were identified, the majority of whom (65.52%) were comorbid with acquired immunodeficiency syndrome. The main clinical features included anemia, fever, abdominal pain, diarrhea, weight loss, and lymphadenopathy. The transverse and descending colon, ileocecum, and ascending colon were the most common sites of lesions. A considerable number of patients (31.03%) developed intestinal obstruction, intestinal perforation, and gastrointestinal bleeding. Of the 29 patients, six underwent surgery, 23 survived successfully with antifungal treatment, five died of T. marneffei infection, and one died of unknown causes. T. marneffei intestinal infection should be considered when immunodeficient patients in endemic areas present with non-specific symptoms, such as fever, abdominal pain, and diarrhea. Appropriate and timely endoscopy avoids delays in diagnosis. Early aggressive antifungal therapy improves the clinical outcomes of patients.</p

Image_1_A potential brain functional biomarker distinguishing patients with Crohn’s disease with different disease stages: a resting-state fMRI study.pdf

BackgroundThe previous studies have demonstrated that patients with Crohn’s disease in remission (CD-R) have abnormal alterations in brain function. However, whether brain function changes in patients with Crohn’s disease in activity (CD-A) and the relationship with CD-R are still unclear. In this study, we aimed to investigate whether the different levels of disease activity may differentially affect the brain function and to find the brain functional biomarker distinguishing patients with different disease stages by measuring the amplitude of low frequency fluctuations (ALFF).Methods121 patients with CD and 91 healthy controls (HCs) were recruited. The clinical and psychological assessment of participants were collected. The criteria for the disease activity were the Crohn’s disease activity index (CDAI) scores. CD-R refers to CD patients in remission which the CDAI score is less than 150. Conversely, CD-A refers to CD patients in activity which the CDAI score is ≥150. The ALFF was compared among three groups by performing one-way analysis of variance, followed by a post hoc two-sample t-test. Differences among the groups were selected as seeds for functional connectivity analyses. We also investigated the correlation among clinical, psychological scores and ALFF. Binary logistic regression analysis was used to examine the unique contribution of the ALFF characteristics of the disease stages.ResultsThere were widespread differences of ALFF values among the 3 groups, which included left frontal pole (FP_L), right supramarginal gyrus (SG_R), left angular gyrus (AG_L), right cingulate gyrus (CG_R), right intracalcarine cortex (IC_R), right parahippocampal gyrus (PG_R), right lingual gyrus (LG_R), right precuneous cortex (PC_R), left occipital fusiform gyrus (OFG_L). Significant brain regions showing the functional connections (FC) increased in FP_L, SG_R, PC_R and OFG_L between CD-A and HCs. The erythrocyte sedimentation rate had a negative correlation with the ALFF values in PC_R in the patients with CD. The phobic anxiety values had a negative correlation with the ALFF values in OFG_L. The psychoticism values had a negative correlation with ALFF values in the IC_R. And the hostility values had a positive correlation with the ALFF values in CG_R. Significant brain regions showing the FC increased in FP_L, SG_R, CG_R, PG_R, LG_R and OFG_L between CD-R and HCs. In binary logistic regression models, the LG_R (beta = 5.138, p = 0.031), PC_R (beta = 1.876, p = 0.002) and OFG_L (beta = 3.937, p = 0.044) was disease stages predictors.ConclusionThe results indicated the significance of the altered brain activity in the different disease stages of CD. Therefore, these findings present a potential identify neuroimaging-based brain functional biomarker in CD. Additionally, the study provides a better understanding of the pathophysiology of CD.</p

SRC-1 Regulates Blood Pressure and Aortic Stiffness in Female Mice

<div><p>Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expression of steroid receptor coactivator-1 protein in mouse brain, especially in regions implicated in the regulation of blood pressure. Steroid receptor coactivator-1 protein was found in central amygdala, medial amygdala, supraoptic nucleus, arcuate nucleus, ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus of the solitary tract. To determine the effects of steroid receptor coactivator-1 protein on cardiovascular system we measured blood pressures, blood flow velocities, echocardiographic parameters, and aortic input impedance in female steroid receptor coactivator-1 knockout mice and their wild type littermates. Steroid receptor coactivator-1 knockout mice had higher blood pressures and increased aortic stiffness when compared to female wild type littermates. Additionally, the hearts of steroid receptor coactivator-1 knockout mice seem to consume higher energy as evidenced by increased impedance and higher heart rate pressure product when compared to female wild type littermates. Our results demonstrate that steroid receptor coactivator-1 may be functionally involved in the regulation of blood pressure and aortic stiffness through the regulation of sympathetic activation in various neuronal populations.</p></div

Cardiac flow velocity indices.

<p>Peak aortic outflow velocity (<b>A</b>), peak mitral-E flow velocity (<b>B</b>), peak mitral-A flow velocity (<b>C</b>) and mitral E/A ratio (<b>D</b>) obtained from cardiac Doppler flow velocity signals in female WT and SRC-1-KO mice. Data are presented as mean±SEM (n = 4-6/group); <b>*</b>—p<i><</i> 0.05. The information supporting this figure is in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168644#pone.0168644.s004" target="_blank">S4 Dataset</a>.</p

Validation of SRC-1-KO mice.

<p>3,3′-diaminobenzidine immunohistochemistry staining for SRC-1 in the medial amygdala of female WT (<b>A</b>) or SRC-1-KO (<b>B</b>) mice. OPT, optic tract; MeA, medial amygdala. Scale bar = 100 μm.</p

Loss of SRC-1 in female mice results in aortic stiffness.

<p>Parameters of aortic impedance in female WT and SRC-1-KO mice. Total peripheral resistance, Z_P (<b>A</b>), impedance at first harmonic, Z₁ (<b>B</b>), characteristic impedance, Z_C (<b>C</b>), and impedance based pulse wave velocity, PWV_Z (<b>D</b>). Data are presented as mean±SEM (n = 4-6/group); <b>* =</b> p<i><</i> 0.05. The information supporting this figure is in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168644#pone.0168644.s005" target="_blank">S5 Dataset</a>.</p

Expression of SRC-1 in the brain.

<p>Immunofluorescence staining of SRC-1 in various brain regions of WT female mice. 3V, third ventricle; ARC, arcuate nucleus of the hypothalamus; CeA, central amygdala; DMH, dorsal medial nucleus of the hypothalamus; MeA, medial amygdala; NTS, the nucleus of the solitary tract; OPT, optic tract; PVN, paraventricular nucleus of the hypothalamus; Sch, suprachiasmatic nucleus; SON, supraoptic nucleus; VMH, ventromedial nucleus of the hypothalamus (VMH). Scale bars = 100 μm.</p

Echocardiographic parameters of female WT and SRC-1 KO mice.

<p>Echocardiographic parameters of female WT and SRC-1 KO mice.</p

Aortic blood pressure and rate pressure product.

<p>Aortic blood pressure parameters of female WT and SRC-1-KO mice. (<b>A</b>) Systolic blood pressure (SBP), (<b>B</b>) Diastolic blood pressure (DBP), (<b>C</b>) Mean blood pressure (MBP), (<b>D</b>) Pulse pressure, (<b>E</b>) Heart rate, and (<b>F</b>) Rate pressure product (RPP). Data are presented as mean±SEM (n = 5-7/group); <b>*</b>—p<i><</i> 0.05. The information supporting this figure is in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168644#pone.0168644.s001" target="_blank">S1 Dataset</a>.</p

Diameter of the aortic arch.

<p>Representative B-mode images of aortic arch in female WT (<b>A</b>) and SRC-1-KO (<b>B</b>) mice. Quantification (<b>C</b>) revealed a decrease in diameter of the aortic arch in SRC-1-KO mice. Data are presented as mean±SEM (n = 4-5/group); <b>*</b>—p<i><</i> 0.05. The information supporting this figure is in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168644#pone.0168644.s003" target="_blank">S3 Dataset</a>.</p