Background There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. Methods and findings FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dualenergy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m 2 and 41.3 ± 5.1 kg/m 2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus −3% ± 32% in placebo group, mean difference 9%, 95% CI −5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI −0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference −0.1 kg,
Preclinical models of breast cancer have established mechanistic links between psychological stress and cancer progression. However, epidemiological evidence linking stress and cancer is equivocal. We tested the impact of stress exposure in female mice expressing the mouse mammary tumor virus polyoma middle-T antigen (MMTV-PyMT), a spontaneous model of mammary adenocarcinoma that mimics metastatic hormone receptor–positive human breast cancer development. MMTV-PyMT mice were socially isolated at 6 to 7 weeks of age during premalignant hyperplasia. To increase the potency of the stressor, singly housed mice were exposed to acute restraint stress (2 hours per day for 3 consecutive days) at 8 to 9 weeks of age during early carcinoma. Exposure to this dual stressor activated both major stress pathways, the sympathetic nervous system and hypothalamic-pituitary-adrenal axis throughout malignant transformation. Stressor exposure reduced mammary tumor burden in association with increased tumor cleaved caspase-3 expression, indicative of increased cell apoptosis. Stress exposure transiently increased tumor vascular endothelial growth factor and reduced tumor interleukin-6, but no other significant alterations in immune/inflammation-associated chemokines and cytokines or changes in myeloid cell populations were detected in tumors. No stress-induced change in second-harmonic generation-emitting collagen, indicative of a switch to a metastasis-promoting tumor extracellular matrix, was detected. Systemic indicators of slowed tumor progression included reduced myeloid-derived suppressor cell (MDSC) frequency in lung and spleen, and decreased transforming growth factor β (TGF-β) content in circulating exosomes, nanometer-sized particles associated with tumor progression. Chronic β-adrenergic receptor (β-AR) blockade with nadolol abrogated stress-induced alterations in tumor burden and cleaved caspase-3 expression, lung MDSC frequency, and exosomal TGF-β content. Despite the evidence for reduced tumor growth, metastatic lesions in the lung were not altered by stress exposure. Unexpectedly, β-blockade in nonstressed mice increased lung metastatic lesions and splenic MDSC frequency, suggesting that in MMTV-PyMT mice, β-AR activation also inhibits tumor progression in the absence of stress exposure. Together, these results suggest stress exposure can act through β-AR signaling to slow primary tumor growth in MMTV-PyMT mice.
Reverse Takotsubo cardiomyopathy is a rare variant of Takotsubo cardiomyopathy in which ballooning occurs at the base of the heart rather than the apex, which is hyperkinetic. Takotsubo cardiomyopathy is usually considered in postmenopausal women, but a growing number of cases of the reverse variant are emerging in peripartum women. We present a case of peripartum reverse Takotsubo cardiomyopathy in a 23-year-old G1P0 female at 38 weeks gestation, induced by preeclampsia with severe features. An echocardiogram performed in the immediate post-cesarean period demonstrated a severely reduced ejection fraction of 25%, which was improved to 43% over the next 48 hours with diuresis. Therefore, it is imperative to differentiate Takotsubo cardiomyopathy occurring in the peripartum period from peripartum cardiomyopathy, which has a similar clinical presentation, to diagnose this condition and improve patient outcomes.
Various factors can lead to thyroiditis, including any acute inflammatory process, especially viral illness. While coronavirus disease 2019 (COVID-19) has been linked to disorders of various systems, there is a lack of literature showing an association of coronavirus with the cause of Hashimoto's thyroiditis. Several possible mechanisms for this outcome have been proposed; chief among them is molecular mimicry. Here, we are reporting a case of Hashimoto's thyroiditis incited by COVID-19 in a 34-year-old obese female who presented with anxiety, behavioral changes, and repeated head movements. The patient had an elevated thyroid stimulating hormone (TSH) level, a low thyroxine (T4) level, and a positive anti-microsomal antibody screen. The patient also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Ultrasound of the patient's neck showed an enlarged heterogeneous thyroid gland. Thyroid replacement therapy with intravenous levothyroxine was started with the subsequent oral transition. Concurrently, she received antibiotics, steroids, and low-molecular-weight heparin for COVID-19. The patient exhibited significant improvement in her mental status, with an eventual return to baseline. The results of the thyroid panel obtained at the outpatient follow-up were normal. Although there is a paucity of data to show COVID-19 as a cause of this painless thyroiditis, this case demonstrates such causality between these two.
Ovarian hyperstimulation syndrome is one of the complications of treating infertility by ovarian stimulation. As a result of the stimulation, there is a shift of serum from the intravascular space to the third space, leading to complications like ascites and pleural effusion. Here we present a case of a 29-year-old female with polycystic ovarian syndrome who was being treated for infertility using ovarian stimulation agents for in-vitro fertilization. After egg retrieval, the patient complained of shortness of breath and was found to have right-sided pleural effusion. Her symptoms were eventually relieved following an ultrasound-guided diagnostic and therapeutic thoracentesis. Upon discharge, a repeat chest radiograph in the pulmonary clinic showed no pleural effusion. In conclusion, although severe complications like pleural effusion from ovarian stimulation are rare, the physician should be able to recognize this phenomenon to prevent any further deterioration of the patient.
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