The Postbiotic Butyrate Mitigates Gut Mucosal Disruption Caused by Acute Ethanol Exposure.

We aimed to test how the postbiotic butyrate impacts select gut bacteria, small intestinal epithelial integrity, and microvascular endothelial activation during acute ethanol exposure in mice and primary human intestinal microvascular endothelial cells (HIMECs). Supplementation during an acute ethanol challenge with or without tributyrin, a butyrate prodrug, was delivered to C57BL/6 mice. A separate group of mice received 3 days of clindamycin prior to the acute ethanol challenge. Upon euthanasia, blood endotoxin, cecal bacteria, jejunal barrier integrity, and small intestinal lamina propria dendritic cells were assessed. HIMECs were tested for activation following exposure to ethanol ± lipopolysaccharide (LPS) and sodium butyrate. Tributyrin supplementation protected a butyrate-generating microbe during ethanol and antibiotic exposure. Tributyrin rescued ethanol-induced disruption in jejunal epithelial barrier, elevated plasma endotoxin, and increased mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) expression in intestinal microvascular endothelium. These protective effects of tributyrin coincided with a tolerogenic dendritic response in the intestinal lamina propria. Lastly, sodium butyrate pre- and co-treatment attenuated the direct effects of ethanol and LPS on MAdCAM-1 induction in the HIMECs from a patient with ulcerative colitis. Tributyrin supplementation protects small intestinal epithelial and microvascular barrier integrity and modulates microvascular endothelial activation and dendritic tolerizing function during a state of gut dysbiosis and acute ethanol challenge.

Targeting the Gut Microbiota and Host Immunity with a Bacilli-Species Probiotic during Antibiotic Exposure in Mice.

Antibiotic therapy is necessary for the treatment of bacterial infections; however, it can also disrupt the balance and function of commensal gut microbes and negatively affect the host. Probiotics have been tested as a means to counteract the negative effects of antibiotic therapy, but many probiotics are also likely destroyed by antibiotics when taken together. Here we aimed to test the efficacy of a non-pathogenic spore-forming Bacillus-species containing a probiotic blend provided during antibiotic therapy on host immune defenses in mice. Mice were exposed to antibiotics and supplemented with or without the probiotic blend and compared to control mice. Fecal and cecal contents were analyzed for gut microbes, and intestinal tissue was tested for the expression of key enzymes involved in vitamin A metabolism, serum amyloid A, and inflammatory markers in the intestine. The probiotic blend protected against antibiotic-induced overgrowth of gram-negative bacteria and gammaproteobacteria in the cecum which correlated with host immune responses. Regional responses in mRNA expression of enzymes involved with vitamin A metabolism occurred between antibiotic groups, and intestinal inflammatory markers were mitigated with the probiotic blend. These data suggest prophylactic supplementation with a spore-forming Bacillus-containing probiotic may protect against antibiotic-induced dysregulation of host immune responses.

A Spore-Forming Probiotic Supplement Improves the Intestinal Immune Response and Protects the Intestinal Health During Recurrent Clostridioides difficile Colonization in Mice.

BACKGROUND: Around 15%-30% of patients develop recurrent Clostridioides difficile infection (CDI) as conventional therapies disrupt protective gut microbiota. We tested if supplementation with a spore-forming probiotic would protect intestinal health in a mouse model of recurrent CD colonization. METHODS: Methods: Female CF-1 mice were exposed to CD spores (4-log10 colony-forming units/10 µL) and then randomly assigned to receive either saline (CD-S) or probiotic (CD-PRO). Control mice received only saline (control). Following confirmation of initial CD colonization, mice were treated with vancomycin (10 days). After 5 days, mice recolonized with CD were treated again with vancomycin (10 days) and euthanized 5 days later. Fecal samples were collected at select time points for bacterial analysis. Following euthanasia, blood samples, cecum contents, and the intestine were collected for analysis. RESULTS: Probiotic supplementation mitigated the antibiotic-induced changes in cecum weight (P < .001). Probiotic-supplemented mice had increased messenger RNA expression of several immune parameters, accompanied by lower serum iron levels compared with CD-S mice (P < .05). Lower expressions of TNF α and calprotectin (P ≤ .05) were observed in CD-PRO mice compared with CD-S. The probiotics also supported the expression of intestinal tight junction proteins, which were diminished in the proximal colon of CD-S mice (P < .05). CONCLUSION: Mice supplemented with targeted spore-forming probiotics exhibited improved immune responses and nutrition immunity properties, which were linked with less inflammation and enhanced intestinal barrier proteins during recurrent CD colonization.

Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure.

Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sinusoidal endothelial cells (LSEC), here we evaluated dietary supplementation with a previously studied synbiotic on gut microbial composition, and hepatocyte and LSEC integrity in mice exposed to ethanol. We tested a chronic-binge ethanol feeding mouse model in which C57BL/6 female mice were fed ethanol (5% vol/vol) for 10 days and provided a single ethanol gavage (5 g/kg body weight) on day 11, 6 h before euthanasia. An ethanol-treatment group also received oral supplementation daily with a synbiotic; and an ethanol-control group received saline. Control mice were pair-fed and isocalorically substituted maltose dextran for ethanol over the entire exposure period; they received a saline gavage daily. Ethanol exposure decreased gut microbial abundance and diversity. This was linked with diminished expression of adherens junction proteins in hepatocytes and dysregulated expression of receptors for advanced glycation end-products; and this coincided with reduced expression of endothelial barrier proteins. Synbiotic supplementation mitigated these effects. These results demonstrate synbiotic supplementation, as a means to modulate ethanol-induced gut dysbiosis, is effective in attenuating injury to hepatocyte and liver endothelial barrier integrity, highlighting a link between the gut microbiome and early stages of acute liver injury in ethanol-exposed mice.

Group differences between practitioners and novices in hemispheric processing of attention and emotion before and after a session of Falun Gong qigong.

We examined the hemispheric effects of Falun Gong qigong (FLG), a movement meditation practice, using a systematic approach to hemispheric function by administering the Emotion Lateralized Attention Network Test (ELANT) to measure the interaction of the Conflict Resolution, Spatial Orienting, and Emotion networks. Measuring both behavior (ELANT, DV = accuracy) and physiology (HF-HRV), we compared experienced FLG practitioners (n = 19) to novices serving as an active control group (n = 16) before and after a 91-min sequence of FLG qigong exercises. We compared practitioners and novices using a hierarchy of intrahemispheric and interhemispheric control relations that can be tested with the ELANT. Practitioners exhibited a prominent short-term effect in which they improved relative to novices on trials requiring complex interhemispheric transfer (ηP2 = 0.21). Two baseline group differences, suggesting long-term effects of FLG, both involved the left hemisphere. First, practitioners were selectively spared the negative effects of processing positive emotion cues preceding left hemisphere targets (ηP2 = 0.34). Second, only practitioners showed improved left-hemisphere Conflict Resolution at higher levels of HF-HRV (r2 = 0.40). The data showed that FLG practitioners had increased flexibility in the management of a limited attentional resource pool that is accessible to both hemispheres.

Reduction of PTSD in South African University Students Using Transcendental Meditation Practice.

A study was conducted on South African college students using the Transcendental Meditation technique to reduce posttraumatic stress disorder. Students meeting the criteria for possible posttraumatic stress disorder were included. Thirty-four students at the experimental university in South Africa clinically diagnosed with posttraumatic stress disorder were instructed in and practiced the Transcendental Meditation technique twice daily compared to 34 diagnosed posttraumatic stress disorder comparison students at the comparison university. The multivariate effect was significant for both the posttraumatic stress disorder symptomatology and depression. Results were significantly associated with regularity of practice. The study replicates recent findings and offers an alternative educational treatment for higher education.

Multimodal x-ray and electron microscopy of the Allende meteorite.

Multimodal microscopy that combines complementary nanoscale imaging techniques is critical for extracting comprehensive chemical, structural, and functional information, particularly for heterogeneous samples. X-ray microscopy can achieve high-resolution imaging of bulk materials with chemical, magnetic, electronic, and bond orientation contrast, while electron microscopy provides atomic-scale spatial resolution with quantitative elemental composition. Here, we combine x-ray ptychography and scanning transmission x-ray spectromicroscopy with three-dimensional energy-dispersive spectroscopy and electron tomography to perform structural and chemical mapping of an Allende meteorite particle with 15-nm spatial resolution. We use textural and quantitative elemental information to infer the mineral composition and discuss potential processes that occurred before or after accretion. We anticipate that correlative x-ray and electron microscopy overcome the limitations of individual imaging modalities and open up a route to future multiscale nondestructive microscopies of complex functional materials and biological systems.

Increasing the cervical and lumbar lordosis is possible despite overt osteoarthritis and spinal stenosis using extension traction to relieve low back and leg pain in a 66-year-old surgical candidate: a CBP® case report.

[Purpose] To present the case of the dramatic relief of low back pain, leg pain and disability in an older female with osteoarthritis, lumbar spinal stenosis and hypolordosis of the cervical and lumbar spine. [Participant and Methods] A 66-year-old female presented with chronic low back pain, right leg pain, numbness and weakness. Despite being recommended for surgery, the patient sought alternative treatment. The patient was treated with Chiropractic BioPhysics® rehabilitation of the spine with the objective to increase the lumbar and cervical lordoses. Cervical and lumbar extension exercises and traction were performed as well as spinal manipulation. Treatment was performed approximately three times per week for 6.5 months. [Results] Re-assessment after treatment demonstrated significant reduction of low back pain, leg pain and other health improvements. X-rays showed structural improvements in the cervical and lumbar spine despite advanced osteoarthritis. [Conclusion] Lumbar and cervical hypolordosis subluxation may be increased in those with spinal deformity caused symptoms, despite the presence of osteoarthritis and degenerative stenosis of the spine. Spinal x-rays as used in the assessment and monitoring of patients being treated with contemporary spinal rehabilitation methods are not harmful and should be used for routine screening purposes.

Alleviation of neck pain by the non-surgical rehabilitation of a pathologic cervical kyphosis to a normal lordosis: a CBP® case report.

[Purpose] To present a case of the therapeutic reversal of a cervical kyphosis into a lordosis in a patient who presented with neck pain and headaches. [Subject and Methods] A 24-year-old male irritated his neck while dancing. Upon examination it was revealed he had an excessive, 45 mm forward head translation and a 15° cervical kyphosis from C3-C6. The patient was treated with Chiropractic BioPhysics® methods aimed at restoring the cervical lordosis by mirror image®, neck extension exercises, cervical extension traction, and spinal manipulative therapy. [Results] After two weeks of treatments the patient reported a complete resolution of neck pain. After 24 treatments over 10-weeks, a lateral radiograph demonstrated the restoration of a cervical lordosis and a complete reduction of forward head translation. [Conclusion] This case demonstrates that a cervical kyphosis may be reversed into a lordosis in as little as 10-weeks by specific care incorporating cervical extension protocols. This case also supports the biomechanical literature that suggests those with cervical kyphosis may be predisposed to spinal injury. We suggest that correcting even asymptomatic patients with obvious cervical spine deformity should be accomplished prior to future injury and/or degenerative changes.

Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells.

Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and S-equol from soy, and liquiritigen from licorice root in breast cancer and liver cells. BEs and estradiol (E2), acting through ERα, stimulated proliferation, ERα chromatin binding and target-gene expression. BEs but not E2, acting through AhR, bound to xenobiotic response element-containing chromatin sites and enhanced AhR target-gene expression (CYP1A1, CYP1B1). While E2 and TCDD acted quite selectively through their respective receptors, BEs acted via both receptors, with their AhR activity moderated by negative crosstalk through ERα. Both ERα and AhR should be considered as mediators of the biology and pharmacology of BEs.

Self-regulation evaluation of therapeutic yoga and walking for patients with irritable bowel syndrome: a pilot study.

With limited efficacy of medications for symptom relief, non-medication treatments may play an important role in the treatment of irritable bowel syndrome (IBS), the most common functional gastrointestinal (GI) disorder. This study aimed to evaluate the efficacy of two self-regulation strategies for symptom relief and mood management in IBS patients. Thirty-five adult participants meeting ROME III criteria for IBS were enrolled, 27 of the 35 participants (77%) completed treatment and pre- and post-treatment visits (89% women, 11% men; M (SD) age = 36 (13)), and 20 of the 27 (74%) completed a 6-month follow-up. Participants were randomly assigned to 16 biweekly group sessions of Iyengar yoga or a walking program. Results indicated a significant group by time interaction on negative affect with the walking treatment showing improvement from pre- to post-treatment when compared to yoga (p < .05). There was no significant group by time effect on IBS severity. Exploratory analyses of secondary outcomes examined change separately for each treatment condition. From pre- to post-treatment, yoga showed significant decreases in IBS severity measures (p < .05), visceral sensitivity (p < .05), and severity of somatic symptoms (p < .05). Walking showed significant decreases in overall GI symptoms (p < .05), negative affect (p < .05), and state anxiety (p < .05). At 6-month follow-up, overall GI symptoms for walking continued to significantly decline, while for yoga, GI symptoms rebounded toward baseline levels (p < .05). When asked about self-regulated home practice at 6 months, significantly more participants in walking than in yoga practiced at least weekly (p < .05). In sum, results suggest that yoga and walking as movement-based self-regulatory behavioral treatments have some differential effects but are both beneficial for IBS patients, though maintenance of a self-regulated walking program may be more feasible and therefore more effective long term.

Heart rate variability and treatment outcome in major depression: a pilot study.

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p<0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.

Significant reductions in posttraumatic stress symptoms in Congolese refugees within 10 days of Transcendental Meditation practice.

This follow-up pilot study tested whether Transcendental Meditation® (TM) practice would significantly reduce symptoms of posttraumatic stress in Congolese refugees within 10 days after instruction. The Posttraumatic Stress Disorder Checklist-Civilian (PCL-C) was administered to nonmatched waitlist controls from a previous study 3 times over a 90-day period. Within 8 days of the third baseline measure, 11 refugees were taught TM, then retested 10 days and 30 days after instruction. Average PCL-C scores dropped 29.9 points from 77.9 to 48.0 in 10 days, then dropped another 12.7 points to 35.3 at 30 days. Effect size at 10 days was high (d = 4.05). There were no adverse events. All participants completed the study and were able to practice TM.

Stress reactivity in traditional Chinese medicine-based subgroups of patients with irritable bowel syndrome.

OBJECTIVES: This study aimed to examine differences in autonomic responses to stress, pain perception, and the role of negative affect in these responses in individuals with irritable bowel syndrome (IBS) according to Traditional Chinese Medicine (TCM) classifications. DESIGN: Fifty-nine female patients with IBS age 18-65 years diagnosed by TCM practitioners as showing primarily an excess (n=32) or an overlap (n=27) pattern (mixed excess and deficiency) were assessed for symptom differences, heart rate, and skin conductance responses to a psychosocial stressor and pain perception. SETTINGS/LOCATIONS: University of California in Los Angeles, California. RESULTS: Compared with the excess group, the overlap group showed significantly greater overall gastrointestinal symptom severity, abdominal pain, and negative affect. The excess group with higher levels of negative affect showed greater reactivity to stress, whereas the overlap group showed an opposite response pattern. The overlap group showed increased cold sensitivity. CONCLUSIONS: IBS patients with the overlap pattern have greater disease severity and comorbidity than those with excess alone. Those with excess showed a pattern of increased stress response with greater negative affect, whereas the overlap group with greater deficiency showed lower physiologic arousal with greater negative affect, consistent with depletion resulting from allostatic load.

Reduction in posttraumatic stress symptoms in Congolese refugees practicing transcendental meditation.

This matched single-blind pilot study tested the effect of Transcendental Meditation® (TM) practice on symptoms of posttraumatic stress (PTS) in Congolese refugees. Urban refugees (N = 102) staying around Kampala, Uganda attended introductory meetings. After initial random assignment to the TM group, 30 refugees who revealed that they were unable to attend all meetings and were eliminated from the study. The remaining 21 TM group participants were then instructed in TM and matched with refugees in the control group on age, sex, and baseline scores on the Post-traumatic Stress Disorder Checklist-Civilian (PCL-C). All participants completed the PCL-C measure of PTS symptoms at baseline, and 30-day and 135-day posttests. The PCL-C scores in the control group trended upward. In contrast, the PCL-C scores in the TM group went from 65 on average at baseline indicating severe PTS symptoms to below 30 on average after 30 days of TM practice, and remained low at 135 days. Effect size was high (d > 1.0). Compliance with TM practice was good; most reported regular practice throughout the study. There were no adverse events. All refugees who learned TM completed the study and were able to practice TM successfully, with subsequent substantial reduction in PTS symptoms.

Rapid intrapartum or postpartum HIV testing at a midwife obstetric unit and a district hospital in South Africa.

OBJECTIVE: To compare the prepartum and postpartum feasibility and acceptance of voluntary counseling and rapid testing (VCT) among women with unknown HIV status in South Africa. METHODS: Eligible women were randomized according to the calendar week of presentation to receive VCT either while in labor or after delivery. RESULTS: Of 7238 women approached, 542 (7.5%) were eligible, 343 (63%) were enrolled, and 45 (13%) were found to be HIV infected. The proportions of eligible women who accepted VCT were 66.8% (161 of 241) in the intrapartum arm and 60.5% (182 of 301) in the postpartum arm, and the difference of 6.3% (95% CI, -1.8% to 14.5%) was not significant. The median times (44 and 45 minutes) required to conduct VCT were also similar in the 2 arms. In the intrapartum arm, all women in true labor received their test results before delivery and all those found to be HIV positive accepted prophylaxis with nevirapine before delivery. CONCLUSIONS: Rapid testing in labor wards for women with an unknown HIV status is feasible and well accepted, and allows for a more timely antiretroviral prophylaxis than postpartum testing.

Low concentrations of the soy phytoestrogen genistein induce proteinase inhibitor 9 and block killing of breast cancer cells by immune cells.

The risks and benefits of diets and supplements containing the estrogenic soy isoflavone genistein are not well established. We report that 10 nm genistein potently induces the granzyme B inhibitor, proteinase inhibitor 9 (PI-9) in MCF-7 human breast cancer cells. By inducing PI-9, genistein inhibits the ability of human natural killer (NK) cells to lyse the target breast cancer cells. In ERalphaHA cells, stably transfected MCF-7 cells, which contain elevated levels of estrogen receptor-alpha (ERalpha), 100 pm genistein or 17beta-estradiol potently induce PI-9 and prevent NK cells from killing the target breast cancer cells. The concentrations of genistein that fully induce PI-9 in MCF-7 cells, and in ERalphaHA cells, are far lower than those previously reported to elicit estrogenic responses through ERalpha. Because 4-hydroxytamoxifen, raloxifene, and ICI 182,780/Faslodex all block genistein induction of PI-9 and elevated levels of ERalpha enhance induction of PI-9, genistein acts via ERalpha to induce PI-9. Increasing levels of ERalpha in breast cancer cells results in a progressive increase in induction of PI-9 by genistein and in the cell's ability to evade killing by NK cells. Moderate levels of dietary genistein and soy flour effectively induce PI-9 in human breast cancers grown in ovariectomized athymic mice. A significant population consumes levels of genistein in soy products that may be high enough to induce PI-9, perhaps potentiating the survival of some preexisting breast cancers by enabling them to evade immunosurveillance.

Moods in everyday situations: effects of combinations of different arousal-related factors.

OBJECTIVE: This study examined women's mood responsiveness associated with patterns of stress hormone levels in everyday situations. METHODS: Self-reports of negative, positive, and energy dimensions of mood were obtained from 203 nurses throughout the day on a workday and on an off-work day during the luteal and follicular phases of the menstrual cycle. Individual differences in daytime norepinephrine and cortisol were assessed. RESULTS: Patterns of norepinephrine and cortisol levels were associated with ratings of the following moods: tired, sad, and happy. Phase of the menstrual cycle and the day factor (workday, off-work day) modified the association of mood ratings and stress hormone patterns. CONCLUSION: The experience of negative mood is associated with both hypoarousal and hyperarousal conditions. A homeostatic arousal-related concept of mood regulation is discussed.