Disrupted white matter integrity in primary insomnia and major depressive disorder: relationships to sleep quality and depression severity.

This study examined the integrity of white matter tracts in 25 participants with primary insomnia (PI), 50 participants with major depressive disorder (MDD), and 25 healthy controls. Seven white matter tracts, selected based on prior research, were quantified by fractional anisotropy (FA) as well as by related measures of diffusivity using diffusion tensor imaging (DTI) on a 3-T scanner. All 100 participants were free of significant medical, psychiatric (excluding the MDD group) and sleep disorders (excluding the PI group), were free of central nervous system medications, and completed an extensive clinical assessment. Subjective and objective sleep measures revealed significant sleep disruption in both the PI and MDD groups. Relative to the controls, both the PI and MDD groups demonstrated impaired integrity in three of the seven white matter tracts: the genu of the corpus callosum (GenuCC), the superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF). We demonstrated reduced FA in the GenuCC, reduced FA and reduced axial diffusivity (AD) in the SLF, as well as reduced AD and radial diffusivity in the ILF. Finally, in an exploratory analysis of the combined cohorts, FA in the GenuCC and FA in the SLF were negatively correlated with depression severity and positively correlated with total sleep time. Abnormalities documented in the GenuCC, SLF and ILF, and present in both the PI and MDD groups may suggest some shared neurobiology.

1H MRS Measurement of Cortical GABA and Glutamate in Primary Insomnia and Major Depressive Disorder: Relationship to Sleep Quality and Depression Severity.

BACKGROUND: Both Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions. The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear. METHODS: We used single-voxel proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and in the parieto-occipital cortex (POC) of 51 non-medicated adults with MDD, 24 adults with Primary Insomnia (PI), and 25 age- and sex-matched good sleeper controls (HC). Measures of depression severity and subjective and objective sleep quality were compared with 1H MRS metabolite measures. RESULTS: MDD subjects exhibited a 15% decrease in Glu/Cr in the dACC compared to HC. Within the MDD group, there was a trend inverse correlation between dACC Glu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACC Glu/Cr in those with MDD. LIMITATIONS: The protocol and data interpretation would have been enhanced by the recruitment of MDD subjects with a broader range of affect severity and a more comprehensive assessment of clinical features. CONCLUSIONS: These findings support the role of cortical glutamatergic mechanisms in the pathophysiology of MDD. Insomnia severity did not further contribute to the relative deficiency of glutamatergic measures in MDD.

Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend.

PURPOSE: To compare three fractions of a medicinal mushroom blend (MMB), MyCommunity, on immune-activation, inflammation-regulation, and induction of biomarkers involved in regenerative functions. METHODS: A seventeen-species MMB was sequentially extracted: first, saline solution at ambient temperature, followed by re-extraction of the solids in ethanol, and finally resuspension of the homogenized ethanol-insoluble solids in cell-culture media. Fractions were tested on peripheral blood mononuclear cells from three healthy donors. Immunostaining, flow-cytometry, and Luminex protein-arrays measured immune-cell activation and cytokine response. Dose-responses for induction of the CD69 early activation marker and individual cytokine and growth-factor responses for each donor were evaluated. The CD69 and the combined cytokine and growth-factor results were subjected to Non-metric Multidimensional Scaling (NMDS) and multivariate ordination to aid interpretation of the aggregate immune response and pairwise permutational MANOVA on a distance-matrix to evaluate statistical differences between treatments on pooled data from all donors. RESULTS: Differential effects were induced by water-soluble, ethanol-soluble, and insoluble immunomodulatory compounds of the MMB. The aqueous and ethanol fractions upregulated expression of CD69 on all tested cell types. Monocyte-activation was correlated with the ethanol fraction, while NKT and non-NK non-T cell-activation was more closely correlated with the aqueous fraction. The solid fraction was the most potent inducer of Tumor Necrosis Factor-α, as well as the anti-viral cytokines interferon-γ, MCP-1 (CCL-2), MIP-1α (CCL-3), and MIP-1ß (CCL-4), and induced G-CSF and b-FGF-growth-factors involved in regenerative functions-and the anti-inflammatory cytokine IL-1ra. CONCLUSION: The aqueous, ethanol, and insoluble compounds within MMB induced differential immune-activating, anti-inflammatory, and regenerative effects. This in vitro data suggests that, upon consumption, MMB may induce a concerted series of immunomodulatory events based on the differential solubility and bioavailability of the active constituents. These differential responses support both immune-activation and resolution of the host defense-induced inflammatory reactions, thus assisting a post-response return to homeostasis.

The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro.

BACKGROUND: The medicinal mushroom Trametes versicolor (Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate. METHODS: Tv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-µm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and the Trametes versicolor mycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays. RESULTS: Both aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells. Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors. CONCLUSION: The results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.

Rapid and selective mobilization of specific stem cell types after consumption of a polyphenol-rich extract from sea buckthorn berries (Hippophae) in healthy human subjects.

PURPOSE: The aim of this study was to evaluate the effects of a proanthocyanidin-rich extract of sea buckthorn berry (SBB-PE) on the numbers of various types of adult stem cells in the blood circulation of healthy human subjects. STUDY DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, cross-over trial was conducted in 12 healthy subjects. Blood samples were taken immediately before and at 1 and 2 hours after consuming either placebo or 500 mg SBB-PE. Whole blood was used for immunophenotyping and flow cytometry to quantify the numbers of CD45dim CD34+ CD309+ and CD45dim CD34+ CD309- stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ mesenchymal stem cells. RESULTS: Consumption of SBB-PE was associated with a rapid and highly selective mobilization of CD45dim CD34+ CD309- progenitor stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ lymphocytoid mesenchymal stem cells. In contrast, only minor effects were seen for CD45dim CD34+ CD309+ pluripotential stem cells. CONCLUSION: Consumption of SBB-PE resulted in selective mobilization of stem cell types involved in regenerative and reparative functions. These data may contribute to the understanding of the traditional uses of SBB for preventive health, regenerative health, and postponing the aging process.

Establishing the Research Agenda for Increasing the Representation of Women in Engineering and Computing.

While there is an extensive body of research on gender equity in engineering and computing, there have been few efforts to glean insight from a dialog among experts. To encourage collaboration and to develop a shared vision of the future research agenda, a 2 day workshop of 50 scholars who work on the topic of gender in engineering and computing was held at a rural conference center. The structure of the conference and the location allowed for time to reflect, dialog, and to craft an innovative research agenda aimed at increasing the representation of women in engineering and computing. This paper has been written by the conference organizers and details the ideas and recommendations from the scholars. The result is an innovative, collaborative approach to future research that focuses on identifying effective interventions. The new approach includes the creation of partnerships with stakeholders including businesses, government agencies, non-profits and academic institutions to allow a broader voice in setting research priorities. Researchers recommend incorporating multiple disciplines and methodologies, while expanding the use of data analytics, merging and mining existing databases and creating new datasets. The future research agenda is detailed and includes studies focused on socio-cultural interventions particularly on career choice, within undergraduate and graduate programs, and for women in professional careers. The outcome is a vision for future research that can be shared with researchers, practitioners and other stakeholders that will lead to gender equity in the engineering and computing professions.

Water-soluble egg membrane enhances the immunoactivating properties of an Aloe vera-based extract of Nerium oleander leaves.

OBJECTIVE: To evaluate a blend of two natural ingredients on immune parameters relevant for their current topical use and potential support of microcirculation in skin tissue. MATERIALS AND METHODS: A blend (BL) of Aloe vera-based Nerium oleander extract (NAE-8i, oleandrin-free) and hydrolyzed water-soluble egg membrane (WSEM) was applied to human whole-blood cultures for 24 hours, with each separate ingredient serving as a control. Immune-cell subsets were analyzed for expression levels of the activation markers CD69 and CD25. Culture supernatants were analyzed for cytokines, chemokines, and immunoregulating peptides. RESULTS: BL increased CD69 expression on lymphocytes, monocytes, and CD3-CD56+ natural killer cells, and CD25 expression on natural killer cells. The number of CD69+CD25+ lymphocytes increased in cultures treated with BL and the separate ingredients. BL triggered production of multiple cytokines and chemokines, where CC chemokines MIP1α and MIP3α, as well as cytokines involved in wound healing - Groα, Groß, ENA78, and fractalkine - reached levels manyfold above treatment with either NAE-8i or WSEM alone. CONCLUSION: Data on BL showed that WSEM strongly enhanced NAE-8i's effects on immunoactivation in vitro. This has potential relevance for support of immunity in skin tissue, including antibacterial and antiviral defense mechanisms, wrinkle reduction, and wound care.

Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.

OBJECTIVE: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract natto from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. RESULTS: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05), and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006). A decrease in vWF was seen in the female population consuming nattokinase (P<0.1). In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h), an increase was seen for 66% of the people after 8-week consumption of nattokinase (P<0.1), in contrast to only 8% in the placebo group. CONCLUSION: The data suggest that nattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation.

The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism.

Support of Joint Function, Range of Motion, and Physical Activity Levels by Consumption of a Water-Soluble Egg Membrane Hydrolyzate.

This study evaluated the effects of consumption of hydrolyzed water-soluble egg membrane (WSEM) on joint function in an otherwise healthy population experiencing chronic pain. A randomized, double-blind, placebo-controlled crossover study included two 4-week periods of placebo and WSEM consumption, separated by a 4-week washout period. Twenty-five study participants were randomized to either the "placebo-first" or "WSEM first" sequence in the crossover trial, and 22 participants completed the study requirements. Range of motion (ROM) was assessed using digital inclinometry for joints associated with vertical weight bearing from neck to knees and for shoulders. Pain at rest and when physically active was scored for the same anatomical areas using visual analog scales (VAS). Physical functioning was tracked using questionnaires with VAS. Consumption of WSEM was associated with improved ROM for neck, spine, hips, and knees, with ROM for the neck and right knee being significantly improved during WSEM consumption compared to placebo (P < .05). ROM improvement for the dominant shoulder was highly significant during WSEM consumption (P < .01). Physical activity levels were significantly higher after WSEM than after placebo consumption (P < .05). Many aspects of physical functioning as part of daily living improved. Subgroup analysis showed rapid improvement of lower back pain after 5 days of WSEM consumption compared to placebo consumption (P < .05) in subjects who participated in the study during the winter season. Daily consumption of 450 mg WSEM was associated with improved joint function, comfort during daily activities, and increased physical activity.

Sleep in Schizophrenia: Pathology and Treatment.

Both subjective and objective assessments of sleep patterns in schizophrenia include a wide range of dyssomnias, with insomnia being the most frequently cited. Early and middle insomnia can range from mild disruption to total sleeplessness. Severe insomnia is a prodromal sign of clinical exacerbation or relapse. In general, most antipsychotic agents (APs) ameliorate this insomnia. However, in some schizophrenics APs can be associated with residual insomnia or with significant daytime somnolence. Furthermore, in some schizophrenics APs can induce or exacerbate comorbid sleep disorders such as restless legs syndrome, sleep-disordered breathing, and parasomnias such as sleepwalking.

Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (nae-8(®)).

OBJECTIVE: The goal for this study was to evaluate the effects of an Aloe vera-based Nerium oleander extract (NAE-8(®)), compared to an extract of A. vera gel alone (ALOE), and to an aqueous extract of N. oleander (AQ-NOE) in bioassays pertaining to dermatologic potential with respect to antioxidant protection, anti-inflammatory effects, and cytokine profiles in vitro. METHODS: Cellular antioxidant protection was evaluated in three separate bioassays: The cellular antioxidant protection of erythrocytes (CAP-e) assay, protection of cellular viability and prevention of apoptosis, and protection of intracellular reduced glutathione levels, where the last two assays were performed using human primary dermal fibroblasts. Reduction of intracellular formation of reactive oxygen species (ROS) was tested using polymorphonuclear cells in the absence and presence of oxidative stress. Changes to cytokine and chemokine profiles when whole blood cells and human primary dermal fibroblasts were exposed to test products were determined using a 40-plex Luminex array as a method for exploring the potential cross-talk between circulating and skin-resident cells. RESULTS: The NAE-8(®) provided significantly better antioxidant protection in the CAP-e bioassay than AQ-NOE. NAE-8(®) and AQ-NOE both protected cellular viability and intracellular reduced glutathione, and reduced the ROS formation significantly when compared to control cells, both under inflamed and neutral culture conditions. ALOE showed minimal effect in these bioassays. In contrast to the NAE-8(®), the AQ-NOE showed induction of inflammation in the whole blood cultures, as evidenced by the high induction of CD69 expression and secretion of a number of inflammatory cytokines. The treatment of dermal fibroblasts with NAE-8(®) resulted in selective secretion of cytokines involved in collagen and hyaluronan production as well as re-epithelialization during wound healing. CONCLUSION: NAE-8(®), a novel component of a commercial cosmetic product, showed beneficial antioxidant protection in several cellular models, without the induction of leukocyte activation and secretion of inflammatory cytokines. The biological efficacy of NAE-8(®) was unique from both ALOE and AQ-NOE.

Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: contribution to bioactivities by the non-phycocyanin aqueous fraction.

The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 µg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.

Oral intake of a liquid high-molecular-weight hyaluronan associated with relief of chronic pain and reduced use of pain medication: results of a randomized, placebo-controlled double-blind pilot study.

The goal for this study was to evaluate the effects of daily oral intake of a consumable liquid fermentate containing high-molecular-weight hyaluronan, as well as to perform a basic evaluation of safety and tolerability. A randomized, double-blind placebo-controlled study design was used to examine the effects of oral intake of hyaluronan on chronic pain conditions. Safety assessment included a complete blood count with differential, blood chemistry and electrocardiogram. The study duration was 4 weeks, where three tablespoons (45 mL) product or placebo was ingested during the first 2 weeks, and two tablespoons (30 mL) was consumed during the last 2 weeks. Seventy-eight people between the age of 19 and 71 years enrolled, and 72 people completed the study. Statistical analysis was performed using the two-tailed independent t-test for between-group significance and using the paired t-test for within-group significance. A reduction in pain scores was seen after 2 weeks of consumption of both placebo (P<.1) and active (P<.065) product; the reduction was more pronounced in the group consuming the active test product. Using "within-subject" analysis, a highly significant reduction in chronic pain scores was seen after 2 weeks of consumption of three tablespoons of active product (P<.001), whereas only a mild nonsignificant reduction in pain scores was seen in the placebo group. During the reduced intake for the last 2 weeks of study participation, pain scores showed a slight increase. During the last 2 weeks, a significant increase in the quality of sleep (P<.005) and level of physical energy (P<.05) was seen. The pain reduction during the initial 2 weeks was associated with significant reduction in the use of pain medication (P<.05). Consumption of an oral liquid formula containing high-molecular-weight hyaluronan was associated with relief of chronic pain.

Anti-inflammatory properties of a dried fermentate in vitro and in vivo.

The aim of this study was to document anti-inflammatory properties of a dried fermentate derived from Saccharomyces cerevisiae (EpiCor(®)), hereafter referred to as dried fermentate in vitro using cell-based bioassays, and in vivo using a skin irritation model in healthy humans. In vitro testing involved parallel assessment of primary human polymorphonuclear (PMN) cell formation of reactive oxygen species (ROS) and migration toward the inflammatory mediator Leukotriene B4. In vivo evaluation used a single-blind placebo-controlled design, where dermal histamine-induced inflammation was used as a model for the complex intercellular signals involved in the initiation, escalation, and resolution of the inflammatory response. Microvascular blood perfusion was evaluated using noninvasive laser Doppler probes applied to the inner forearms of 12 healthy human subjects, where parallel sites were treated with either dried fermentate or saline (placebo). Subjective scores of dermal irritation were also collected. Treatment of PMN cells in vitro resulted in reduced ROS formation and migratory activity toward Leukotriene B4. Clinical results demonstrated significantly reduced microvascular inflammatory responses to histamine-induced skin inflammation, and significantly reduced subjective scores of irritation at the inflamed sites treated with dried fermentate compared with the sites treated with placebo (P<.05). Treatment of inflammatory cells in vitro with dried fermentate resulted in reduced inflammatory responses. This was confirmed in vivo, suggesting that the dried fermentate facilitates the resolution of inflammatory responses. The effects using a topical skin model suggest that similar events may happen when the dried fermentate is introduced across mucosal membranes after consumption.

Trauma exposure and PTSD in women with schizophrenia and coexisting substance use disorders: comparisons to women with severe depression and substance use disorders.

The present study compared rates of trauma exposure and PTSD among three groups of women at high trauma risk: those with substance use disorders (SUD) and schizophrenia (n=42), those with SUD and severe, nonpsychotic depression (n=38), and those with SUD and no other DSM-IV Axis I condition (n=37). We hypothesized that exposure to traumatic stressors and current diagnosis of PTSD would be more common in women with schizophrenia and SUD, when compared to the other two groups. Results indicate that women with schizophrenia and SUD had a more extensive trauma history than women with SUD only, and were also more likely to have PTSD. Women with schizophrenia had a fourfold greater likelihood of meeting criteria for current PTSD than were women with severe, nonpsychotic depression when potential confounds of age, race, education, severity of trauma history, and childhood trauma exposure were controlled. These results lend support to the possibility that women with psychosis have an elevated vulnerability to PTSD symptomology when exposed to life stressors that is distinct from the vulnerability associated with coexisting nonpsychotic SMI. The psychological sequelae of trauma are substantial and should be addressed in women seeking treatment for schizophrenia and problematic substance use.

Consumption of dried apple peel powder increases joint function and range of motion.

The goal for this study was to evaluate the effects of consumption of dried apple peel powder (DAPP) on joint function and range of motion (ROM). Additional in vitro and clinical testing was performed to suggest specific mechanisms of action. An open-label clinical pilot study involved 12 healthy people with moderate loss of joint ROM and associated chronic pain. The subjects consumed 4.25 g DAPP daily for 12 weeks, with evaluations at baseline, 2, 4, 8, and 12 weeks. ROM was evaluated at each visit using dual digital inclinometry. Pain scores were collected using Visual Analogue Scales. Blood draws enabled testing of serum antioxidant protective capacity using the cellular antioxidant protection (CAP-e) bioassay. Additional in vitro testing involved testing of cyclooxygenase-2 (COX-2) and lipoxygenase inhibition, cellular antioxidant protection by the CAP-e bioassay, and formation of reactive oxygen species (ROS) by polymorphonuclear (PMN) cells by flow cytometry. Twelve weeks of consumption of DAPP was associated with improved ROM. DAPP provided antioxidants that were available to enter into and protect cells from oxidative damage in vitro, and consumption of DAPP for 12 weeks was associated with a statistically significant improvement in serum antioxidant protective status. DAPP inhibited both COX-2 and lipoxygenase enzymes, and pretreatment of inflammatory PMN cells with DAPP before inflammatory stimulus resulted in reduced ROS formation. This suggests multifaceted anti-inflammatory properties of DAPP. Consumption of DAPP was associated with improved joint function and improved serum antioxidant protection status. The observed pain reduction may be associated with the improved antioxidant status and linked to the apple polyphenols' anti-inflammatory effects.

Clinical efficacy of a West African sorghum bicolor-based traditional herbal preparation Jobelyn shows increased hemoglobin and CD4+ T-lymphocyte counts in HIV-positive patients.

OBJECTIVES: The purpose of this study was to evaluate a traditional herbal preparation, Jobelyn,® for its effects on anemia and CD4+ T-cell counts in human immunodeficiency virus-positive (HIV+) patients in Nigeria. DESIGN: An open-label pilot study involving 10 confirmed (HIV+) patients who were not receiving antiretroviral therapy (ARVT) was performed, in which the patients consumed Jobelyn for 8 weeks, at a dose of 500 mg twice daily. The pilot study was followed by a controlled trial involving 51 patients, all confirmed HIV+, where the patients with CD4+ T-cell counts below 350 cells/µL were receiving ARVT. The eight patients with baseline CD4+ T-cell counts above 350 cells/µL received Jobelyn. The remaining patients who all received ARVT were randomized to ARVT alone versus ARVT+Jobelyn for 12 weeks. RESULTS: Patients receiving ARVT showed a statistically significant improvement in their CD4+ T-cell counts across the 12-week study period (p<0.01). Patients receiving ARVT+Jobelyn showed a faster improvement, reaching a high level of statistical significance compared to baseline already at 6 weeks (p<0.001), and remained highly significant at 12 weeks (p<0.001). CONCLUSIONS: This is the first controlled study conducted to evaluate efficacy of Jobelyn on immune status in HIV+ patients. The data suggest that consumption of Jobelyn contributed to improved hemoglobin levels and increased CD4+ T-cell counts in Nigerian HIV+ patients. Further studies are needed to examine similar effects in other populations, and to elaborate on the underlying mechanisms, specifically, whether the consumption of Jobelyn supported multiple aspects of bone marrow function.

Increased Rostral Anterior Cingulate Cortex Volume in Chronic Primary Insomnia.

BACKGROUND: Recent studies document alterations in cortical and subcortical volumes in patients with chronic primary insomnia (PI) in comparison with normal sleepers. We sought to confirm this observation in two previously studied PI cohorts. METHODS: Two separate and independent groups of unmedicated patients who met Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) criteria for PI were compared with two separate, healthy control groups (Study 1: PI = 20, controls = 15; Study 2: PI = 21, controls = 20). Both studies included 2 weeks of sleep diaries supplemented by wrist actigraphy. The 3.0 T MRI-derived rostral anterior cingulate cortex (rACC) volumes were measured with FreeSurfer image analysis suite (version 5.0) and results normalized to total intracranial volume (ICV). Unpaired t-tests (two-tailed) were used to compare rACC volumes between groups. Post hoc correlations of rACC volumes to insomnia severity measures were performed (uncorrected for multiplicity). RESULTS: Both studies demonstrated increases in normalized rACC volume in PI compared with control patients (Study 1: right side P = 0.05, left side P = 0.03; Study 2: right side P = 0.03, left side P = 0.02). In PI patients from Study 1, right rACC volume was correlated with sleep onset latency (SOL) by both diary (r = 0.51, P = 0.02) and actigraphy (r = 0.50, P = 0.03), and with sleep efficiency by actigraphy (r = -0.57, P = 0.01); left rACC volume was correlated with SOL by diary (r = 0.48, P = 0.04), and wake after sleep onset (WASO) (r = 0.49, P = 0.03) and sleep efficiency (r = -0.49, P = 0.03) by actigraphy. In Study 2, right rACC volume was correlated with SOL by diary (r = 0.44, P = 0.05) in PI patients. CONCLUSIONS: Rostral ACC volumes are larger in patients with PI compared with control patients. Clinical severity measures in PI correlate with rACC volumes. These data may reflect a compensatory brain response to chronic insomnia and may represent a marker of resilience to depressive illness. CITATION: Winkelman JW; Plante DT; Schoerning L; Benson K; Buxton OM; O'Connor SP; Jensen JE; Renshaw PF; Gonenc A. Increased rostral anterior cingulate cortex volume in chronic primary insomnia. SLEEP 2013;36(7):991-998.

Energetic and cell membrane metabolic products in patients with primary insomnia: a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla.

STUDY OBJECTIVES: Primary insomnia (PI) is a sleep disorder characterized by difficulty with sleep initiation, maintenance, and/or the experience of nonrestorative sleep combined with a subsequent impairment of daytime functioning. The hyperarousal hypothesis has emerged as the leading candidate to explain insomnia symptoms in the absence of specific mental, physical, or substance-related causes. We hypothesized that the cellular energetic metabolites, including beta nucleoside triphosphate, which in magnetic resonance spectroscopy approximates adenosine triphosphate (ATP), and phosphocreatine (PCr), would show changes in PI reflecting increased energy demand. DESIGN AND SETTING: Matched-groups, cross-sectional study performed at two university-based hospitals. PATIENTS: Sixteen medication-free individuals (eight males, eight females; mean ± standard deviation (SD) age = 37.2 ± 8.4 y) with PI and 16 good sleepers (nine males, seven females; mean ± SD age = 37.6 ± 4.7 y). MEASUREMENTS: Diagnosis was established for all individuals by unstructured clinical interview, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), sleep diary, and actigraphy. Polysomnography was collected in individuals with PI. Phosphorous magnetic resonance spectroscopy (31P MRS) data were collected on all individuals at 4 Tesla. We assessed cell membrane (anabolic precursors and catabolic metabolites) and bioenergetic (ATP, phosphocreatine) metabolites in gray matter and white matter to determine their relationship to the presence and severity of PI. RESULTS: Individuals with PI showed lower phosphocreatine in gray matter and an unexpected decrease of phosphocholine, a precursor of the cell membrane compound phosphatidylcholine, in white matter. In addition, there was a trend toward a negative association between polysomnographically determined wake after sleep onset and gray matter beta-nucleoside triphosphate and white matter phosphocholine in the primary insomnia group. CONCLUSIONS: These results support the hyperarousal hypothesis in PI based on lower phosphocreatine in gray matter in the PI group.