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Over the last 15 years there has been an accumulation of data supporting the concept of a gut-brain axis whereby dysbiosis of the gut microbiota can impact neurological function. Such dysbiosis has been suggested as a possible environmental exposure triggering multiple sclerosis (MS). Dysbiosis has been consistently shown to result in a reduction in short-chain fatty acid (SCFA) producing bacteria and a reduction in stool and plasma levels of propionate has been shown for MS patients independent of disease stage and in different geographies. A wealth of evidence supports the action of propionate on T-cell activity, resulting in decreased T-helper cell 1 (Th1) and T-helper cell 17 (Th17) numbers/activity and increased regulatory T cell (Treg cell) numbers/activity and an overall anti-inflammatory profile. These different T-cell populations play various roles in the pathophysiology of MS. A recent clinical study in MS patients demonstrated that supplementation of propionate reduces the annual relapse rate and slows disease progression. This review discusses this data and the relevant mechanistic background and discusses whether taming of the overactive immune system in MS is likely to allow easier bacterial and viral infection.

The nutritional management of depression has long been discussed, due to the perceived benefit of a nutritional product having less side effects than pharmaceutical agents. Candidate nutrients for managing depression include vitamin D, B vitamins, tryptophan, branch chain amino acids, probiotics, omega-3 fatty acids, folate/methylfolate (also known as vitamin B9), and s-adenosylmethionine. This paper provides a narrative review of three nutrients which have significant scientific support for the management of depression. A deficiency in each nutrient is associated with depression, and interventional studies indicate that the correction of the nutritional deficiency may provide clinical benefit. We present epidemiological evidence, a mechanistic explanation and a review of interventional studies for these nutrients. Finally, relevant nutritional guidelines are presented with their conclusion for the role of each nutrient in the management of depression.

Introduction: A recently performed meta-analysis of the effects of omega-3 fatty acids (O3FA: EPA and DHA) on NAFLD patients showed reduced steatosis and beneficial effects on liver enzymes. O3FA have a variety of effects including membrane fluidity maintenance by incorporation into the cell membrane phospholipids, lipid regulation via activation of nuclear receptors, anti-inflammatory effects through various pathway such as NF-kB, competition with omega-6 metabolism, and a potential role as signaling molecules and in formation of lipid rafts. Here we present lipidomic profiling of serum samples collected as part of a randomized placebo controlled study of the effects of O3FA administration in patients with NAFLD. Methods: 172 subjects with ultrasound-confirmed fatty livers were randomized to 3 g/d EPA+DHA or an olive oil placebo and took daily capsules for 24 weeks. Serum samples were taken at baseline, and 24 weeks. Samples from 120 subjects were analysed using UHPLC-MS for 233 lipid metabolites (OWL, Spain). Differences were statistically determined using the paired or unpaired (dependent on the data type) students t-test on log2 change. Results: Significant changes in numerous bioactive lipid metabolites was seen in the O3FA intervention group compared to placebo, particularly in the glycerophospholipids PE, LPE, PC, and LPC. An overall decrease in diglycerides and triglycerides with shorter chain fatty acids was seen whereas an increase was seen in triglycerides with increased fatty acid chain length and double bond number, reflecting EPA and DHA incorporation into these molecules. Some ceramide and sphingolipid species were also significantly decreased in the O3FA group. Conclusion: O3FA supplementation has previously been shown to increase the omega-3 index in NAFLD patients and to have beneficial effects at daily doses at or above 3 g EPA+DHA. Here we show that bioactive lipid species often associated with poor prognosis (diglycerides, ceramides and sphingolipids) are decreased, and beneficial lipid species in particular, PE, LPE, PC and LPC are increased after O3FA intervention. Of particular interest is the change in the bioactive lipids such as LPCs, which may facilitate omega-3 effects associated with NAFLD. O3FA significantly decreased the plasma triglyceride concentration as expected; this lipidomic analysis demonstrated that O3FA significantly shifts the trigflyceride species profile with longer fatty acyl-chain and greater unsaturation.

This randomized controlled trial investigated the safety and efficacy of MF4637, a high concentrate omega-3 fatty acid preparation, in correcting the omega-3 fatty acid nutritional deficiency in non-alcoholic fatty liver disease (NAFLD). The primary end point of the study was set as the change of red blood cell (RBC) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by MF4637. Whether the omega-3 concentrate could lower liver fat was evaluated in a subset of patients. Furthermore, 176 subjects with NAFLD were randomized to receive the omega-3 concentrate (n = 87) or placebo (n = 89) for 24 weeks, in addition to following standard-of-care dietary guidelines. The omega-3 index, omega-6: omega-3 fatty acid ratio and quantitative measurements of RBC EPA and DHA were determined at baseline and study completion. Magnetic resonance imaging of liver fat was conducted in a subset of patients. Administration of high concentrate omega-3 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the RBC omega-6: omega-3 fatty acid ratio (p < 0.0001). A significant reduction in liver fat content was reported in both groups.

Exposure of mammalian skin to UV light results in induced gene transcription, playing a role in inflammation, immunosuppression, and tumor promotion. One important group of transcription factors induced by UV radiation is composed of members of the Rel/NF-κ B family, which are known to play a major role in the transcriptional activation of many genes encoding inflammatory cytokines, adhesion molecules, and viral proteins. However, the upstream events in the transduction of the UVB signal to Rel protein activity are, as yet, unknown. Here, we provide biochemical evidence that exposure of keratinocytes to UVB causes rapid association of tumor necrosis factor (TNF) receptor 1 with its downstream partner TRAF-2. The functional relevance of this association is demonstrated by experiments showing that expression of a dominant negative TNF receptor 1 or TRAF-2 protein inhibits UVB-induced Rel-dependent transcription. Inclusion of a neutralizing antibody toward TNFα has no effect on UVB activation of a Rel-responsive reporter gene. Therefore, UVB-induced activation of Rel proteins via TNF receptor 1, independent of ligand activation, is a key component in the UV response in keratinocytes.

This exciting new book addresses the important issue of how to provide integrated mental health and substance misuse treatment of individuals with these co-occurring disorders. Combining both theory and practice, by the use of illustrative clinical case material, it provides a survey of different approaches to the integration of mental health and substance misuse services. A unique collection of chapters, from authors who are experts in the field and pioneering innovative approaches, provides an international perspective (including UK, Germany, Australia, USA, Canada) of treatment. Arranged in five sections, Section 1 provides an introduction to the issue of substance misuse amongst those with psychosis. Section 2 introduces a range of integrated service models from different countries. The third section provides a practical hands-on guide to assessment and treatment. The fourth section addresses the specific treatment needs of special population groups (including young people, forensic groups, homeless people and those with HIV/AIDS). The final section examines treatment outcome studies and implications for the future. Clinical psychologists, psychiatrists, nurses, case managers, and psychiatric social workers in training and practice in clinic, hospital and community settings will find this book an essential practical resource for working with individuals (and their families) with co-occurring disorders.

Acute inpatient ward staff work with service users who have comorbid mental health and substance misuse problems (dual diagnosis) on a daily basis. Department of Health (DH) guidance for working with this group (DH, 2002; DH, 2006) indicates that training is needed to equip staff with the confidence and skills for this work. This paper describes how the COMPASS Programme, Birmingham and Solihull Mental Health Foundation Trust's (BSMHT) dual diagnosis service, developed, delivered and evaluated a training programme designed to support inpatient staff in this work.

The present study was a proof-of-concept study to provide an initial indication of the efficacy and safety of imaging malignant breast tumors using (99m)Tc-NC100692. The agent is a small peptide with high affinity for integrin receptors that are upregulated and expressed preferentially on proliferating endothelial cells. Sixteen patients with suggestive mammographic findings and 4 patients with benign lesions were included. The \"standard of truth\" was based on the histopathologic diagnosis of the recruited patients. All subjects received up to 75 microg of (99m)Tc-NC100692 with an average (99m)Tc activity of 694 MBq (range, 561-747 MBq). Safety endpoints were treatment-emergent adverse events (AEs) and changes in a limited physical examination, electrocardiogram (ECG) recordings, blood biochemistry, hematology, coagulation, vital signs, and urine analysis after administration of (99m)Tc-NC100692 and throughout the 24-h follow-up. Static images and SPECT were acquired between 40 min and 2.5 h after injection of the agent. Two experienced nuclear medicine physicians read the images in a nonblinded fashion. Nineteen of 22 malignant lesions were detected using (99m)Tc-NC100692 scintigraphy. Twenty lesions confirmed as malignant by histopathology were seen on mammography or ultrasound. Two additional lesions were identified from histopathology alone. Safety parameters evaluated through the follow-up period of 2.5 h included clinical laboratory tests, vital signs, and ECG. Five of 20 subjects experienced nonserious AEs, and all AEs were classified as mild. One subject experienced an AE (dysgeusia) possibly related to administration of (99m)Tc-NC100692. This AE was mild and lasted only for a few minutes. No deaths, serious AEs, or withdrawals due to AEs occurred during the study. Nineteen of 22 malignant lesions (86%) were clearly detected via scintigraphic imaging after administration of (99m)Tc-NC100692. Overall, the efficacy data in subjects with suspected breast lesions suggest that (99m)Tc-NC100692 scintigraphy may be effective in detecting malignant lesions. The use of (99m)Tc-NC100692 in subjects with breast cancer is safe and well tolerated. Further studies are warranted to assess the clinical potential of (99m)Tc-NC100692.

Assertive outreach teams are working with a significant proportion of people with complex needs, including dual diagnosis. Government policy has highlighted the role of assertive outreach in engaging and intervening with this group. This paper reports on the development and evaluation of a specific teamfocused training package and its trial in the Eastern and West Midlands regions.

Assertive outreach teams are working with a significant proportion of people with complex needs, including dual diagnosis. Government policy has highlighted the role of assertive outreach in engaging and intervening with this group. This paper reports on the development and evaluation of a specific team-focused training package and its trial in the Eastern and West Midlands regions.