Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 2 new and emerging therapies and their efficacy

In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes.

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies

Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS.

MicroRNA pathways : an emerging role in identification of therapeutic strategies

For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.

Nanocapsules loaded with iron-saturated bovine lactoferrin have antimicrobial therapeutic potential and maintain calcium, zinc and iron metabolism

Aim: This study aimed to evaluate the potential antimicrobial efficacy of alginate gel-encapsulated ceramic nanocarriers loaded with iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (AEC-CP-Fe-bLf NCs). Materials & methods: The antimicrobial activities of non-nanoformulated apo (iron free), Fe-bLf and native forms of Australian bLf against pathogenic Salmonella typhimurium (wild strain) were studied in vitro. The efficacy of AEC-CP-Fe-bLf NCs were checked in vivo using Balb/c mice model. Results: The study revealed that native bLf is more effective in combating infection than the conventional drug ciprofloxacin (0.4 mg/ml). The efficacy of the drug was also revealed in vivo when BALB/c mice that, after being challenged with S. typhimurium (200 μl of 10(8) CFU/ml suspension), were fed orally with a nanoformulated bLf diet and the infection was observed to be eliminated. However, chronic infection developed in the group of infected mice that did not receive any drug treatment, as well as the mice treated with ciprofloxacin. The immune response to bacterial infection and to various drug treatments thereafter was studied in the mice. Conclusion: The study concludes that bLf and nanoformulated Fe-bLf are more effective in the treatment of Salmonella-infected mice than ciprofloxacin.

Adherence to therapeutic guidelines for patients with community-acquired pneumonia in Australian hospitals

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, particularly in elderly patients, and is associated with a considerable economic burden on the healthcare system. The combination of high incidence and substantial financial costs necessitate accurate diagnosis and appropriate management of patients admitted with CAP. This article will discuss the rates of adherence to clinical guidelines, the use of severity scoring tools and the appropriateness of antimicrobial prescribing for patients diagnosed with CAP. The authors maintain that awareness of national and hospital guidelines is imperative to complement the physicians' clinical judgment with evidence-based recommendations. Increased use of pneumonia severity assessment tools and greater adherence to therapeutic guidelines will enhance concordant antimicrobial prescribing for patients with CAP. A robust and multifaceted educational intervention, in combination with antimicrobial stewardship programs, may enhance compliance of CAP guidelines in clinical practice in Australia.

Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

Nonparametric discovery of learning patterns and autism subgroups from therapeutic data

Autism Spectrum Disorder (ASD) is growing at a staggering rate, but, little is known about the cause of this condition. Inferring learning patterns from therapeutic performance data, and subsequently clustering ASD children into subgroups, is important to understand this domain, and more importantly to inform evidence-based intervention. However, this data-driven task was difficult in the past due to insufficiency of data to perform reliable analysis. For the first time, using data from a recent application for early intervention in autism (TOBY Play pad), whose download count is now exceeding 4500, we present in this paper the automatic discovery of learning patterns across 32 skills in sensory, imitation and language. We use unsupervised learning methods for this task, but a notorious problem with existing methods is the correct specification of number of patterns in advance, which in our case is even more difficult due to complexity of the data. To this end, we appeal to recent Bayesian nonparametric methods, in particular the use of Bayesian Nonparametric Factor Analysis. This model uses Indian Buffet Process (IBP) as prior on a binary matrix of infinite columns to allocate groups of intervention skills to children. The optimal number of learning patterns as well as subgroup assignments are inferred automatically from data. Our experimental results follow an exploratory approach, present different newly discovered learning patterns. To provide quantitative results, we also report the clustering evaluation against K-means and Nonnegative matrix factorization (NMF). In addition to the novelty of this new problem, we were able to demonstrate the suitability of Bayesian nonparametric models over parametric rivals.

Orally administered anti-cancer nanocarriers loaded with therapeutic proteins

 Anti-cancerous ability of orally fed therapeutic proteins was potentiated by further strengthening their digestive resistance by means of nano encapsulation. In this regard, formulation of a novel polymer encapsulated ceramic anti-cancer nanocarriers (ACSC NCs) loaded with anti-cancer proteins (Fe-bLf and SurR9-C84A) were synthesized. These NCs were successfully evaluated for their anti-cancer efficacy in vitro and in nude mice bearing human cancers.

Diet and bipolar disorder: a review of its relationship and potential therapeutic mechanisms of action

OBJECTIVES: It is well accepted that diet quality has an important role in the prevention and treatment of several physical diseases. However, its influence on mental health has received far less attention, although there is increasing evidence to support a relationship with depression. In this narrative review, investigations into the relationship between diet and bipolar disorder are examined and the potential implications in the management and treatment of bipolar disorder are reviewed. METHODS: The authors provide a narrative review of the relevant information. RESULTS: Research is limited, although there are preliminary findings to suggest a relationship between diet and bipolar disorder. Findings from cross-sectional research suggest that people with bipolar disorder consume an unhealthier dietary pattern. This has significant treatment implications as bipolar disorder has a high comorbidity with several physical diseases. In addition, diet also influences several biological processes that are dysregulated in bipolar disorder, namely monoaminergic activity, immune/inflammatory processes, oxidative stress, mitochondrial activity, and neuroprogression. CONCLUSIONS: The role of diet in bipolar disorder requires further attention in research as it presents as a factor that may contribute to the worsening course of this condition and may potentially enhance current treatment outcomes.

The therapeutic alliance and personality dysfunction in offending behaviour programs

 Therapists in offending behaviour programs use a range of strategies to develop the therapeutic alliance to promote treatment collaboration. They described significant difficulties, however, in responding to personality dysfunction. Analysis of treatment sessions revealed therapists often attempted to engage clients but did not often use ruptures in the alliance as therapeutic opportunities or attend to withdrawn clients. Recommendations are made to better support correctional therapists utilise the alliance to maximise treatment