Managing bipolar depression:a therapeutic challenge?

Most people with bipolar disorder first seek treatment for depressive rather than manic symptoms. However, effective management of bipolar depression remains a challenge. In this review, Celia Feetam highlights how bipolar depression differs from unipolar depression both in its characteristics and in the approach to its treatment. © 2011 John Wiley & Sons, Ltd.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

An ethnopharmacological approach to multidrug -resistant Staphylococcus aureus: Evaluation of Italian plants used in the traditional healing of skin disease

One-third of botanical remedies from southern Italy are used to treat skin and soft tissue infections (SST's). Methicillin-resistant Staphylococcus aureus (MRSA), a common cause of SSTIs, is responsible for increased morbidity and mortality from infections. Therapeutic options are limited by antibiotic resistance. Many plants possess potent antimicrobial compounds for these disorders. Validation of traditional medical practices is important for the people who rely on medicinal plants. Moreover, identification of novel antibiotics and anti-pathogenic agents for MRSA is important to global healthcare.^ I took an ethnopharmacological approach to understand how Italian medicinal plants used for the treatment of SSTIs affect MRSA growth and virulence. My hypothesis was that plants used in folk remedies for SSTI would exhibit lower cytotoxicity and greater inhibition of bacterial growth, biofilm formation and toxin production in MRSA than plants used for remedies unrelated to the skin or for plants with no ethnomedical application. The field portion of my research was conducted in the Vulture-Alto Bradano area of southern Italy. I collected 104 plant species and created 168 crude extracts. In the lab, I screened samples for activity against MRSA in a battery of bioassays. Growth inhibition was analyzed using broth microtiter assays for determination of the minimum inhibitory concentration. Interference with quorum-sensing (QS) processes, which mediate pathogenicity, was quantified through RP-HPLC of δ-toxin production. Interference with biofilm formation and adherence was assessed using staining methods. The mammalian cytotoxicity of natural products was analyzed using MTT cell proliferation assay techniques.^ Although bacteriostatic activity was limited, extracts from six plants used in Italian folk medicine (Arundo donax, Ballota nigra, Juglans regia, Leopoldia comosa, Marrubium vulgare, and Rubus ulmifolius ) significantly inhibited biofilm formation and adherence. Moreover, plants used to treat SSTI demonstrated significantly greater anti-biofilm activity when compared to plants with no ethnomedical application. QSI activity was evident in 90% of the extracts tested and extracts from four plants ( Ballota nigra, Castanea saliva, Rosmarinus officinalis, and Sambucus ebulus) exhibited a significant dose-dependent response. Some of the plant remedies for SSTI identified in this study can be validated due to anti-MRSA activity.^

Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20–32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD– and the sequence motifs –VALGAVSK– or –GKAAL(N/G/S) (V/A)V– in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77 μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3–fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11 μM). CZS-1 reached 100% haemolysis at 120.87 μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use.

A Cognitive Behavioural Therapy approach to Suicide Assessment and Intervention

An evaluation of training delivered to undergraduate nursing students on the therapeutic benefits and efficacy of the application of a basic CBT model and the use of simple CBT techniques for the assessment and intervention of service users with suicidal intent.

Therapeutic Potential of RNAi Through Endocytotic Methods

The ability to manipulate gene expression promises to be an important tool for the management of infectious diseases and genetic disorders. However, a major limitation to effective delivery of therapeutic RNA to living cells is the cellular toxicity of conventional techniques. Team PANACEA’s research objective was to create new reagents based on a novel small-molecule delivery system that uses a modular recombinant protein vehicle consisting of a specific ligand coupled to a Hepatitis B Virus-derived RNA binding domain (HBV-RBD). Two such recombinant delivery proteins were developed: one composed of Interleukin-8, the other consisting of the Machupo Virus GP1 protein. The ability of these proteins to deliver RNA to cells were then tested. The non-toxic nature of this technology has the potential to overcome limitations of current methods and could provide a platform for the expansion of personalized medicine.

Postoperative Treatment in a Patient After Hemithyroidectomy: the Therapeutic Challenges of a Hidden Thyrotropinoma

Objectives: We report the unusual case of a patient with a thyrotropinoma, discovered after a hemithyroidectomy for a suspicious thyroid nodule, and its therapeutic challenges. Materials and methods: In a patient who underwent hemithyroidectomy for cold thyroid nodule, hyperthyroid symptoms persisted, despite stopping levothyroxine treatment. Further investigation was carried out through the following laboratory tests: thyroid-stimulating hormone (TSH) test; free thyroxine (fT4) test; and the thyrotropin releasing hormone (TRH) test. A pituitary magnetic resonance imaging (MRI) scan and genetic analysis was also carried out. The test results confirmed the diagnosis of a thyrotropinoma. Results: Treatment with long-acting somatostatin analogues normalised thyroid hormones and symptoms of hyperthyroidism. Conclusion: The diagnostic approach to the thyroid nodule should include a detailed clinical and biochemical examination. Initial biochemical evaluation by TSH alone does not allow detecting inappropriate TSH secretion that may increase the risk of thyroid malignancy. In case of a thyrotropinoma, the ideal treatment consists of combined care of central and peripheral thyroid disease.

Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children’s respiratory diseases: the experience of a unique pediatric unit in Tunisia.

Objective: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children’s respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. Methods: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. Results: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). Conclusion: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician. Keywords:

Chapter 1 - Play Therapy: A Non-directive approach for children and adolescents

The book provides a detailed practical guide to non-directive play therapy as a therapeutic model. Substantially updated since the first edition published ten years ago, it sets play therapy within a Piagetian framework and using numerous case examples, demonstrates that it is a robust and relatively short-term intervention which may be used to address the difficulties of a range of troubled children and young adolescents. New chapters include using drawings, role play and structured exercises in working with children and young people, and using non-directive play therapy within statory and court settings.

Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach

Background and Purpose: At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size. Methods: Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta meta-analysis to obtain a summary measure of the impact of the various design characteristics. Results: Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score. Conclusions: We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

Biotechnological, nutritional and therapeutic uses of Pleurotus spp. (Oyster mushroom) related with its chemical composition: A review on the past decade findings

The particular characteristics of growth and development of mushrooms in nature result in the accumulation of a variety of secondary metabolites, several of them with biological activities. The genus Pleurotus is a cosmopolitan group of mushrooms with high nutritional value and therapeutic properties, besides a wide array of biotechnological and environmental applications. Scope and approach: The present report aims to provide a critical review on aspects related to chemical compounds isolated from the genus Pleurotus with possible biotechnological, nutritional and therapeutic uses. Investigations on the genus have immensely accelerated during the last ten years, so that only reports published after 2005 have been considered. Key findings and conclusions: The most important Pleurotus species cultivated in large scale are P. ostreatus and P. pulmonarius. However, more than 200 species have already been investigated to various degrees. Both basidiomata and mycelia of Pleurotus are a great renewable and easily accessible source of functional foods/nutraceuticals and pharmaceuticals with antioxidant, antimicrobial, anti-inflammatory, antitumor and immunomodulatory effects. A series of compounds have already been precisely defined including several polysaccharides, phenolics, terpenes and sterols. However, intensification of structure determination is highly desirable and demands considerable efforts. Further studies including clinical trials need to be carried out to ascertain the safety of these compounds as adequate alternatives to conventional drugs. Not less important is to extend the search for novel bioactives to less explored Pleurotus species.

A New Multi-Objective Approach for Molecular Docking Based on RMSD and Binding Energy

Ligand-protein docking is an optimization problem based on predicting the position of a ligand with the lowest binding energy in the active site of the receptor. Molecular docking problems are traditionally tackled with single-objective, as well as with multi-objective approaches, to minimize the binding energy. In this paper, we propose a novel multi-objective formulation that considers: the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands and the binding (intermolecular) energy, as two objectives to evaluate the quality of the ligand-protein interactions. To determine the kind of Pareto front approximations that can be obtained, we have selected a set of representative multi-objective algorithms such as NSGA-II, SMPSO, GDE3, and MOEA/D. Their performances have been assessed by applying two main quality indicators intended to measure convergence and diversity of the fronts. In addition, a comparison with LGA, a reference single-objective evolutionary algorithm for molecular docking (AutoDock) is carried out. In general, SMPSO shows the best overall results in terms of energy and RMSD (value lower than 2A for successful docking results). This new multi-objective approach shows an improvement over the ligand-protein docking predictions that could be promising in in silico docking studies to select new anticancer compounds for therapeutic targets that are multidrug resistant.

Initial approach to irst-time seizures in pediatrics

Objective: Prove that conducting complementary studies at laboratories and imaging studies are unnecessary in irst-time unprovoked seizures, since there is no change in the evolution and prognosis of the disease, as well as the study of our population, the incidence rate and the proportion of our patients that have been studied and given maintenance treatment, so it can be determined whether or not our population should follow the suggestions of the American Academy of Pediatrics and the Spanish Pediatric Association. Methods: An observational study, including patients diagnosed with irst-time unprovoked seizures. They were followed up on by the emergency department and information was collected from their clinical history and compared with the results of the different studies between patients that suffered just one seizure and the ones that had recurrent seizures. Results: Thirty one patients were included, 14 males and 17 females. The average age was 5.5 years old. The 100% of patients were studied, and the groups were compared. The signiicant study was the electroencephalogram (EEG) with a p=0.02 (signiicance p<0.05), incidence of 41%. Conclusions: The study and diagnosis of irst-time unprovoked seizures is based on clinical manifestations. The EEG is important in the study and classiication of unprovoked seizures. Our population has an incidence and recurrence rate similar to that in the bibliography, and for that reason, this study suggests that the diagnostic and therapeutic guidelines of the American Academy of Pediatrics and the Spanish Pediatric Association should be followed.

Nutritional approach of inpatients with anorexia nervosa

Anorexia nervosa (AN) is the most prevalent of eating disorders in children and adolescents, and its treatment is long and complex, involving a multidisciplinary team. Nutritional rehabilitation and restoration of a healthy body weight is one of the central goals in the initial stages of inpatient treatment. However, current recommendations on initial energy requirements for these patients are inconsistent, with a clear lack of controlled studies, available scientific evidence and global consensus on the most effective and safe refeeding practices in hospitalized adolescents with anorexia nervosa (AN). Conservative refeeding recommendations have been classically established in order to prevent the refeeding syndrome. Nevertheless, various works have recently appeared advocating a higher initial caloric intake, without observing more complications or refeeding syndrome, and allowing a shorter average stay. We present our experience in the treatment of restricting AN with a conservative progressive treatment. We have obtained good results with this approach, which was well tolerated by patients, with no observing complications. As a consequence, the medical team could establish a pact about the therapeutic goals with the patients in an easier way.

Serious games applied to attention deficithyperactivity disorder: development of two games for therapeutic purpose

Attention Deficit-Hyperactivity Disorder is a disease that affects 3 to 5 percent of children globally. Many of those live in areas with very few or no medical professionals qualified to help them. To help assuage this problem a system was developed that allows physicians to accompany their patient’s progress and prescribe treatments. These treatments can be drugs or behavioral exercises. The behavioral exercises were designed in the form of games in order to motivate the patients, children, for the treatment. The system allows the patients to play the prescribed games, under the supervision of their tutors. Each game is designed to improve the patient’s handling of their disease through training in a specific mental component. The objective of this approach is to complement the traditional form of treatment by allowing a physician to prescribe therapeutic games and maintaining the patients under supervision between their regular consultations. The main goal of this project is to provide the patients with a better control of their symptoms that with just traditional therapy. Experimental field tests with children and clinical staff, offer promising results. This research is developed in the context of a financed project involving INESC C (Polytechnic Institute of Leiria delegation), the Santo André Hospital of Leiria, and the start-up company PlusrootOne (that owns the project).