World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia Part 3: Update 2015 Management of special circumstances: Depression,Suicidality, substance use disorders and pregnancy and lactation

These updated guidelines are based on the first edition of the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia published in the years 2005 and 2006. For this 2015 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations which are clinically and scientifically relevant. They are intended to be used by all physicians diagnosing and treating patients with schizophrenia. Based on the first version of these guidelines a systematic review, as well as a data extraction from national guidelines have been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and subsequently categorised into six levels of evidence (A–F) and five levels of recommendation (1–5). This third part of the updated guidelines covers the management of the following specific treatment circumstances: comorbid depression, suicidality, various comorbid substance use disorders (legal and illegal drugs), and pregnancy and lactation. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication and other pharmacological treatment options) of patients with schizophrenia.     

A 12 month clinical study of bond failures of recycled versus new stainless steel orthodontic brackets

The purpose of this prospective longitudinal randomized study was to compare the clinical performance of recycled brackets with that of new stainless steel brackets (Orthos). Twenty patients treated with fixed appliances were included in the investigation. Using a 'split-mouth' design, the dentition of each patient was divided into four quadrants. In 11 randomly selected patients, the maxillary left and mandibular right quadrants were bonded with recycled brackets, and the remaining quadrants with new stainless steel brackets. In the other nine patients the quadrants were inverted. Three hundred and ten stainless steel brackets were examined: 156 were recycled and the remaining 154 were new. All the brackets were bonded with a self-cured resin-modified glass ionomer (GC Fuji Ortho). The number, cause, and date of bracket failures were recorded over 12 months. Statistical analysis was performed by means of a paired t-test, Kaplan-Meier survival estimates, and the log-rank test. No statistically significant differences were found between: (a) the total bond failure rate of recycled and new stainless steel brackets; (b) the upper and lower arches; (c) the anterior and posterior segments. These findings demonstrate that recycling metallic orthodontic brackets can be of benefit to the profession, both economically and ecologically, as long as the orthodontist is aware of the various aspects of the recycling methods, and that patients are informed about the type of bracket that will be used for their treatment.     

Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: a novel mechanism for evasion of host defenses

Cryptosporidium parasites are pathogens of human intestinal epithelial cells. To determine which genes are regulated during early infection, human ileal mucosa cultured as explants was infected with C. parvum or C. hominis, and gene expression was analyzed by microarray. The gene for osteoprotegerin (OPG) was up-regulated by both parasites. OPG mRNA was also significantly increased in biopsy specimens obtained from a volunteer experimentally infected with C. meleagridis, compared with levels in a prechallenge biopsy specimen. After in vitro infection of HCT-8 cells, there was an early peak in production of OPG mRNA protein. Treatment of infected cells with the OPG ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced epithelial cell apoptosis and reduced parasite numbers, and recombinant OPG blocked these effects. These results suggest a novel TRAIL-mediated pathway for elimination of Cryptosporidium infection and a role for OPG in modulating this host response.     

Long-term followup of temporomandibular joint involvement in juvenile idiopathic arthritis

OBJECTIVE: Temporomandibular joint (TMJ) involvement is a frequent feature in cross-sectional prevalence studies among patients with juvenile idiopathic arthritis (JIA). In this followup study, patients were reviewed after 5 years to study the course of TMJ involvement in relation to disease characteristics. METHODS: Children with JIA from a previous study on TMJ involvement were included. A rheumatologic evaluation including the 6 parameters of the JIA core set and an orthodontic evaluation including an orthopantomogram (OPT) were performed. OPTs were scored according to Rohlin's grading system (grades 0-5). RESULTS: The overall prevalence of patients with condylar alterations decreased from 49% to 40%. Improvement of the alterations was seen in 69% of the initially affected condyles, and consequently improvement was seen in 83% of the initially affected patients. Normalization of the alterations was seen in 67% of the improved condyles, and consequently in 44% of the patients. This proves that the condyle has a regenerative capacity. Improvement was related to low disease activity and a less extensive therapeutic regimen. CONCLUSION: In patients with JIA, condylar alterations can improve and even regenerate. Condylar improvement is associated with a low disease activity.     

Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention

Selective serotonin reuptake inhibitors (SSRIs) are frequently combined to the antipsychotic medication of schizophrenia patients, to treat their depressed, cognitive or negative symptoms. No convincing neurochemical theory exists for this combination. The role of serotonin in those psychophysiological parameters of attention that are already found to be disturbed in schizophrenia, e.g. processing negativity (PN), mismatch negativity (MMN) and P300 amplitude, is poorly understood. In the present study the effects of increased serotonergic activity on these psychophysiological parameters is investigated. In a balanced, double-blind, placebo-controlled, cross-over experiment 18 healthy male volunteers received an oral dose of either placebo or of 10 mg escitalopram (a highly specific SSRI) on two separate test days, after which they were tested in an auditory selective attention paradigm and a MMN paradigm. Escitalopram significantly increased PN and MMN compared to placebo, without affecting the P300 amplitude. Furthermore, administration of escitalopram resulted in a small, yet significant, reduction of task performance in the selective attention paradigm compared to placebo, while it did not affect reaction time. Contrary to what was expected, escitalopram enhanced PN and MMN, without affecting the P300 amplitude. The results are discussed in the light of dosage issues and subtypes of serotonergic receptors.     

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis-free survival in node-negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress-induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.