The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

The Protection of Animals through Human Rights. The Case-Law of the European Court of Human Rights

The chapter discusses the potential of a human rights framework to contribute to the growth and development of global animal law. It takes as example the jurisprudence of the European Court of Human Rights, and examine the major trends in the Court’s judgments and admissibility decisions that directly or indirectly concern the rights or welfare of animals. It is concluded that the Court is not indifferent to the welfare of animals, but that animal welfare is instrumentalised: it is understood not as a good in itself, but is instead valued for its implications for human welfare and rights. The chapter then considers the obstacles that the anthropocentrism of the human rights idea and the instrumentalisation of animal concerns present to the use of human rights frameworks to further the development of global animal law, as well as the opportunities that exist in the meeting of these paradigms. It concludes that although the telos of human rights law is different from that of animal law, nevertheless there exist many overlapping concerns within which mutually beneficial interactions are possible

Reliability of MRI findings in candidates for lumbar disc prosthesis

Introduction: Limited reliability data exist for localised magnetic resonance imaging (MRI) findings relevant to planning of treatment with lumbar disc prosthesis and later outcomes. We assessed the reliability of such findings in chronic low back pain patients who were accepted candidates for disc prosthesis. Methods: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three experienced radiologists independently rated Modic changes, disc findings and facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126 examinations. For each MRI finding at each disc level, agreement was analysed using the kappa statistic and differences in prevalence across observers using a fixed effects model. Results: All findings at L3/L4 and facet arthropathy at L5/S1 had a mean prevalence <10% across observers and were not further analysed, ensuring interpretable kappa values. Overall interobserver agreement was generally moderate or good (kappa 0.40–0.77) at L4–S1 for Modic changes, nucleus pulposus signal, disc height (subjective and measured), posterior high-intensity zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height at L4/L5 differed up to threefold in prevalence between observers (p< 0.0001). Intraobserver agreement was mostly good or very good (kappa 0.60–1.00). Conclusion: In candidates for disc prosthesis, mostly moderate interobserver agreement is expected for localised MRI findings

What should an ideal spinal injury classification system consist of? A methodological review and conceptual proposal for future classifications

Since Böhler published the first categorization of spinal injuries based on plain radiographic examinations in 1929, numerous classifications have been proposed. Despite all these efforts, however, only a few have been tested for reliability and validity. This methodological, conceptual review summarizes that a spinal injury classification system should be clinically relevant, reliable and accurate. The clinical relevance of a classification is directly related to its content validity. The ideal content of a spinal injury classification should only include injury characteristics of the vertebral column, is primarily based on the increasingly routinely performed CT imaging, and is clearly distinctive from severity scales and treatment algorithms. Clearly defined observation and conversion criteria are crucial determinants of classification systems’ reliability and accuracy. Ideally, two principle spinal injury characteristics should be easy to discern on diagnostic images: the specific location and morphology of the injured spinal structure. Given the current evidence and diagnostic imaging technology, descriptions of the mechanisms of injury and ligamentous injury should not be included in a spinal injury classification. The presence of concomitant neurologic deficits can be integrated in a spinal injury severity scale, which in turn can be considered in a spinal injury treatment algorithm. Ideally, a validation pathway of a spinal injury classification system should be completed prior to its clinical and scientific implementation. This review provides a methodological concept which might be considered prior to the synthesis of new or modified spinal injury classifications

Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study

BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments. METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease. The eight subjects existing in the country at the moment received, as in-patients, 1 × 10(6 )IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines. Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly. RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients. Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case. Clinical improvement was also evident; body mass index increased in general. Interferon gamma was well tolerated. Few adverse events were registered, mostly mild; fever and arthralgias prevailed. CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB. Further controlled clinical trials are encouraged

Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

<p>Abstract</p> <p>Background</p> <p>High antibiotic resistance is described in atypical Mycobacteriosis, mainly by <it>Mycobacterium avium </it>complex (MAC).</p> <p>Methods</p> <p>A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 10⁶IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment.</p> <p>Results</p> <p>Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms predominated in the IFN gamma group. No severe events were recorded.</p> <p>Conclusion</p> <p>These data suggest that IFN gamma is useful and well tolerated as adjuvant therapy in patients with pulmonary atypical Mycobacteriosis, predominantly MAC. Further wider clinical trials are encouraged.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN70900209.</p

DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik