Magneto-optical diagnosis of symptomatic malaria in Papua New Guinea.

Improved methods for malaria diagnosis are urgently needed. Here, we evaluate a novel method named rotating-crystal magneto-optical detection (RMOD) in 956 suspected malaria patients in Papua New Guinea. RMOD tests can be conducted within minutes and at low cost. We systematically evaluate the capability of RMOD to detect infections by directly comparing it with expert light microscopy, rapid diagnostic tests and polymerase chain reaction on capillary blood samples. We show that compared to light microscopy, RMOD exhibits 82% sensitivity and 84% specificity to detect any malaria infection and 87% sensitivity and 88% specificity to detect Plasmodium vivax. This indicates that RMOD could be useful in P. vivax dominated elimination settings. Parasite density correlates well with the quantitative magneto-optical signal. Importantly, residual hemozoin present in malaria-negative patients is also detectable by RMOD, indicating its ability to detect previous infections. This could be exploited to reveal transmission hotspots in low-transmission settings.

Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort.

BACKGROUND: DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD: We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS: The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS: NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

The impact of emotion awareness and regulation on social functioning in individuals at clinical high risk for psychosis.

BACKGROUND: Social functioning (SF) difficulties are ubiquitous among individuals at clinical high risk for psychosis (CHR), but it is not yet clear why. One possibility is suggested by the observation that effective SF requires adaptive emotion awareness and regulation. Previous reports have documented deficits in emotion awareness and regulation in individuals with schizophrenia, and have shown that such deficits predicted SF. However, it is unknown whether these deficits are present prior to the onset of psychosis or whether they are linked to SF in CHR individuals. METHOD: We conducted a cross-sectional comparison of emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia and 50 healthy controls (HC). Then, within the CHR group, we examined links between emotion awareness, emotion regulation and SF as indexed by the Global Functioning Scale: Social (Cornblatt et al. 2007). RESULTS: Group comparisons indicated significant differences between HC and the two clinical groups in their ability to identify and describe feelings, as well as the use of suppression and reappraisal emotion-regulation strategies. Specifically, the CHR and schizophrenia groups displayed comparable deficits in all domains of emotion awareness and emotion regulation. A hierarchical multiple regression analysis indicated that difficulties describing feelings accounted for 23.2% of the SF variance. CONCLUSIONS: The results indicate that CHR individuals display substantial emotion awareness and emotion-regulation deficits, at severity comparable with those observed in individuals with schizophrenia. Such deficits, in particular difficulties describing feelings, predate the onset of psychosis and contribute significantly to poor SF in this population.

Using the LHB score for assessment of LHB pathologies and LHB surgery: a prospective study.

INTRODUCTION: The long head of biceps tendon (LHB) score was designed to clinically assess LHB pathologies. Purpose of this study was to prospectively assess patients with LHB pathologies preoperatively and after LHB surgery using the LHB score. MATERIALS AND METHODS: Fifty-seven patients (29 f/28 m, Ø age 61.0 years), showing clinical signs of LHB pathologies, were prospectively included into this study. In 43 patients LHB pathologies could be confirmed intraoperatively. Among these, in 26 patients a biceps tenodesis (group I; 8 f/18 m, Ø age 61.2 years), and in 17 patients a biceps tenotomy was performed (group II; 12 f/5 m, Ø age 64.2 years). In 14 patients no intraoperative correlate concerning the biceps symptoms could be found (group III; 9 f/5m, Ø age 56.8 years). In these patients no further LHB treatment was carried out. The clinical evaluation contained the Constant score (CS) as well as the LHB score preoperatively and 2 years postoperatively. RESULTS: The CS improved significantly in all the three groups [group I: 41.7 (20-70) to 81.3 (62-100); group II: 42.2 (18-66) to 75.3 (41-84); group III: 45.7 (22-77) to 72.9 (48-85)] (p < 0.05). Also the LHB score increased significantly in all three groups [group I: 74.3 (41-97) to 94.2 (80-100); group II: 73.4 (57-97) to 84.2 (49-100); group III: 71.1 (58-80) to 90.8 (70-100)] (p < 0.05). Compared to group II, group I showed significant better results in the total LHB score and in the cosmetic result (p < 0.05). CONCLUSIONS: We recommend that patients with LHB pathologies are evaluated using the LHB score, since it provides LHB related information and is a proper tool to assess the clinical outcome after surgery. However, the score is not appropriate to detect LHB pathologies preoperatively. LEVEL OF EVIDENCE: II.

Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid cells. Acylation of OspA and the synthetic peptides was requisite for cell activation. Polymyxin B abrogated only the response to LPS. By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the LPS receptor), it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission. The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses.

Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes/macrophages.

The observation that the major membrane immunogens of the spirochetal pathogens. Treponema pallidum and Borrelia burgdorferi are lipoproteins prompted studies to investigate macrophage activation by the 47-kDa lipoprotein of T. pallidum and the acylated outer surface protein A (OspA) of B. burgdorferi. Both lipoproteins induced the synthesis of biologically active TNF-alpha and chloramphenicol acetyltransferase in a murine macrophage cell line transfected with a chloramphenicol acetyltransferase reporter gene controlled by a TNF promoter (TB2 cells). Nonacylated forms of these polypeptides did not induce cell activation. Comparison between purified OspA and B. burgdorferi cellular lipids revealed that the former was the more potent inducer of TNF-alpha. Synthetic lipohexapeptides corresponding to the N-termini of the 47-kDa lipoprotein of T. pallidum and OspA also activated TB2 cells in a dose-dependent fashion, whereas the nonlipidated hexapeptides were without effect, further underscoring the importance of protein acylation to cell activation. Among several lines of evidence supporting that macrophage stimulation by LPS and lipopeptides proceeds via different mechanisms, the most notable was that lipopeptides activated peritoneal macrophages from LPS-nonresponsive C3H/HeJ mice. The potential for spirochetal lipoproteins to function as general macrophage activators was demonstrated by the ability of the synthetic analogues to induce IL-1 beta, IL-6, and IL-12, in addition to TNF, in murine and/or human macrophages. Our findings indicate that spirochetal lipoproteins may be important immunomodulators in syphilis and Lyme disease and that the synthetic lipopeptides will be useful surrogates for studying immune mechanisms operative in the two spirochetal diseases.

Critical review of psychosocial interventions in cancer care.

The need for a large variety of psychosocial interventions is enhanced as increasing numbers of patients with cancer have longer survival. This article reviews the four interventions used most commonly: (1) education, (2) behavioral training, (3) individual psychotherapy, and (4) group interventions. It examines the outcomes of each type of intervention. This comprehensive review of the intervention literature reveals the availability of a wide range of options for patients with cancer and their potential psychological and physical health benefits.

Solid-phase synthesis of biologically active lipopeptides as analogs for spirochetal lipoproteins.

Bacterial lipoproteins, which are of particular interest because of their immunomodulatory activities, share a common N-terminal structural motif that consists of an N-acyl-S-diacylglyceryl cysteine residue. Synthetic tripalmitoylated analogs of the N-terminal sequences of several bacterial lipopetides have been found to reproduce the immunological activities of the corresponding intact lipoproteins. Methods for the synthesis of lipopeptide analogs of bacterial lipoproteins have hitherto relied upon the coupling of peptide moieties, lacking the N-terminal cystienyl residue, with a tripalmitoylglyceryl cysteine moiety synthesized separately in solution. A method is described here by which rapid and convenient synthesis of the entire lipopeptide is accomplished by solid-phase methods in which the N-terminal cysteinyl derivative is assembled stepwise while attached to the completed peptide moiety prior to cleavage from the resin. The method has been used to synthesize two lipohexapeptides representing the N-terminal sequences of the 47-kDa membrane lipoprotein of the syphilis spirochete, Treponema pallidum, and the outer surface protein A (OspA) of the Lyme disease spirochete, Borrelia burgdorferi. These lipopeptides, which were synthesized without detectable endotoxin contamination, exhibit macrophage-stimulating activity that is not expressed by the corresponding non-acylated hexapeptides. The data indicate that synthetic lipopeptides based on spirochetal lipoproteins are appropriate substitutes for the intact lipoproteins in immunological studies.

A preoperative chymopapain sensitivity test for chemonucleolysis candidates.

A fluorescence enzyme immunoassay (ChymoFAST test) for the quantitation of chymopapain-specific IgE antibody concentration in human serum is described. The IgE antibody is recognized as the major immunologic mediator for anaphylactic reactions. Serum chymopapain-specific IgE levels serve as an objective screening method for identifying patients most likely to tolerate chymopapain, thereby minimizing associated risks. Preoperative sera obtained from 11,658 chemonucleolysis candidates were tested, of which 0.94% (110/11,658) were found to be positive. Good predictive values for both positive and negative findings are evident based on 4776 postmarketing surveillances obtained from the surgeons.

Chymopapain-induced hypersensitivity following chemonucleolysis.

This study describes the changes in chymopapain-specific IgE antibody levels in patients following chemonucleolysis with Chymodiactin. Using the ChymoFAST method, chymopapain-specific IgE values were studied in 91 patients prior to and for 2 months post-Chymodiactin chemonucleolysis. A total of 8.8% (17/91) developed IgE levels greater than or equal to 0.06 IU/ml. Those patients with detectable IgE levels prior to chemonucleolysis were more likely than those with nondetectable preinjection levels (36.4% versus 4%) to develop chymopapain-specific IgE levels greater than or equal to 0.06 IU/ml.

Use of a modified procedure for treating small amounts of red blood cells with 2-aminoethylisothiouronium bromide.

Kell null red blood cell samples can be prepared using 2-aminoethylisothiouronium bromide (AET). This article describes a modification whereby only three drops of a 5% red blood cell suspension may be AET treated. This procedure has been used routinely in the authors' laboratory for more than a year. One patient's serum contained anti-Kpb plus anti-C and anti-D. Tests with panel cells pretreated with AET made it possible to identify underlying Rh antibodies without using a panel of genetic Kpb negative red blood cells. Of 24 red blood cell eluates from patient sample with warm autoantibodies, one had specificity within the Kell blood group system. This small volume AET-treatment method is a quick screen for the differentiation of a Kell-related specificity from a non-Kell specificity of both warm autoantibodies and alloantibodies to high-incidence antigens.

Complications of cerebral angiography: prospective assessment of risk.

A prospective study of 1,517 consecutive cerebral angiographic examinations is reported. The incidence of all complications was 8.5%, and the incidence of all neurologic complications was 2.6%. The overall incidence of permanent neurologic deficit was 0.33%. The incidence of permanent neurologic deficit in patients referred for evaluation of symptomatic cerebrovascular disease was 0.63%. Older age, increased serum creatinine concentration, and the use of more than one catheter all were significantly associated with serious neurologic complications. Although patients with a recent stroke or frequent transient ischemic attacks had a higher incidence of serious neurologic complications, this increase was not statistically significant for this sample.