The validity of the whitaker index of schizophrenic thinking

The Whitaker Index of Schizophrenic Thinking was designed to address an important clinical and research problem–the objective assessment of thought disorder. The present study assessed this test's convergent and discriminant validity and its diagnostic discriminating power (N = 56). We found that the WIST has limited clinical utility as a specific measure of disordered thought and as a diagnostic tool, but that it might still have certain important research applications.     

Gut Microbiome Composition Is Predictive of Incident Type 2 Diabetes in a Population Cohort of 5,572 Finnish Adults

OBJECTIVETo examine the previously unknown long-term association between gut microbiome composition and incident type 2 diabetes in a representative population cohort.RESEARCH DESIGN AND METHODSWe collected fecal samples from 5,572 Finns (mean age 48.7 years; 54.1% women) in 2002 who were followed up for incident type 2 diabetes until 31 December 2017. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident diabetes using multivariable-adjusted Cox regression models. We first used the eastern Finland subpopulation to obtain initial findings and validated these in the western Finland subpopulation.RESULTSAltogether, 432 cases of incident diabetes occurred over the median follow-up of 15.8 years. We detected four species and two clusters consistently associated with incident diabetes in the validation models. These four species were Clostridium citroniae (hazard ratio [HR] 1.21; 95% CI 1.04–1.42), C. bolteae (HR 1.20; 95% CI 1.04–1.39), Tyzzerella nexilis (HR 1.17; 95% CI 1.01–1.36), and Ruminococcus gnavus (HR 1.17; 95% CI 1.01–1.36). The positively associated clusters, cluster 1 (HR 1.18; 95% CI 1.02–1.38) and cluster 5 (HR 1.18; 95% CI 1.02–1.36), mostly consisted of these same species.CONCLUSIONSWe observed robust species-level taxonomic features predictive of incident type 2 diabetes over long-term follow-up. These findings build on and extend previous mainly cross-sectional evidence and further support links between dietary habits, metabolic diseases, and type 2 diabetes that are modulated by the gut microbiome. The gut microbiome can potentially be used to improve disease prediction and uncover novel therapeutic targets for diabetes.     

Analysis During Sinus Rhythm of Critical Sites in Reentry Circuits of Postinfarction Ventricular Tachycardia

Background: Critical sites within reentry circuits of postinfarction ventricular tachycardia (VT) were identified during sinus rhythm (SR) and VT to determine whether electrogram characteristics during SR may be helpful in identifying successful ablation sites. Methods: In 33 patients (mean age 67 ± 11 yrs) with prior infarction, mapping and radiofrequency (RF) catheter ablation of 57 hemodynamically-tolerated VT's (cycle length 478 ± 96) were performed. The morphologies of electrograms (EGM) at sites of concealed entrainment (CE) were compared during SR and VT. RF energy was delivered at 94 sites (51 successful and 43 unsuccessful ablation sites). Results: During SR, isolated potentials (IP), but not late potentials (LP) recorded via the mapping catheter, were associated with successful ablation. At 29/39 sites with an IP during sinus rhythm, an isolated diastolic potential (IDP) also was present during VT, whereas at 4 sites IP's were present only during SR (p < 0.001). At 11/29 sites where isolated potentials were present during SR and VT, the morphology of the isolated potential during VT and SR was similar; and all but one of these sites were successful ablation sites (p = 0.01). The EGM amplitude during VT correlated with the amplitude during SR (R = 0.9, p < 0.001). An identical pacemap was present during SR at 33/94 sites; this was not associated with successful ablation. Conclusion: SR mapping may be helpful in identifying critical sites of reentry in postinfarction VT. At sites within the reentry circuit, characteristics of sinus rhythm EGM's that are associated with successful ablation include the presence of IP's, but not the presence of LP's.     

Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody

Glycoprotein (GP) VI is the major receptor responsible for platelet activation by collagen, but the collagen-binding surface of GPVI is unknown. To address this issue we expressed, from insect cells, the immunoglobulin (Ig)-like ectodomains (residues 1-185) of human and murine GPVI, called hD1D2 and mD1D2, respectively. Both proteins bound specifically to collagen-related peptide (CRP), a GPVI-specific ligand, but hD1D2 bound CRP more strongly than did mD1D2. Molecular modeling and sequence comparison identified key differences between hD1D2 and mD1D2. Ten mutant hD1D2s were expressed, of which 4 had human residues replaced by their murine counterpart, and 6 had replacements by alanine. CRP binding studies with these mutants demonstrated that the exchange of lysine at position 59 for the corresponding murine glutamate substantially reduced binding to CRP. The position of lysine59 on the apical surface of GPVI suggests a mode of CRP binding analogous to that used by the related killer cell Ig-like receptors to bind HLA. This surface was confirmed as critical for collagen binding by epitope mapping of an inhibitory phage antibody against GPVI. This anti-GPVI, clone 10B12, gave dose-dependent inhibition of the hD1D2-collagen interaction. Clone 10B12 inhibited activation of platelets by CRP and collagen in aggregometry and thrombus formation by the latter in whole blood perfusion. Antibody 10B12 showed significantly reduced binding to the hD1D2-E59, and, on that basis, the GPVI:10B12 interface was modeled.     

A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study

OBJECTIVES: This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN). BACKGROUND: Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment. METHODS: We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men). RESULTS: Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash. CONCLUSIONS: Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.     

Influence of postischemic administration of oxyradical antagonists on ischemic injury to rabbit skeletal muscle

The aim of this study was to determine whether the administration of free radical antagonists, immediately before and during the early minutes of reperfusion, improves muscle survival 24 hr after a period of ischemia. Rabbit rectus femoris muscles were isolated, made ischemic for 3½ hr and treated with either desferrioxamine (DFX), an Fe³⁺ chelator, superoxide dismutase and catalase (SOD & CAT), which quench superoxide and hydrogen peroxide, or allopurinol, an inhibitor of xanthine oxidase (XO). After 24 hr reperfusion, muscle viability (±s.e.m.), measured by the nitro blue tetrazolium (NBT) vital staining technique, was 41.6 ± 11.3% for saline-treated ischemic controls, 30.6 ± 7.6% for DFX-treated, 46.7 ± 10.3% for SOD & CAT-treated, and 43.3 ± 9.5% for allopurinol-treated muscles. None of the treated groups differed significantly from the ischemic control group. Tissue myeloperoxidase, ATP and reduced glutathione levels, and plasma lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels were increased by ischemia and reperfusion in all groups, but the changes did not differ between the treatment groups. Levels of XO in the rabbit muscle were determined and found to be very low in both normal and postischemic muscle. As XO is the target enzyme of allopurinol, its absence provides a basis for the lack of effect of this agent. However, it is not clear why DFX and SOD & CAT had no protective effect © 1997 Wiley-Liss, Inc MICROSURGERY 17:517–523 1996     

Regenerative potential of silk conduits in repair of peripheral nerve injury in adult rats

Various attempts have been made to develop artificial conduits for nerve repair, but with limited success. We describe here conduits made from Bombyx mori regenerated silk protein, and containing luminal fibres of Spidrex^®, a silk-based biomaterial with properties similar to those of spider silk. Assessment in vitro demonstrated that Spidrex^® fibres support neurite outgrowth. For evaluation in vivo, silk conduits 10 mm in length and containing 0, 100, 200 or 300 luminal Spidrex^® fibres, were implanted to bridge an 8 mm gap in the rat sciatic nerve. At 4 weeks, conduits containing 200 luminal Spidrex^® fibres (PN200) supported 62% and 59% as much axon growth as autologous nerve graft controls at mid-conduit and distal nerve respectively. Furthermore, Spidrex^® conduits displayed similar Schwann cell support and macrophage response to controls. At 12 weeks, animals implanted with PN200 conduits showed similar numbers of myelinated axons (81%) to controls, similar gastrocnemius muscle innervation, and similar hindpaw stance assessed by Catwalk footprint analysis. Plantar skin innervation was 73% of that of controls. PN200 Spidrex^® conduits were also effective at bridging longer (11 and 13 mm) gaps. Our results show that Spidrex^® conduits promote excellent axonal regeneration and function recovery, and may have potential for clinical application.