INCLEN diagnostic tool for autism spectrum disorder (INDT-ASD): Development and validation

Objective

To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD).

Design

Diagnostic test evaluation by cross sectional design

Setting

Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India.

Methods

Children aged 2–9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard).

Main outcome measures

Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.

Results

154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for’ ASD group’ was 82.52% [Cohen’s κ=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = ?0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance.

Conclusion

INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.     

Critical design aspects involved in the study of Paneth cells and the intestinal microbiota

Paneth cells are long-lived secretory cells that reside in the base of the crypts of Lieberkühn of the small intestine. They produce an arsenal of molecules that are involved in numerous biological processes, ranging from the control of gut microbial populations to supporting the intestinal stem cell niche. Because of these important functions, Paneth cell abnormalities are becoming implicated in a variety of disease processes. As such, it is necessary to establish parameters that will allow for the comprehensive study of Paneth cells in health and disease. In this addendum, we highlight critical design aspects involved in the study of Paneth cells and their downstream effects on the intestinal microbiota. The importance of this approach is demonstrated by our recent findings that Nod2 does not regulate mouse Paneth cell antimicrobial function, in contrast to previous reports. This work defines key issues to consider when studying Paneth cells in mouse systems.     

Left Main Coronary Atresia in a Child with Absent Pulmonary Valve Syndrome: Early Entrapment of an Innocent Bystander

Atresia of the left main coronary artery is a rare anomaly that, if left untreated, has an unfavorable outcome. We hereby report left main coronary artery atresia in a child with tetralogy of Fallot with absent pulmonary valve and discuss the possible developmental basis of the association.     

Lupus anticoagulant and ANCA associated thrombotic vasculopathy due to cocaine contaminated with levamisole: a case report and review of the literature

A 2010 US report recently detected the presence of levamisole in greater than 77 % of seized cocaine samples. A syndrome of retiform purpura, often involving ears and flanks, with vasculopathy or vasculitis on biopsy, associated with anti-nuclear cytoplasmic antibodies as well as antiphospholipid antibodies, previously associated with therapeutic use of levamisole has now re-emerged, and is associated with cocaine adulterated with levamisole. Patients with this unusual constellation of signs and laboratory findings should be questioned about exposure to cocaine.     

Thrombotic microangiopathy and acute kidney injury following vivax malaria

Background

Infection with Plasmodium vivax, a common human parasite, is occasionally recognized to cause severe organ dysfunction similar to P. falciparum infection. Acute kidney injury (AKI) in malaria is attributed to acute tubular necrosis; thrombotic microangiopathy is not described.

Methods

This observational study includes patients referred to a tertiary care center in North India during June to September 2011 with severe AKI, anemia, and thrombocytopenia following vivax malaria. Renal biopsies were processed by light, immunofluorescence, and electron microscopy.

Results

Nine patients (including 5 children) had persistent AKI with thrombocytopenia and variable anemia following the diagnosis of malaria. Based on peripheral smear, eight patients were diagnosed with vivax malaria and had received antimalarial therapy prior to referral; a laboratory diagnosis of P. vivax infection was made for one patient at this center. Renal histology in all cases showed features of thrombotic microangiopathy, including fibrin thrombi, subendothelial widening, and mesangiolysis, along with variable tubulointerstitial nephritis and acute tubular or cortical necrosis. Ultrastructural examination confirmed endothelial injury and subendothelial widening. All patients required hemodialysis, and six were dialysis dependent at four weeks. Delayed presentation to the hospital (P = 0.019), hemolysis on peripheral smear (P = 0.083), and prolonged oligoanuria (P = 0.036) were associated with dialysis dependence.

Conclusion

The association of anemia, thrombocytopenia, and renal histological evidence of thrombotic microangiopathy with vivax malaria is novel, and suggests the presence of severe endothelial injury. Further studies are necessary to confirm the association and examine the factors associated with its occurrence.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.     

Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges

Introduction: The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO₂ nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization.

Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity.

Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.