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A thorough literature search is a key feature of scoping reviews. We investigated the search practices used by social science researchers as reported in their scoping reviews. We collected scoping reviews published between 2015 and 2021 from Social Science Citation Index. In the 2484 included studies, we observed a 58% average annual increase in published reviews, primarily from clinical and applied social science disciplines. Bibliographic databases comprised most of the information sources in the primary search strategy (n = 9565, 75%), although reporting practices varied. Most scoping reviews (n = 1805, 73%) included at least one supplementary search strategy. A minority of studies (n = 713, 29%) acknowledged an LIS professional and few listed one as a co-author (n = 194, 8%). We conclude that to improve reporting and strengthen the impact of the scoping review method in the social sciences, researchers should consider (1) adhering to PRISMA-S reporting guidelines, (2) employing more supplementary search strategies, and (3) collaborating with LIS professionals., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above., Methods: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains., Results: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (60-70 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains., Conclusion: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs., (Copyright © 2024 Copyright: © 2024 Annals of Indian Academy of Neurology.)

Dermatomyositis (DM) and polymyositis are idiopathic inflammatory myopathies (IIMs), most associated with solid organ malignancies, and less commonly hematological malignancies. We discuss a case of DM associated with diffuse large B-cell lymphoma, followed by a review of literature on the pathogenesis, clinical course, treatment, and prognosis. Various challenges with the diagnosis and management of underlying lymphoproliferative disorders (LPDs) in patients with IIM are discussed. The case demonstrates the importance of being vigilant of the association between IIM and LPD. Cancer screening in patients with IIM is discussed, including the recently published International Guideline for IIM-Associated Cancer Screening. More research is required to address knowledge gaps in cancer screening in IIM., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adversarial perturbations have demonstrated the vulnerabilities of deep learning algorithms to adversarial attacks. Existing adversary detection algorithms attempt to detect the singularities; however, they are in general, loss-function, database, or model dependent. To mitigate this limitation, we propose DAMAD-a generalized perturbation detection algorithm which is agnostic to model architecture, training data set, and loss function used during training. The proposed adversarial perturbation detection algorithm is based on the fusion of autoencoder embedding and statistical texture features extracted from convolutional neural networks. The performance of DAMAD is evaluated on the challenging scenarios of cross-database, cross-attack, and cross-architecture training and testing along with traditional evaluation of testing on the same database with known attack and model. Comparison with state-of-the-art perturbation detection algorithms showcase the effectiveness of the proposed algorithm on six databases: ImageNet, CIFAR-10, Multi-PIE, MEDS, point and shoot challenge (PaSC), and MNIST. Performance evaluation with nearly a quarter of a million adversarial and original images and comparison with recent algorithms show the effectiveness of the proposed algorithm.

Inborn errors of metabolism (IEM) lead to the physical and mental disability and death of infants, which can be prevented if treated early. Hence it is imperative in diagnosing these disorders at the earliest. The study is planned to differentiate suspected IEM by quantifying the lactate-pyruvate ratio (L/P ratio), Amino acid profiling by HPLC in addition to blood ammonia using the basic methodology in comparison to globally accepted mass spectroscopy technique and specific enzyme activity assays. The objective of this study is not to compete with the existing gold standard methodology rather makes the best of basic diagnostic modalities available. Five cases out of 100 referred cases of IEM suspicion showed the altered pattern of Aminogram correlating with high L/P ratio and Hyperammonemia, which were positive cases, as confirmed by the clinician who referred. Hence study parameters could be used as preliminary protocol to investigate and screen the IEM., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Clinical Biochemists of India 2019.)

Introduction: The Government of India has formulated the Cigarettes and Other Tobacco Products Act (COTPA) to implement measures to ensure that effective protection is provided to nonsmokers from involuntary exposure to tobacco smoke. Bhubaneswar is the capital city of Odisha, India, was declared as " Tobacco Smoke Free City " in 2010. For strengthening the implementation of the COTPA Act, an effective regular assessment is needed, and hence, an observational study was planned to assess the current violations of Tobacco Smoking in Bhubaneswar., Materials and Methods: In this observational study, 416 different places were chosen from four different zones of Bhubaneswar. Data were collected with the help of Mobile enabled global positioning system (GPS) technology and pretested structured questionnaire., Results: In this study, 52.88% places were found to be having smoking violations. The study shows maximum violations have occurred in public places (90.89%) followed by transit places (75%). Violations were found to be very low in government buildings, educational, medical institutes, and hotel/restaurants. The average number of smokers in the city was found to be 4.90/place and the average number of smokers was found to be 4.37/public place., Conclusion: In this study, GPS-enabled Mobile App can be used to identify the different locations, where a violation of law occurs. This may help administrators to properly plan and implement the law. Even though Bhubaneswar was declared " Tobacco Smoke free city " in 2010, it is still lacking behind in fulfilling the implementation of law, to reduce Second Hand Smoking ., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Community Medicine.)

Methyl malonic acid and branched-chain keto acids are important biomarkers for the diagnosis of cobalamin deficiencies and maple syrup urine disease. We report the development and validation of a HILIC-ESI-MS2 method for the quantification of these organic acids from neonatal urine. The samples were 100 times diluted and analyzed on a ZIC-HILIC column with 25-mM formic acid in water: 25-mM formic acid in acetonitrile (45:55) at a flow rate of 0.8 mL/min with a runtime of only 6 minutes. The method demonstrated a lower limit of detection of 10 ng/mL, Limit of Quantification (LOQ) of 50 ng/mL, linearity of r2 ≥ 0.990 and recoveries of 87-105% for all analytes. The intraday and interday precision CV's were <10% and 12%, respectively. Extensive stability studies demonstrated the analytes to be stable in stock and in matrix with a percent change within ±15%. The Bland-Altman analysis of the developed method with the gold standard GCMS method demonstrated a bias of 0.44, 0.11, 0.009 and -0.19 for methyl malonic acid, 3-methyl-2-oxovaleric acid, 2-hydroxy-3methylbutyric acid and 4-methyl-2-oxovaleric acid, respectively, proving the methods are comparable. The newly developed method involves no derivatization and has a simple sample preparation and a low runtime, enabling it to be easily automated with a high sample throughput in a cost-effective manner., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background and Aims: Chronic perineal pain (CPP) is a poorly localized pain. Its etiology may be benign or malignant. The ganglion impar is a solitary retroperitoneal structure at sacrococcygeal junction. It provides the nociceptive and sympathetic supply to the perineal structures. CPP has been effectively managed by ganglion impar block. Here, we describe a case series of neurolytic ganglion impar block by transcoccygeal approach, analyzing its safety and efficacy., Material and Methods: In this study, five consecutive patients who were given ganglion impar block for CPP using a transcoccygeal approach were followed up for 2 months. The visual analog scale (VAS) score for pain at presentation, time required for the pain to reduce by 50% after the block, VAS during a 2-month follow-up, time required to perform the procedure, number of attempts, and any complications were noted., Results: All the five patients had an excellent pain relief. The mean duration for decrease in VAS by 50% was 14.8 ± 3.1 min. The mean duration to perform the procedure was 10.2 ± 1.5 min. There were no complications. All the patients had clinically significant pain relief with VAS score of 2 till 2-month follow-up., Conclusion: Transcoccygeal ganglion impar block may offer a safe and effective treatment option for CPP as compared to opioids. This approach for neurolysis of the ganglion impar may be recommended in view of the direct course, appreciable end point, and smaller volume of neurolytic requirement., Competing Interests: There are no conflicts of interest.

Background: Establishing an intravenous access is indispensable for safe administration of anesthesia. Most of the times, it is executed without any analgesia although the pain associated with this procedure is quite agonizing to the patients., Aims: This study aims to evaluate the role of 3 different nonpharmacological measures such as Valsalva maneuver, flash of light, and distraction method in attenuation of pain during venous cannulation., Design: A clinical randomized controlled study., Materials and Methods: Two hundred patients of either sex, aged between 18 and 65 years, posted for elective surgery were enrolled in this study. Patients were randomly allocated into four groups, Group C-control, Group V (valsalva) - blew into sphygmomanometer raising the mercury column up to 30 mm of Hg, Group D (distraction) - pressed a rubber ball and Group L (light) - photographed with a flash of light before venous cannulation. During the process of cannulation, patients were observed and questioned, and pain was graded using a 4- point scale. After the cannulation, pain during the procedure was also assessed using visual analog scale (VAS) score. Data analysis was done using SPSS statistical package version 17., Results: A significant reduction in the incidence of pain was noted in distraction group 36% as compared to 44% in Group L, 46% in Group V, and 100% in the control group. The severity of pain as assessed by 4-point score was significantly lowest in Group D (0.26 ± 0.53) as compared to other three groups (Group V and L = 0.54 ± 0.16, Group C = 1.64 ± 0.6, P < 0.001). Mean VAS score was significantly low in Group D (0.6 ± 1.11) and Group L (0.54 ± 1.06) as compared to Group V (1.26 ± 1.76) and Group C (5.0 ± 1.21, P < 0.001)., Conclusion: We conclude that distraction can be considered as a diligent, reasonable, and simple method to attenuate procedural pain during peripheral venous cannulation., Competing Interests: There are no conflicts of interest.

In the present study, the effect of 900 MHz radiation exposure on blood biochemical and reproductive parameters was evaluated in adolescent rats. Male albino Wistar rats (8-10 weeks of age) were exposed to 900 MHz radiation (1hr/day, power density - 146.60 µW/cm2) from a mobile phone for 28 days. On 29th day the animals were euthanized and malondialdehyde (MDA), total antioxidants (TA) levels and Glutathione-S transferase (GST) activity were studied in the blood. Reproductive parameters such as total sperm count, percentage of non-motile sperms, and sperm morphology were determined. Testes sections were stained with H(et)E staining and their cellular integrity was evaluated. Caspase-3 activity in the testes was also determined. MDA concentration was increased but TA levels and GST activity were not found to be different in 900 MHz group compared to controls. Sperm motility was found to be slightly reduced in 900 MHz group. Percentage of abnormal sperm was significantly elevated in 900 MHz group. Additionally, loss of germ cells particularly spermatocytes and spermatids was found in the testes of 900 MHz group. Testes caspase-3 activity was slightly elevated in 900 MHz exposed rats. Chronic 900 MHz exposure induced oxidative damage in the blood and lead to alterations in reproductive parameters in rats (Fig. 4, Ref. 33).

The present study was undertaken to investigate the effect of dietary replacement of commonly used vegetable oil (sunflower oil, SFO) with n-3 polyunsaturated fatty acids (PUFA) rich oil sources on broiler chicken performance, carcass yield, meat fatty acid composition, keeping quality and sensory attributes of meat. In the current experiment, 300 day-old Krishibro broiler chicks were randomly distributed to 5 dietary groups (50 replicates with 6 chicks in each) prepared by replacing SFO (2% and 3% of diet during starter and finisher periods, respectively) with n-3 PUFA rich soybean oil (SO), mustard oil (MO), linseed oil (LO) or fish oil (FO) on weight basis. Variation in oil sources had no influence ( P  > 0.05) on performance and carcass yield. Supplementation of MO, LO or FO significantly ( P  < 0.01) increased the n-3 PUFA, lowered the n-6 PUFA deposition and n-6:n-3 ratio in breast and thigh without affecting the organoleptic characters (appearance, flavour, juiciness, tenderness and overall acceptability) of meat. However, thiobarbituric acid reacting substances concentration in meat was increased ( P  < 0.01) with LO and FO supplementation compared with SFO. It is concluded that, dietary incorporation of MO, LO or FO at 2% and 3% levels during starter and finisher phase can enrich broiler chicken meat with n-3 PUFA without affecting the bird's performance and sensory characters of meat.

The microbiome affects development and activity of the immune system, and may modulate immune therapies, but there is little direct information about this control in vivo. We studied how the microbiome affects regulation of human immune cells in humanized mice. When humanized mice were treated with a cocktail of 4 antibiotics, there was an increase in the frequency of effector T cells in the gut wall, circulating levels of IFN-γ, and appearance of anti-nuclear antibodies. Teplizumab, a non-FcR-binding anti-CD3ε antibody, no longer delayed xenograft rejection. An increase in CD8+ central memory cells and IL-10, markers of efficacy of teplizumab, were not induced. IL-10 levels were only decreased when the mice were treated with all 4 but not individual antibiotics. Antibiotic treatment affected CD11b+CD11c+ cells, which produced less IL-10 and IL-27, and showed increased expression of CD86 and activation of T cells when cocultured with T cells and teplizumab. Soluble products in the pellets appeared to be responsible for the reduced IL-27 expression in DCs. Similar changes in IL-10 induction were seen when human peripheral blood mononuclear cells were cultured with human stool samples. We conclude that changes in the microbiome may impact the efficacy of immunosuppressive medications by altering immune regulatory pathways.

Aim: We aimed to compare white matter structural changes in specific tracts by diffusion tensor imaging (DTI) tractography in patients with bipolar disorder (BD) I, non-ill first-degree relatives (FDR) of the patients, and healthy controls (HC)., Methods: In a cross-sectional study, we studied right-handed subjects consisting of 16 euthymic BD I patients, 15 FDR, and 15 HC. The anterior thalamic radiation, uncinate fasciculus, corpus callosum, and cingulum bundle were reconstructed by DTI tractography. Mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were compared for group differences followed by post-hoc analysis., Results: The three groups did not differ in terms of sociodemographic variables. There were significant group differences in the FA values among the BD I patients, their FDR, and the HC for the corpus callosum, the dorsal part of the right cingulum bundle, the hippocampal part of the cingulum bundle bilaterally, and the uncinate fasciculus (P < 0.001). The FA values in the patients were significantly lower than in controls, and FDR also showed similar differences; however, they were smaller than those in patients. No significant difference was found between the groups for FA values of the dorsal part of the left cingulum bundle and anterior thalamic radiation. Significant differences were present for ADC values among the groups for the corpus callosum, the dorsal and hippocampal parts of the cingulum, anterior thalamic radiation, and uncinate fasciculus bilaterally (P < 0.01). The FA and ADC values did not correlate significantly with age or any clinical variables., Conclusion: These findings suggest that BD patients and their FDR show alterations in microstructural integrity of white matter tracts, compared to the healthy population., (© 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.)

Background and Purpose: Vein of Galen aneurysmal malformation (VGAM) is a rare developmental intracranial vascular malformation. We analyzed the clinical presentations, imaging findings, angioarchitecture, management options, and outcome in a demographically heterogeneous set of VGAM patients., Methods: We retrospectively analyzed cases of VGAM from our departmental archive collected between 1988 and January 2015. Demographic, clinical, therapeutic, and follow-up details were obtained for each patient from the available records., Results: We identified 36 patients with VGAM including 6 neonates, 18 infants, 7 children aged 2-10 years, and 5 adults. Macrocrania was the commonest presenting feature. Type of fistulae was mural in 14 and choroidal in 18 patients while 4 had a thrombosed sac at presentation. In 3 cases the dilated venous sac had connection with the deep venous system. Bilateral jugular atresia and stenosis were seen in 9 and 6 patients, respectively. Giant venous sac (>4 cm) was significantly correlated with mural type (p=0.0001). Dural arterial recruitment was seen in 4 patients including 3 adults. Among the 23 patients treated by endovascular means, 14 had a good outcome, 5 had a poor outcome, and 4 died. A significant correlation was noted between jugular atresia and poor outcome (p=0.003)., Conclusions: We encountered a wide range of demographic, clinical, and angiographic features in VGAM. Mural type malformations were associated with giant venous sacs. Good outcome after embolization was seen in selected neonates and in most of the infants, children, and adults. Jugular atresia was significantly associated with poor outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Fall is an important cause of injury morbidity in older adults. However, epidemiological information on fall is limited in low- and middle-income countries. We investigated the extent, pattern, characteristics, and context of falls in Chandigarh., Methods: A cross sectional survey was carried out among 300 persons (≥60 years), sampled from urban, rural and slums areas of Chandigarh, India from March 2011 to October 2012 using multistage cluster sampling. A pre-tested interview schedule was used and relevant medical examinations were conducted. Multivariable logistic regression was carried out to estimate Odds Ratio (OR) and 95% confidence interval (CI)., Results: In the past one year, 31% (92/300) respondents reported one or more falls. On an average 0.67 fall episodes occurred/person/year (202/300). Most (68%; 63/92) falls occurred at home; 75% (47/63) occurred while carrying out activities such as toileting, bathing, sleeping and eating etc. Injuries due to falls were reported by 67% (62/92). In these cases, lower extremities, 37% (23/62) were the most common site of injury. Eight percent (5/62) reported fractures. A general physician was consulted by 44% (27/62), and 11% (7/62) utilized emergency services whilst another 11% (7/62) of fall injuries required hospital admission. Risk of fall was higher among females (OR 1.6, 95%CI 1.0-2.8, p 0.068), those taking four or more medicines (OR 2.1, 95%CI 1.2-3.5, p 0.009) and having poor body balance (OR 1.9, 95%CI 1.0-3.4, p 0.037)., Conclusion: Fall injuries were common in older adults of Chandigarh. Large cohort studies are needed to identify risk factors particularly those related to home environment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Face recognition algorithms are generally trained for matching high-resolution images and they perform well for similar resolution test data. However, the performance of such systems degrades when a low-resolution face image captured in unconstrained settings, such as videos from cameras in a surveillance scenario, are matched with high-resolution gallery images. The primary challenge, here, is to extract discriminating features from limited biometric content in low-resolution images and match it to information rich high-resolution face images. The problem of cross-resolution face matching is further alleviated when there is limited labeled positive data for training face recognition algorithms. In this paper, the problem of cross-resolution face matching is addressed where low-resolution images are matched with high-resolution gallery. A co-transfer learning framework is proposed, which is a cross-pollination of transfer learning and co-training paradigms and is applied for cross-resolution face matching. The transfer learning component transfers the knowledge that is learnt while matching high-resolution face images during training to match low-resolution probe images with high-resolution gallery during testing. On the other hand, co-training component facilitates this transfer of knowledge by assigning pseudolabels to unlabeled probe instances in the target domain. Amalgamation of these two paradigms in the proposed ensemble framework enhances the performance of cross-resolution face recognition. Experiments on multiple face databases show the efficacy of the proposed algorithm and compare with some existing algorithms and a commercial system. In addition, several high profile real-world cases have been used to demonstrate the usefulness of the proposed approach in addressing the tough challenges.

Human TCRαβ(+) CD4(-)CD8(-) double-negative (DN) T cells represent a minor subset in peripheral blood, yet are important in infectious diseases and autoimmune responses. We examined the frequency of DN T cells in 17 patients after allogeneic hematopoietic stem cell transplantation (aHSCT) at 1, 2, 3, 6, and 12 months post-aHSCT and show that these cells increase early after aHSCT and decrease with time after aHSCT. DN T cells reside in the terminally differentiated effector (CD45RA(+)CCR7(-)) T-cell population and are polyclonal, determined by T-cell receptor Vβ CDR3 analysis. Gene expression analysis of ex vivo sorted DN T cells showed a distinct set of gene expression, including interleukin-8, as compared with CD4(+) or CD8(+) T cells. DN T cells contributed to MHC class I-restricted EBV-directed immune responses, defined by antigen-specific cytokine production and by detection of HLA-A*02:01-restricted EBV BMLF-1 (GLCTLVAML), LMP-2A (CLGGLLTMV), and HLA-A*24:02-restricted EBV BRLF-1 (DYCNVLNKEF) and EBNA3 (RYSIFFDY)-specific T cells. We created retroviral-transfected Jurkat cell lines with a Melan-A/MART-1-specific TCR(+) and the CD8α chain to study TCR(+) DN T cells in response to their nominal MHC class I/peptide ligand. We show that DN T cells exhibit increased TCRζ chain phosphorylation as compared with the TCR(+)CD8(+) transgenic T-cell line. DN T cells contribute to antigen-specific T-cell responses and represent an effector T-cell population that may be explored in immunotherapeutic approaches against viral infections or transformed cells.

Immune-deficient mice, reconstituted with human stem cells, have been used to analyze human immune responses in vivo. Although they have been used to study immune responses to xenografts, allografts, and pathogens, there have not been models of autoimmune disease in which the mechanisms of the pathologic process can be analyzed. We have found that reconstituted "humanized" mice treated with anti-CTLA-4 Ab (ipilimumab) develop autoimmune disease characterized by hepatitis, adrenalitis, sialitis, anti-nuclear Abs, and weight loss. Induction of autoimmunity involved activation of T cells and cytokine production, and increased infiltration of APCs. When anti-CTLA-4 mAb-treated mice were cotreated with anti-CD3 mAb (teplizumab), hepatitis and anti-nuclear Abs were no longer seen and weight loss did not occur. The anti-CD3 blocked proliferation and activation of T cells, release of IFN-γ and TNF, macrophage infiltration, and release of IP-10 that was induced with anti-CTLA-4 mAb. We also found increased levels of T regulatory cells (CD25(+)CD127(-)) in the spleen and mesenteric lymph nodes in the mice treated with both Abs and greater constitutive phosphorylation of STAT5 in T regulatory cells in spleen cells compared with mice treated with anti-CTLA-4 mAb alone. We describe a model of human autoimmune disease in vivo. Humanized mice may be useful for understanding the mechanisms of biologics that are used in patients. Hepatitis, lymphadenopathy, and other inflammatory sequelae are adverse effects of ipilimumab treatment in humans, and this study may provide insights into this pathogenesis and the effects of immunologics on autoimmunity., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Aneurysmal bone cyst is a locally aggressive benign tumor accounting for 3 % of all benign bone tumors. It most commonly arises from ends of long bones and relatively rare in flat bones. Clavicle is a very rare site for bone tumors with secondaries more common than primaries. Very few cases of aneurysmal bone cyst have been reported in literature. We hereby report interesting and a rare case of aneurysmal bone cyst of medial end of clavicle in a eight year old lady which was treated with extended curettage and calcium sulfate bone grafting.

Introduction: Type 1 diabetes is an organ-specific autoimmune disease, characterized by selective destruction of insulin-producing pancreatic β-cells by T-cell-mediated inflammation. Beginning with studies of cyclosporin A in the 1980s, but with more activity in the past decade, there have been a number of clinical trials to test whether immunotherapies can arrest the decline in C-peptide, which is associated with progression of type 1 diabetes leading to the metabolic instability that characterizes the disease. One of the most promising agents, teplizumab , is an FcR-nonbinding anti-CD3 monoclonal antibody that has been tested in Phase II - III clinical trials and was shown to preserve the C-peptide levels and reduce the need for exogenous insulin., Areas Covered: In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug's postulated mechanism of action and the identification of responders to therapy. We highlight the results of recent trials as well as the lessons that have been learned from the clinical trials involving selection of end points and the inclusion of diverse study populations., Expert Opinion: Teplizumab has been shown to preserve β cell function in patients; however, it does not represent a 'cure' for patients, and its efficacy does entail a significant advance in arresting the progression of the disease toward complete insulin deficiency and reliance on exogenous insulin.

Cytomegalovirus (CMV) reactivation may lead to CMV disease associated with high morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT); the identification of clinically relevant markers may aid in the identification of patients at increased risk for developing CMV-associated complications. We evaluated the phosphorylation of signal transducer and activator of transcription 5 (STAT5) in CD4(+) T cells, CD8(+) T cells, and TCRγδ T cells in response to stimulation with IL-7 or IL-2 after HSCT by analyzing blood samples taken monthly 1 to 6 months after HSCT. Patients were monitored weekly with a quantitative PCR from the time of engraftment for CMV viral load in whole blood until at least day 100 after HSCT. We identified a correlation between clinical outcome regarding CMV replication and the ability to respond to IL-7 and IL-2 defined by STAT5 phosphorylation (pSTAT5). Patients with recurrent or prolonged CMV replications had significantly lower pSTAT5 upon stimulation of T cells with either IL-7 or IL-2 at time points 1 through 3 than those without CMV replication (P < .05). This was also found after stimulation of CD8(+) T cells at time point 2 (P < .05). We conclude that reduced responses to IL-7, reflected by pSTAT5, may represent a clinically relevant functional biomarker for individuals at increased risk for CMV reactivation; our data may also aid in designing better strategies to improve anti-CMV immune responses without increasing the risk of developing graft-versus-host disease., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Goto R, You S, Zaitsu M, Chatenoud L, Wood KJ. Delayed anti-CD3 therapy results in depletion of alloreactive T cells and the dominance of Foxp3(+) CD4(+) graft infiltrating cells. Am. J. Transplant. 13(7), 1655-1664 (2013). Humanized Fc receptor nonbinding anti-CD3 monoclonal antibodies have been tested in patients with autoimmune diseases with the goal of inducing immune tolerance. However, the timing of drug administration may be an important determinant of the biologic effects, since not all T cells are equally affected, and there may be different subsets of cells involved during the evolution of immune responses. The study by Goto et al. showed that delayed administration of anti-CD3 therapy was more effective in depleting alloreactive T cells than administration at the time of transplant, and resulted in long-term survival of the graft by promoting infiltration of CD4 Tregs into the graft.

Objective: To examine the role of immune dysregulation in antibiotic-refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic- responsive arthritis and patients with antibiotic-refractory arthritis., Methods: Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic-responsive arthritis were compared with those from 16 patients with antibiotic-refractory arthritis, using flow cytometry, suppression assays, and cytokine assays., Results: Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25(high) population, a cell subset usually composed of FoxP3-positive Treg cells. In patients with antibiotic-refractory arthritis, this cell population often had fewer FoxP3-positive cells and a greater frequency of FoxP3-negative (Teff) cells compared with patients with antibiotic-responsive arthritis. Moreover, the expression of glucocorticoid-induced tumor necrosis factor receptor and OX40 on CD4+CD25(high) cells was significantly higher in the antibody-refractory group. Suppression assays showed that CD4+CD25(high) cells in patients with antibiotic-refractory arthritis did not effectively suppress proliferation of CD4+CD25- cells or secretion of interferon-γ and tumor necrosis factor α, whereas those cells in patients with antibiotic-responsive arthritis did suppress proliferation of CD4+CD25- cells and secretion of interferon-γ and tumor necrosis factor α. Finally, in the antibiotic-refractory group, higher ratios of CD25(high) FoxP3-negative cells to CD25(high) FoxP3-positive cells correlated directly with a longer duration of arthritis after antibiotic treatment., Conclusion: Patients with antibiotic-refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic-refractory arthritis., (Copyright © 2013 by the American College of Rheumatology.)

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates., Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29)., Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c., Conclusions: The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Purpose: To study the outcomes of toric and multifocal intraocular lens (IOL) implantation performed by resident surgeons., Setting: Parkland Health and Hospital System, Dallas, Texas, USA., Design: Case series., Methods: Patients seen between July 2008 and May 2011 and meeting inclusion criteria (including >1.0 diopter [D] of astigmatism in toric group and <0.75 D astigmatism in multifocal group) were offered implantation of the study IOLs. Major outcomes were uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) and, for the multifocal IOL, near visual acuity. Residents were surveyed about their knowledge regarding these IOLs., Results: Seventy-nine eyes of 60 patients received an Alcon Acrysof toric IOL. Eighteen eyes of 10 patients received an Alcon Acrysof Restor IOL. In the toric group, 57% of eyes achieved a postoperative UDVA of 20/25 or better and 90% achieved 20/40 or better. The CDVA was 20/25 or better in 92% of eyes. The mean refractive cylinder was 1.69 D preoperatively and 0.38 D postoperatively. In the multifocal group, 78% of patients achieved a UDVA of 20/25 or better and 94% achieved 20/40 or better. All patients had a CDVA of 20/25 or better. Near vision was Jaeger 3 or better in 94%. The survey showed that residents have a strong comfort level with preoperative and surgical techniques for premium IOLs after their experience in the residency setting., Conclusion: Residents in public county hospitals can be taught to use premium IOLs with good success rates, comparable to those in other published studies., Financial Disclosure: Dr. McCulley is a consultant to Alcon Laboratories, Inc., and Dr. Aggarwal is on the speaker's bureau for Alcon Laboratories, Inc. No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Noncontact biometrics such as face and iris have additional benefits over contact-based biometrics such as fingerprint and hand geometry. However, three important challenges need to be addressed in a noncontact biometrics-based authentication system: ability to handle unconstrained acquisition, robust and accurate matching, and privacy enhancement without compromising security. In this paper, we propose a unified framework based on random projections and sparse representations, that can simultaneously address all three issues mentioned above in relation to iris biometrics. Our proposed quality measure can handle segmentation errors and a wide variety of possible artifacts during iris acquisition. We demonstrate how the proposed approach can be easily extended to handle alignment variations and recognition from iris videos, resulting in a robust and accurate system. The proposed approach includes enhancements to privacy and security by providing ways to create cancelable iris templates. Results on public data sets show significant benefits of the proposed approach.

Background: Treatment of cancers with cytotoxic agents such as tyrosine kinase inhibiting drugs often, but not always, result in transient to permanent testicular dysfunction. Germ cells are important targets of many chemicals. Most of the drugs are genotoxins and induce irreversible effect on genetic makeup. These mutagenic changes are proportionally related to carcinogenesis. This is alarmingly dangerous in youth and children, since these effects last longer, affecting fertility or forming basis for carcinogenesis. There is paucity of reports on planned studies of imatinib on the testicular function. Hence, the study was planned to assess the effects of imatinib on biochemical markers of testicular functions in male Swiss albino mice., Materials and Methods: Male Swiss albino mice were treated with imatinib and sacrificed at the end of first, second, fourth, fifth, seventh, and tenth week after the last exposure to imatinib. The testis were removed, weighed, and processed for biochemical analysis., Results: The intratesticular testosterone level was significantly (P<0.001) reduced in treated groups and severe effect was observed on week 4 and 5. The intratesticular lactate dehydrogenase (LDH) level was significantly increased by imatinib in all treated groups up to week 5., Conclusion: Imatinib does affect testosterone and LDH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.

Purpose: To examine incidence, risk factors, and outcomes of glaucoma following infantile cataract extraction., Methods: A retrospective chart review of all patients who underwent cataract extraction between January 1, 1993, and December 31, 2006, at the Children's Medical Center in Dallas., Results: Sixty-four eyes met inclusion criteria, of which 11 eyes (17.2%) developed glaucoma during a mean follow-up of 65.1 ± 4.3 months. Age younger than 3 months at cataract diagnosis (odds ratio 4.89, P = .05) or cataract extraction (odds ratio 4.4, P = .047) and the presence of anterior chamber anomalies (odds ratio 8.0, P = .01) were the only risk factors found to have statistical significance for the development of glaucoma. Eight of 11 eyes with glaucoma (72.2%) required at least one surgical intervention. Three of 10 eyes (30%) had a final best-corrected visual acuity below 20/400 and another 4 eyes (40%) demonstrated some degree of amblyopia., Conclusion: Despite modern microsurgical techniques, infantile cataract surgery continues to pose a risk of secondary glaucoma. This was particularly true when cataract was diagnosed and/or extracted in patients younger than 3 months of age. Most eyes that developed glaucoma required surgical management and visual outcomes continue to be poor in this group.

Purpose: To examine the clinical and gonioscopic findings in patients with glaucoma associated with Sturge-Weber syndrome., Methods: Retrospective review of clinical findings of all patients with Sturge-Weber syndrome who presented between January 1978 and December 2003. Koeppe gonioscopy was performed under general anesthesia and findings were photographed when feasible. Iris color was documented by color sketch or photograph at initial presentation. Fisher exact test was used to determine whether the presence of heterochromia was statistically higher in the glaucomatous group., Results: Fifty-five patients who met inclusion criteria were identified, of whom 44 (80%) had glaucoma. Unilateral glaucoma was diagnosed in 30 eyes and bilateral glaucoma in 14 eyes, yielding 58 eyes with glaucoma and 52 eyes without. Gonioscopic examination revealed distinct anatomic abnormalities in the anterior chamber angle in 32 (55%) of the glaucomatous eyes in contrast to the normal fellow eyes in patients with unilateral glaucoma and to the patients without glaucoma. Heterochromia iridis with darker iris on the glaucomatous side was present in 11 of the 30 patients with unilateral glaucoma (37%, P < .001) but in none of the patients without glaucoma., Conclusion: The characteristics observed in the anterior chamber angle in this large, uniquely examined series are the first reported to the authors' knowledge and may support a role for neural crest derived anomalies in the pathogenesis of glaucoma in these infant eyes. Careful examination for heterochromia iridis may be judicious in these patients., (Copyright 2010, SLACK Incorporated.)

A better understanding of similarities and differences in the composition of the cellular immune system in non-human primates (NHPs) compared with human subjects will improve the interpretation of preclinical studies. It will also aid in addressing the usefulness of NHPs as subjects for studying chronic diseases, vaccine development and immune reconstitution. We employed high content colour flow cytometry and analysed simultaneously the expression of CD3, CD4, CD8alpha, CD8beta, CD16/CD56, CD45RA, CCR7, CD27, CD28, CD107a and the interleukin-7 receptor alpha-chain (IL-7Ralpha) in peripheral blood mononuclear cells (PBMCs) of 27 rhesus macaques and 16 healthy human subjects. Regulatory T cells (Tregs) were identified using anti-CD3, -CD4, -CD25, -FoxP3, and -IL-7Ralpha monoclonal antibodies. Responsiveness to IL-7 was gauged in a signal transducer and activation of transcription 5 (STAT-5) phosphorylation assay. Human and NHP PBMCs showed a similar T-cell composition pattern with some remarkable differences. Similarities: human and NHP CD4(+) and CD8(+) cells showed a similar STAT-5 phosphorylation pattern in response to IL-7. Multicolour flow cytometric analysis identified a CD4(+) CD8alphaalpha(+) CD8alphabeta(+) T-cell population in NHPs as well as in human subjects that expressed the degranulation marker CD107a and may represent a unique CD4(+) T-cell subset endowed with cytotoxic capacity. Differences: we identified in PBMCs from NHPs a higher proportion (5.16% in CD3(+) T cells) of CD8alphaalpha(+) T cells when compared with human donors (1.22% in CD3(+) T cells). NHP CD8alphaalpha(+) T cells produced tumour necrosis factor-alpha / interferon-gamma (TNF-alpha/IFN-gamma) or TNF-alpha, whereas human CD8alphaalpha(+) T cells produced simultaneously TNF-alpha/IFN-gamma and IL-2. A minor percentage of human CD8(+) T cells expressed CD25(bright) and FoxP3 (0.01%). In contrast, 0.07% of NHP CD8(+) T cells exhibited the CD25(bright) FoxP3(+) phenotype. PBMCs from NHPs showed less IL-7Ralpha-positive events in all T-cell subsets including CD4(+) Tregs (median 5%) as compared with human (median 12%). The data visualize commonalities and differences in immune cell subsets in humans and NHPs, most of them in long-lived memory cells and cells with suppressive functions. This provides a matrix to assess future efforts to study diseases and vaccines in NHPs.

Purpose: To identify the incidence of and risk factors for intraocular pressure (IOP) elevation after Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: Retrospective review was conducted of 68 consecutive DSAEK procedures alone, or in combination with phacoemulsification with intraocular lens implantation or exchange, performed by two surgeons at the University of Texas Southwestern Medical Center between 2005 and 2009. Eyes that developed IOP elevation above 21 mm Hg after DSAEK and requiring initiation or escalation of glaucoma therapy were evaluated., Results: Thirty-seven (54%) eyes showed IOP elevation responsive to medical treatment by a mean follow-up of 11.38 +/- 7.81 months. Six (8.8%) eyes required glaucoma surgery. In the eyes, which developed elevated IOP, gonioscopy did not reveal any new peripheral anterior synechiae formation. Prolonged topical steroid usage, rebubbling, combined DSAEK/cataract surgery, or repeat DSAEK were not significant factors (P>0.05) for development of elevated IOP, but history of previous glaucoma or ocular hypertension (OHTN) was significant (P=0.007)., Conclusions: Intraocular pressure elevation is not uncommon in eyes after DSAEK, but most cases can be controlled with conservative management. Intraocular pressure elevation post-DSAEK occurred by mechanisms other than peripheral anterior synechial angle closure. The only significant risk factor for development of elevated IOP in our series was a previous history of glaucoma or OHTN.

In an attempt to see if frog blood vessels possess a plasma membrane electron transport system, the postcaval vein and aorta isolated from Rana tigrina were tested for their ability to reduce ferricyanide, methylene blue, and 2,6-dichloroindophenol. While the dyes remained unchanged, ferricyanide was reduced to ferrocyanide. This reduction was resistant to inhibition by cyanide and azide. Heptane extraction or formalin fixation of the tissues markedly reduced the capability to reduce ferricyanide. Denuded aortas retained only 30% of the activity of intact tissue. Our results indicate that the amphibian postcaval vein and aorta exhibit plasma membrane electron transport.

Antitryptic, antichymotryptic and alpha 2- macroglobulin activities were measured in sera of normal nonpregnant and normal pregnant women and women with tubal ectopic pregnancy and molar pregnancies in the first 5 to 7 weeks of pregnancy calculated from the last menstrual period. While alpha 2-macroglobulin decreased in early normal pregnancy compared to nonpregnant state (p<0.001), in ectopic and molar pregnancies there was an increase in alpha 2- macroglobulin activity (p < 0.001), as compared to nonpregnant and normal pregnant women. Antitryptic activity did not increase in normal and ectopic pregnancy, however was increased in molar pregnancy (p < 0.01). Antichymotryptic activities did not show a change either in normal pregnancy or in cases of ectopic and molar pregnancy. Drop in alpha 2- macroglobulin activity to near normal levels in ectopic, 6 weeks post surgery, correlated well with the decrease in β-hCG. However, in molar pregnancy, alpha 2- macroglobulin remained elevated even when the β-hCG levels in serum returned to zero 10 weeks after surgery. The studies suggest a major role for circulating proteinase inhibitors especially alpha 2-macroglobulin in regulating proteinase activity in normal, ectopic and molar pregnancy.

Purpose: To report a case of Ahmed tube exposure secondary to Prokera implantation., Methods: Case report., Results: We present a 48-year-old woman who developed tube erosion after penetrating keratoplasty and Prokera implantation for dense vascularized corneal scar. The patient subsequently underwent wound revision with repeat scleral patch graft and closure of the conjunctival defect., Conclusions: The case presented demonstrates that caution should be exercised in using this implant in patients who have irregular elevations of the ocular surface because of glaucoma drainage devices.

Objective: Since it was first described, normal pressure hydrocephalus (NPH) and its treatment by means of cerebrospinal fluid (CSF) shunting have been the focus of much investigation. Whatever be the cause of NPH, it has been hypothesized that in this disease there occurs decreased arterial expansion and an increased brain expansion leading to increased transmantle pressure. We cannot measure the latter, but fortunately the effect of these changes (increased peak flow velocity through the aqueduct) can be quantified with cine phase-contrast magnetic resonance imaging (MRI). This investigation was thus undertaken to characterize and measure CSF peak flow velocity at the level of the aqueduct, before and after lumbar CSF drainage, by means of a phase-contrast cine MRI and determine its role in selecting cases for shunt surgery., Patients and Methods: 37 patients with clinically suspected NPH were included in the study. Changes in the hyperdynamic peak CSF flow velocity with 50 ml lumbar CSF drainage (mimicking shunt) were evaluated in them for considering shunt surgery., Results: 14 out of 15 patients who were recommended for shunt surgery, based on changes peak flow velocity after lumbar CSF drainage, improved after shunt surgery. None of the cases which were not recommended for shunt surgery, based on changes in CSF peak flow velocity after lumbar CSF drainage, improved after shunt surgery (2 out of 22 cases)., Conclusion: The study concluded that the phase-contrast MR imaging, done before and after CSF drainage, is a sensitive method to support the clinical diagnosis of normal pressure hydrocephalus, selecting patients of NPH who are likely to benefit from shunt surgery, and to select patients of NPH who are not likely to benefit from shunt surgery.

Biometrics-based authentication systems offer obvious usability advantages over traditional password and token-based authentication schemes. However, biometrics raises several privacy concerns. A biometric is permanently associated with a user and cannot be changed. Hence, if a biometric identifier is compromised, it is lost forever and possibly for every application where the biometric is used. Moreover, if the same biometric is used in multiple applications, a user can potentially be tracked from one application to the next by cross-matching biometric databases. In this paper, we demonstrate several methods to generate multiple cancelable identifiers from fingerprint images to overcome these problems. In essence, a user can be given as many biometric identifiers as needed by issuing a new transformation "key." The identifiers can be cancelled and replaced when compromised. We empirically compare the performance of several algorithms such as Cartesian, polar, and surface folding transformations of the minutiae positions. It is demonstrated through multiple experiments that we can achieve revocability and prevent cross-matching of biometric databases. It is also shown that the transforms are noninvertible by demonstrating that it is computationally as hard to recover the original biometric identifier from a transformed version as by randomly guessing. Based on these empirical results and a theoretical analysis we conclude that feature-level cancelable biometric construction is practicable in large biometric deployments.

Spinal dural arteriovenous fistulas (DAVFs), the most common of spinal vascular malformations, are AVFs in the dura mater of the nerve root and/or adjacent spinal dura. These fistulas are most often solitary and are fed by a single radicular artery that primarily supplies the dura mater. Multiple spinal DAVFs are rarely reported in the literature. Those that have been documented have been synchronous in their presentation in that they were found during the same examination or were present at the initial examination but missed and only recognized at the second examination. The authors report the case of a patient with two spinal DAVFs occurring at different spinal levels at different points in time (metachronous).

Background: A randomized double-blind placebo controlled clinical study was undertaken to investigate the safety and efficacy of a plant-based formulation (DCBT1234-Lung KR), which earlier through 2 trials was found to improve FEV1 and the quality of life of COPD patients., Objective: The efficacy of DCBT1234-Lung KR was assessed using pulmonary function tests, arterial blood gas (ABG) analyses and the clinical symptoms of COPD in a 6-month study period against a matching placebo and a biomedical drug combination (salbutamol+theophylline+bromhexine)., Methods: One hundred and five subjects aged between 35 and 85 years with a smoking history of more than 20 pack years, showing little or no improvement in FEV1 upon a bronchial challenge of 200 microg of inhaled salbutamol and exhibiting ABG percentage of less than 85% of oxygen saturation were taken up for the study. The study had 3 arms viz., the plant-based formulation (DCBT1234-Lung KR), placebo and salbutamol (12 mg/day) plus theophylline (300 mg/day) plus bromhexine (24 mg/day). The end point of the study was determined as an improvement of FEV1 by 200 mL and/or increased ABG values (>90% PaO2) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances., Results: DCBT1234-Lung KR patients showed statistically significant (95% level) improvement in FEV1 and PaO2 in comparison with salbutamol+theophylline+bromhexine and placebo patients. Twenty-three per cent of DCBT1234-Lung KR patients, 19% of salbutamol+theophylline+bromhexine group and 12% of placebo group patients showed the desired 200 mL improvement in FEV1 values in comparison with the other 2 arms. Improved PaO2 was observed in 15.4% of the DCBT1234-Lung KR patients while no improvement was seen with patients in any other arms. Symptoms like dyspnoea, wheezing, cough, expectoration, disability and sleep disturbances also significantly reduced in DCBT1234-Lung KR and the biomedical group patients, but not in the placebo arm., Conclusions: DCBT1234-Lung KR was equivalent, if not better than the present day treatment with salbutamol, theophylline and bromhexine combination in COPD patients and this was ascertained using FEV1 and ABG values.

Background: Plant-based medicine is the 3rd most popular choice of both adults (11%) and children (6%) suffering from Asthma. While several plant-based formulations have been reported for the treatment of asthma in the past, many authors have published their reservations on clinical trials carried out using complementary and alternative medicines., Objectives: The authors desired to eliminate the shortcomings of the earlier clinical trials carried out by many investigators in a structured study. Therefore, a 12-week randomized double-blind placebo-controlled clinical study was conducted to investigate the efficacy of a plant-based formulation (DCBT4567-Astha-15) in comparison with oral salbutamol, salbutamol + theophylline and a matching placebo in patients with reversible asthma., Methods: Ninety-four patients between 15 and 50 years of age, showing 15% improvement in forced expiratory volume in 1 s (FEV(1)) 15 min after a bronchial challenge of inhaled salbutamol (200 microg) were recruited, and the end point of the study was determined as a 15% improvement in FEV(1) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, sleep disturbances and respiration rate., Results: DCBT4567-Astha-15, salbutamol and salbutamol + theophylline patients showed statistically significant improvement in FEV(1), while placebo patients did not show any improvement. Fifty percent of DCBT4567-Astha-15, 48% of salbutamol, 58% of salbutamol + theophylline and 26% of placebo patients showed the desired 15% improvement in FEV(1). Improved mean FEV(1) values at the end of the trial indicated that the salbutamol - theophylline combination was superior followed by salbutamol and DCBT4567-Astha-15. Clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances were significantly reduced in DCBT4567-Astha-15 patients compared to patients of the other three arms., Conclusions: DCBT4567-Astha-15 was as efficacious as salbutamol (12 mg/day) or salbutamol (12 mg/day) in combination with theophylline (200 mg/day) in the treatment of reversible asthmatics. Quality of life of patients also improved with DCBT4567-Astha-15 drug treatment.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.

Ewing's sarcomas (ES) account for approximately 10% of primary malignant bone tumors. Primary Ewing's sarcoma of the skull is a very rare entity. We report a case of Ewing's sarcoma of the sphenoid bone in a 5-year-old boy. CT scan showed heterogeneously enhancing mass with associated spiculated new bone formation along the posterolateral wall of the orbit. Magnetic resonance (MR) imaging showed markedly heterogeneously signal intensity mass lesion containing areas of hemorrhage and fluid-fluid levels. Spiculated new bone formation and fluid-fluid levels had not been reported previously in skull Ewing's sarcomas and may be helpful features for preoperative diagnosis.

Reverse signalling of membrane-integrated ligands is a common phenomenon in the tumour necrosis factor (TNF) family and contributes to the pleiotropy of this pro-inflammatory cytokine and to the plasticity of the immune system in general. Transmembrane TNF (mTNF) itself can induce resistance to bacterial endotoxin in monocytes and can stimulate the immune activity of mitogen-activated, as well as of virus-infected, T cells. The aim of the present study was to investigate the influence of reverse signalling of mTNF on the allogeneic activity of CD4+ and CD8+ T cells against human microvascular endothelial cells (HMEC), as targets of various inflammatory responses. The proliferative potential of CD4+ T cells towards HMEC was attenuated by mTNF signalling, whereas stimulation of mTNF on CD8+ T cells increased their cytotoxic potential against HMEC. These effects were specific for reverse signalling of mTNF, as a blockade of the classical TNF-TNF receptor interaction by a neutralizing TNF receptor antibody had no effect. Cytokine profiling of the effector cells revealed that the anti-endothelial CD4+ T cells were of a T helper 2 (Th2) phenotype, whereas CD8+ T cells mainly produced cytotox. T cell 1 (Tc1) cytokines. From the results obtained in this study, we conclude that reverse signalling of mTNF differentially modulates CD4+ and CD8+ T-cell activity against allogeneic endothelial cells, which should be taken into account in settings of therapeutic cytokine antagonisms.

A 63-year-old man presented with marked swelling and inability to open the left eye immediately after laparoscopic nephrectomy for a left renal mass. A diagnosis of periorbital emphysema was made, and within 3 days, the emphysema spontaneously improved. This case demonstrates that periorbital emphysema, a rare condition, can be a benign complication of laparoscopic nephrectomy.

Treatment with 100 mg/kg of Clitoria ternatea aqueous root extract (CTR), for 30 days in neonatal and young adult age groups of rat, significantly increased acetylcholine (ACh) content in their hippocampi as compared to age matched controls. Increase in ACh content in their hippocampus may be the neurochemical basis for their improved learning and memory., (Copyright 2002 Elsevier Science B.V.)

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

A rapid and simple isocratic chromatographic procedure for the determination of insulin in human and rat plasma using reversed-phase (RP) high-performance liquid chromatography with an ultraviolet/visible detector is described. The method includes extraction of insulin from human and rat plasma into dichloromethane, followed by back-extraction into 0.05 N hydrochloric acid. The organic phase was evaporated under a stream of nitrogen. The aqueous phase was filtered and a 100 microliters aliquot was analyzed on a RP-C18 column eluted with a mobile phase consisting of a mixture of 74 vol of 0.2 M sodium sulfate anhydrous adjusted to pH 2.3 with phosphoric acid and 26 vol of acetonitrile. The flow rate was 1.2 ml/min and the wavelength was set at 214 nm. The calibration curve was linear over the range of 75-800 microIU/ml. The precision of the assay expressed as coefficients of variation was less than 6% over the entire concentration range. The recovery for insulin ranged from 79 to 81% from human and rat plasma, with coefficients of variation less than 6%. The intra- and interassay coefficients of variation were less than 5.7%. The limit of detection was 50 microIU/ml.