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Introduction: India grapples with a formidable health challenge, with an estimated 315 million adults afflicted with hypertension and 100 million living with diabetes mellitus. Alarming statistics reveal rates for poor treatment and control of hypertension and diabetes. In response to these pressing needs, the Community Control of Hypertension and Diabetes (CoCo-HD) program aims to implement structured lifestyle interventions at scale in the southern Indian states of Kerala and Tamil Nadu., Aims: This research is designed to evaluate the implementation outcomes of peer support programs and community mobilisation strategies in overcoming barriers and maximising enablers for effective diabetes and hypertension prevention and control. Furthermore, it will identify contextual factors that influence intervention scalability and it will also evaluate the program's value and return on investment through economic evaluation., Methods: The CoCo-HD program is underpinned by a longstanding collaborative effort, engaging stakeholders to co-design comprehensive solutions that will be scalable in the two states. This entails equipping community health workers with tailored training and fostering community engagement, with a primary focus on leveraging peer supportat scale in these communities. The evaluation will undertake a hybrid type III trial in, Kerala and Tamil Nadu states, guided by the Institute for Health Improvement framework. The evaluation framework is underpinned by the application of three frameworks, RE-AIM, Normalisation Process Theory, and the Consolidated Framework for Implementation Research. Evaluation metrics include clinical outcomes: diabetes and hypertension control rates, as well as behavioural, physical, and biochemical measurements and treatment adherence., Discussion: The anticipated outcomes of this study hold immense promise, offering important learnings into effective scaling up of lifestyle interventions for hypertension and diabetes control in low- and middle-income countries (LMICs). By identifying effective implementation strategies and contextual determinants, this research has the potential to lead to important changes in healthcare delivery systems., Conclusions: The project will provide valuable evidence for the scaling-up of structured lifestyle interventions within the healthcare systems of Kerala and Tamil Nadu, thus facilitating their future adaptation to diverse settings in India and other LMICs., (© 2024. The Author(s).)

The simplest way to produce high density hydrogen plasmas is to form an arc between the arcing electrode and the plasma chamber (cathode). For arc-based hydrogen plasma generation, a pulsed power supply that delivers 2 ms-long constant current pulse has been developed. This pulsed power supply employs a high frequency buck converter topology with a nonlinear filter inductor. This paper describes the development and testing of a constant current pulsed power supply that operates at 50 A and 550 V with a pulse width of 2 ms and a pulse repetition rate of 2 Hz. By changing the arc current, the arc impedance and the positive hydrogen ion current were also measured. The extraction of positive hydrogen ions was carried out using a three-electrode extraction design, which results in a current of 80 mA of positive hydrogen ions at an energy of 50 keV., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Neoliberal globalization contributes to the out-migration of labour from sending countries in the global South. Supported by multilateral organizations including the IMF and World Bank, the migration and development nexus holds that nations and households in migrant sending countries can migrate their way out of poverty. Two countries that embrace this paradigm, the Philippines and Indonesia, are major suppliers of migrant labour including domestic workers, and Malaysia is a primary destination country., Theory and Methods: We deployed a multi-scalar and intersectional lens to highlight the impact of global forces and policies, interacting with constructions of gender and national identity, to explore the health and wellbeing of migrant domestic workers in Malaysia. In addition to documentary analysis, we conducted face-to-face interviews with 30 Indonesian and 24 Filipino migrant domestic workers, five representatives from civil society organizations, three government representatives, and four individuals engaged in labour brokerage and the health screening of migrant workers in Kuala Lumpur., Results: Migrant domestic workers in Malaysia work long hours in private homes and are not protected by labour laws. Workers were generally satisfied with their access to health services; however, their intersectional status, which is both an outcome of, and contextualized by, the lack of opportunities in their own country, prolonged familial separation, low wages, and lack of control in the workplace, contributed to stress and related disorders-which we regard as the embodied manifestation of their migratory experiences. Migrant domestic workers eased these ill effects through self-care, spiritual practices, and the embrace of gendered values of self-sacrifice for the family as a form of solace., Conclusions: Structural inequities and the mobilization of gendered values of self-abnegation underpin the migration of domestic workers as a development strategy. While individual self-care practices were used to cope with the hardships of their work and family separation, these efforts did not remedy the harms nor redress structural inequities wrought by neoliberal globalization. Improvements in the long-term health and wellbeing of Indonesian and Filipino migrant domestic workers in Malaysia cannot focus solely on the preparation and maintenance of healthy bodies for productive labour, but must attend to workers' attainment of adequate social determinants of health, which challenges the migration as development paradigm. Neo-liberal policy instruments such as privatization, marketisation and commercialization of migrant labour have led to both host and home countries benefitting, but at the expense of the migrant domestic workers' well-being., (© 2023. The Author(s).)

Human aromatase enzyme is a microsomal cytochrome P450 and catalyzes aromatization of androgens into estrogens during steroidogenesis. For breast cancer therapy, third-generation aromatase inhibitors (AIs) have proven to be effective; however patients acquire resistance to current AIs. Thus there is a need to predict aromatase-related proteins to develop efficacious AIs. A machine learning method was established to identify aromatase-related proteins using a five-fold cross validation technique. In this study, different SVM approach-based models were built using the following approaches like amino acid, dipeptide composition, hybrid and evolutionary profiles in the form of position-specific scoring matrix (PSSM); with maximum accuracy of 87.42%, 84.05%, 85.12%, and 92.02% respectively. Based on the primary sequence, the developed method is highly accurate to predict the aromatase-related proteins. Prediction scores graphs were developed using the known dataset to check the performance of the method. Based on the approach described above, a webserver for predicting aromatase-related proteins from primary sequence data was developed and implemented at https://bioinfo.imtech.res.in/servers/muthu/aromatase/home.html. We hope that the developed method will be useful for aromatase protein related research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Selvaraj, Kaur. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Rhodopsin is a seven-transmembrane protein covalently linked with retinal chromophore that absorbs photons for energy conversion and intracellular signaling in eukaryotes, bacteria, and archaea. Haloarchaeal rhodopsins are Type-I microbial rhodopsin that elicits various light-driven functions like proton pumping, chloride pumping and Phototaxis behaviour. The industrial application of Ion-pumping Haloarchaeal rhodopsins is limited by the lack of full-length rhodopsin sequence-based classifications, which play an important role in Ion-pumping activity. The well-studied Haloarchaeal rhodopsin is a proton-pumping bacteriorhodopsin that shows promising applications in optogenetics, biosensitized solar cells, security ink, data storage, artificial retinal implant and biohydrogen generation. As a result, a low-cost computational approach is required to identify Ion-pumping Haloarchaeal rhodopsin sequences and its subtype., Results: This study uses a support vector machine (SVM) technique to identify these ion-pumping Haloarchaeal rhodopsin proteins. The haloarchaeal ion pumping rhodopsins viz., bacteriorhodopsin, halorhodopsin, xanthorhodopsin, sensoryrhodopsin and marine prokaryotic Ion-pumping rhodopsins like actinorhodopsin, proteorhodopsin have been utilized to develop the methods that accurately identified the ion pumping haloarchaeal and other type I microbial rhodopsins. We achieved overall maximum accuracy of 97.78%, 97.84% and 97.60%, respectively, for amino acid composition, dipeptide composition and hybrid approach on tenfold cross validation using SVM. Predictive models for each class of rhodopsin performed equally well on an independent data set. In addition to this, similar results were achieved using another machine learning technique namely random forest. Simultaneously predictive models performed equally well during five-fold cross validation. Apart from this study, we also tested the own, blank, BLAST dataset and annotated whole-genome rhodopsin sequences of PWS haloarchaeal isolates in the developed methods. The developed web server ( https://bioinfo.imtech.res.in/servers/rhodopred ) can identify the Ion Pumping Haloarchaeal rhodopsin proteins and their subtypes. We expect this web tool would be useful for rhodopsin researchers., Conclusion: The overall performance of the developed method results show that it accurately identifies the Ionpumping Haloarchaeal rhodopsin and their subtypes using known and unknown microbial rhodopsin sequences. We expect that this study would be useful for optogenetics, molecular biologists and rhodopsin researchers., (© 2023. The Author(s).)

Objective: Patient monitoring in general wards primarily involves intermittent observation of temperature, heart rate (HR), respiratory rate (RR) and blood pressure performed by the nursing staff. Several hours can lapse between such measurements, and the patient may go unobserved. Despite the growing widespread use of sensors to monitor vital signs and physical activities of healthy individuals, most acutely ill hospitalised patients remain unmonitored, leaving them at an increased risk. We investigated whether a contactless monitoring system could measure vital parameters, such as HR and RR, in a real-world hospital setting., Design: A cross-sectional prospective study., Setting and Participants: We examined the suitability of employing a non-contact monitoring system in a low-acuity setup at a tertiary care hospital in India. Measurements were performed on 158 subjects, with data acquired through contactless monitoring from the general ward and dialysis unit., Outcome Measures: Vital parameters (RR and HR) were measured using a video camera in a non-acuity setting., Results: Three distinct combinations of contactless monitoring afforded excellent accuracy. Contactless RR monitoring was linearly correlated with Alice NightOne and manual counts, presenting coefficients of determination of 0.88 and 0.90, respectively. Contactless HR monitoring presented a coefficient of determination of 0.91. The mean absolute errors were 0.84 and 2.15 beats per minute for RR and HR, respectively., Conclusions: Compared with existing Food and Drug Administration-approved monitors, the findings of the present study revealed that contactless monitoring of RR and HR accurately represented study populations in non-acuity settings. Contactless video monitoring is an unobtrusive and dependable method for monitoring and recording RR and HR. Further research is needed to validate its dependability and utility in other settings, including acute care., Trial Registration Number: CTRI/2018/11/016246., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Occupational therapy (OT) enhances functional independence in the daily activities of people with disabilities and subsequently their quality of life. Research in OT generates evidence to provide safe and effective services to the disabled. However, OT research in India has been shown to have various methodological limitations. These methodological limitations are expected to impact the quality of OT research as well as the evidence derived from this research to inform decision-making in rehabilitation. The majority of the OT research is disseminated and promoted through the All India Occupational Therapists' Association's (AIOTA) annual national conference (ANC). Analyzing the abstracts, selected for the presentation at the ANC could help understand and strategically improve the quality of OT research in India., Objectives: To explore and describe the quality of OT research in India., Study Design: Descriptive analysis., Methods: Descriptive, nonsystematic review and analysis of the key methodological aspects of the conference abstracts submitted for the AIOTA ANC published in the Indian Journal of OT (IJOT) from 2017 to 2021 was carried out. Information related to the methodological aspects of the research abstracts was extracted using a data extraction form and the data were synthesized and reported descriptively., Results: About 218 abstracts had been selected for either poster or oral presentations in the AIOTA ANC. All the abstracts were included for the review. A total of 8055 participants were recruited for the studies conducted from 2017 to 2021. About 5757 (72%) of the participants were recruited for cross-sectional studies. Nearly 72 (33%) of the abstracts presented were related to cross-sectional studies, 52 (24%) were case studies and 66 (30%) were experimental studies. However, research designs implying highest level of evidence such as systematic reviews were only 4 (2%) and randomized controlled trials were only 9 (4%) with 297 participants. Notably, 203 (98%) of the all the studies evaluating effectiveness of interventions or aiming to investigate associations reported positive results with statistically significant improvements and associations., Conclusion: The review provides invaluable information related to the quality of OT research in India. It implies the need to improve the scientific rigor of the evidence generated in relation to OT research in India. This review also implies the need for a radical change and strengthening of OT research within OT education and professional practice in India. National and global OT associations need to prioritize good quality OT research by enhancing the research skills and competencies of OTs in India. This could help promote evidence-based OT science and develop the OT profession in the world's second-most populous country. In addition, it is also expected to encourage those OT researchers who have been striving to build OT research standards in India., Competing Interests: Conflicts of Interest There are no conflicts of interest.

Michler's ketone (4,4' bis(N,N-dimethylamino)benzophenone) mk is a potential ultraviolet radiation (UVR) absorber in various materials. In this study, we have tested the UVR filtering ability of mk on cotton fabric. The beta-cyclodextrin (β-CD) inclusion complex of mk enhances ultraviolet protection factor (UPF) drastically. The impact of β-CD on the UVR filtering of mk are demonstrated by investigating the guest (mk:absorbers)-host (β-CD:enhancer) inclusion complex. Spectral and molecular docking analysis of mk:β-CD complex infers the vertical insertion of the guest molecule by positioning -C=O group of mk at the center of the host molecule with the exclusion of the terminal atoms of guest molecule outside the β-CD cavity. Thus, the host; β-CD renders an inflexible fit to the guest:mk. The inflexible fit of mk into the β-CD cavity enhances the UVR dissipation when it is incorporated on the poplin cotton fabric. With UPF = 46 mk:β-CD complex is proposed as a potential UVR absorber suitable for manufacturing sun protective textiles. The holding of mk by β-CD enhances the UVR dissipation and hence facilitates the native red-shifted emission and non-radiative relaxation by the formation of twisted intramolecular charge transfer in mk., (© 2022 American Society for Photobiology.)

Integrated photonic architectures based on optical waveguides are one of the leading candidates for the future realisation of large-scale quantum computation. One of the central challenges in realising this goal is simultaneously minimising loss whilst maximising interferometric visibility within waveguide circuits. One approach is to reduce circuit complexity and depth. A major constraint in most planar waveguide systems is that beamsplitter transformations between distant optical modes require numerous intermediate SWAP operations to couple them into nearest neighbour proximity, each of which introduces loss and scattering. Here, we propose a 3D architecture which can significantly mitigate this problem by geometrically bypassing trivial intermediate operations. We demonstrate the viability of this concept by considering a worst-case 2D scenario, where we interfere the two most distant optical modes in a planar structure. Using femtosecond laser direct-writing technology we experimentally construct a 2D architecture to implement Hong-Ou-Mandel interference between its most distant modes, and a 3D one with corresponding physical dimensions, demonstrating significant improvement in both fidelity and efficiency in the latter case. In addition to improving fidelity and efficiency of individual non-adjacent beamsplitter operations, this approach provides an avenue for reducing the optical depth of circuits comprising complex arrays of beamsplitter operations.

Introduction: The use of artificial intelligence (AI) to support the diagnosis of acute ischaemic stroke (AIS) could improve patient outcomes and facilitate accurate tissue and vessel assessment. However, the evidence in published AI studies is inadequate and difficult to interpret which reduces the accountability of the diagnostic results in clinical settings. This study protocol describes a rigorous systematic review of the accuracy of AI in the diagnosis of AIS and detection of large-vessel occlusions (LVOs)., Methods and Analysis: We will perform a systematic review and meta-analysis of the performance of AI models for diagnosing AIS and detecting LVOs. We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines. Literature searches will be conducted in eight databases. For data screening and extraction, two reviewers will use a modified Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. We will assess the included studies using the Quality Assessment of Diagnostic Accuracy Studies guidelines. We will conduct a meta-analysis if sufficient data are available. We will use hierarchical summary receiver operating characteristic curves to estimate the summary operating points, including the pooled sensitivity and specificity, with 95% CIs, if pooling is appropriate. Furthermore, if sufficient data are available, we will use Grading of Recommendations, Assessment, Development and Evaluations profiler software to summarise the main findings of the systematic review, as a summary of results., Ethics and Dissemination: There are no ethical considerations associated with this study protocol, as the systematic review focuses on the examination of secondary data. The systematic review results will be used to report on the accuracy, completeness and standard procedures of the included studies. We will disseminate our findings by publishing our analysis in a peer-reviewed journal and, if required, we will communicate with the stakeholders of the studies and bibliographic databases., Prospero Registration Number: CRD42020179652., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The European Health Literacy Survey Questionnaire (HLS-EU-Q47) is becoming a widely used tool to measure health literacy (HL), including in Malaysia. There are efforts to reduce the 47-item scale to parsimonious short item scales that still reflect the assumptions and requirements of the conceptual model. This study used confirmatory factor analysis to reduce the 47-item scale to a short scale that can offer a feasible HL screening tool with sufficient psychometric properties., Methods: A cross-sectional survey was conducted on the Malaysian population based on ethnic distribution to ensure that the short version instrument reflects the country's varied ethnicities. The survey was administered by well-trained interviewers working for the Ministry of Health Malaysia. A total of 866 responses were obtained. Data was analysed using multi-factorial confirmatory factor analysis (CFA) with categorical variables., Results: The analysis resulted in a satisfactory 18-item model. There were high correlations among the 18 items. The internal consistency reliability was robust, with no floor/ceiling effects. These results represented equivalence and consistency among the responses to items, suggesting that these items were homogenous in measuring Malaysian health literacy. The strong convergent and discriminant validity of the model makes the proposed 18 items a suitable short version of the health literacy instrument for Malaysia., Conclusions: The researchers propose the 18-item instrument to be named HLS-M-Q18. This short version instrument may be used in measuring health literacy in Malaysia as it achieved robust reliability, structural validity and construct validity that fulfilled goodness-of-fit criteria.

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causes the coronavirus disease 2019 (COVID-19). It quickly became pandemic, and so did a new concern about COVID-19 infections increasing the risk for cerebrovascular diseases. There is an association between COVID-19 illness in people and acute stroke. Several chemical, mechanical, and/or inflammatory central nervous system pathologies are proposed to explain how this viral infection might induce acute cerebrovascular disease. Timely available evaluation and/or intervention is imperative for patients with concerns about acute cerebrovascular issues., (© 2020 S. Karger AG, Basel.)

Background: Dengue fever is the most prevalent form of flavivirus infection in humans. We have investigated whether corneoscleral tissue of the donor affected by dengue virus (DENV) harbors the virus., Purpose: To identify the risk for viral transmission through corneal transplants in areas where DENV circulates., Methods: Excised corneoscleral tissue from a cadaver with a history of viral hemorrhagic fever was analyzed using reverse transcriptase-polymerase chain reaction for the presence of DENV and chikungunya virus (CHIV)., Results: DENV was detected in RNA extracted from the donor corneoscleral rim. Further genotyping of the viral isolate from the virus-infected cell harvest revealed DENV type 3 as the causative agent. CHIV was not detected., Conclusions: The data presented in this study recommend the implementation of polymerase chain reaction for detection of DENV and CHIV to analyze excised corneoscleral tissue of a donor with viral hemorrhagic fever.

Purpose: To evaluate the effect of lignocaine on growth and apoptosis indication of primary human Tenon's capsule fibroblast (HTFs) in an in vitro model., Patients and Methods: Tenon's capsule tissue obtained from patients undergoing trabeculectomy were grown in cell culture medium. The effect of different concentrations of lignocaine (0.5, 1.0, 1.5, and 2%) on the morphology and growth of the fibroblasts was studied using microscopy, cell viability, and proliferation assay, and apoptosis was detected using the FITC Annexin V Apoptosis Kit., Results: Morphological changes similar to those of apoptotic cells, including cytoplasmic vacuolation, shrinkage, and rounding were visualized in the cells treated with concentrations greater than 1.0% (i.e., 1.5, 2.0%). Though proliferation inhibition was found with all four concentrations (0.5-2.0%), the viability of cells decreased from 1.0% lignocaine., Conclusion: 0.5% lignocaine prevents proliferation of fibroblasts without causing apoptosis in vitro., (Copyright © 2018 by S. Karger AG, Basel.)

Pyrethroid-mediated changes on microelectrode array (MEA) parameters, such as mean firing rate (MFR), mean burst rate (MBR), and number of active channels (nAC) were investigated by exposing neuronal networks to cumulative concentrations (0.01, 0.1, 1, 10, and 100μM) of pyrethroids (Type-1, bifenthrin and permethrin; Type-2, beta-cyfluthrin, cypermethrin, deltamethrin, and lambda-cyhalothrin). The average MFR, MBR, and nAC increased for all pyrethroids (except nAC for deltamethrin) at lower concentrations and decreased at higher concentrations. The increase in the average MFR, MBR, and nAC was not statistically significant in most of the cases. Increase in MFR, MBR, and nAC was observed in 19/19, 18/19, and 12/19 individual experiments, respectively, at lower concentrations. The IC 50 s calculated on MEA parameters were more or less similar. The relative potencies calculated on the IC 50 s of MEA parameters had a strong positive correlation. These observations indicate that the MEA parameters MFR, MBR, and nAC follow the same trend for pyrethroid-mediated changes, and provide a similar outcome. The rank orders of relative potencies on the IC 50 s of the MEA parameters distinguish type-1 pyrethroids from type-2 pyrethroids, with type-2 being more potent. As increase in MFR at the lower concentrations of pyrethroids was observed in all the individual experiments (19/19), it may be considered as the characteristic effect of pyrethroids on neuronal excitability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To determine the rate of occurrence and genotypes of Epstein-Barr Virus (EBV) among pediatric renal and liver transplants recipients., Design: Observational study., Setting: Vision Research Foundation referral center and Institute of Liver Disease and Transplantation, Chennai, India., Participants: 70 pediatric solid organ transplant recipients and 60 voluntary healthy donors., Methods: Polymerase chain reaction (PCR) for detection and genotyping of EBV were carried out using genes targeting Viral capsid antigen, Nuclear antigen 1, 2 and 3, followed by real time PCR for viral load determination and further confirmed by phylogenetic analysis., Results: EBV was detected in 35 (51.4%) samples (32 liver and 4 renal transplants) with high viral load. Type A was detected in 33 samples, Type B in 2 liver transplant patients, and co-infection in one liver transplant patient who developed Post-transplant Lymphoproliferative Disorder (PTLD). Real time PCR results correlated with conventional PCR. The mean viral load for patients who did not develop PTLD was 50,424 copies/mL. Overall EBV load in patient with PTLD ranged from 1,40,392 copies/mL prior to PTLD diagnosis to 62,124 copies /mL post treatment., Conclusion: EBV infection is the high risk factor for PTLD after liver transplantation. PCR targeting of EBV can be applied to diagnose EBV infections and monitor treatment for EBV in pediatric solid organ transplant recipients.

Introduction: Infectious mononucleosis (IM) caused by the Epstein-Barr virus (EBV) is commonly diagnosed by detection of antibodies in the patient's sera. Differentiation of acute from chronic and differential diagnosis of EBV-induced IM from IM-like syndrome caused by human cytomegalovirus (CMV) is important. The objective of this study was to standardize and use polymerase chain reaction (PCR) for diagnosis of EBV and evaluate it against enzyme-linked immunosorbent assay (ELISA)., Methodology: ELISA for detection of IgM and IgG antibodies to viral capsid antigen (VCA) and PCR targeting the VCA and EBNA1 gene of EBV and mtrII gene of CMV were performed on180 peripheral blood samples collected from 180 patients with suspected IM. The analytical sensitivity of PCR was evaluated against that of ELISA., Results: Using the standard serological profile as the reference, the EBV-VCA gene was detected in 41 (95%) of 45 samples collected from patients with early primary infections, in 41 (54%) of 75 with recent primary infections, and in7 (17%) of 39 with past infections. The result of VCA PCR was statistically significant in virus detection during early or primary stage of infection. Nineteen (49%) EBV-seropositive samples were positive for CMV by PCR. All control samples tested negative for both VCA and EBNA1by PCR., Conclusions: VCA PCR is sensitive for the detection of EBV DNA in the early or primary stage of infection and can be considered a reliable method to rule out the cross-reactivity and differential diagnosis of EBV-induced IM from IM-like syndrome.

Purpose: To evaluate the diagnostic value of PCR on aqueous humour for detection and genotyping of Epstein Bar Virus in patients with viral retinitis., Methods: 70 AH samples were collected from 20 HIV positive patients with clinically suspected viral retinitis and 25 patients with serpignous choroiditis and 25 AH from patients undergoing cataract surgery. PCR was performed to screen HHV-1 to HHV-5, Mtb and Toxoplasma gondii. Genotype prevalence was confirmed by phylogenetic analysis targetig EBV., Results: EBV was detected in 17 (37.7%) samples. Genotyping to subtype EBV, revealed the circulation of only one subtype (Type 1). PCR results for other infective agents were negative except for the presence of CMV in 5 (11.1%) AH., Conclusion: The application of PCR to detect genotypes can be used as an epidemiological tool for clinical management. To our knowledge this is the first report on genotyping of EBV performed on intra ocular samples.

Background: Over the last two decades, numerous studies have indicated the feasibility of minimally invasive surgery for early cervical cancer without compromising the oncological outcome., Objective: Systematic literature review and meta analysis aimed at evaluating the outcome of laparoscopic and robotic radical hysterectomy (LRH and RRH) and comparing the results with abdominal radical hysterectomy (ARH)., Search Strategy: Medline, PubMed, Embase, Cochrane library and Reference lists were searched for articles published until January 31(st) 2011, using the terms radical hysterectomy, laparoscopic radical hysterectomy, robotic radical hysterectomy, surgical treatment of cervical cancer and complications of radical hysterectomy., Selection Criteria: Studies that reported outcome measures of radical hysterectomy by open method, laparoscopic and robotic methods were selected., Data Collection and Analysis: Two independent reviewers selected studies, abstracted and tabulated the data and pooled estimates were obtained on the surgical and oncological outcomes., Results: Mean sample size, age and body mass index across the three types of RH studies were similar. Mean operation time across the three types of RH studies was comparable. Mean blood loss and transfusion rate are significantly higher in ARH compared to both LRH and RRH. Duration of stay in hospital for RRH was significantly less than the other two methods. The mean number of lymph nodes obtained, nodal metastasis and positive margins across the three types of RH studies were similar. Post operative infectious morbidity was significantly higher among patients who underwent ARH compared to the other two methods and a higher rate of cystotomy in LRH., Conclusions: Minimally invasive surgery especially robotic radical hysterectomy may be a better and safe option for surgical treatment of cervical cancer. The laparoscopic method is not free from complications. However, experience of surgeon may reduce the complications rate.

Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in premature infants and has been linked with viral antigens in as much as 40% of cases in single-center cohorts. We examined 28 tissue sections from surgically resected ileum from 27 preterm infants with NEC from 2 separate institutions for 15 common bacterial, viral, and parasitic gastrointestinal pathogens using multiplex reverse transcriptase polymerase chain reaction amplification and suspension array detection methods. We did not detect infectious enteritis pathogens in any of the NEC tissues and conclude that gastrointestinal pathogens are a rare cause of NEC.

Endometrial stromal sarcomas are rare malignant tumors of the uterus, and most of the information available in literature is based on small series or case reports. A proper preoperative diagnosis is difficult and in most cases the diagnosis is confirmed after hysterectomy for a presumed benign disease. Endometrial sampling, ultrasound, and magnetic resonance imaging can provide diagnostic clues. Total hysterectomy with bilateral salpingo-oopherectomy is the main line of management and for early disease complete cure is a reality. Ovarian conservation may be possible in young women with early stage disease and the role of lymphadenectomy is controversial. Adjuvant hormone therapy in the form of progesterone, gonadotropin releasing hormone analogues, and aromatase inhibitors are found to be effective in preventing recurrences. Hormone therapy, radiotherapy and surgical excision of the metastasis are recommended for recurrences.

Micrographia is a condition, in which the sufferers write with small handwriting. Hypophonia is described as low volume speech. Both conditions have been described in neurological conditions, such as lesions in the deep white matter of the brain, Parkinson's disease etc. In this case report, we are presenting a 22-years-old female patient with anorexia nervosa who suffered from both these conditions. The patient also suffered from epilepsy. The onset of these symptoms, progress, and current status provides scope for discussing both the possible biological and psychodynamic etiology for these symptoms in this young woman., (© 2009 by Wiley Periodicals, Inc.)

Granulosa cell tumours are rare, potentially malignant sex cord stromal tumours of the ovary. They are unique in their presentation and histological features. Many of them are hormone-producing and this property helps them to present early unlike other epithelial ovarian cancers. As a result, most of them will be in an early stage at the time of initial diagnosis. The tumour can manifest in young girls as a juvenile form and conservative management with unilateral salpingo-opherectomy may be an option in them as 95% are unilateral. Surgery is the treatment of choice and initial staging laparatomy a determinant recurrence. Advance stage of the tumour, its size (>5 cm), mitotic figures (>10/hpf), nuclear atypia and absence of call-exner bodies are poor prognostic factors. Such tumours are characterised by late recurrences and this necessitates a prolonged follow-up. Tumour markers such as inhibin and estradiol are useful in follow-up. Chemotherapy, radiotherapy and hormone replacement therapy have very little role in the initial treatment and may be suggested in case of recurrences. With appropriate treatment, a better survival rate can be achieved as against other ovarian malignancies. Methods used for locating, selecting and synthesising data: A search of Medline and Cochrane data base for the period from 1999 to 2010 was carried out to include relevant systematic reviews, meta-analysis, randomised controlled and other clinical and rare case reports. The date of the last search was January 2010.

Lifestyle factors related to breast cancer risk were examined in a case-control study nested in a cohort in Karunagappally, Kerala, South India. We sought interviews with all the residents in Karunagappally with the population of 385,103 (191,149 males and 193,954 females) in the 1991 census and established a cohort of 359,619 (93% of the population in 1991) in 1990. For analysis 264 breast cancer cases with age > or = 20 years were selected from 438 breast cancer cases reported during the period 1990-2004 and for each case 3 non-cancer controls were randomly selected matched for age, religion and place of residence through the Cancer Registry, Karunagappally. Conditional logistic regression was used for the analysis. In the present study, in addition to a low number of pregnancies (P <0.001 and P for trend <0.001), more frequent intake of roots and tubers except tapioca (cassava) (OR for > or = 5 times =1.56, 95% CI=1.09, 3.09, P for trend <0.05), milk drinking (OR=1.78, 95% CI=1.17-2.69, P<0.01) and consumption of chicken meat (OR=1.84, 95% CI=1.09-3.09, P<0.05) were found to increase breast cancer risk. The present study further showed that consumption of tapioca which is a commonly used food item in South India, particularly in Kerala, reduced breast cancer risk (OR=0.55, 95% CI=0.37-0.83, P<0.01). Risk analysis was attempted among pre- and post-menopausal women separately and similar odds ratio were obtained. Consumption of tapioca (cassava) decreased risk of developing breast cancer among premenopausal women (P<0.001 and OR=0.35, 95% CI=0.18, 0.65) and a low number of pregnancies (P<0.01), consumption of roots & tubers (P<0.05), usage of chicken meat (P=0.05) increased the risk of breast cancer among post-menopausal women. Further studies seem warranted to confirm the possible protective effect of tapioca consumption. There is an increasing need of breast cancer prevention programs responsive to the cultural practices of the people and the study results should provide leads to cancer control programs especially in rural areas.

The coastal belt of Karunagappally, Kerala, India, is known for high background radiation (HBR) from thorium-containing monazite sand. In coastal panchayats, median outdoor radiation levels are more than 4 mGy y-1 and, in certain locations on the coast, it is as high as 70 mGy y-1. Although HBR has been repeatedly shown to increase the frequency of chromosome aberrations in the circulating lymphocytes of exposed persons, its carcinogenic effect is still unproven. A cohort of all 385,103 residents in Karunagappally was established in the 1990's to evaluate health effects of HBR. Based on radiation level measurements, a radiation subcohort consisting of 173,067 residents was chosen. Cancer incidence in this subcohort aged 30-84 y (N = 69,958) was analyzed. Cumulative radiation dose for each individual was estimated based on outdoor and indoor dosimetry of each household, taking into account sex- and age-specific house occupancy factors. Following 69,958 residents for 10.5 years on average, 736,586 person-years of observation were accumulated and 1,379 cancer cases including 30 cases of leukemia were identified by the end of 2005. Poisson regression analysis of cohort data, stratified by sex, attained age, follow-up interval, socio-demographic factors and bidi smoking, showed no excess cancer risk from exposure to terrestrial gamma radiation. The excess relative risk of cancer excluding leukemia was estimated to be -0.13 Gy-1 (95% CI: -0.58, 0.46). In site-specific analysis, no cancer site was significantly related to cumulative radiation dose. Leukemia was not significantly related to HBR, either. Although the statistical power of the study might not be adequate due to the low dose, our cancer incidence study, together with previously reported cancer mortality studies in the HBR area of Yangjiang, China, suggests it is unlikely that estimates of risk at low doses are substantially greater than currently believed.

The association of lung cancer incidence with bidi smoking was examined using a cohort study data in Karunagappally, Kerala, India. We sought interview of all the residents in Karunagappally with the population of 385,103 in 1991 census, and established a cohort of 359,619 (93% of the population in 1991) in the 1990s. There were 65,829 men aged 30-84 at interview after excluding those diagnosed as cancer or died of any cause before 1997. Among them, 212 newly diagnosed lung cancer cases were ascertained during the 8-year period between 1997 and 2004 through Karunagappally Cancer Registry. The relative risk (RR) of lung cancer was obtained from Poisson regression analysis of grouped data. Lung cancer incidence was relatively high among Moslem people and those with lower educational history. When taking into account attained age, religion and education, the RR between current bidi smokers and those who had never smoked bidis was 3.9 (95%CI = 2.6-6.0, p < 0.001). The lung cancer risk did not return to the level of non-smokers within 10 years after cessation. In further analyses using only those never smoked cigarettes to examine the effect of bidi smoking alone on lung cancer risk, current smokers of bidis had the RR of 4.6 (95%CI = 2.5-8.5, p < 0.001). Lung cancer incidence increased with larger amounts of bidi smoked a day (p < 0.001), with longer durations of smoking bidis (p < 0.001), and with younger ages starting smoking bidis (p < 0.001). Immediate measures should be taken to stop bidi smoking, which is common in south Asia., (Copyright 2008 Wiley-Liss, Inc.)

Purpose: ABI-007 is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. This multicenter phase II study was designed to evaluate the efficacy and safety of ABI-007 for the treatment of metastatic breast cancer (MBC)., Patients and Methods: Sixty-three women with histologically confirmed and measurable MBC received 300 mg/m2 ABI-007 by intravenous infusion over 30 minutes every 3 weeks without premedication. Forty-eight patients received prior chemotherapy; 39 patients received no prior treatment for metastatic disease., Results: Overall response rates (complete or partial responses) were 48% (95% CI, 35.3% to 60.0%) for all patients. For patients who received ABI-007 as first-line and greater than first-line therapy for their metastatic disease, the respective response rates were 64% (95% CI, 49.0% to 79.2%) and 21% (95% CI, 7.1% to 42.1%). Median time to disease progression was 26.6 weeks, and median survival was 63.6 weeks. No severe hypersensitivity reactions were reported despite the lack of premedication. Toxicities observed were typical of paclitaxel and included grade 4 neutropenia (24%), grade 3 sensory neuropathy (11%), and grade 4 febrile neutropenia (5%). Patients received a median of six treatment cycles; 16 patients had 25% dose reductions because of toxicities, and two of these patients had subsequent dose reductions., Conclusion: ABI-007, the first biologically interactive albumin-bound form of paclitaxel in the nanoparticle state, uses the natural carrier albumin rather than synthetic solvents to deliver paclitaxel and allows for safe administration of high paclitaxel doses without premedication, resulting in significant antitumor activity in patients with MBC, including those receiving the drug as first-line therapy.

The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique. The expression index of these molecules and various clinicopathological factors were statistically correlated with treatment end points to assess its prognostic efficacy after following up these patients up to a maximum of 48 months with a median of 23 months. Rb pathway proteins, Rb (P=0.016), cyclin D1 (P=0.0001) and p16 (P=0.012) showed significant association with disease-free survival, and p16 (P=0.041) and cyclin D1 (P=<0.0001) with the overall survival. Among p53 pathway proteins studied, only p53 expression index showed association with both disease-free survival and overall survival. Multivariate analyses confirmed that the biological variables, cyclin D1 and p16 and the clinical variable, 'stage of disease' were independent predictors of disease-free survival and overall survival. Subgrouping of the patients on the basis of p16 and cyclin D1 expression revealed that the subgroup having downregulation of p16 and overexpression of cyclin D1 exhibited the worst disease-free survival and overall survival compared to the other subgroups. The present data showed that disabling of the Rb and p53 pathways were frequent events in oral carcinoma. The study also demonstrated that the Rb pathway proteins are comparatively more important than p53 pathway proteins for the prognostication of oral carcinoma patients. The combined evaluation of p16 and cyclin D1 in oral carcinoma could identify a group of patients with the worst survival who might therefore need alternate or more intense treatment strategies.

A lot of emphasis is now being placed in early identification of 'distress', a state that lies between the feelings of sadness and apprehension, and clinically defined syndromes. It is assumed that an intervention at this stage will check the progression along the continuum in cancer patients. We have been working in global distress in cancer patients undergoing multimodality treatment with curative intent, for over 5 years. It all started with the generation of a hypothesis which led to the development of the 'Distress Inventory for Cancer', its refinement, and finally to modelling distress. This article gives a brief overview of our work on distress as conceptualised by the National Comprehensive Cancer Network in 1998, adopted and modified by us using informal patient interviews, expert Delphi exercise and structured patient interviews., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Squamous cell carcinoma of the buccal mucosa is predominantly a cancer of elderly people and is seen rarely in young adults. Although many aetiological factors have been postulated, tobacco alone has been implicated as the main factor in the aetiology of such cancers at any age., Patients and Methods: A retrospective analysis of 46 patients with cancer of the buccal mucosa who were under the age of 35 years at the time of presentation was made to evaluate their survival and predictors of survival. The details were extracted from the computerised records and case records of the Regional Cancer Centre, Trivandrum, India. These were analysed with particular emphasis on risk factors, clinical extent, and treatment. Survival was analysed by the Kaplan-Meier method, and differences in survival were compared using the log-rank test., Results: The male:female ratio was 6.7:1. Almost all the patients (n = 42, 91%) used either tobacco or alcohol, with tobacco chewing being the most common. The 3 and 5 years disease-free survival were 72 and 61%, respectively. Non-smokers and patients with an advanced T stage at presentation had significantly worse prognoses.

Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far. Our study analyses a set of proteins that previously demonstrated radio response influence for their possible prognostic value in decision-making process between the respective fractionation schemes. Expression patterns of regulatory proteins such as p53, cyclin D1, p16, Cdk4, p21, Rb, bcl-2 and PCNA were determined by immunohistochemistry utilizing monoclonal antibodies in 125 patients who received curative radiotherapy dose. Among these 125 patients, 90 (72%) received altered fractionation, whereas 35 (28%) received conventional fractionation. p53 over-expression correlated with local treatment failure among the patients treated with conventional fractionation whereas cyclin D1 over-expression and p16 underexpression were associated with local treatment failure as well as overall survival in altered fractionation treated cases. Our findings suggest that wild-type p53 status may be an important parameter for achieving high local control in those patients undergoing conventional fractionation, where as intact p16 and cyclin D1 status may be beneficial for effective local control in patients who are treated with altered fractionation. Furthermore, it can be assumed that conventional fractionation employs p53-mediated apoptosis, whereas altered fractionation activates the functional G1 cell-cycle checkpoint for tumor growth suppression., (Copyright 2004 Wiley-Liss, Inc.)

Introduction: Genetic testing is increasingly being used to evaluate susceptibility to hereditary diseases because it is a cost effective screening method. Predictive testing for retinoblastoma can help to save the vision and avoid unnecessary (and invasive) eye examinations for probands and their close relatives. This study was undertaken to evaluate the cost effectiveness of the retinoblastoma genetic screening strategy established in our hospital., Study Design: Cytogenetic study of peripheral blood, mutational, and methylation analyses from the tumor DNA of 25 patients with retinoblastoma was undertaken. The cost for retinoblastoma (RB1) gene screening was calculated based on the cost of the chemicals and consumables used and the clinical examination charges at our hospital. A comparison was made between the cost of genetic screening and clinical testing for retinoblastoma. Retinoblastoma patients underwent clinical management and genetic testing at Sankara Nethralaya, Chennai, India., Results: By adopting a genetic screening strategy, a 3.5-fold cost saving was seen for a proband while a 6-fold saving was seen for a family with two sibs compared to the cost of clinical examination. The clinical examination fee and cost of genetic screening for a proband was dollarUS536 and dollarUS152, respectively, while for a nuclear family with two sibs the costs were dollarUS1071 and dollarUS175, respectively., Discussion: Savings for a family will be higher if indirect costs, such as savings in travel times to and from the hospital and labor savings, were taken into account. Cost will be a major factor in determining the implementation of genetic screening for RB1 gene in the clinical practice., Conclusion: In our study in India, genetic screening for retinoblastoma was cheaper than conventional screening and was useful in the genetic counseling of the families.

Simple and inexpensive methods based on visual examination of the cervix are currently being investigated as alternative methods of cervical screening. The test characteristics of visual inspection with 4% acetic acid (VIA), and Lugol's iodine (VILI) and conventional cytology were investigated in a cross-sectional study involving 4,444 women aged 25 to 65 years in Kerala, India. While detection of any acetowhite area constituted a low-threshold positive VIA, detection of well-defined, opaque acetowhite lesions close to or touching the squamocolumnar junction constituted a high-threshold positive VIA test. Detection of definite yellow iodine nonuptake areas in the transformation zone close to or touching the squamocolumnar junction constituted a positive VILI test. Cytology was considered positive if reported as atypia or worse lesions. All screened women were evaluated by colposcopy and biopsies were directed in 1,644 women (37.0%), which allowed the direct estimation of sensitivity, specificity and predictive values. The reference diagnosis was based on a combination of histology and/or colposcopy. True disease status was defined as CIN 2 and worse lesions. A total of 149 (3.4%) women had CIN 2 or worse lesions. The sensitivities of low-threshold VIA, high-threshold VIA, VILI and cytology to detect CIN 2 or worse disease were 88.6%, 82.6%, 87.2% and 81.9%, respectively; the corresponding specificities were 78.0%, 86.5%, 84.7% and 87.8%. Our results indicate that VIA and VILI are suitable alternate screening tests to cytology for detecting cervical neoplasia in low-resource settings., (Copyright 2003 Wiley-Liss, Inc.)

A cluster randomized controlled oral cancer screening trial is on-going in the Trivandrum district, India, to evaluate the efficacy of screening in reducing oral cancer mortality. Subjects, aged 35 years and above, in 13 clusters in the Trivandrum district, India, were randomized to the intervention (screening) group (7 clusters, 78969 subjects) to receive three rounds of screening by oral visual inspection by trained health workers at 3-year intervals or to a control group (6 clusters, 74739 subjects). Two rounds of screening were completed between 1995 and 2002 during which 69896 (88.5%) subjects were screened at least once, and 59.7% of the 4408 screen-positive subjects were further investigated. In the intervention group, 344404 person-years were accrued and 329326 person-years were in the control group. In the intervention group, 149 incident oral cancer cases and 65 deaths from oral cancer were observed, and 106 incident cases and 62 deaths from oral cancer were observed in the control group. The programme sensitivity for detection of oral precancerous lesions and cancer was 81.5% and the programme specificity was 84.8%; the programme positive predictive value was 39.6%. In the intervention group 37.6% of the cases were in stages I-II, as opposed to 18.9% in the control group. The 3 year survival rate was 57.5% in the intervention and 38.8% in the control group (P<0.05). The age standardized oral cancer mortality rates were 21.2/100000 person-years in the intervention and 21.3/100000 in the control group. After completing two rounds of screening, oral cancer mortality rates were similar in both study groups.

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly., (Copyright 2002 Wiley-Liss, Inc.)

Ethnomedical survey has shown that the seeds of Barringtonia racemosa Roxb are traditionally used in certain remote villages of Kerala (India) to treat cancer like diseases. So the seed extracts were tested for their antitumour activity and toxicity. Intraperitoneal (i.p.) daily administration of 50% methanol extract of this seed to mice challenged with 1 million Dalton's Lymphoma Ascitic (DLA) cells resulted in remarkable dose dependent anti-DLA activity in mice. The optimum dose was found to be 6 mg/kg. This dose protected all the animals challenged with the tumour cells. The efficacy of the drug was found to be better than that of a standard drug, vincristine in this tumour model. However, the oral administration showed only marginal activity compared to i.p. administration. The extract was found to be devoid of conspicuous acute and short-term toxicity to mice, when administered daily, (i.p.) for 14 days up to a dose of 12 mg/kg (which was double the concentration of optimum therapeutic dose). The treated mice showed conspicuous toxic symptoms only at 24 mg/kg. The LD(50) to male mice for a single i.p. dose was found to be 36 mg/kg. The seed extract is an attractive material for further studies leading to drug development.

Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. To explore the contribution of BRCA1 mutations to hereditary breast cancer among Indian women, we examined the coding sequence of the BRCA1 gene in 14 breast cancer patients with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation sensitive gel electrophoresis (CSGE) followed by sequencing. Three mutations (21%) in the BRCA1 gene were identified. Two of them are novel mutations of which one is a missense mutation in exon 7 near the RING finger domain, while the other is a one base pair deletion in exon 11 which results in protein truncation. The third mutation, 185 delAG, has been previously described in Ashkenazi Jewish families. To our knowledge this is the first report of a study of germline BRCA1 mutation analysis in familial breast cancer in India. Our data from 14 different families suggests a lower prevalence but definite involvement of germline mutations in the BRCA1 gene among Indian women with breast cancer and a family history of breast cancer.

Important to the immunopathology associated with the autoimmune disease systemic lupus erythematosus, is the production of autoantibody to DNA. Crucial to understanding the immunological basis for autoimmunity to DNA is knowing whether the anti-DNA autoantibody is the product of clonally-selective, antigen-specific B cell stimulation or non-selective, polyclonal B cell activation. Structural analyses of the immunoglobulin variable-regions of both early, IgM and late, IgG anti-DNA antibodies from lupus-prone (NZB x NZW) F1 mice have indicated that both IgM and IgG anti-DNA autoantibodies are generated by clonally-selective B cell stimulation. Within individual autoimmune mice the later appearing, IgG anti-DNA autoantibodies are structurally similar to the earlier appearing, IgM antibodies, and in some cases both IgM and IgG may be produced by the same B cell clones. The variable-region structural data also suggest that DNA or complexes containing DNA may be the immunogenic stimuli for autoantibody to DNA. In support of this conclusion, normal mice immunized with immunogenic peptide-DNA complexes produce anti-DNA antibodies with structural and serological characteristics similar if not identical to those of autoimmune anti-DNA antibodies. Normal mice immunized with peptide-DNA complexes eventually develop immunopathology that resembles lupus nephritis. These results suggest that autoimmunity to DNA and subsequent autoimmune disease in SLE may result from a specific immune response to DNA containing antigens.