Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.

BACKGROUND: Non-invasive high-resolution echocardiography to evaluate cardiovascular function of small animals is increasingly being used due to availability of genetically engineered murine models. Even though guidelines and standard values for humans were revised by the American Society of Echocardiography, evaluations on murine models are not performed according to any standard protocols. These limitations are preventing translation of preclinical evaluations to clinical meaningful conclusions. We have assessed the right heart of two commonly used murine models according to standard clinical guidelines, and provided the practical guide and sample values for cardiac assessments. METHODS: Right heart echocardiography evaluations of CD1 and C57BL/6 mice were performed under 1–3% isoflurane anesthesia using Vevo® 2100 Imaging System with a high-frequency (18–38 MHz) probe (VisualSonics MS400). We have provided a practical guide on how to image and assess the right heart of a mouse which is frequently used to evaluate development of right heart failure due to pulmonary hypertension. RESULTS: Our results show significant differences between CD1 and C57BL/6 mice. Right ventricle structural assessment showed significantly larger (p < 0.05) size, and pulmonary artery diameter in CD1 mice (n = 11) compared to C57BL/6 mice (n = 15). Right heart systolic and diastolic functions were similar for both strains. CONCLUSION: Our practical guide on how to image and assess the right heart of murine models provides the first comprehensive values which can be used for preclinical research studies using echocardiography. Additionally, our results indicate that there is a high variability between mouse species and experimental models should be carefully selected for cardiac evaluations.
Anesthesia ; Animals ; Echocardiography* ; Heart ; Heart Failure ; Heart Ventricles* ; Humans ; Hypertension, Pulmonary ; Isoflurane ; Mice ; Models, Theoretical ; Pulmonary Artery

Background & Objective: Transthyretin (TTR) has been associated with spinocerebellar ataxia (SCA) by several independent case reports. Coexistence of TTR and SCA mutations, overlapping clinical symptoms as well as altered levels of TTR in SCA patients suggest a correlation between TTR and SCA. To our knowledge, no large cohort based study has been attempted to examine the association of SCA with polymorphism in TTR gene. Here, we chose to investigate TTR variations in SCA patients (n=266) and controls (n=192) of North Indian ethnicity. Methods: We sequenced the exons including exon-intron boundaries of TTR gene in 55 patients and 55 controls. We observed four variations which were further genotyped by single base extension method (SNaPshot) in a larger cohort (SCA patients n=211 and controls n=137). Results: A novel synonymous variation c.372 C>G in exon 4 was detected in heterozygous condition in one control sample. We found nominal association for rs1800458 (Gly6Ser), with SCA (p-value < 0.05) which did not remain after Bonferroni correction for multiple tests. Pairwise linkage disequilibrium (LD) analysis revealed no LD between studied SNPs. Further, we employed two-marker sliding window analysis and observed a weak association of haplotype AT of rs1800458 and rs1667251 with SCA patients (p-value <0.05) which was not retained after Bonferroni correction. Conclusion: Our data suggests no association of genetic variations of TTR in SCA pathology.

Objective: Controlled ovarian stimulation leads to profound changes in the endocrine characteristics of the ovarian cycle. Serum luteinising hormone (LH) levels on the day of trigger have been shown to correlate with oocyte quality and pregnancy rate in antagonist cycles. Methods: This is an observational study of 86 women undergoing an antagonist in-vitro fertilisation cycle. Oocyte maturation trigger used was either Inj. human chorionic gonadotropin or Inj. triptorelin 0.2 mg s/c or a combination of both. Women were categorised into four groups based on serum LH levels on the day of trigger i.e., LH ≤0.5 (n=8), LH=0.6- 1.0 international units (IU)/L (n=12), LH=1.0-1.5 IU/L (n=13), and LH >1.6 IU/L (n=53) and the subgroup analysis was done based on type of trigger used. Results: Mature oocyte (MII) retrieval rate did not show a significant relation with serum LH levels (87%, 89%, 77%, and 76% in groups with LH <0.5, 0.5-1.0, 1.0-1.5, and >1.5 IU/L respectively; P-value=0.243). There was no significant difference in the clinical pregnancy rate either when women were split according to the type of trigger given or according to trigger day LH levels. Women with low LH levels (<0.5 IU/L) required significantly more doses of gonadotropins compared to women with LH levels of 1.0-1.5 IU/L. (3,531+1,133 vs. 2,281+938; P-value=0.01). Conclusion Based on the observation from the current study, there was no significant association of serum LH levels with MII retrieval rate and clinical pregnancy rate. The group with low LH levels required slightly longer days of stimulation.

OBJECTIVES: Efficient identification of subject experts or expert communities is vital for the growth of any organization. Most of the available expert finding systems are based on self-nomination, which can be biased, and are unable to rank experts. Thus, the objective of this work was to develop a robust and unbiased expert finding system which can quantitatively measure expertise. METHODS: Medical Subject Headings (MeSH) is a controlled vocabulary developed by the National Library of Medicine (NLM) for indexing research publications, articles and books. Using the MeSH terms associated with peer-reviewed articles published from India and indexed in PubMed, we developed a Web-based program which can be used to identify subject experts and subjects associated with an expert. RESULTS: We have extensively tested our system to identify experts from India in various subjects. The system provides a ranked list of experts where known experts rank at the top of the list. The system is general; since it uses information available with the PubMed, it can be implemented for any country. CONCLUSIONS: The expert finding system is able to successfully identify subject experts in India. Our system is unique because it allows the quantification of subject expertise, thus enabling the ranking of experts. Our system is based on peer-reviewed information. Use of MeSH terms as subjects has standardized the subject terminology. The system matches requirements of an ideal expert finding system.
Abstracting and Indexing as Topic ; Bias (Epidemiology) ; Data Mining ; Expert Systems ; India ; Medical Subject Headings* ; National Library of Medicine (U.S.) ; Online Systems ; Professional Competence ; Vocabulary, Controlled

OBJECTIVE: To determine which computed tomography (CT) imaging features predict pleural malignancy in patients with advanced epithelial ovarian carcinoma (EOC) using video-assisted thoracic surgery (VATS), pathology, and cytology findings as the reference standard. METHODS: This retrospective study included 44 patients with International Federation of Obstetrics and Gynecology (FIGO) stage III or IV primary or recurrent EOC who had chest CT < or =30 days before VATS. Two radiologists independently reviewed the CT studies and recorded the presence and size of pleural effusions and of ascites; pleural nodules, thickening, enhancement, subdiaphragmatic tumour deposits and supradiaphragmatic, mediastinal, hilar, and retroperitoneal adenopathy; and peritoneal seeding. VATS, pathology, and cytology findings constituted the reference standard. RESULTS: In 26/44 (59%) patients, pleural biopsies were malignant. Only the size of left-sided pleural effusion (reader 1: rho=-0.39, p=0.01; reader 2: rho=-0.37, p=0.01) and presence of ascites (reader 1: rho=-0.33, p=0.03; reader 2: rho=-0.35, p=0.03) were significantly associated with solid pleural metastasis. Pleural fluid cytology was malignant in 26/35 (74%) patients. Only the presence (p=0.03 for both readers) and size (reader 1: rho=0.34, p=0.04; reader 2: rho=0.33, p=0.06) of right-sided pleural effusion were associated with malignant pleural effusion. Interobserver agreement was substantial (kappa=0.78) for effusion size and moderate (kappa=0.46) for presence of solid pleural disease. No other CT features were associated with malignancy at biopsy or cytology. CONCLUSION: In patients with advanced EOC, ascites and left-sided pleural effusion size were associated with solid pleural metastasis, while the presence and size of right-sided effusion were associated with malignant pleural effusion. No other CT features evaluated were associated with pleural malignancy.
Ascites ; Biopsy ; Gynecology ; Humans ; Neoplasm Metastasis ; Obstetrics ; Ovarian Neoplasms ; Pleural Diseases ; Pleural Effusion ; Pleural Effusion, Malignant ; Pleural Neoplasms ; Retrospective Studies ; Seeds ; Thoracic Surgery, Video-Assisted ; Thorax

Background/Aims: Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality rate in patients suffering from liver diseases. The drug of choice used in advanced-stage of HCC is sorafenib. However, adaptive resistance has been observed in HCC patients undergoing long-term sorafenib treatment, lowering its effectiveness. Hence, it is important to overcome drug resistance to improve overall management of HCC. Here, we have identified a candidate biomarker for sorafenib resistance in a HCC model cell line, HepG2. Methods: Initially, comparative proteomic profiling of parental HepG2 [HepG2 (P)] and sorafenib-resistant HepG2 [HepG2 (R)] cells was performed via MALDI (matrix-assisted laser desorption/ionization) which revealed the deregulation of vimentin in HepG2 (R) cells. Gene and protein level expression of vimentin was also observed through quantitative real-time polymerase chain reaction (qRT PCR) and fluorescence-activated cell sorting (FACS), respectively. Furthermore, withaferin A was used to study regulation of vimentin expression and its significance in sorafenib resistance. Results: Both gene and protein level of vimentin expression was found to be downregulated in HepG2 (R) in comparison to HepG2 (P). Interestingly, the study demonstrated that withaferin A further lowered the expression of vimentin in HepG2 (R) cells in a dose-dependent manner. Also, inhibition of vimentin lowered ABCG2 expression and decreased cell viability in parental as well as sorafenib resistant HepG2 cells. Conclusions Hence, our study for the first time highlighted the probable therapeutic potential of vimentin in sorafenib resistant HepG2, a HCC model cell line.

OBJECTIVE: Tobacco consumption among patients with schizophrenia has been investigated extensively in western countries, but there is a dearth of studies in India, where socio-economic and cultural variables are different. This study aims to investigate the patterns of tobacco consumption among schizophrenia patients compared with their non-psychotic siblings. METHODS: Consenting, successive male outpatients diagnosed with schizophrenia (n=100, DSM-IV criteria), and their non-psychotic brothers (n=100) were compared. Following a structured diagnostic interview, detailed information about tobacco consumption (including smokeless tobacco) was obtained using the Fagerstrom Test for Nicotine Dependence for smoked tobacco, and FTND-smokeless tobacco. The University of Pennsylvania Computerized Neurocognitive battery (CNB) was administered to a sub-group of patients (n=48). RESULTS: Schizophrenia patients initiated tobacco use at a significantly earlier age than their brothers, but there was no significant difference with regard to type, quantity or frequency of tobacco use (smoke or smokeless varieties). Patients who consumed tobacco had significantly higher positive symptom scores compared with non-users (p=0.043). There were no significant differences between nicotine dependent and non-dependent patients with regard to CNB domains except attention. CONCLUSION: Patterns of tobacco consumption were similar among schizophrenia patients and their non-psychotic brothers. Tobacco use was associated with increased positive symptom scores, but there were no significant differences in cognitive measures among nicotine dependent and non-dependent patients.
Diagnostic and Statistical Manual of Mental Disorders ; Humans ; India ; Lobeline ; Male ; Nicotine ; Outpatients ; Pennsylvania ; Schizophrenia ; Siblings ; Smoke ; Tobacco ; Tobacco Use Disorder