Association of Sex Hormones and Androgens with Disease Activity in Premenopausal Females with Rheumatoid Arthritis.

Background: Gonadal sex hormone dysfunction is frequently reported in patients with Rheumatoid arthritis (RA). The relationship of these hormones with disease activity is still not clear and whether the hormone imbalance leads to increased severity of RA is not well studied in this part of the world. The present study aimed to elucidate this fact. Methods: It was a cross-sectional observational study performed in 80 premenopausal females with definite RA at a tertiary care hospital in New Delhi, India over one year. Patients were subjected to investigations as per the protocol and a fasting venous blood sample for hormone levels was collected in the follicular phase of their menstrual cycle. Results: A statistically significant correlation by linear logistic regression analysis was found between disease activity (as measured by DAS28) and serum progesterone, FSH, and prolactin, while serum testosterone and DHEAS showed an inverse relationship with disease activity. Low s. prolactin, and s. FSH as well as high s. testosterone and s. DHEAS were found to be associated with target clinical goals in RA (ie, remission and low disease activity). On multivariate logistic regression analysis, serum prolactin showed a direct association. (p=0.016, OR= 1.009. C.I.= 1.0021.017) and serum testosterone were found to have an inverse relationship (p=0.002, OR= 0.017, C.I.=0.001-0.237) with disease activity in this group of individuals. Conclusion: Serum levels of sex hormones may be helpful in predicting disease activity among patients with RA, and in future, may be used to guide treatment of severe refractory disease, unresponsive to conventional treatment with DMARDs, especially in resource-poor settings.

Turbulence suppression by cardiac-cycle-inspired driving of pipe flow.

Flows through pipes and channels are, in practice, almost always turbulent, and the multiscale eddying motion is responsible for a major part of the encountered friction losses and pumping costs1. Conversely, for pulsatile flows, in particular for aortic blood flow, turbulence levels remain low despite relatively large peak velocities. For aortic blood flow, high turbulence levels are intolerable as they would damage the shear-sensitive endothelial cell layer2-5. Here we show that turbulence in ordinary pipe flow is diminished if the flow is driven in a pulsatile mode that incorporates all the key features of the cardiac waveform. At Reynolds numbers comparable to those of aortic blood flow, turbulence is largely inhibited, whereas at much higher speeds, the turbulent drag is reduced by more than 25%. This specific operation mode is more efficient when compared with steady driving, which is the present situation for virtually all fluid transport processes ranging from heating circuits to water, gas and oil pipelines.

CT coronary angiography as an alternative imaging method to ascertain cardiac output and its correlation with echocardiography.

AIM: To assess the feasibility and accuracy of cardiac output (CO) obtained using a test bolus in patients scanned with single-source prospective-gated cardiac computed tomography (CT), and comparing it with CO obtained from unenhanced two-dimensional (2D) echocardiography using biplane Simpson's method. MATERIALS AND METHODS: In the present study, 100 patients with a mean age of 55 ± 12 years who underwent coronary CT angiography with prospective electrocardiogram (ECG)-gated CT in which the scan delay was evaluated using a test bolus. The time-attenuation curves obtained from the test bolus were used to calculate the CO of the patients. The CO obtained was then compared with that obtained after follow-up 2D echocardiography using biplane modified Simpson method. RESULTS: Linear regression was calculated between the CO and contrast enhancement: CO = -0.16(HUmax) + 7.65. The study showed good correlation between the two methods with r=0.77, p<0.001. On Bland-Altman analysis, no significant difference was noted between the two methods. CONCLUSION: This less researched method for CO estimation appears feasible; however, the clinical usefulness of this parameter is uncertain in absence of further clinical and reference standard validation.

BA3338, a surface layer homology domain possessing protein augments immune response and protection efficacy of protective antigen against Bacillus anthracis in mouse model.

AIM: Category A classified Bacillus anthracis is highly fatal pathogen that causes anthrax and creates challenges for global security and public health. In this study, development of a safe and ideal next-generation subunit anthrax vaccine has been evaluated in mouse model. METHOD AND RESULTS: Protective antigen (PA) and BA3338, a surface layer homology (SLH) domain possessing protein were cloned, expressed in heterologous system and purified by IMAC. Recombinant PA and BA3338 with alum were administered in mouse alone or in combination. The humoral and cell-mediated immune response was measured by ELISA and vaccinated animals were challenged with B. anthracis spores via intraperitoneal route. The circulating IgG antibody titre of anti-PA and anti-BA3338 was found significantly high in the first and second booster sera. A significant enhanced level of IL-4, IFN-γ and IL-12 was observed in antigens stimulated supernatant of splenocytes of PA + BA3338 vaccinated animals. A combination of PA and BA3338 provided 80% protection against 20 LD50 lethal dose of B. anthracis spores. CONCLUSION: Both antigens induced admirable humoral and cellular immune response as well as protective efficacy against B. anthracis spores. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has been evaluated for the first time using BA3338 as a vaccine candidate alone or in combination with well-known anthrax vaccine candidate PA. The findings of this study demonstrated that BA3338 could be a co-vaccine candidate for development of dual subunit vaccine against anthrax.

Characterization of liver specific promoters in a foamy viral vector pMD09.

Foamy viruses (FVs) or spumaviruses are retroviruses that are explored as vectors for gene therapy. The good feature of foamy viruses is its broad tropism; however, their infections result in non-targeted gene expression. Here, we attempted to design the liver targeted viral gene delivery by employing liver specific gene promoters like albumin (ALB), transthyretin (TTR) and hepatitis B virus (HBV) promoters. We compared the relative gene expression of liver specific promoters versus the U3 promoter in liver cell line (HepG2) and non-liver cell lines: human fibrosarcoma cell line (HT1080), baby hamster kidney cell line (BHK), human embryonic kidney cell line (HEK 293T) and cervical cancer cell line (HeLa). We have found that the promoter exchange didn't affect viral assembly. The ability to drive gene expression was best with TTR promoter which was followed by HBV and ALB promoter. The use of TTR, HBV and ALB promoters are helpful in achieving liver specific gene expression. Keywords: foamy virus; gene therapy; liver; albumin; transthyretin promoter; HBV promoter.

Syndrome of remitting seronegative symmetrical synovitis with pitting edema: a case series.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) is a rare clinical entity that is easily missed due to lack of knowledge. It was formerly considered as a subset of rheumatoid arthritis (RA), but is now regarded as a distinct disease/syndrome. The diagnosis of RS3PE is not easy, as it is always hindered by the lack of definite diagnostic criteria and presence of other much common rheumatological disorders that mimic it. We report a series of seven cases that attended our clinic in the last year, which highlight the salient features of the disease. The disease was found to have a heterogeneous presentation. Immunogenetic, clinical, laboratory, radiological, and possible etiological factors and associations with the neoplasm are described, as also other peculiar presentations. Finally, a comparison with other common rheumatological disorders is made to alert the clinician about this rare, but easily treatable disease.

Diagnostic imaging of canine hepatobiliary affections: a review.

Hepatic disease is often treatable and has a predictable prognosis when a definitive diagnosis is made. The aim of clinicopathological evaluation of hepatobiliary affections is to identify and characterize hepatic damage and dysfunction, identify possible primary causes of secondary liver disease, differentiate causes of icterus, evaluate potential anaesthetic risks, assess prognosis and response to xenobiotics, and monitor response to therapy. This paper describes the different diagnostic methods and imaging techniques employed in diagnosis of hepatobiliary affections in dogs. Besides reviewing the significant clinical manifestations and imaging structural abnormalities in diagnostic approach to different hepatic affections, it also depicts radiographic, ultrasonographic, and wherever applicable, the laparoscopic characterization of different hepatic affections and target lesions encountered in clinical cases presented in the Teaching Veterinary Clinical Complex, COVAS, Palampur in the year 2007-2008.

Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. AIM/OBJECTIVE: In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. SUBJECTS AND METHODS: Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. RESULTS: We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. CONCLUSIONS: 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Hierarchical Exploration of Volumes Using Multilevel Segmentation of the Intensity-Gradient Histograms.

Visual exploration of volumetric datasets to discover the embedded features and spatial structures is a challenging and tedious task. In this paper we present a semi-automatic approach to this problem that works by visually segmenting the intensity-gradient 2D histogram of a volumetric dataset into an exploration hierarchy. Our approach mimics user exploration behavior by analyzing the histogram with the normalized-cut multilevel segmentation technique. Unlike previous work in this area, our technique segments the histogram into a reasonable set of intuitive components that are mutually exclusive and collectively exhaustive. We use information-theoretic measures of the volumetric data segments to guide the exploration. This provides a data-driven coarse-to-fine hierarchy for a user to interactively navigate the volume in a meaningful manner.

School eye survey in rural population in UP, India.

OBJECTIVE: To find out the prevalence of refractive errors and pattern of ocular morbidity amongst the school children of a rural village. MATERIALS AND METHODS: A cross sectional study was carried out in children of age group 3 - 12 years in a rural village of Hathras, Uttar Pradesh, India. All the children were examined including visual acuity measurement using Snellen's E chart, retinoscopy and refraction under cycloplegia. Examination of the anterior segment, media, and fundii was also done. Myopia was defined as spherical/cylindrical equivalent refractive error of at least -0.50 D and hypermetropia as +0.50 D or more (Dandona et al 2002). RESULTS: In the survey 220 eyes of 110 children were examined, majority of them were in 5-10 year age group. The prevalence of uncorrected visual acuity of 6/6 was 85.40%. Refractive error was the cause in 6.81% of eyes with vision impairment, out of which myopia and hypermetropia were present in 26.67% of eyes. Blepharo-conjunctivitis was present in 15.45% of children and Bitot's spots were present in 0.90% of them. Colour blindness was found in one child. CONCLUSION: The prevalence of refractive error in rural school is 6.81 %. Blepharitis is the commonest cause of ocular morbidity.

Clinical efficacy of a novel new injectable diclofenac formulation designed for intradeltoid use in post-operative pain management.

OBJECTIVE: A randomized study comparing efficacy and safety of a new 75 mg/1 ml formulation of injectable diclofenac sodium designed for intra-deltoid use with the conventional 75 mg/3 ml formulation given by the intra-gluteal route. DESIGN: This was an open-label, multicentric, randomized clinical trial. METHODS: A total of 250 adult patients with post-operative pain were randomized to receive either an injection diclofenac 75 mg/1 ml or diclofenac 75 mg/3 ml. Primary efficacy criteria were time to onset of analgesia and reduction in pain intensity. Severity of pain at site of injection and side effects were also evaluated. RESULTS: 232 patients completed the study. The mean times to onset of anal-gesia were comparable (16.17 ± 12.70 min in the diclofenac 75 mg/1 ml group and 19.16 ± 11.79 min in the diclofenac 75 mg/3 ml group). However, significantly more patients achieved analgesia in less than 5 min and had less pain at the site of injection with the 1 ml formulation. The need for rescue medication was also lower with the 1 ml formulation (2.5% vs. 9.82%). No side effects were reported. A significantly larger number of patients and physicians rated the efficacy and safety of injectable diclo-fenac 75 mg/1 ml as excellent. CONCLUSION: Both formulations were effective and safe in the management of post-operative pain with a significantly lower need for rescue analgesia and less pain at site of injection with diclofenac 75 mg/1 ml formulation. The 1 ml formulation had an added advantage of intra-deltoid use. This would be specially helpful in obese/overweight patients with a thick subcutaneous pad of fat over the gluteal region.

Ultrasonographic imaging for structural characterization of renal affections and diagnosis of associated chronic renal failure in 10 dogs.

The present study comprises of 10 dogs of either sex with primary indication of azotaemia. All the dogs were subjected to detailed clinical, haematobiochemical, urinalysis, and microbiological examination along with radiographical and ultrasonographical examination. Based on the ultrasonographic structural abnormalities, the different renal affections associated with CRF in majority of dogs were diagnosed. The different affections included "end-stage" kidneys (n = 4), hydronephrosis (n = 1), renomegaly (n = 1), nephritis (n = 1), nephrolithiasis (n = 1), nephrocalcinosis (n = 1), and renal cyst (n = 1). The significant ultrasonographic features in these affections included small kidneys with loss of corticomedullary demarcation ("end-stage" kidneys); increased cortical echogenicity (nephritis); dilation of the renal pelvis, separation of the central renal sinus with anechoic space, atrophy of renal medulla, (hydronephrosis); enlarged kidneys with increased overall echogenicity of renal cortex (renomegaly and associated nephritis); hyperechoic-mineralized structure with shadowing (nephrolithiasis); diffuse, small, multiple hyperechoic structures in the renal parenchyma with distal acoustic shadowing (nephrocalcinosis); small spherical intercortical anechoic structures fluid (renal cysts). In the present study, ultrasound proved to be a quick, convenient, and sensitive modality in detecting alterations in renal size and parenchymal architecture. All the dogs so diagnosed with CRF were rendered conservative medical treatment to control clinical signs of uraemia; maintain adequate fluid, electrolyte, and acid/base balance; provide adequate nutrition; minimize progression of renal failure.

Social snapshot: a system for temporally coupled social photography.

Social Snapshot actively acquires and reconstructs temporally dynamic data. The system enables spatiotemporal 3D photography using commodity devices, assisted by their auxiliary sensors and network functionality. It engages users, making them active rather than passive participants in data acquisition.

Effect of trifluoroethanol on native and acid-induced states of glucose oxidase from Aspergillus niger.

We have studied the effect of trifluoroethanol (TFE) on the native (pH 7.0), acid unfolded (pH 2.6), and molten globule (pH 1.4) states of glucose oxidase (GOX) by circular dichroism and fluorescence spectroscopy. In the presence of 50% TFE, at pH 7.0 and 2.6, GOX exhibited a transition from native coiled-coil and acid unfolded state to non-associating alpha-helical state. Interestingly, at pH 1.4, 15% TFE induced the formation of beta-structured intermediate by loss of 1-anilino-8-naphthalenesulfonate binding site and almost all tertiary contacts. The beta-structured intermediate converted into open helical conformation on further addition of TFE.

A report on a rare case of Kearns Sayre-like syndrome.

PURPOSE: To report the presentation of a rare case of Kearns-Sayre-like syndrome (KSS) CASE: A 14-year-old boy presented with progressive drooping of both upper eyelids for 10 years. Past history of right sided hemi-plegia and left facial nerve palsy was present. Examination (OU) showed total external ophthalmoplegia, ptosis and pigmentary retinopathy. The patient also had a short stature (height 121.9 cm) for his age.

pH-Dependent urea-induced unfolding of stem bromelain: unusual stability against urea at neutral pH.

Equilibrium unfolding of stem bromelain (SB) with urea as a denaturant has been monitored as a function of pH using circular dichroism and fluorescence emission spectroscopy. Urea-induced denaturation studies at pH 4.5 showed that SB unfolds through a two-state mechanism and yields DeltaG (free energy difference between the fully folded and unfolded forms) of approximately 5.0 kcal/mol and C(m) (midpoint of the unfolding transition) of approximately 6.5 M at 25 degrees C. Very high concentration of urea (9.5 M) provides unusual stability to the protein with no more structural loss and transition to a completely unfolded state.

Synthetic, structural, and biochemical studies of organotin(IV) with Schiff bases having nitrogen and sulphur donor ligands.

Three bidentate Schiff bases having nitrogen and sulphur donor sequences were prepared by condensing S-benzyldithiocarbazate (NH(2)NHCS(2)CH(2)C(6)H(5)) with heterocyclic aldehydes. The reaction of diphenyltin dichloride with Schiff bases leads to the formation of a new series of organotin(IV) complexes. An attempt has been made to prove their structures on the basis of elemental analyses, conductance measurements, molecular weights determinations, UV, infrared, and multinuclear magnetic resonance ((1)H, (13)C, and (119)Sn) spectral studies. Organotin(IV) complexes were five- and six-coordinate. Schiff bases and their corresponding organotin complexes have also been screened for their antibacterial and antifungal activities and found to be quite active in this respect.

Development and validation of CAPS and AFLP markers for white rust resistance gene in Brassica juncea.

White rust, caused by Albugo candida, is a very serious disease in crucifers. In Indian mustard (Brassica juncea), it can cause a yield loss to the extent of 89.9%. The locus Ac2(t) controlling resistance to white rust in BEC-144, an exotic accession of mustard, was mapped using RAPD markers. In the present study, we developed: (1) a more tightly linked marker for the white rust resistance gene, using AFLP in conjunction with bulk segregant analysis, and (2) a PCR-based cleaved amplified polymorphic sequence (CAPS) marker for the closely linked RAPD marker, OPB06(1000). The data obtained on 94 RILs revealed that the CAPS marker for OPB06(1000) and the AFLP marker E-ACC/M-CAA(350) flank the Ac2(t) gene at 3.8 cM and 6.7 cM, respectively. Validation of the CAPS marker in two different F(2) populations of crosses Varuna x BEC-144 and Varuna x BEC-286 was also undertaken, which established its utility in marker-assisted selection (MAS) for white rust resistance. The use of both flanking markers in MAS would allow only 0.25% misclassification and thus provide greater efficiency to selection.