A sustainable bioprocess technology for producing food-flavour (+)-γ-decalactone from castor oil-derived ricinoleic acid using enzymatic activity of Candida parapsilosis: Scale-up optimization and purification using novel composite.

Ricinoleic acid (RA) from castor oil was employed in biotransformation of peach-flavoured γ-decalactone (GDL), using a Candida parapsilosis strain (MTCC13027) which was isolated from waste of pineapple crown base. Using four variables-pH, cell density, amount of RA, and temperature-the biotransformation parameters were optimized using RSM and BBD. Under optimized conditions (pH 6, 10 % of microbial cells, 10 g/L RA at 28°C), the conversion was maximum and resulted to 80 % (+)-GDL (4.4 g/L/120 h) yield in shake flask (500 mL). Furthermore, optimization was achieved by adjusting the aeration and agitation parameters in a 3 L bioreactor, which were then replicated in a 10 L bioreactor to accurately determine the amount of (+)-GDL. In bioreactor condition, 4.7 g/L (>85 %) of (+)-GDL is produced with 20 % and 40 % dissolved oxygen (1.0 vvm) at 150 rpm in 72 h and 66 h, respectively. Further, a new Al-Mg-Ca-Si composite column-chromatography method is developed to purify enantiospecific (+)-GDL (99.9 %). This (+)-GDL is 100 % nature-identical as validated through 14C-radio-carbon dating. Thorough chemical investigation of enantiospecific (+)-GDL is authenticated for its use as flavour. This bioflavour has been developed through a cost-effective biotechnological process in response to the demand from the food industry on commercial scale.

Anti-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight from Molecular Docking and Experimental Studies.

BACKGROUND: Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules. Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have, herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung cancer. METHODS: In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1- ß (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID: 5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool. RESULTS: Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2- carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-ß, Il6, vimentin, COX-2, Il8, and TNF-α in vitro. The ability of the molecule to effectively suppress the proliferation and migration of lung cancer cells in vitro has been further demonstrated by the colony formation unit assay and wound healing assay. Molecular docking analysis showed the maximal binding affinity (- 7.54 kcal/mol) to be exhibited by compound 3c against IL8. CONCLUSION: A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been developed. All the molecules were screened for their activity against lung cancer and the data suggested that the presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, in vitro and in silico modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of such small molecules against cancer.

Electrochemical and computational insights into the utilization of 2, 2- dithio bisbenzothiazole as a sustainable corrosion inhibitor for mild steel in low pH medium.

Industries today place a high premium on environmentally friendly supplies that may effectively inhibit metal dissolution at a reasonable cost. Hence, in this paper, we assessed the corrosion inhibition effectiveness of the Thiazole derivative namely, 2, 2-Dithio Bisbenzothiazole (DBBT) against mild steel (MS) corrosion in 1 M HCl. Several experimental approaches, including gravimetric analysis, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and surface exploration using scanning electron/atomic force microscopy (SEM/AFM) and contact angle (CA), were utilized to conduct the measurements. In 1 M HCl corrosive medium at 298 K in the subsistence of 800 ppm of DBBT, this experiment indicated DBBT as an environment-friendly and sustainable corrosion inhibitor (CI) for MS, demonstrating an inhibition efficiency (IE %) of 97.71%. To deliver a deeper knowledge of the mechanism behind inhibitive behavior, the calculated thermodynamic and activation characteristics were applied. The calculated Gibbs free energy values indicated that the CI interacted physically and chemically with the MS surface, validating physio-chemical adsorption. The findings of the EIS research revealed that an upsurge in the doses of the CI is escorted by an upsurge in polarization resistance (Rp) from (88.05 → 504.04) Ωcm2, and a diminution in double layer capacitance (Cdl) from (97.46 → 46.33) µFcm-2 at (50 → 800) ppm respectively, affirming the inhibitive potential of DBBT. Additionally, the greatest displacement in Ecorr value being 76.13 mV < 85 mV, indicating that DBBT act as a mixed-form CI. To study the further impacts of DBBT on the inhibition capabilities of the compound under investigation, density functional theory (DFT) and molecular dynamics (MD) simulation were employed. Chemical and electrochemical approaches are in agreement with the computational analysis indicating DBBT is the most efficient CI.

Case Report: An Unusual Case of Subacute Sclerosing Panencephalitis with Distinctive Clinical and Neuroimaging Features.

Subacute sclerosing panencephalitis (SSPE) is a relentlessly progressive brain disorder with invariable mortality. Subacute sclerosing panencephalitis is common in measles-endemic areas. We report an unusual SSPE patient with distinctive clinical and neuroimaging features. A 9-year-old boy came with a 5-month history of spontaneously dropping objects from both hands. Subsequently, he developed mental decline, a loss of interest in his surroundings, decreased verbal output, and inappropriate crying and laughing along with generalized periodic myoclonus. On examination, the child was akinetic mute. The child demonstrated intermittent generalized axial dystonic storm with flexion of upper limbs, an extension of lower limbs, and opisthotonos. Dystonic posturing was more dominant on the right side. Electroencephalography revealed periodic discharges. Cerebrospinal fluid antimeasles IgG antibody titer was markedly elevated. Magnetic resonance imaging revealed marked diffuse cerebral atrophy, and periventricular T2/fluid-attenuated inversion recovery hyperintensity. T2/fluid-attenuated inversion recovery images also revealed multiple cystic lesions present in the region of periventricular white matter. The patient was given a monthly injection of intrathecal interferon-α. The patient is currently continuing in the akinetic-mute stage. In conclusion, in this report, we described an unusual case of acute fulminant SSPE in which neuroimaging demonstrated unusual multiple small discrete cystic lesions in the cortical white matter. The pathological nature of these cystic lesions currently is not clear and needs to be explored.

Value of whole-body MRI for the assessment of response to albendazole in disseminated neurocysticercosis: a prospective follow-up study.

BACKGROUND: Disseminated neurocysticercosis is defined as simultaneous involvement of the brain (≥3 cysts) and at least one additional body site/organ. We aimed to identify disseminated cystic lesions in other body parts and investigate the effect of albendazole. METHODS: We enrolled patients with multiple (≥3) neurocysticercosis brain lesions. Whole-body MRI (short tau inversion recovery coronal sequences) was performed to assess the number of lesions in the brain and other body parts at baseline and 3 months after albendazole therapy. RESULTS: We screened 35 patients with multiple brain neurocysticercosis. In 13 patients, whole-body MRI demonstrated disseminated neurocysticercosis lesions. Ten patients were treated with albendazole. We excluded three patients. Brain MRI showed a mean lesion count of 163.6±193.8. Whole-body MRI (excluding the brain) showed a mean lesion count of 629.9±486.1. After albendazole therapy, the lesion load of the brain reduced significantly (163.6±193.8 to 99±178.3; p=0.008). Similarly, whole-body MRI showed a significant reduction in extracerebral neurocysticercosis lesion load (629.9±486.1 to 183.4±301.9; p=0.005). Three patients had complete resolution, five patients showed ≥50% reduction and two patients had <50% reduction in extracerebral lesion load. CONCLUSION: Whole-body MRI should routinely be performed in multiple neurocysticercosis lesions of the brain. Albendazole treatment leads to a remarkable reduction in neurocysticercosis lesions throughout the body.

Does Calcified Neurocysticercosis Affect Migraine Characteristics and Treatment Responsiveness? A Case-Control Study.

Recently, inflammation and free-radical release has been described in the surrounding brain parenchyma of seemingly inert calcified lesions of neurocysticercosis. These free radicals can induce migraine by stimulating calcitonin gene-related peptide release. This stipulated mechanism led us to hypothesize that calcified neurocysticercosis may increase migraine severity. This case-control study included patients (migraine with calcified neurocysticercosis) and control subjects (migraine without calcified neurocysticercosis) in a 1:1 ratio. Headache frequency, visual analog scale (VAS) score, and Migraine Disability Assessment (MIDAS) score were assessed at baseline and at the end of 3 months. To compare treatment responsiveness between patients and control subjects, we treated both groups identically so that difference in treatment would not confound the results. Each group comprised 78 patients. Baseline headache frequency (11.3 ± 3.3 versus 7.9 ± 3.4), VAS score (7.5 ± 1.1 versus 6.0 ± 1.2), and MIDAS score (15 ± 7.6 versus 9.6 ± 4.5) were significantly greater in patients than control subjects. Interestingly, the change from baseline to the end of 3 months in headache frequency (6.0 ± 1.7 versus 2.8 ± 1.4), VAS score (2.6 ± 0.02 versus 1.4 ± 0.01), and MIDAS score (8.3 ± 5.0 versus 3.6 ± 2.0) were significantly greater in patients than control subjects. Our study emphasizes that calcified lesions of neurocysticercosis are not inert, and cause an increase in the frequency and severity of migraine attacks. Interestingly, these patients also showed a better response to treatment with amitriptyline, possibly resulting from its anti-inflammatory action. Further studies are warranted to explore possible inflammatory mechanisms in calcified neurocysticercosis, which influences migraine physiology.

The Multiple Cranial Nerve Palsies: A Prospective Observational Study.

BACKGROUND: Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies. METHODS: This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis. RESULTS: Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients. CONCLUSION: Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.

Extra-central nervous system tuberculosis in HIV-uninfected patients of tuberculous meningitis: A prospective evaluation.

OBJECTIVE: Disseminated tuberculosis is characterized with involvement of two or more non-contiguous sites. In this work we evaluated patients of tuberculous meningitis for possible extra-central nervous system tuberculosis. METHOD: This prospective observational study was performed at a tertiary care institute in Northern India. We included consecutive HIV-uninfected cases of TBM. Patients were evaluated for extra-central nervous system (CNS) tuberculosis. We focussed on peripheral lymph nodes, chest, abdomen, and spinal involvement. All patients were subjected to MRI brain and spine. Patients were also subjected to CT thorax and abdomen. Enlarged lymph nodes, if present, were biopsied. Ascitic and pleural fluid were subjected to biochemical, cellular analysis as well as cartridge-based nucleic acid amplification test (CBNAAT) for detection of Mycobacterium tuberculosis and rifampicin resistance. RESULTS: We enrolled 110 patients of TBM. After cerebrospinal fluid examination alone, 14 (12.7%) patients had microbiologically-confirmed TBM. After planned work-up for extra CNS tuberculosis, 5 additional cases were microbiologically confirmed. Similarly, before work-up for extra CNS tuberculosis, 29 (26.4%) patients were categorized as probable TBM. The number of probable cases increased to 72 (65.5%) (P<0.001) with identification of tuberculosis elsewhere. Lung (83.6%) was the most involved site. Abdominal tuberculosis was noted in 29 (26.4%) patients. On imaging spine, 17 (15.5%) patients demonstrated presence of spinal tuberculous. Lymph adenopathy recorded in 2 cases. Lymph node biopsy revealed tuberculous granuloma in both the cases. All 7 patients, who died, had disseminated tuberculosis. CONCLUSION: Extra CNS tuberculous involvement is common in TBM. Search for extra CNS tuberculous enables upgrading diagnostic accuracy.

A study of acute muscle dysfunction with particular reference to dengue myopathy.

BACKGROUND: Acute myopathy is a common cause of acute motor quadriparesis which has various etiologies with different courses of illness and prognosis depending on the cause. Understanding this diversity helps us in proper approach toward diagnosis, predicting the prognosis, and possible complications and in improving the treatments that are being provided. This study was planned to study the clinical, electrophysiological, and etiological profile of patients presenting with acute myopathy. We also studied how dengue-related acute myopathy differs from other causes and also difference between myopathy due to myositis and hypokalemia in cases of dengue. MATERIALS AND METHODS: This was a prospective, observational study involving all clinically suspected cases of acute myopathy of not more than 4 weeks duration with raised serum creatine kinase (CK) level. They were subjected to detailed clinical evaluation along with hematological, biochemical, microbiological, and electrophysiological studies and followed-up for outcome at 1 and 3 months. Muscle biopsy and histopathological examination were done in selected patients after taking informed consent. Statistical analysis was performed by appropriate methods using SPSS version 16.0 (Chicago, IL, USA). RESULTS: We evaluated thirty patients of acute myopathy with raised CK level. Seventeen patients had fever, 11 had myalgia, and 5 had skin lesions. All presented with symmetric weakness, 17 (56.7%) patients having predominantly proximal weakness, neck or truncal weakness in 6 (20%), hyporeflexia in 12 (40%), with mean Medical Research Council (MRC) sum score of 46.67 ± 6.0. Eight (mean modified Barthel index [MBI] at presentation - 15 ± 3.7) patients had poor functional status according to MBI and 15 according to modified Rankin scale (MRS) (mean MRS score - 2.5 ± 1.2). Etiology was dengue viral infection in 14 patients; hypokalemia due to various causes other than dengue in 8; pyomyositis in 3; dermatomyositis, polymyositis, thyrotoxicosis, systemic lupus erythematosus, and unknown etiology in one each. Only eight patients had abnormal electrophysiology and seven among nine biopsies done were abnormal. At 1 month, 24 (80.0%) and 23 (76.7%) patients had achieved normal MBI and MRS scores with 28 (93.3) and 27 (90%) patients, respectively, at 3 months. Dengue with hypokalemia had less myalgia, more of hyporeflexia, and lower serum CK compared to those without hypokalemia. CONCLUSION: Dengue infection and hypokalemia due to various causes are the most common causes of acute myopathy and are associated with rapid and complete recovery within 1 month. Shorter duration of illness, higher MRC sum score, better disability status at presentation, lower serum CK correlate with better outcome. Biopsy was decisive in <20% cases; hence, it is not primary investigation in acute myopathy.

Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole: A prospective follow-up of 60 cases with a review of 56 published cases.

In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India.Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available.There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment.Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in 27 patients. Of the 4 deaths recorded, 3 had a heavy parasitic load and died after praziquantel therapy.Toll-like receptor-4 gene polymorphisms are associated with an increased susceptibility to disseminated cysticercosis, in the Indian population. Albendazole treatment seems to reduce the lesion load and improve symptoms.

Predictors of Lesion Calcification in Patients with Solitary Cysticercus Granuloma and New-Onset Seizures.

Solitary cysticercus granuloma is a common neuroimaging abnormality in Indian patients with new-onset epilepsy. Calcific transformation of cysticercus granuloma is frequently associated with seizure recurrence. We evaluated predictors of lesion calcification in patients with solitary cysticercus granuloma and new-onset seizures. One hundred twenty-two patients, with new-onset seizures and a solitary cysticercus granuloma of the brain, were enrolled. All patients were clinically and radiologically evaluated and were treated with antiepileptic drug drugs. No patient received albendazole or corticosteroids. The follow-up period was of 1 year. Follow-up computed tomography was performed after 3 and 6 months. In 68 (54.8%) patients, solitary cysticercus granuloma had transformed into a calcified lesion. On logistic regression analysis, moderate-to-severe edema was a significant factor that predicted calcific transformation of the cysticercus granuloma (odds ratio: 3.325; 95% confidence interval: 1.502-7.362). During 1 year of follow-up, 19 (15.6%) patients experienced seizure recurrence. In 16 patients with seizure recurrence, cysticercus granuloma had transformed in to a calcified lesion. In conclusion, in solitary cysticercus granuloma, calcification of the lesion can be predicted if larger amount of perilesional edema is present. Calcification of the granuloma significantly predicts seizure recurrence.

Paradoxical reaction in tuberculous meningitis: presentation, predictors and impact on prognosis.

BACKGROUND: Awareness about paradoxical reactions in tuberculous meningitis is crucial as a paradoxical reaction may lead to certain wrong conclusions (for example, an erroneous diagnosis, and a possibility of treatment failure, mycobacterial drug-resistance, drug toxicity, or presence of a malignancy). The present study was planned to evaluate the incidence and predictive factors of paradoxical reactions in light of clinical, cerebrospinal fluid, and neuroimaging characteristics. METHODS: In this prospective cohort study, consecutive patients fulfilling the International Consensus criteria of tuberculous meningitis were included. Patients were subjected to clinical evaluation, cerebrospinal fluid evaluation, and neuroimaging. Patients were treated with anti-tuberculosis drugs along with corticosteroids. Patients were regularly followed up at 3 monthly intervals. At each follow up patients were evaluated clinically and repeat cerebrospinal fluid analysis was performed along with repeat neuroimaging. Disability assessment was done using Barthel index. RESULTS: We enrolled 141 patients of tuberculous meningitis. Approximately one-third of patients (44/141; 31.2 %) developed a paradoxical reaction. Twenty-seven patients developed hydrocephalus, 26 developed tuberculomas, 12 developed optochiasmatic arachnoiditis and 4 patients had spinal arachnoiditis. In 41 patients (out of 44) cerebrospinal fluid paradoxically worsened (increase in cells and/or protein); 2 demonstrated a decrease in cells with polymorph predominance while in one it was normal. In 3 patients, paradoxical cerebrospinal fluid changes were not associated with neuroimaging changes. On multivariate analysis, predictors of paradoxical reaction were female gender (p = 0.013), HIV positivity (p = 0.01) and a shorter duration of illness (p = 0.049). Development of paradoxical reactions did not predict the disability status of the patients. CONCLUSIONS: Paradoxical reaction occurs in approximately one-third of patients with tuberculous meningitis. Female gender, concomitant HIV infection, and a shorter duration of illness were significant predictors. Paradoxical reactions did not adversely affect the outcome.

Toll-like Receptor-4 Polymorphisms and Serum Matrix Metalloproteinase-9 in Newly Diagnosed Patients With Calcified Neurocysticercosis and Seizures.

We evaluated seizure profile, Toll-like receptor (TLR)-4 polymorphisms, and serum matrix metalloproteinases (MMPs) in patients with calcified neurocysticercosis.One-hundred nine patients with calcified neurocysticercosis with newly diagnosed seizures and 109 control subjects were enrolled. TLR-4 Asp299Gly and Thr399Ile polymorphisms and serum MMP-9 levels were evaluated. The patients were followed for 1 year.Asp/Gly (P = 0.012) and Thr/Ile (P = 0.002), Gly (Asp/Gly plus Gly/Gly) (P = 0.008) and Ile (Thr/Ile plus Ile/Ile) (P = 0.003) genotypes were significantly associated with calcified neurocysticercosis compared with controls. Gly/Gly and Ile/Ile genotypes were not significantly associated (P = 0.529 for Gly/Gly, P = 0.798 for Ile/Ile) with either group. The levels of MMP-9 were higher in calcified neurocysticercosis (P =  < 0.001). The levels of MMP-9 were higher in patients with multiple calcified neurocysticercosis compared with single calcified neurocysticercosis (P =  < 0.001).Headache (P = 0.031), status epilepticus (P = 0.029), Todd paralysis (P = 0.039), lesion size >10 mm (P = 0.001), and perilesional edema (P =  < 0.001) were significantly associated with seizure recurrence. Heterozygous form Asp/Gly (P =  < 0.001) and heterozygous form Thr/Ile (P =  < 0.001) were significantly associated with seizure recurrence. The Gly (Asp/Gly plus Gly/Gly) (P =  < 0.001) and Ile (Thr/Ile plus Ile/Ile) (P =  < 0.001) genotypes were also significantly associated with seizure recurrence. Higher serum MMP-9 levels were significantly associated with seizure recurrence (P =  < 0.001).The TLR-4 gene abnormalities may trigger inflammation around calcified neurocysticercosis leading to an increase in perilesional edema and provocation of seizures.

Natural course of typical and atypical parenchymal solitary cysticercus granuloma of the brain: a 3-year prospective clinico-radiological study.

OBJECTIVE: To evaluate the role of advanced magnetic resonance (MR) sequences (fast imaging employing steady-state acquisition (FIESTA), T2 star-weighted angiography (SWAN) and spoiled gradient recalled echo (SPGR)) in patients with single small enhancing computed tomography lesions and scolex demonstration in typical and atypical parenchymal neurocysticercosis. METHODS: In this study, 59 patients of new-onset seizures with single small enhancing computed tomography lesions of the brain were included. Along with routine MR sequences, advanced MR sequences, like SWAN, FIESTA, and pre and post-contrast SPGR, were performed. Follow-up MR studies focussing on the morphology of the lesions and demonstration of scolex were performed 6 monthly for 3 years. RESULTS: The majority of patients (62.7%) were men with partial seizure as the most common manifestation. On SPGR, contrast lesions were identified as either 'typical' (42, 71.2%) or 'atypical' (17, 28.8%). In the typical lesion group, SWAN and FIESTA sequences detected scolex in 30 (71.4%) and 32 (76.2%), respectively. The combination of SPGR-contrast, FIESTA and SWAN sequences detected scolex in 35 (83.3%) patients compared to 19 (45.2%) by routine sequences (P < 0.001). In the atypical lesion group, SWAN and FIESTA sequences detected scolex in 15 (88.2%) and 16 (94.1%) patients, respectively. The combination of SPGR-contrast, FIESTA and SWAN sequences detected scolex in 16 (94.1%) patients compared to 10 (58.8%) by routine sequences (P < 0.001). Follow-up showed greater resolution with lesser calcification in the typical group compared to the atypical group. CONCLUSION: This study provides an insight into the natural course of typical and atypical solitary cysticercus granuloma lesions, and the utility of SPGR-contrast, FIESTA and SWAN MR sequences in scolex demonstration and identification of atypical lesions.

Cytokines and matrix metalloproteinases in the cerebrospinal fluid of patients with acute transverse myelitis: an outcome analysis.

BACKGROUND: Role of cytokines as well as matrix metalloproteinases (MMPs) is well defined in various central nervous system inflammatory diseases. However, the role of these cytokines and MMPs in acute transverse myelitis is inadequately studied. MATERIALS AND METHODS: Patients with acute transverse myelitis, fulfilling the inclusion and exclusion criteria defined by Transverse Myelitis Consortium Working Group, were enrolled along with age and sex matched controls. A detailed clinical evaluation and magnetic resonance imaging of patients was done. Cerebrospinal fluid (CSF) samples both from patients and controls were collected. CSF samples were analyzed for cytokines [interleukin (IL)-6, IL-8, IL-10 and IL-17)] and matrix metalloproteinases (MMP-2, MMP-9). Patients were followed up for 3 months. Disability was assessed using modified Barthel index (MBI). RESULTS: CSF levels of all cytokines IL-6, IL-8, IL-10, MMP-2 and MMP-9, except IL-17, were significantly higher in patients with acute transverse myelitis (p < 0.001). CSF IL-6 and IL-8 were significantly associated with severity of the disease (MBI ≤ 12). After 3 months, quadriparesis (p = 0.001, odd's ratio 19.5, 95 % CI 2.34-62.39) and long-segment myelitis (p = 0.035, odd's ratio 4.37, 95 % CI 1.17-5.95) were significantly associated with poor outcome. Among cytokines and MMPs, IL-6 levels at baseline correlated significantly with the MBI at 3 months (Spearmen's ρ = -0.335, p = 0.01). CONCLUSION: In conclusion, both anti-inflammatory and pro-inflammatory cytokines, MMP-2, and MMP-9 are elevated in the acute phase of transverse myelitis. Possibly, IL-6 plays a role in determining the disability.

Toll like receptor-4 gene polymorphisms in patients with solitary cysticercus granuloma.

BACKGROUND: Solitary cysticercus granuloma (SCG) of the brain is the most common type of neurocysticercosis in India. In this study, we evaluated TLR4 polymorphisms in patients with SCG. METHODS: One-hundred-forty-three patients with SCG and 134 controls were enrolled. Assessment for TLR4 Asp299Gly and Thr399Ile polymorphism was done. TLR4 genotype was determined by PCR-sequencing chain termination method. The patients were followed for 6 months. RESULTS: Asp/Gly (P=0.024) and Thr/Ile (P=0.004) genotypes were significantly associated with the SCG. The Gly (Asp/Gly plus Gly/Gly) genotype (P=0.025) and Ile (Thr/Ile plus Ile/Ile) genotype (P=0.008) were significantly associated with the SCG. Gly/Gly and Ile/Ile genotypes were not significantly associated with SCG (P=0.767 for Gly/Gly, P=0.936 for Ile/Ile). At 6 months, TLR4 299Asp/Gly (P=0.02) and 399Ile/Thr (P=0.023) polymorphisms were significantly associated with the calcification or persistence of SCG. CONCLUSIONS: TLR4 polymorphisms are associated with the susceptibility to infection with SCG.

Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus granuloma.

OBJECTIVES: In patients with neurocysticercosis, perilesional inflammatory activity is thought to be responsible for seizures. This study was designed to evaluate the serum and cerebrospinal fluid (CSF) concentrations of cytokines as well as matrix metalloproteinase (MMP)-2 and MMP-9 in patients with a solitary cysticercus granuloma. MATERIALS AND METHODS: The study included 47 patients suffering from seizures in whom a solitary cysticercus granuloma was detected on a computed tomography (CT) scan. The study also included 47 control subjects. Their serum and cerebrospinal fluid (CSF) was analysed for cytokines and MMP levels. A follow-up CT was performed after 6 months. RESULTS: The median levels of cytokines, interleukin (IL)-1ß, IL-5, IL-6, IL-10 and tissue necrosis factor (TNF)-α, MMP-2 and MMP-9 were significantly elevated, both in the serum and CSF of patients having an intracerebral solitary cysticercus granuloma, in comparison to that of controls. The follow-up CT revealed that in 27 patients, the lesions were calcified and in 5 patients, there was complete resolution of the lesions. In 15 patients, the lesions remained unchanged. Higher baseline CSF MMP-2 and TNF-α level were seen in patients with persisting lesions. Higher serum baseline MMP-2, IL-6 and a low CSF IL-10 level were seen in patients with complete resolution of the granuloma. A high baseline IL-1ß level was associated with a calcified lesion. Fourteen patients had recurrence of seizures. A high baseline serum TNF-α level was independently associated with seizure recurrence (P = 0.021, OR = 1.041, CI = 1.006 to 1.078). CONCLUSION: In patients with a solitary cysticercus granuloma, cytokines and matrix metalloproteinases in the CSF and serum are elevated. Different patterns of immunological changes were observed in patients following resolution or calcification of the lesion.

Serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis.

AIMS AND OBJECTIVES: Both pro-inflammatory and anti-inflammatory cytokines play key roles in the pathogenesis of various forms of tuberculosis. In this study, we evaluated the role of various cytokines and matrix metalloproteinases (MMPs) in patients with spinal tuberculosis. MATERIALS AND METHODS: In this prospective study, we enrolled 55 histopathologically/microbiologically confirmed patients with spinal tuberculosis. We also included 55 control subjects. Blood and cerebrospinal fluid (CSF) were collected both from cases and controls. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-8, IL-10, matrix metalloproteinases MMP-2 and MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA). Disability and outcome were measured by modified Barthel Index (MBI). Measured inflammatory parameters were correlated with the outcome after 6 months of follow-up. RESULTS: We observed that serum and CSF cytokines and MMPs were significantly higher in patients with spinal tuberculosis than in controls (p < 0.001). Spearman's rank order correlation test for correlation of baseline MBI (measure of disability) and cytokine/MMP levels showed that baseline MBI had significant negative correlation with serum levels of IFN-γ (r = -0.517; p < 0.001), IL-1ß (r = -0.355; p = 0.008), IL-6 (r = -0.306; p = 0.023), IL-8 (r = -0.275; p = 0.042), MMP-9 (r = -0.311; p = 0.021) and CSF levels of TNF-α (r = -0.327; p = 0.015); whereas baseline MBI had a positive correlation with the serum level of anti-inflammatory cytokine IL-10 (r = 0.327; p = 0.015). Poor outcome, after 6 months, was associated with higher serum TNF-α (p = 0.015) and IFN-γ (p = 0.021) and CSF MMP-9 (p = 0.006) and a lower serum IL-10 (p = 0.018) level. CONCLUSIONS: To conclude, in patients of spinal tuberculosis, poor outcome is associated with higher pro-inflammatory serum TNF-α and IFN-γ, and CSF MMP-9 levels, and a lower anti-inflammatory serum IL-10 level.

Dose optimization in gynecological 3D image based interstitial brachytherapy using martinez universal perineal interstitial template (MUPIT) -an institutional experience.

The aim of this study was to evaluate the dose optimization in 3D image based gynecological interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT). Axial CT image data set of 20 patients of gynecological cancer who underwent external radiotherapy and high dose rate (HDR) interstitial brachytherapy using MUPIT was employed to delineate clinical target volume (CTV) and organs at risk (OARs). Geometrical and graphical optimization were done for optimum CTV coverage and sparing of OARs. Coverage Index (CI), dose homogeneity index (DHI), overdose index (OI), dose non-uniformity ratio (DNR), external volume index (EI), conformity index (COIN) and dose volume parameters recommended by GEC-ESTRO were evaluated. The mean CTV, bladder and rectum volume were 137 ± 47cc, 106 ± 41cc and 50 ± 25cc, respectively. Mean CI, DHI and DNR were 0.86 ± 0.03, 0.69 ± 0.11 and 0.31 ± 0.09, while the mean OI, EI, and COIN were 0.08 ± 0.03, 0.07 ± 0.05 and 0.79 ± 0.05, respectively. The estimated mean CTV D90 was 76 ± 11Gy and D100 was 63 ± 9Gy. The different dosimetric parameters of bladder D2cc, D1cc and D0.1cc were 76 ± 11Gy, 81 ± 14Gy, and 98 ± 21Gy and of rectum/recto-sigmoid were 80 ± 17Gy, 85 ± 13Gy, and 124 ± 37Gy, respectively. Dose optimization yields superior coverage with optimal values of indices. Emerging data on 3D image based brachytherapy with reporting and clinical correlation of DVH parameters outcome is enterprizing and provides definite assistance in improving the quality of brachytherapy implants. DVH parameter for urethra in gynecological implants needs to be defined further.

Prevalence, severity, and risk factors of symptomatic gastroesophageal reflux disease among employees of a large hospital in northern India.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is considered to be a common and chronic gastrointestinal disorder. The prevalence of GERD is believed to be less in Asia than in Western countries. Population-based data on GERD are lacking from India. The present study aimed at determining the prevalence of GERD symptoms in an adult Indian community and the potential risk factors associated with GERD. METHODS: The study population consisted of all the employees of All India Institute of Medical Sciences, New Delhi. An interview-based observational study was done on the basis of an earlier validated questionnaire. The subjects were asked about the frequency and severity of heartburn and/or regurgitation experienced by them in the previous year. These symptoms were then scored from 0 to 18. Subjects with a score of at least 4 were considered to have symptomatic GERD. Association of GERD with factors like age, sex, BMI, Kuppuswamy social class index, smoking, alcohol, NSAID use, and comorbid illness was analyzed. RESULTS: A total of 4079 employees were interviewed in person on a 29-item questionnaire from June 2003 to January 2005. Of the 4039 eligible subjects, 653 (16.2%) had GERD; 3.6% had heartburn on daily basis and 5.9% on a weekly basis. The corresponding prevalences for regurgitation were 3.3% and 5.0%, respectively. One hundred and eight of 4039 (2.7%) had severe GERD symptoms. Higher BMI (OR=1.90, 95% CI: 1.4-2.6 for BMI ≥25), current smoking (OR=1.48, 95% CI: 1.19-1.83), asthma (OR=3.13, CI: 2.06-4.76) and hypertension (OR=1.71, 95% CI: 1.16-2.50) were associated with the presence of GERD symptoms. CONCLUSIONS: Prevalence of GERD in an urban adult population from northern India is 16.2% which is similar to other industrialized countries. Higher body mass index, current smoking, and presence of asthma or hypertension predisposes to GERD in our population.