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2.  Association of Polymorphisms of Phase I Metabolizing Genes with Sister Chromatid Exchanges in Occupational Workers Exposed to Toluene Used in Paint Thinners 
This study investigated genetic damage in paint workers mainly exposed to toluene as it is a major solvent used in paint thinners. Sister chromatid exchange (SCE) assay was used as biomarker of genotoxicity. Blood samples were collected from 30 paint workers and 30 control subjects matched with respect to age and other confounding factors except for exposure to toluene. SCE frequency was found to be significantly higher in paint workers (4.81 ± 0.92) as compared to control individuals (1.73 ± 0.54) (p < 0.05). We also investigated influence of polymorphisms of CYP2E1 and CYP1A1m2 genes on SCE frequency. Our results showed that there was significant increase in frequencies of SCE among the mutant genotypes of CYP2E1 and CYP1A1m2 as compared to wild genotypes. Our study indicated that long term exposure of toluene can increase genotoxic risk in paint workers.
PMCID: PMC4672146  PMID: 26688756
4.  To Identify Myocardial Changes in Severely Malnourished Children: A Prospective Observational Study 
Aim and objective
The main purpose of this study is to identify the myocardial changes in severely malnourished children.
Materials and methods
This prospective, observational study, conducted for a period of 1 year, enrolled 200 children (120 males and 80 females) between 6 months and 5 years of age with severe protein–energy malnutrition, according to the criteria of the World Health Organization. The parents were duly informed, the study was explained and written consent was obtained. A random selection of cases was carried out, and they were further divided into five groups according to their age as follows: <1, 1–2, 2–3, 3–4, and 4–5 years. Electrocardiograms (ECGs) were taken at the time of admission for all the cases and the control group and were taken again after nutritional therapy either at the time of discharge or after a fortnight. The differences were then compared.
On admission, 32% of cases had flat P-wave, out of which 75% reverted to normal with therapy. Similarly, 84% of cases had increased corrected QT interval at the time of admission. ST segment was depressed only in 8% of cases. 88% of cases had altered (flat to depressed) T wave at the time of admission. With the help of nutritional supplementation, all these abnormalities were back to a normal level at the time of discharge.
Electrocardiographic changes may be of help in assessing the severity and prognosis of severe acute malnutrition. The reversibility of ECG changes with dietary treatment suggests that the cardiac changes are not permanent in nature and may not affect adult life if the malnutrition is corrected. The cardiac status as denoted by heart rate remained the same even after a fortnight, suggesting that prolonged therapy and assessment of cardiac status is warranted even after fortnight therapy.
PMCID: PMC4558470  PMID: 26389105
malnutrition; body weight; height; BMI; ECG
5.  Acute confusional migraine: a variant not to be missed 
BMJ Case Reports  2013;2013:bcr2013010504.
A middle age woman who had frequent migraines was admitted with memory loss following severe unilateral headache, restlessness and confusion. Investigations including haematology, biochemistry, cerebrospinal fluid analysis serology and imaging were normal. As she had frequent migraines with a history of ophthalmoplegic migraine, acute confusional migraine was thought of as a possibility. The patient responded dramatically to intravenous sodium valproate. We report this case to emphasise that acute confusional migraine, a rare variant of migraine, is occasionally encountered in adults and prompt recognition will lead to appropriate management.
PMCID: PMC3761691  PMID: 23912657
6.  Role of Areca Nut Induced TGF-β and Epithelial-Mesenchymal Interaction in the Pathogenesis of Oral Submucous Fibrosis 
PLoS ONE  2015;10(6):e0129252.
Areca nut consumption has been implicated in the progression of Oral Submucous fibrosis (OSF); an inflammatory precancerous fibrotic condition. Our previous studies have demonstrated the activation of TGF-β signaling in epithelial cells by areca nut components and also propose a role for epithelial expressed TGF-β in the pathogenesis of OSF. Although the importance of epithelial cells in the manifestation of OSF has been proposed, the actual effectors are fibroblast cells. However, the role of areca nut and TGF-β in the context of fibroblast response has not been elucidated. Therefore, to understand their role in the context of fibroblast response in OSF pathogenesis, human gingival fibroblasts (hGF) were treated with areca nut and/or TGF-β followed by transcriptome profiling. The gene expression profile obtained was compared with the previously published transcriptome profiles of OSF tissues and areca nut treated epithelial cells. The analysis revealed regulation of 4666 and 1214 genes by areca nut and TGF-β treatment respectively. The expression of 413 genes in hGF cells was potentiated by areca nut and TGF-β together. Further, the differentially expressed genes of OSF tissues compared to normal tissues overlapped significantly with areca nut and TGF-β induced genes in epithelial and hGF cells. Several positively enriched pathways were found to be common between OSF tissues and areca nut +TGF-β treated hGF cells. In concordance, areca nut along with TGF-β enhanced fibroblast activation as demonstrated by potentiation of αSMA, γSMA and collagen gel contraction by hGF cells. Furthermore, TGF-β secreted by areca nut treated epithelial cells influenced fibroblast activation and other genes implicated in fibrosis. These data establish a role for areca nut influenced epithelial cells in OSF progression by activation of fibroblasts and emphasizes the importance of epithelial-mesenchymal interaction in OSF.
PMCID: PMC4479469  PMID: 26107172
7.  Clinical Reasoning: A 55-year-old man with weight loss, ataxia, and foot drop 
Neurology  2014;82(24):e214-e219.
A 55-year-old man with prior alcohol abuse and an 80 pack-year smoking history was referred for evaluation of a 3-month history of subacute-onset, progressively worsening imbalance without back pain. He began using a cane to ambulate after multiple falls. He also described recent right foot weakness, numbness in his feet and fingertips, and unintentional 25-pound weight loss over the past year. His medical history was significant for hypertension, gastroesophageal reflux disease, diverticulitis, and pelvic abscesses. A paternal grandfather had lung cancer. He reported a remote history of IV drug use. General examination revealed cachexia. Neurologic examination findings were complex. Gait examination revealed severe ataxia, a high steppage gait on the right, and a positive Romberg sign. The total ataxia score using the Scale for Assessment and Rating of Ataxia (higher scores indicate increased severity)1 was 14/40, including gait, 5/8; stance, 4/6; sitting, 1/4; speech disturbance, 0/4; finger chase, 0/4; nose-finger test, 0/4; fast alternating hand movements, 2/4; and heel-shin slide, 2/4. Nystagmus was not present. Strength testing revealed hip and knee flexion weakness bilaterally (grade 4/5) and severe (grade 2/5) weakness of right ankle dorsiflexion and eversion but preserved inversion strength. Reflexes were brisk in the upper extremities and normal in the lower extremities and plantar responses were flexor. Sensory testing revealed absent lower extremity vibration, absent joint position at the toes, and reduced pinprick in the feet without a sensory level. Initial laboratory testing revealed a hemoglobin of 9.3 g/dL (normal range 13.5–17.5).
PMCID: PMC4113461  PMID: 24960835
8.  Development of Novel Ionic Liquid-Based Microemulsion Formulation for Dermal Delivery of 5-Fluorouracil 
AAPS PharmSciTech  2014;15(4):810-821.
The present study was aimed at synthesizing an imidazole-based ionic liquid 1-butyl-3-methylimidazolium bromide (BMIMBr) and subsequent development of a novel ionic liquid-in-oil (IL/o) microemulsion (ME) system for dermal delivery of a poorly permeating drug 5-fluorouracil (5-FU). A significant enhancement in the solubility of 5-FU was observed in BMIMBr. IL/o MEs of 5-FU were prepared using isopropyl myristate, Tween 80/Span 20, and BMIMBr. Results of ex vivo skin permeation studies through mice skin indicated that the selected IL/o ME exhibited 4-fold enhancement in percent drug permeation as compared to aqueous solution, 2.3-fold as compared to hydrophilic ointment, and 1.6-fold greater permeation than water in oil (w/o) ME. The results of in vivo studies against dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mice skin carcinogenesis demonstrated that the IL/o ME could effectively treat skin cancer in 4 weeks. In addition, the side effects such as erythema and irritation associated with the conventional formulations were not observed. Histopathological studies showed that the use of IL/o ME caused no anatomic and pathological changes in the skin structure of mice. These studies suggest that the use of IL-based ME system can efficiently enhance the solubility and permeability of 5-FU and hence its therapeutic efficacy.
PMCID: PMC4113608  PMID: 24668136
5-fluorouracil; dermal delivery; ionic liquids; ionic liquid in oil (IL/o) microemulsion; skin cancer
9.  Intercondylar Humerus Fracture- Parallel Plating and Its Results 
Background: Intercondylar fracture of humerus is one of the commonest fractures of young adult and counts for about 30% of all elbow fractures. The treatment of these fractures continues to present challenges despite advances in internal fixation. Although orthogonal plating use to provid adequate functional results in these fractures, parallel plating is said to be mechanically more stable construct thus allowing early mobilization and better range of motion.
Aim: Aim of the study is to assess the clinical as well functional results of these fractures treated with parallel plating.
Study and Design: Prospective study in a tertiary care hospital.
Materials and Methods: A total of 23 fresh patients of intercondylar fracture of humerus from Jan 2013 to May 2014 were included in the study and were treated with parallel plating. These patients were followed at 3, 6, 12, 24 weeks and at 1year of follow up and assessed in terms of time for union, range of motion, MAYO score, DASH score and complication rate.
Results: At final follow up Mayo score was 96.32±04.96 from 5.00±01.26 and DASH SCORE was 31.42±2.04 which dropped from 150±05.34, Range of motion improved from 21.38±05.70 to 116.1±07.92 with 100% union rate and complications less than 19%.
Conclusion: Parallel plating for intercondylar fracture of humerus is excellent method of fixation and results are similar to those treated with orthogonal plating.
PMCID: PMC4347137  PMID: 25738046
Fixation; Intercondylar fracture; Orthogonal plating
10.  Anatomical Variations of Brachial Artery - Its Morphology, Embryogenesis and Clinical Implications 
Background: Accurate knowledge of variation pattern of the major arteries of upper limb is of considerable practical importance in the conduct of reparative surgery in the arm, forearm and hand however brachial artery and its terminal branches variations are less common.
Aim: Accordingly the present study was designed to evaluate the anatomical variations of the brachial artery and its morphology, embryogenesis and clinical implications.
Materials and Methods: In an anatomical study 140 upper limb specimens of 70 cadavers (35 males and 35 females) were used and anatomical variations of the brachial artery have been documented.
Results: Accessory brachial artery was noted in eight female cadavers (11.43%). Out of eight cadavers in three cadavers (4.29%) an unusual bilateral accessory brachial artery arising from the axillary artery and it is continuing in the forearm as superficial accessory ulnar artery was noted. Rare unusual variant unilateral accessory brachial artery and its reunion with the main brachial artery in the cubital fossa and its variable course in relation to the musculocutaneous nerve and median nerve were also noted in five cadavers (7.14%).
Conclusion: As per our knowledge such anatomical variations of brachial artery and its terminal branches with their relation to the surrounding structures are not reported in the modern medical literature. An awareness of such a presence is valuable for the surgeons and radiologists in evaluation of angiographic images, vascular and re-constructive surgery or appropriate treatment for compressive neuropathies.
PMCID: PMC4316237  PMID: 25653931
Entrapment neuropathy; Median nerve; Paraesthesia
11.  Neuroimaging and clinical features in type II (late-onset) Alexander disease 
Neurology  2014;82(1):49-56.
To describe the imaging and clinical features in type II (late-onset) Alexander disease (AxD).
We retrospectively identified all cases of type II AxD evaluated at Mayo Clinic, Rochester from January 1996 to February 2012. Clinical and neuroimaging data abstracted from the record included age at onset of symptoms, age at diagnosis, first symptom, neurologic symptoms, physical/neurologic findings on examination, genetic testing and/or biopsy (if performed), and MRI findings.
Thirteen patients with type II AxD were identified. Median age at onset was 38 years (range: 12–63). Five patients were female. Eleven of 13 patients had atrophy of the medulla while all 13 had medullary T2 hyperintensity. In 7 patients, these brainstem regions showed patchy enhancement. Five subjects had T2 signal change in the middle cerebellar peduncle, with associated contrast enhancement in 4 subjects. Eleven of 12 patients with T2 fluid-attenuated inversion recovery (FLAIR) imaging had pial FLAIR signal change in the medulla. Nine of 12 patients with spinal cord imaging had cord atrophy, and 3 of 9 of these evaluated with contrast had cervical cord enhancement.
Our study confirms prior reports of atrophy and signal change of the medulla and spinal cord in late-onset AxD. We expand on previous imaging studies by identifying middle cerebellar peduncle and pial FLAIR signal changes as important diagnostic clues. Variable patchy enhancement may occur in regions of T2 hyperintensity, leading to diagnostic uncertainty. In addition, we demonstrate that previously emphasized clinical features such as palatal tremor may not be common. We affirm that age at onset predicts clinical phenotype and imaging findings.
PMCID: PMC3873623  PMID: 24306001
12.  Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery 
Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.
PMCID: PMC4313779  PMID: 25699255
iPSC; reprogramming; pluripotency; differentiation; disease modeling; drug discovery; gene therapy
13.  Antibiotic Resistance in Uropathogenic E. Coli Strains Isolated from Non-Hospitalized Patients in Pakistan 
Purpose: To study multidrug-resistance in Uropathogenic E. Coli (UPEC) isolated from non-hospitalized patients.
Materials and Methods: Altogether, 250 bacterial samples were collected from non-hospitalized patients. Their identifications were done on basis of Gram-staining, colony morphology, biochemical testing and PCR. Susceptibility testing was performed by using standard protocols which were recommended by CLSI.
Statistical analysis: For comparisons, statistical analysis was performed by using software, Graphpad Prism 5.0
Results: In total, 32% (n = 80) of the isolates were identified as E. Coli strains and their susceptibility patterns for different antibiotics were determined. The data indicated least resistance against tazocin [(TZP) -1.25%], amikacin [(AK) -1.8%], tigecycline [(TGC)- 2.5%] and nitrofurantoin [(F) -3.75%]. For both minocycline (MH) and sulzone (SUL), resistance rate was 5%, for gentamicin (CN), it was 16.25%, while higher resistances were observed against cephalothine [(KF)- 70%], cefotaxime [(CTX) -58.5%], ceftazidime [(CAZ)- 57.5%], cefepime [(FEP) -55%], cefuroxime and cefixime [(CXM) (CFM)- 53.75 %]. Resistance against ciprofloxacin (CIP) was 57.5%, for norfloxacine (NOR), it was 52.5% and incase of sparfloxacin (SPX), it remained 55%. High percentage of the isolates were resistant to cotrimoxazole [(SXT) -86%] and Amoxicillin [AMX-CLA (AMC)- 76%]. No resistance against meropenem (MEM) was observed.
Conclusion: Highest level of drug-resistance was observed against trimethoprim-sulfamethoxazole (TMP-SMZ) among clinical isolates of uropathogenic E. Coli collected from non-hospitalized patients.
PMCID: PMC4225882  PMID: 25386430
Antibiotic susceptibility; Beta-lactamase; Cotrimoxazole; E. Coli; Plasmids; UPEC
14.  PHA-4/FOXA-regulated microRNA feed forward loops during Caenorhabditis elegans dietary restriction 
Aging (Albany NY)  2014;6(10):835-851.
Dietary restriction (DR) increases life span and delays the onset of age-related diseases across species. However, the molecular mechanisms have remained relatively unexplored in terms of gene regulation. In C. elegans, a popular model for aging studies, the FOXA transcription factor PHA-4 is a robust genetic regulator of DR, although little is known about how it regulates gene expression. We profiled the transcriptome and miRNAome of an eat-2 mutant, a genetic surrogate of DR, by Next Generation sequencing and find that most of the miRNAs are upregulated in the young-adult worms, none significantly downregulated. Interestingly, PHA-4 can potentially regulate the expression of most of these miRNA genes. Remarkably, many of the PHA-4-regulated genes that are induced during DR are also targets of the PHA-4-upregulated miRNAs, forming a large feed-forward gene regulatory network. The genes targeted by the feed-forward loops (FFLs) are enriched for functions related to ubiquitin-mediated decay, lysosomal autophagy, cellular signalling, protein folding etc., processes that play critical roles in DR and longevity. Together our data provides a framework for understanding the complex and unique regulatory network employed during DR, suggesting that PHA-4 employs such FFLs to fine-tune gene expression and instil robustness in the system during energy crisis.
PMCID: PMC4247386  PMID: 25504288
microRNA; dietary restriction; PHA-4/FOXA; Transcription factor; miRNA; feed forward loops; aging
15.  Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism 
Journal of Toxicology  2014;2014:404236.
In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P < 0.05) was observed in the frequencies of SCEs in presence of 10 μg/mL and 15 μg/mL concentrations of curcumin as compared to parathion exposed sample. Similarly carvacrol had significant (P < 0.05) antigenotoxic effect at the concentrations of 2.5 μg/mL and 5.0 μg/mL against the parathion. We also studied the effect of GSTT1 and GSTM1 on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol. We did not observe any significant effect (P > 0.05) of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol.
PMCID: PMC4195395  PMID: 25328519
16.  Diagnostic dilemma in CNS Behçet's disease 
BMJ Case Reports  2012;2012:bcr2012006610.
A 23-year-old gentleman presented to the emergency department with new onset neurological dysfunction and painful oral and genital ulcers. Biopsies of the lesions noted non-specific inflammatory changes. MRI of the brain revealed a large mass-like lesion involving the pons, medulla, midbrain and surrounding cerebral tissue with T2 signal enhancement that was not amenable for biopsy. Both the ulcer biopsy results and the MRI findings could be attributed to either central nervous system (CNS) lymphoma or CNS Behçet's disease. A diagnosis of CNS Behçet's disease was thought to be most likely based on the clinical presentation and MRI findings. He was treated with high-dose immunosuppression and made a significant recovery.
PMCID: PMC4543980  PMID: 22952274
17.  Development of Novel Elastic Vesicle-Based Topical Formulation of Cetirizine Dihydrochloride for Treatment of Atopic Dermatitis 
AAPS PharmSciTech  2013;14(4):1284-1293.
Cetirizine is a piperazine-derived second-generation antihistaminic drug recommended for treatment of pruritus associated with atopic dermatitis. The present investigation encompasses development of a nanosized novel elastic vesicle-based topical formulation of cetirizine dihydrochloride using combination of Phospholipon® 90G and edge activators with an aim to have targeted peripheral H1 antihistaminic activity. The formulation was optimized with respect to phospholipid/drug/charge inducer ratio along with type and concentration of edge activator. The optimized formulation was found to be satisfactory with respect to stability, drug content, entrapment efficiency, pH, viscosity, vesicular size, spreadability, and morphological characteristics. The ex vivo permeation studies through mice skin were performed using Franz diffusion cell assembly. It was found that the mean cumulative percentage amount permeated in 8 h was almost twice (60.001 ± 0.332) as compared to conventional cream (33.268 ± 0.795) and aqueous solution of drug (32.616 ± 0.969), suggesting better penetration and permeation of cetirizine from the novel vesicular delivery system. Further, therapeutic efficacy of optimized formulation was assessed against oxazolone-induced atopic dermatitis in mice. It was observed that the developed formulation was highly efficacious in reducing the itching score (4.75 itches per 20 min) compared to conventional cream (9.75 itches per 20 min) with profound reduction in dermal eosinophil count and erythema score. To conclude, a novel vesicular, dermally safe, and nontoxic topical formulation of cetirizine was successfully developed and may be used to treat atopic dermatitis after clinical investigation.
PMCID: PMC3840784  PMID: 23959702
atopic dermatitis; cetirizine; elastic vesicles; oxazolone; topical
18.  Early recanalisation of cerebral venous sinus thrombosis in an unusual case associated with severe protein S deficiency 
BMJ Case Reports  2012;2012:bcr2012006496.
An inherited or acquired deficiency of protein S leads to a prothrombotic state, with predisposition to venous thrombosis. We describe a case of cerebral venous sinus thrombosis (CVST) associated with acquired protein S deficiency and recanalisation within 15 days of anticoagulation. A 38-year-old man presented with recurrent headache, vomiting, altered sensorium and one episode of transient left hemiparesis. Magnetic resonance venography showed poor flow in the deep cerebral venous sinuses with extensive collateral venous channel formation, which resolved after 15 days of anticoagulation, along with clinical improvement. Serum protein S activity was found to be markedly low (16% of biological reference). CVST should be suspected in a patient with acute features of raised intracranial pressure or focal neurological deficit, and a patient without obvious clinical predisposition for a prothrombotic state should be evaluated for underlying thrombophilic states like protein S deficiency.
PMCID: PMC4543489  PMID: 22847569
19.  Extraction and purification of C-phycocyanin from Spirulina platensis (CCC540) 
In this study a simple protocol was developed for purifying phycocyanin (PC) from Spirulina platensis (CCC540) by using ammonium sulphate precipitation, followed by a single step chromatography by using DEAE-Cellulose-11 and acetate buffer. Precipitation with 65 % ammonium sulphate resulted in 80 % recovery of phycocyanin with purity of 1.5 (A620/A280). Thro1ugh chromatography an 80 % recovery of phycocyanin with a purity of 4.5 (A620/A280) was achieved. In SDS_PAGE analysis, the purified PC showed the presence of two subunit α (16 kD) and β (17 kD).
Electronic supplementary material
The online version of this article (doi:10.1007/s40502-014-0094-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4113674  PMID: 25089058
Spirulina; DEAE-Cellulose-11; Phycocyanin
20.  MRS in Early and Presymptomatic Carriers of a Novel Octapeptide Repeat Insertion in the Prion Protein Gene 
To evaluate the proton MR spectroscopy (1H MRS) changes in carriers of a novel octapeptide repeat insertion in the Prion Protein Gene (PRNP) and family history of frontotemporal dementia with ataxia. Four at-risk mutation carriers and 13 controls were compared using single voxel, short TE, 1H MRS from the posterior cingulate gyrus. The mutation carriers had an increased choline/creatine, p=0.003 and increased myoinositol/creatine ratio, p=0.003. 1H MRS identified differences in markers of glial activity and choline metabolism in pre- and early symptomatic carriers of a novel PRNP gene octapeptide insertion. These findings expand the possible diagnostic utility of 1H MRS in familial prion disorders.
PMCID: PMC3480551  PMID: 22612156
MRS; MRI; familial prion disorders; frontotemporal dementia
21.  Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress 
Cell Stress & Chaperones  2013;19(1):61-81.
An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P < 0.05/P < 0.01) on hematological profile (erythrocyte count, hemoglobin, and hematocrit), serum protein (total protein, albumin, and globulin) and lipid profile (cholesterol and triglyceride), anti-oxidative status (ascorbic acid content of muscle, liver, brain, and kidney and activity of anti-oxidative enzymes: catalase and superoxide dismutase), neurotransmission (acetylcholinesterase activity in muscle and brain), immunological attributes (WBC count, albumin to globulin ratio, phagocytic activity, and serum cortisol), and metabolic plasticity as revealed from enzyme activities (muscle lactate dehydrogenase, liver and kidney glucose-6-phosphatase dehydrogenase-G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value Vmax, catalytic efficiency and Michaelis constant Km) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and lecithin at the levels used, improve erythropoiesis, serum protein and lipid profile, anti-oxidant status, immunocompetence, neurotransmission, and protect the livers of L. rohita fingerlings even when continuously exposed to low-dose endosulfan.
PMCID: PMC3857435  PMID: 23666764
Lipotropes; Pesticide stress; Hematological profile; Serum protein and lipid profile; Anti-oxidant status; Immunocompetence; Acetylcholinesterase activity; Biochemical plasticity; G6PDH kinetics; Labeo rohita; Immunostimulants
22.  Impact of Smoking on Speed and Coordination of Upper Limb Movement 
Addiction & Health  2014;6(3-4):155-158.
The purpose of this study was to determine the effect of smoking on speed and coordination of upper-limb movement.
A total of 62 healthy, young individuals were randomly selected for participation in this study. Out of total subjects, 31 were smokers with a mean age 20.84 years and 31 were non-smokers with a mean age 19.97 years and placed in group A and group B, respectively. Plate taping test was administered to all the subjects to determine their speed and coordination of upper limb.
Student’s t-test was applied between both groups to see the difference in their plate taping test’s time; its t-value was 5.03.
Statistical significant difference was seen between both the groups in the result of plate taping test, which suggests that smoking can affect the speed and coordination of upper limb in a negative way and cause its deterioration. Therefore, immediate quitting from smoking is of high value and requirements to have a good speed and coordination of upper-limb movements.
PMCID: PMC4354221  PMID: 25984283
Smoking; Speed; Coordination; Plate tapping test
23.  Lipotropes Protect against Pathogen-Aggravated Stress and Mortality in Low Dose Pesticide-Exposed Fish 
PLoS ONE  2014;9(4):e93499.
The decline of freshwater fish biodiversity corroborates the trends of unsustainable pesticide usage and increase of disease incidence in the last few decades. Little is known about the role of nonlethal exposure to pesticide, which is not uncommon, and concurrent infection of opportunistic pathogens in species decline. Moreover, preventative measures based on current knowledge of stress biology and an emerging role for epigenetic (especially methylation) dysregulation in toxicity in fish are lacking. We herein report the protective role of lipotropes/methyl donors (like choline, betaine and lecithin) in eliciting primary (endocrine), secondary (cellular and hemato-immunological and histoarchitectural changes) and tertiary (whole animal) stress responses including mortality (50%) in pesticide-exposed (nonlethal dose) and pathogen-challenged fish. The relative survival with betaine and lecithin was 10 and 20 percent higher. This proof of cause-and-effect relation and physiological basis under simulated controlled conditions indicate that sustained stress even due to nonlethal exposure to single pollutant enhances pathogenic infectivity in already nutritionally-stressed fish, which may be a driver for freshwater aquatic species decline in nature. Dietary lipotropes can be used as one of the tools in resurrecting the aquatic species decline.
PMCID: PMC3972094  PMID: 24690771
24.  The Effect of N-Alkyl Substituents on the Usability of Imidazolium Cation-Based Ionic Liquids in Microemulsion Systems: A Technical Note 
AAPS PharmSciTech  2013;14(2):551-557.
PMCID: PMC3666005  PMID: 23463260
drug delivery; hemolysis; imidazolium; ionic liquids; microemulsion
25.  Feedback about action performed can alter the sense of self-agency 
Sense of agency refers to the sense of authorship of an action and its outcome. Sense of agency is often explained through computational models of motor control (e.g., the comparator model). Previous studies using the comparator model have manipulated action-outcome contingency to understand its effect on the sense of agency. More recent studies have shown that cues related to outcome, priming outcome and priming action have an effect on agency attribution. However, relatively few studies have focused on the effect of recalibrating internal predictions on the sense of agency. This study aims to investigate how feedback about action can recalibrate prediction and modulates the sense of agency. While participants performed a Flanker task, we manipulated the feedback about the validity of the action performed, independent of their responses. When true feedback is given, the sense of agency would reflect congruency between the sensory outcome and the action performed. The results show an opposite effect on the sense of agency when false feedback was given. We propose that feedback about action performed can recalibrate the prediction of sensory outcome and thus alter the sense of agency.
PMCID: PMC3933776  PMID: 24611059
sense of agency; motor control; forward model; error monitoring mechanisms; Flanker task; error feedback; action intention

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