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2.  Proteome Analysis of Disease Resistance against Ralstonia solanacearum in Potato Cultivar CT206-10 
The Plant Pathology Journal  2016;32(1):25-32.
Potato is one of the most important crops worldwide. Its commercial cultivars are highly susceptible to many fungal and bacterial diseases. Among these, bacterial wilt caused by Ralstonia solanacearum causes significant yield loss. In the present study, integrated proteomics and genomics approaches were used in order to identify bacterial wilt resistant genes from Rs resistance potato cultivar CT-206-10. 2-DE and MALDI-TOF/TOF-MS analysis identified eight differentially abundant proteins including glycine-rich RNA binding protein (GRP), tomato stress induced-1 (TSI-1) protein, pathogenesis-related (STH-2) protein and pentatricopeptide repeat containing (PPR) protein in response to Rs infection. Further, semi-quantitative RT-PCR identified up-regulation in transcript levels of all these genes upon Rs infection. Taken together, our results showed the involvement of the identified proteins in the Rs stress tolerance in potato. In the future, it would be interesting to raise the transgenic plants to further validate their involvement in resistance against Rs in potato.
PMCID: PMC4755672  PMID: 26889112
genomics; MALDI-TOF-MS; potato; proteomics; Ralstonia solanacearum
3.  A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman syndrome 
Molecular Vision  2016;22:73-81.
To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS.
The siblings underwent a thorough ophthalmological examination, including retinal optical coherence tomography (OCT) imaging, and an extensive physical examination with abdominal ultrasonography to characterize the disease phenotype. Next-generation sequencing (NGS) using a panel targeting retinal degeneration genes was performed on genomic DNA samples from the siblings and parents. Upon identification of the causative mutation, functional characterization was accomplished by performing protein–protein interaction studies in human embryonic kidney (HEK-293T) and human adult retinal pigmented epithelium (ARPE-19) cells.
The two siblings showed signs of RP and polydactyly. The patients did not have truncal obesity, renal anomalies, hydrometrocolpos, congenital heart disease, or overt cognitive defects. NGS identified a homozygous c.1184A>G mutation in the MKKS/BBS6 gene in both patients resulting in a p.H395R substitution in the MKKS/BBS6 protein. This mutant protein decreased the interaction of MKKS/BBS6 with BBS12 but did so to a different extent in the HEK-293T versus ARPE-19 cells. Nonetheless, the effect of the H395R variant on disrupting interactions with BBS12 was not as profound as other reported MKKS/BBS6 mutations associated with syndromic RP.
We identified a novel H395R substitution in MKKS/BBS6 that results in a unique phenotype of only RP and polydactyly. Our observations reaffirm the notion that mutations in MKKS/BBS6 cause phenotypic heterogeneity and do not always result in classic MKKS or BBS findings.
PMCID: PMC4734152  PMID: 26900326
4.  Asymmetrical F-18 Flurorodeoxyglucose uptake in the breasts: A dilemma solved by patient history 
The present case highlights the importance of history taking in solving the dilemmas of variant F-18 FDG uptake on PET/CT. Asymmetrically increased, abnormal looking, FDG uptake in the right breast of our patient was related to her breast feeding practice. Because of personal preference the patient suckled her child from the right breast only. This resulted in asymmetry of size, increase in glandular breast parenchyma and FDG uptake in the breast that was suckled.
PMCID: PMC4746856  PMID: 26917909
Breast; F-18 fluorodeoxygluocose; lactating; positron emission tomography/computed tomography
5.  Presleep thoughts and dysfunctional beliefs in subjects of insomnia with or without depression: Implications for cognitive behavior therapy for insomnia in Indian context 
Indian Journal of Psychiatry  2016;58(1):77-82.
Presleep thoughts may vary between patients of insomnia with or without depression. They are important for cognitive behavior therapy for insomnia (CBT-I), but they have never been systemically examined in Indian population.
Materials and Methods:
Patients with insomnia (>1 month) who were willing to undergo CBT-I were included in this study after obtaining informed consent. They were requested to fill a sleep diary and return after 15 days. At the time of intake, diagnosis of depression and anxiety disorders was made according to Diagnostic and Statistical Manual - IV-Text Revision. They were encouraged to provide information regarding presleep thoughts through open-ended and then, close-ended questions. Dysfunctional attitudes and beliefs about sleep were assessed with Hindi version of “dysfunctional beliefs and attitudes scale-brief version”. Hindi version of “insomnia severity index” was used to assess the severity of insomnia. Subjects were divided into two-groups - insomnia without depression (I) and insomnia with major depressive disorder (I-MDD+).
Statistical Analysis:
It was done with the help of SPSS v 21.0. Descriptive statistics was calculated. Proportions between groups were tested with Chi-square analysis and categorical variables were compared using independent sample t-test.
This study included a total of 63 subjects, out of which 60% were women. Mean age of the whole group was 41.7 ± 11.8 years. About 40% of all the subjects were diagnosed as having I-MDD+. Forty-one percent of the subjects had clinically significant anxiety. Both groups - I and I-MDD+ had comparable proportion of female subjects (χ2 = 0.002; P = 0.96) and there was no difference regarding precipitating factors for insomnia (χ2 = 0.97; P = 0.61). They were also comparable with regards to sleep-related measures, themes of presleep thoughts, and dysfunctional beliefs and attitudes about sleep and insomnia severity. Major themes of presleep thoughts included family issues and health issues. Only a small proportion had recurrent thoughts related to insomnia and its consequences.
Insomnia is a co-morbid illness with depression and it needs to be separately addressed during therapy. CBT-I should include the element of problem-solving technique, especially when we are dealing with the Indian population.
PMCID: PMC4776587  PMID: 26985109
Cognitive behavior therapy for insomnia; depression; insomnia; presleep thoughts
Neuro-Oncology  2014;16(Suppl 5):v145.
BACKGROUND: Glioblastoma multiforme (GBM) typically presents in the supratentorial white matter, commonly within the centrum semiovale as a ring-enhancing lesion with areas of necrosis. An atypical presentation of this lesion, both anatomically as well as radiographically is significant and must be part of the differential for a neoplasm in this location. CASE DESCRIPTION: We present a case of a sixty-two year old female with headaches, increasing somnolence and cognitive decline for several weeks. The MRI showed mild left ventricular dilatation with a well-marginated, homogenous, and non-hemorrhagic lesion located at the ceiling of the third ventricle within the junction of the septum pellucidum (SP) and fornix, without exhibiting the typical radiographic features of hemorrhage or necrosis. Final pathology reports confirmed the diagnosis of GBM. CONCLUSION: This case report describes an unusual location for the most common primary brain neoplasm. Moreover, this case identifies the origin of a GBM related to the paracentral ventricular structures infiltrating the body of the fornix and leaves of the septum pellucidum. To our knowledge this is report is the first reported case of a GBM found in this anatomical location with an entirely atypical radiographic presentation.
PMCID: PMC4218358
7.  Third Ventricular Glioblastoma Multiforme: Case Report and Literature Review 
Background Glioblastoma multiforme (GBM) typically presents in the supratentorial white matter, commonly within the centrum semiovale as a ring-enhancing lesion with areas of necrosis. An atypical presentation of this lesion, both anatomically as well as radiographically, is significant and must be part of the differential for a neoplasm in this anatomical location.
Case Description We present a case of a 62-year-old woman with headaches, increasing somnolence, and cognitive decline for several weeks. Magnetic resonance imaging demonstrated mild left ventricular dilatation with a well-marginated, homogeneous, and nonhemorrhagic lesion located at the ceiling of the third ventricle within the junction of the septum pellucidum and fornix, without exhibiting the typical radiographic features of hemorrhage or necrosis. Final pathology reports confirmed the diagnosis of GBM.
Conclusion This case report describes an unusual location for the most common primary brain neoplasm. Moreover, this case identifies the origin of a GBM related to the paracentral ventricular structures infiltrating the body of the fornix and leaves of the septum pellucidum. To our knowledge this report is the first reported case of a GBM found in this anatomical location with an entirely atypical radiographic presentation.
PMCID: PMC4648723  PMID: 26623232
glioblastoma multiforme; third ventricle; foramen of Monroe; gliosarcoma; septum pellucidum; hydrocephalus; fornix
8.  Sleep Disorders in Postmenopausal Women 
One of the core symptoms of the menopausal transition is sleep disturbance. Peri-menopausal women often complain of difficulties initiating and/or maintaining sleep with frequent nocturnal and early morning awakenings. Factors that may play a role in this type of insomnia include vasomotor symptoms, changing reproductive hormone levels, circadian rhythm abnormalities, mood disorders, coexistent medical conditions, and lifestyle. Other common sleep problems in this age group, such as obstructive sleep apnea and restless leg syndrome, can also worsen the sleep quality. Exogenous melatonin use reportedly induces drowsiness and sleep and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age and the menopausal transition. Recently, more potent melatonin analogs (selective melatonin-1 (MT1) and melatonin-2 (MT2) receptor agonists) with prolonged effects and slow-release melatonin preparations have been developed. They were found effective in increasing total sleep time and sleep efficiency as well as in reducing sleep latency in insomnia patients. The purpose of this review is to give an overview on the changes in hormonal status to sleep problems among menopausal and postmenopausal women.
PMCID: PMC4621258  PMID: 26512337
Aging; Circadian; Hormone; Melatonin; Menopause; Old; Premenopausal; Perimenopausal; Postmenopausal; Sleep; Women
9.  Consumption of indigenous medicines by pregnant women in North India for selecting sex of the foetus: what can it lead to? 
Sex ratio is an important indicator of development. Despite all the measures undertaken for improvement, it remains an issue of concern in India, with Haryana having a very low sex ratio in the country. Studies have been conducted indicating that consumption of indigenous drugs used for sex selection (SSD) could be strongly associated with adverse effects on the foetal development, including congenital malformations. Some samples of SSDs were collected from parts of North India and analysed in a standard laboratory for its components.
Thirty SSDs used by the local community were procured from various sources in north India through a rigorous process of collection. These were subjected to laboratory tests to investigate the presence of phytoestrogen and testosterone. Following sample extraction, thin layer chromatography and high performance liquid chromatography were carried out for analysing phytoestrogen content.
SSDs were available in various forms such as powder, tablets, mostly from faith healers. Around 87 % of the samples collected from sources like doctors, quacks and faith healers were to be taken by the pregnant women after conception; 63 % drugs were strongly positive for phytoestrogens (genistein, daidzein, formononetin) and 20 % drugs were positive for testosterone. The average dose of the components as calculated after analyses was as follows: daidzein - 14.1 mg/g sample, genistein - 8.6 mg/g sample, formononetin - 5 mg/g sample.
These SSDs could be potentially detrimental to the growth and development of the foetus. This is likely to have implications on the health of the community. In view of the results obtained in our study, we strongly attest the importance in curbing this harmful practice by banning the supply of the drugs as well as by advocating behavioural changes in the community.
PMCID: PMC4560877  PMID: 26341639
11.  Early goal-directed resuscitation of patients with septic shock: current evidence and future directions 
Critical Care  2015;19(1):286.
Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.
PMCID: PMC4552276  PMID: 26316210
12.  Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire for RLS (CHRLSq) 
Restless legs syndrome also known as Willis-Ekbom's Disease (RLS/WED) is a common illness. Cambridge-Hopkins diagnostic questionnaire for RLS (CHRLSq) is a good diagnostic tool and can be used in the epidemiological studies. However, its Hindi version is not available. Thus, this study was conducted to translate and validate it in the Hindi speaking population.
Materials and Methods:
After obtaining the permission from the author of the CHRLSq, it was translated into Hindi language by two independent translators. After a series of forward and back translations, the finalized Hindi version was administered to two groups by one of the authors, who were blinded to the clinical diagnosis. First group consisted of RLS/WED patients, where diagnosis was made upon face to face interview and the other group — the control group included subjects with somatic symptoms disorders or exertional myalgia or chronic insomnia. Each group had 30 subjects. Diagnosis made on CHRLSq was compared with the clinical diagnosis.
Statistical Analysis:
Analysis was done using Statistical Package for Social Sciences (SPSS) v 21.0. Descriptive statistics was calculated. Proportions were compared using chi-square test; whereas, categorical variables were compared using independent sample t-test. Sensitivity, specificity, and positive predictive value of the translated version of questionnaire were calculated.
Average age was comparable between the cases and control group (RLS/WED = 39.1 ± 10.1 years vs 36.2 ± 11.4 years in controls; P = 0.29). Women outnumbered men in the RLS/WED group (87% in RLS/WED group vs 57% among controls; χ2 = 6.64; P = 0.01). Both the sensitivity and specificity of the translated version was 83.3%. It had the positive predictive value of 86.6%.
Hindi version of CHRLSq has positive predictive value of 87% and it can be used to diagnose RLS in Hindi speaking population.
PMCID: PMC4564465  PMID: 26425008
CHRLSq; restless legs syndrome; translation; validation; Willis-Ekbom's disease
13.  Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC 
PLoS ONE  2015;10(6):e0129123.
Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.
PMCID: PMC4457876  PMID: 26046767
14.  Comparative impact of diverse regulatory loci on Staphylococcus aureus biofilm formation 
MicrobiologyOpen  2015;4(3):436-451.
The relative impact of 23 mutations on biofilm formation was evaluated in the USA300, methicillin-resistant strain LAC. Mutation of sarA, atl, codY, rsbU, and sigB limited biofilm formation in comparison to the parent strain, but the limitation imposed by mutation of sarA was greater than that imposed by mutation of any of these other genes. The reduced biofilm formation of all mutants other than the atl mutant was correlated with increased levels of extracellular proteases. Mutation of fur- and mgrA-enhanced biofilm formation but in LAC had no impact on protease activity, nuclease activity, or accumulation of the polysaccharide intercellular adhesin (PIA). The increased capacity of these mutants to form a biofilm was reversed by mutation of sarA, and this was correlated with increased protease production. Mutation of sarA, mgrA, and sigB had the same phenotypic effect in the methicillin-sensitive strain UAMS-1, but mutation of codY increased rather than decreased biofilm formation. As with the UAMS-1 mgrA mutant, this was correlated with increased production of PIA. Examination of four additional clinical isolates suggests that the differential impact of codY on biofilm formation may be a conserved characteristic of methicillin-resistant versus methicillin-sensitive strains.
PMCID: PMC4475386  PMID: 25810138
Biofilm; protease; regulation; sarA; Staphylococcus aureus
15.  Arthroscopic decompression of paralabral cyst around suprascapular notch causing suprascapular neuropathy 
A case of 22 year old male gymnast, who suffered from suprascapular neuropathy due to compression of suprascapular nerve by paralabral cysts around suprascapular notch, leading to marked atrophy of supraspinatus and infraspinatus muscles. After arthroscopic decompression of paralabral cysts, weakness and atrophy of the supraspinatus and infraspinatus muscles improved.
PMCID: PMC4487971  PMID: 26155054
Suprascapular neuropathy; Paralabral cyst; Arthroscopic decompression
16.  Headache secondary to sleep-related bruxism: A case with polysomnographic findings 
Sleep-related bruxism may present with headache. However, in clinical practice it may be difficult to differentiate from other causes of headache, especially in subjects with substance abuse. We are presenting a case of sleep-related bruxism that presented with headache and sleep-related symptoms in the presence of substance abuse. Polysomnography was used to ascertain cause of headache. How the other possible causes of headache ruled out is also discussed in report. In short, Sleep-related bruxism can cause headache that is worse in the morning. It is associated with poor quality sleep.
PMCID: PMC4387823  PMID: 25883492
Headache; I sleep initiation and maintenance disorders; sleep bruxism
17.  Acetabular fractures labelled poor surgical choices: Analysis of operative outcome 
We report the surgical outcome in 52 patients with acetabular otherwise considered as poor surgical choices.
43 male and 9 female patients were operated at a mean age of 43 years and followed up for a mean duration of 60.3 months. There were 22 elementary fractures and 31 associated ones according to Letournal and Judet classification. Osteosynthesis was attempted in 48 patients whereas a primary total hip arthroplasty was performed in 4 patients. Outcome was assessed radiologically and functionally employing Harris Hip Score (HHS).
Average HHS in osteosynthesis group was 82.56 ± 12.4 with excellent to good results in 59.6% of the cases. Symptomatic osteoarthritis occurred in 13.5% of cases, avascular necrosis and severe heterotopic ossification in 7.7% each, infection and nerve palsy in 11.5% each.
Although the complication rates in this series is marginally more than that reported in literature, we recommend that the indications of surgical fixation in acetabular fractures need to be extended to those which were considered poor surgical choices.
PMCID: PMC4411371  PMID: 25983515
Acetabulum; Fractures; Neglected; Osteoporosis
18.  Association of Naso-Oro-Pharyngeal Structures with the Sleep Architecture in Suspected Obstructive Sleep Apnea 
The study was conducted to find out the association of various naso-oro-pharyngeal structures with sleep macro-architecture in suspected obstructive sleep apnea subjects. Study included 51 subjects with suspected obstructive sleep apnea. Subjects with possible central apnea and those consuming any substance that can affect sleep architecture were excluded. Level I polysomnography was performed after thorough physical examination. Overnight study was scored in 30 s epochs to find out the polysomnographic variables. Surgical treatment was offered wherever indicated. Subjects with moderate to severe obstructive sleep apnea were manually titrated on CPAP with the polysomnogram. SPSS v 17.0 was used for statistical analysis. We did not find any difference in the sleep architecture between genders. Sleep Efficiency was better in subjects with dental overjet, dental attrition, high tongue base, macroglossia, lesser oral cavity volume, edematous uvula, increased submental fat, hypertrophied facial muscles and Mallampatti grade III–IV. Shorter Sleep Latency was seen in subjects with tender TMJ and Mallampatti Gr III–IV. REM latency was shorter in subjects with high tongue base, macroglossia and hypertrophied muscles of mastication. Increased REM was observed in subjects with high tongue base, edematous uvula and tender TMJ. Enlarged tonsils had reversed effect with poor sleep efficiency, increased REM latency and decreased REM. CPAP therapy (N = 20) lessened awake time, decreased N2 and increased REM. Oro-pharyngeal structures affect the sleep architecture in suspected OSA subjects. Nasal structures do not affect the sleep architecture in these subjects and enlarged tonsils have opposite effect. Sleep architecture changes on the titration night with CPAP.
PMCID: PMC3918340  PMID: 24533364
Sleep-architecture; Sleep-apnea; Oro-naso-pharyngeal anatomy
19.  Calloso-frontal tuberculoma presenting with symptoms of psychosis and catatonia 
Indian Journal of Psychiatry  2015;57(1):104-105.
PMCID: PMC4314905  PMID: 25657474
20.  Time to dig deep into the plant proteome: a hunt for low-abundance proteins 
PMCID: PMC4311630  PMID: 25688253
low-abundance proteins; high-abundance proteins; two-dimensional gel electrophoresis; RuBisCO; post-translational modifications
21.  Physiological and proteomic analyses on artificially aged Brassica napus seed 
Plant seeds lose their viability when they are exposed to long term storage or controlled deterioration treatments, by a process known as seed aging. Based on previous studies, artificially aging treatments have been developed to accelerate the process of seed aging in order to understand its underlying mechanisms. In this study, we used Brassica napus seeds to investigate the mechanisms of aging initiation. B. napus seeds were exposed to artificially aging treatment (40°C and 90% relative humidity) and their physio-biochemical characteristics were analyzed. Although the treatment delayed germination, it did not increase the concentration of cellular reactive oxygen species (ROS). Comparative proteomic analysis was conducted among the control and treated seeds at different stages of germination. The proteins responded to the treatment were mainly involved in metabolism, protein modification and destination, stress response, development, and miscellaneous enzymes. Except for peroxiredoxin, no changes were observed in the accumulation of other antioxidant enzymes in the artificially aged seeds. Increased content of abscisic acid (ABA) was observed in the artificially treated seeds which might be involved in the inhibition of germination. Taken together, our results highlight the involvement of ABA in the initiation of seed aging in addition to the ROS which was previously reported to mediate the seed aging process.
PMCID: PMC4340179  PMID: 25763006
Brassica napus; seed aging; controlled deterioration treatments; proteomics
22.  Understanding the plant-pathogen interactions in the context of proteomics-generated apoplastic proteins inventory 
The extracellular space between cell wall and plasma membrane acts as the first battle field between plants and pathogens. Bacteria, fungi, and oomycetes that colonize the living plant tissues are encased in this narrow region in the initial step of infection. Therefore, the apoplastic region is believed to be an interface which mediates the first crosstalk between host and pathogen. The secreted proteins and other metabolites, derived from both host and pathogen, interact in this apoplastic region and govern the final relationship between them. Hence, investigation of protein secretion and apoplastic interaction could provide a better understanding of plant-microbe interaction. Here, we are briefly discussing the methods available for the isolation and normalization of the apoplastic proteins, as well as the current state of secretome studies focused on the in-planta interaction between the host and the pathogen.
PMCID: PMC4451336  PMID: 26082784
apoplast; apoplastic proteins; pattern-triggered immunity; effector-triggered immunity; secretome; protein secretion; plant-pathogen interaction
23.  MgrA Activates Expression of Capsule Genes, but Not the α-Toxin Gene in Experimental Staphylococcus aureus Endocarditis 
The Journal of Infectious Diseases  2013;208(11):1841-1848.
Background. Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection.
Methods. The production of capsule and α-toxin, and the expression of their respective genes, cap5 and hla, were analyzed by comparing CYL11481 (derivative of Newman) and its isogenic regulatory mutants in vitro. The temporal expression of cap5 and hla and the regulatory genes in vivo was carried out using a rat infective endocarditis model.
Results. In vitro analyses showed that capsule was positively regulated by MgrA, Agr, Sae, ArlR, and ClpC, and negatively by CodY and SbcDC. The α-toxin was positively regulated by MgrA, Agr, Sae, ArlR, and SbcDC but negatively by ClpC and CodY. In vivo analyses showed that cap5 expression correlated best with mgrA expression, whereas hla expression correlated best with sae expression. Mutation in mgrA drastically reduced cap5 expression in vivo.
Conclusions. Our results suggest that, in vitro, Agr is the most important regulator for capsule and α-toxin production, as well as for cap5 transcription, but SaeR is the most critical for hla transcription. However, in vivo, MgrA is the major transcriptional regulator of capsule, but not α-toxin, whereas saeR expression correlates best with hla expression.
PMCID: PMC3814835  PMID: 23901087
Staphylococcus aureus; virulence; infective endocarditis model; mgrA; capsule; α-toxin
24.  Higher rates of metabolic syndrome among women taking zidovudine as compared to tenofovir in rural Africa: preliminary data from the CART-1 study 
Journal of the International AIDS Society  2014;17(4Suppl 3):19552.
Due to its side effects stavudine (D4T) has been replaced by zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have been described extensively, studies from LMICs comparing metabolic profiles between patients on AZT and TDF are scarce. Given the high number of patients in LMICs still taking AZT, data on their metabolic profile are needed. We present rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF-containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimens.
Materials and Methods
Data derived from a cross-sectional multi-disease screening conducted in ten facilities in two rural districts of Lesotho, Southern Africa [2]. Patients were eligible if aged ≥25 years and on NNRTI-containing first-line ART ≥6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed potential predictors for MS were age, time on ART, virologic suppression, body-mass index (BMI), alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF). Statistical analyses – stratified for sex – comprised univariate logistic regression for each predictor variable with subsequent construction of a multivariate model including all predictors with an association to MS at a significance level<0.1 in univariate analysis.
Out of 1026 patients, 660 (64.3%) were female. MS prevalence was 9.8% (95% CI 6.9–13.4) in men and 22.9% (19.7–26.3) in women. In women, aged ≥35 years, AZT-backbone, NVP-base, BMI ≥25kg/m2 and taking ART for ≥4.5 years were associated with MS in univariate analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI 1.4–3.6; p=0.001) and BMI ≥25kg/m2 (9.8; 2.8–34.1, p<0.001) were associated with MS. For men, age, higher wealth quintile, history of D4T exposure and BMI were associated with MS in univariate analysis. In the multivariate model only a BMI ≥25kg/m2 was associated with MS (8.9; 3.8–20.9, p<0.001).
In rural Lesotho, Southern Africa, the use of AZT instead of TDF among women who are on ART for ≥6 months predisposes to the development of metabolic syndrome. Given that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to be verified in other settings in Sub-Saharan Africa.
PMCID: PMC4224833  PMID: 25394059
25.  Navigated pedicle screw placement using computed tomographic data in dorsolumbar fractures 
Indian Journal of Orthopaedics  2014;48(6):555-561.
Computed tomographic (CT) based navigation is a technique to improve the accuracy of pedicle screw placement. It is believed to enhance accuracy of pedicle screw placement, potentially avoiding complications arising due to pedicle wall breach. This study aims to assess the results of dorsolumbar fractures operated by this technique.
Materials and Methods:
Thirty consecutive skeletally mature patients of fractures of dorsolumbar spine (T9–L5) were subjected to an optoelectronic navigation system. All patients were thoroughly examined for neurological deficit. The criterion for instability were either a tricolumnar injury or presence of neurological deficit or both. Patients with multilevel fractures and distorted spine were excluded from study. Time taken for insertion of each pedicle screw was recorded and placement assessed with a postoperative CT scan using Laine's grading system.
Only one screw out of a total of 118 screws was misplaced with a Laine's Grade 5 placement, showing a misplacement rate of 0.847%. Average time for matching was 7.8 min (range 5-12 min). Average time taken for insertion of a single screw was 4.19 min (range 2-8 min) and total time for all screws after exposure was 34.23 min (range 24-45 min) for a four screw construct. No neurovascular complications were seen in any of the patients postoperatively and in subsequent followup of 1-year duration.
CT-based navigation is effective in improving accuracy of pedicle screw placement in traumatic injuries of dorsolumbar spine (T9-L5), however additional cost of procuring CT scan to the patient and cost of equipment is of significant concern in developing countries. Reduced radiation exposure and lowered ergonomic constraints around the operation table are its additional benefits.
PMCID: PMC4232823  PMID: 25404766
Dorso lumbar spine; Laine's grading; navigation; paired point matching; Spine; spinal fractures; bone screws; neuronavigation; tomography

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