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1.  Nontypeable Haemophilus influenzae inhibits autolysis and fratricide of Streptococcus pneumoniae in vitro 
Streptococcus pneumoniae (SP) and nontypeable Haemophilus influenzae (NTHi) are common commensals of the human airway and major bacterial pathogens of otitis media (OM) and other upper airway infections. The interaction between them may play an important role in the pathogenesis of polymicrobial infections. Although previous studies suggested NTHi could promote pneumococcal survival and biofilm formation, how NTHi affects pneumococcal activities has not been defined. Our data in the present studies indicated that the outcome of the interaction between SP and NTHi was in a cell-density-dependent manner and the enhancement of pneumococcal survival happened at the later stages of culturing. Using quantitative PCR, we found that the expression of pneumococcal genes regulating autolysis and fratricide, lytA and cbpD, were significantly down-regulated in co-culture with NTHi. We further observed that influence of NTHi was not on direct cell-to-cell contact, but that this contact may contribute to the interaction between these two microorganisms. These results suggest that pneumococcal survival and biofilm formation can be enhanced by down-regulating pneumococcal cell wall hydrolase production thereby inhibiting pneumococcal autolysis and fratricide in the presence of NTHi.
PMCID: PMC4080417  PMID: 24269704
Streptococcus pneumoniae; nontypeable Haemophilus influenzae; survival; inhibit; autolysis; fratricide
2.  Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells 
Nature communications  2014;5:3071.
Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200+/ITGA6+ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200+/ITGA6+ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200+/ITGA6+ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15+ stem cell population and produce hair shafts expressing hair specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.
PMCID: PMC4049184  PMID: 24468981
3.  The Rational Design of Specific Peptide Inhibitor against p38α MAPK at Allosteric-Site: A Therapeutic Modality for HNSCC 
PLoS ONE  2014;9(7):e101525.
p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC). The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK) exploited for the design of inhibitors. This study demonstrated design of peptide inhibitor on the basis of allosteric site using Glide molecular docking software and the biochemical analysis of the best modeled peptide. The best fitted tetrapeptide (FWCS) in the allosteric site inhibited the pure recombinant and serum p38α of HNSCC patients by 74 and 72%, respectively. The potency of the peptide was demonstrated by its IC50 (4.6 nM) and KD (3.41×10−10 M) values, determined by ELISA and by surface plasmon resonance (SPR) technology, respectively. The cell viability of oral cancer i.e. KB cell line was reduced in dose dependent manner by 60 and 97% by the treatment of peptide and the IC50 was 600 and 210 µM after 24 and 72 h incubation, respectively. Our result provides an insight for the development of a proficient small peptide as a promising anticancer agent targeting DFG site of p38α kinase.
PMCID: PMC4077802  PMID: 24983631
4.  Transcriptomic Analysis of Cultured Whale Skin Cells Exposed to Hexavalent Chromium [Cr(VI)] 
Hexavalent chromium Cr(VI) is known to produce cytotoxic effects in humans and is a highly toxic environmental contaminant. Interestingly, it has been shown that free ranging sperm whales (Phyester macrocephalus) may have exceedingly high levels of Cr in their skin. Also, it has been demonstrated that skin cells from whales appear more resistant to both cytotoxicity and clastogenicity upon Cr exposure compared to human cells. However, the molecular genetic mechanisms employed in whale skin cells that might lead to Cr tolerance are unknown.
In an effort to understand the underlying mechanisms of Cr(VI) tolerance and to illuminate global gene expression patterns modulated by Cr, we exposed whale skin cells in culture to varying levels of Cr(VI) (i.e., 0.0, 0.5, 1.0 and 5.0 μg/cm2) followed by short read (100 bp) next generation RNA sequencing (RNA-seq). RNA-seq reads from all exposures (≈280 million reads) were pooled to generate a de novo reference transcriptome assembly. The resulting whale reference assembly had 11K contigs and an N50 of 2,954 bp.
Using the reads from each dose (0.0, 0.5, 1.0 and 5.0 μg/cm2) we performed RNA-seq based gene expression analysis that identified 35 up-regulated genes and 19 down-regulated genes. The experimental results suggest that low dose exposure to Cr (1.0 μg/cm2) serves to induce up-regulation of oxidative stress response genes, DNA repair genes and cell cycle regulator genes. However, at higher doses (5.0 μg/cm2) the DNA repair genes appeared down-regulated while other genes that were induced suggest the initiation of cytotoxicity.
The set of genes identified that show regulatory modulation at different Cr doses provide specific candidates for further studies aimed at determination of how whales exhibit resistance to Cr toxicity and what role(s) reactive oxygen species (ROS) may play in this process.
PMCID: PMC3739694  PMID: 23584427
Sperm whale; Chromium; RNA-seq; Illumina HiSeq; ROS (reactive oxygen species); cytotoxicity
5.  Molecular Pathogenesis of Sporadic Melanoma and Melanoma-Initiating Cells 
Recent advances in molecular genetics and cancer stem cell biology have shed some light on the molecular basis of melanomagenesis. In this review, we will focus on major genetic alterations in the melanoma, particularly pathways involved in cell proliferation, apoptosis, and tumor suppression. The potential role of melanoma-initiating cells during melanomagenesis and progression will also be discussed. Understanding pathogenesis of melanoma may uncover new diagnostic clues and therapeutic targets for this increasingly prevalent disease.
PMCID: PMC4049155  PMID: 21128770
6.  Knowledge and Awareness of Diabetes and Diabetic Ketoacidosis (DKA) Among Medical Students in a Tertiary Teaching Hospital: An Observational Study 
Background: The management of Diabetes Mellitus and its important complication Diabetic Ketoacidosis is very crucial in today’s world where the prevalence of Diabetes is very high. Medical students are the pillars of our future healthcare system and it is important to evaluate and update their knowledge and awareness regarding these both conditions.
Materials and Methods: This study was a cross-sectional; Questionnaire based observational study conducted in a tertiary care hospital. The respondents were final year MBBS students of that college. Study instrument was a self developed, pre-validated, semi-structured questionnaire.
Results: A total of 73 questionnaires were considered for analysis, giving a response rate of 90.12% with 43.83% and 56.16% were male and female respondents respectively. About 81.25% and 90.24% of male and female respondents gave correct answer to question related to the best indicator of glycemic control. Lack of knowledge was seen regarding the world Diabetes day. Approximately 37% of the respondent’s parents were diabetic. Only 12 out of 73 respondents were aware about the factors leading to DKA.8 out of 73 were aware about investigations to be done in DKA. Around 43.84% of responders knew regarding the proper screening duration in person with risk of diabetes.
Conclusion: From the study it was concluded that most of the students have basic knowledge regarding diabetes mellitus, its clinical features and management etc but only 50 % of the respondent were aware about DKA and further teaching and post teaching evaluation are needed in future direction.
PMCID: PMC4064852  PMID: 24959462
Awareness; Diabetes mellitus; Diabetic Ketoacidosis; Knowledge; MBBS Students
7.  Antifungal and Antiproliferative Protein from Cicer arietinum: A Bioactive Compound against Emerging Pathogens 
BioMed Research International  2014;2014:387203.
The emergence of epidemic fungal pathogenic resistance to current antifungal drugs has increased the interest in developing alternative antibiotics from natural sources. Cicer arietinum is well known for its medicinal properties. The aim of this work was to isolate antimicrobial proteins from Cicer arietinum. An antifungal protein, C-25, was isolated from Cicer arietinum and purified by gel filtration. C-25 protein was tested using agar diffusion method against human pathogenic fungi of ATCC strains and against clinical isolates of Candida krusei, Candida tropicalis, and Candida parapsilosis, and MIC values determined were varied from 1.56 to 12.5 μg/mL. The SEM study demonstrated that C-25 induces the bleb-like surface changes, irregular cell surface, and cell wall disruption of the fungi at different time intervals. Cytotoxic activity was studied on oral cancer cells and normal cells. It also inhibits the growth of fungal strains which are resistant to fluconazole. It reduced the cell proliferation of human oral carcinoma cells at the concentration of 37.5 μg/mL (IC50) and no toxic effect was found on normal human peripheral blood mononuclear cells even at higher concentration of 600 μg/mL. It can be concluded that C-25 can be considered as an effective antimycotic as well as antiproliferative agent against human oral cancer cells.
PMCID: PMC4053179  PMID: 24963482
8.  Higher Caspase-like activity in symptomatic isolates of Blastocystis spp 
Parasites & Vectors  2014;7:219.
Biochemical evidence of a caspase-like execution pathway has been demonstrated in a variety of protozoan parasites, including Blastocystis spp. The distinct differences in the phenotypic characterization reported previously have prompted us to compare the rate of apoptosis in Blastocystis spp. isolated from individuals who were symptomatic and asymptomatic. In the current study, we analysed the caspase activation involved in PCD mediated by a cytotoxic drug, (metronidazole) in both symptomatic & asymptomatic isolates.
Apoptosis was induced in Blastocystis spp. by treating cultures of symptomatic and asymptomatic isolates of 3 sub-types namely 1, 3 and 5 with two different concentrations, 0.1 and 0.0001 mg/ml of metronidazole (with and without pre-treatment with a pan-caspase inhibitor, zVAD.fmk). The experiment was repeated to assess the number of apoptotic cells in all the isolates of both conditions.
Symptomatic isolates of subtype 3 (without pre-treatment with a pan-caspase inhibitor, zVAD.fmk) showed high fluorescence intensity for active caspase-like proteases [0.0001 mg/ml, 88% (p < 0.001) at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 65%, at 0.1 mg/ml, 55%]. The number of apoptotic cells was higher [0.0001 mg/ml, 89% (p < 0.001) and at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour of in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 66% (p < 0.001) and at 0.1 mg/ml, 45% (p < 0.01)]. Cells treated with metronidazole in the presence of zVAD.fmk showed less than 10% caspase activation.
The high number of symptomatic cells expressing active caspase-like proteases and becoming apoptotic compared to asymptomatic cells clearly demonstrates that the response to metronidazole treatment is isolate dependent. Hence this justifies the conflicting reports on the curative success rates when treated with this drug. The study has also created a need to identify apoptosis effectors in Blastocystis spp of different isolates especially as it was shown that apoptosis was sub-typed related. These findings can be exploited for the development of diagnostic markers and novel therapeutic drugs to enhance the effectiveness of the diagnosis and treatment of the patients infected with Blastocystis spp.
PMCID: PMC4049410  PMID: 24886677
Blastocystis spp; Apoptosis; Symptomatic; Asymptomatic; Caspase-like proteases; Programmed cell death; Metronidazole
9.  Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: Involvement of iNOS and COX-2 
Pharmacognosy Magazine  2014;10(Suppl 2):S306-S310.
Colon cancer (CRC) is a serious health problem through worldwide. Development of novel drug without side effect for this cancer was crucial. Luteolin (LUT), a bioflavonoid has many beneficial effects such as antioxidant, anti-inflammatory, anti-proliferative properties. Azoxymethane (AOM), a derivative of 1, 2-Dimethyl hydrazine (DMH) was used for the induction of CRC in Balb/C mice. CRC was induced by intraperitoneal injection of AOM to mice at the dose of 15 mg/body kg weight for 3 weeks. Mouse was treated with LUT at the dose of 1.2 mg/body kg weight orally until end of the experiment. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygense (COX)-2 were analyzed by RT-PCR and immunohistochemistry. The expressions of iNOS and COX-2 were increased in the case of AOM induction. Administration of LUT effectively reduced the expressions of iNOS and COX-2. The present study revealed that, LUT suppresses both iNOS and COX-2 expressions and act as an anti-inflammatory role against CRC.
PMCID: PMC4078326  PMID: 24991108
Azoxymethane; colon cancer; COX-2; iNOS; Luteolin
10.  Fall in Vitamin D Levels during Hospitalization in Children 
Plasma levels of 25-hydroxyvitamin D [25(OH)D] were measured by competitive Electrochemiluminescence Immunoassay (ECLIA) in 92 children (67 boys, 25 girls) aged 3 months to 12 years at admission to hospital (timepoint 1, T1) and at discharge (timepoint 2, T2). There was a significant fall in the mean 25(OH)D from T1 (71.87 ± 27.25 nmol/L) to T2 (49.03 ± 22.25 nmol/L) (mean change = 22.84 nmol/L, P value = 0.0004). Proportion of patients having VDD (levels <50 nmol/L) at admission (25%, 23/92) increased significantly at the time of discharge (51.09%, 47/92) (P = 0.0004). There was a trend towards longer duration of hospital stay, requirement of ventilation and inotropes, development of healthcare-associated infection, and mortality in vitamin D deficient as compared to nondeficient patients though the difference was statistically insignificant. In conclusion, vitamin D levels fall significantly and should be monitored during hospital stay in children. Large clinical studies are needed to prospectively evaluate the effect of vitamin D supplementation in vitamin D deficient hospitalized children on various disease outcome parameters.
PMCID: PMC3985317  PMID: 24860607
11.  Primary amyloidoma of chest wall – a rare condition 
BMJ Case Reports  2012;2012:bcr0120125552.
Organ specific amyloidosis has been shown to be confined to various organs like liver, lung, spleen, urinary bladder and gastro-intestinal tract, but amyloidoma or tumoural amyloidosis of chest wall with no evidence of systemic amyloidosis is an extremely rare presentation and only two cases have been reported till now. The authors report a case of chest wall amyloidoma with review of literature.
PMCID: PMC3316792  PMID: 22605798
12.  Sweet’s syndrome in a patient with infective endocarditis: a rare clinical entity 
BMJ Case Reports  2012;2012:bcr1220115398.
Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis, has been associated with malignancy, autoimmune disease and collagen vascular disease. The association of infective endocarditis and Sweet’s syndrome is rare. The authors report a case of Sweet’s syndrome in a patient with infective endocarditis. Infective endocarditis should be excluded in patients of rheumatic heart disease presenting with Sweet’s syndrome. Alternatively, Sweet’s syndrome should be considered as a differential diagnosis when a patient with infective endocarditis develops skin lesions.
PMCID: PMC3316874  PMID: 22605716
13.  MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1–Snail1 pathway in melanoma 
The Journal of pathology  2011;226(1):61-72.
MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate gene expression. Hsa-miR-9 has been shown to have opposite functions in different tumour types; however, the underlying mechanism is unclear. Here we show that hsa-miR-9 is down-regulated in metastatic melanomas compared to primary melanomas. Overexpression of miR-9 in melanoma cells resulted in significantly decreased cell proliferation and migratory capacity with decreased F-actin polymerization and down-regulation of multiple GTPases involved in cytoskeleton remodelling. miR-9 overexpression induced significant down-regulation of Snail1 with a concomitant increase in E-cadherin expression. In contrast, knockdown of miR-9 increased Snail1 expression as well as melanoma cell proliferation and migration capacity. Mechanistically, miR-9 expression down-regulated NF-κB1 in melanoma and the effect was abolished by mutations in the putative miR-9 binding sites within the 3′-untranslated region (UTR) of NF-κB1. Anti-miR-9 miRNA inhibitor also increased the expression of NF-κB1. The effects of miR-9 on Snail1 expression and melanoma cell proliferation and migration were rescued by overexpression of NF-κB1 in these cells. Furthermore, miR-9 overexpression resulted in significantly decreased melanoma growth and metastasis in vivo. In summary, miR-9 inhibits melanoma proliferation and metastasis through down-regulation of the NF-κB1-Snail1 pathway. This study finds a new mechanism that miR-9 utilizes to decrease E-cadherin expression and inhibit melanoma progression. The results suggest that function of microRNAs is context and tumour type-specific.
PMCID: PMC3959162  PMID: 22131135
miR-9; NF-κB1; E-cadherin; Snail1; melanoma
14.  The effect of age on sagittal plane profile of the lumbar spine according to standing, supine, and various sitting positions 
The sagittal alignment of the spine changes depending on body posture and degenerative changes. This study aimed to observe changes in sagittal alignment of the lumbar spine with different positions (standing, supine, and various sitting postures) and to verify the effect of aging on lumbar sagittal alignment.
Whole-spine lateral radiographs were obtained for young volunteers (25.4 ± 2.3 years) and elderly volunteers (66.7 ± 1.7 years). Radiographs were obtained in standing, supine, and sitting (30°, 60°, and 90°) positions respectively. We compared the radiological changes in the lordotic and segmental angles in different body positions and at different ages. Upper and lower lumbar lordosis were defined according to differences in anatomical sagittal mobility and kinematic behavior.
Lumbar lordosis was greater in a standing position (52.79° and 53.90° in young and old groups, respectively) and tended to decrease as position changed from supine to sitting. Compared with the younger group, the older group showed significantly more lumbar lordosis in supine and 60° and 90° sitting positions (P = 0.043, 0.002, 0.011). Upper lumbar lordosis in the younger group changed dynamically in all changed positions compared with the old group (P = 0.019). Lower lumbar lordosis showed a decreasing pattern in both age groups, significantly changing as position changed from 30° to 60° (P = 0.007, 0.007).
Lumbar lordosis decreases as position changes from standing to 90°sitting. The upper lumbar spine is more flexible in individuals in their twenties compared to those in their sixties. Changes in lumbar lordosis were concentrated in the lower lumbar region in the older group in sitting positions.
PMCID: PMC3974054  PMID: 24571953
Spine; Lumbar lordosis; Position change; Age
15.  Dilatation and curettage of urinary bladder: A rarity 
Twenty-eight-year-old female while undergoing a medical termination of pregnancy (MTP) encounter complete urethral loss and massive bladder curettage. After resuscitation, she developed continuous urinary leakage followed by progressive decline in urine output. Case is highlighted here because of the massive vesico-urethral trauma because of MTP, leading to permanent urinary diversion.
PMCID: PMC3928834  PMID: 24592378
Massive bladder curettage; obstetric trauma; permanent urinary diversion
16.  Pyopneumothorax Following Kerosene Poisoning 
Toxicology International  2014;21(1):112-114.
Kerosene poisoning is a common poisoning in India especially in childhood, and clinical spectrum can range from meager chemical pneumonitis to grave complications such as hypoxia, pneumothorax, pneumomediastinum, and emphysema. Pyopneumothorax that may require aggressive management in the form of thoracotomy has not been reported in literature. We hereby report a 22-year young female who had developed series of respiratory complications including pyopneumothorax following ingestion of kerosene with suicidal intent and was treated successfully.
PMCID: PMC3989908  PMID: 24748745
Chemical pneumonitis; kerosene poisoning; pyopneumothorax
17.  Isolated primary craniosynostosis in an adult: Imaging findings of a case 
Craniosynostosis means premature closure of calvarial sutures. It may be primary or secondary. The patient presents with unexplained neuropsychological impairment and radiological imaging clinches the diagnosis. We present a case of 31-year-old female having primary isolated craniosynostosis who survived into adulthood without any surgical intervention. The imaging findings of such a case are rarely described in the literature.
PMCID: PMC3992780  PMID: 24753669
Craniosynostosis; convolutional; imaging; sutures; syndrome
18.  Phosphatidylethanolamine at the Luminal Endothelial Surface—Implications for Hemostasis and Thrombotic Autoimmunity 
Accumulating evidence suggests that phosphatidylethanolamine (PE) is physically present at the luminal endothelial surface, where it tentatively functions as a critical anticoagulant. The goal of the current investigation was 3-fold: to characterize the distribution profile of PE at the luminal endothelial surface; to examine the immunoreactivity to the vascular endothelium by anti-PE (aPE) sera from patients presenting with thrombosis; and to discuss the potential mechanism of PE upregulation by endothelial cells.
The rat aortic arch was selected as major conduit vessel under significant hemodynamic burden. The presence of PE and the antigenic profile of aPE sera at the luminal endothelial surface were examined using duramycin as a PE-binding probe and immunohistochemistry. Phosphatidylethanolamine upregulation at endothelial cell surface was investigated using cultured monolayer subject to laminar shear stress or thrombin treatment.
High levels of PE were detected at the luminal endothelial surface of aortic flow dividers, the ascending aorta, and the outer curvature of the aortic arch. The antigenic profiles of aPE sera, which are highly associated with elevated thrombotic risks in patients, are consistent with PE distribution along the endothelial surface. Finally, PE is upregulated at the surface of cultured endothelial cells in response to luminal shear stress but not thrombin.
The current data describe the physical distribution of vascular PE at the blood–endothelium interface. The luminal PE presents a vulnerability to anti-PE autoimmunity and is consistent with the association between aPE and elevated risk for idiopathic thrombosis.
PMCID: PMC3866907  PMID: 19903695
phosphatidylethanolamine; endothelium; duramycin; aPE; thrombosis
19.  Primary total elbow arthroplasty 
Indian Journal of Orthopaedics  2013;47(6):608-614.
Primary total elbow arthroplasty (TEA) is a challenging procedure for orthopedic surgeons. It is not performed as frequently as compared to hip or knee arthroplasty. The elbow is a nonweight-bearing joint; however, static loading can create forces up to three times the body weight and dynamic loading up to six times. For elderly patients with deformity and ankylosis of the elbow due to posttraumatic arthritis or rheumatoid arthritis or comminuted fracture distal humerus, arthroplasty is one of the option. The aim of this study is to analyze the role of primary total elbow arthroplasty in cases of crippling deformity of elbow.
Materials and Methods:
We analyzed 11 cases of TEA, between December 2002 and September 2012. There were 8 females and 3 males. The average age was 40 years (range 30-69 years). The indications for TEA were rheumatoid arthritis, comminuted fracture distal humerus with intraarticular extension, and posttraumatic bony ankylosis of elbow joint. The Baksi sloppy (semi constrained) hinge elbow prosthesis was used. Clinico-radiological followup was done at 1 month, 3 months, 6 months, 1 year, and then yearly basis.
In the present study, average supination was 70° (range 60-80°) and average pronation was 70° (range 60-80°). Average flexion was 135° (range 130-135°). However, in 5 cases, there was loss of 15 to 35° (average 25°) of extension (45°) out of 11 cases. The mean Mayo elbow performance score was 95.4 points (range 70-100). Arm length discrepancy was only in four patients which was 36% out of 11 cases. Clinico-radiologically all the elbows were stable except in one case and no immediate postoperative complication was noted. Radiolucency or loosening of ulnar stem was seen in 2 cases (18%) out of 11 cases, in 1 case it was noted after 5 years and in another after 10 years. In second case, revision arthroplasty was done, in which only ulnar hinge section, hinge screw and lock screw with hexagonal head were replaced.
Elbow arthroplasty remains a valuable option for deformed and ankylosed elbows especially in the demanding patients with crippling deformity of the elbow.
PMCID: PMC3868144  PMID: 24379468
Ankylosis; comminuted fracture of distal humerus; total elbow arthroplasty
20.  Further insights into the syndrome of prolapsing non-coronary aortic cusp and ventricular septal defect 
Ventricular septal defect (VSD) with prolapse of the right coronary cusp and aortic regurgitation can be managed surgically with the anatomical correction technique. However when the VSD is located underneath the non coronary cusp surgical management differs due to anatomical constraints and secondary pathological changes seen in the non coronary cusp. It is therefore important that the location of the VSD and the morphology of prolapsing cusp be characterised preoperatively in order to plan appropriate surgical repair. We present a case study in which we discuss the salient differences in the surgical management of the prolapsing right and the prolapsing non coronary cusps.
PMCID: PMC3963734  PMID: 24689005
aortic regurgitation; ventricular septal defect; aortic cusp prolapse; sinus of valsalva
21.  In vivo fate mapping identifies pre-TCRα expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis 
A novel pre-TCRα (pTα) reporter mouse reveals that expression of pTα is confined to the T lineage and does not occur on prethymic progenitors.
Expression of the pre–T cell receptor α (pTα) gene has been exploited in previous studies as a molecular marker to identify tiny cell populations in bone marrow (BM) and blood that were suggested to contain physiologically relevant thymus settling progenitors (TSPs). But to what extent these cells genuinely contribute to thymopoiesis has remained obscure. We have generated a novel pTαiCre knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pTα-expressing progenitors to distinct differentiation pathways and to the genealogy of mature hematopoietic cells under physiological in vivo conditions. Using these mice in combination with fluorescent reporter strains, we observe highly consistent labeling patterns that identify pTα expression as a faithful molecular marker of T lineage commitment. Specifically, the fate of pTα-expressing progenitors was found to include all αβ and most γδ T cells but, in contrast to previous assumptions, to exclude B, NK, and thymic dendritic cells. Although we could detect small numbers of T cell progenitors with a history of pTα expression in BM and blood, our data clearly exclude these populations as physiologically important precursors of thymopoiesis and indicate that they instead belong to a pathway of T cell maturation previously defined as extrathymic.
PMCID: PMC3620354  PMID: 23509324
22.  The pitfalls of premature closure: clinical decision-making in a case of aortic dissection 
BMJ Case Reports  2011;2011:bcr0820114594.
Premature closure is a type of cognitive error in which the physician fails to consider reasonable alternatives after an initial diagnosis is made. It is a common cause of delayed diagnosis and misdiagnosis borne out of a faulty clinical decision-making process. The authors present a case of aortic dissection in which premature closure was avoided by the aggressive pursuit of the appropriate differential diagnosis, and discuss the importance of disciplined clinical decision-making in the setting of chest pain.
PMCID: PMC3189641  PMID: 22679162
23.  Induction of mitochondrial dependent apoptosis and cell cycle arrest in human promyelocytic leukemia HL-60 cells by an extract from Dorstenia psilurus: a spice from Cameroon 
The use of edible plants is an integral part of dietary behavior in the West region of Cameroon. Dorstenia psilurus (Moraceae) is widely used as spice and as medicinal plant for the treatment of several diseases in Cameroon. The aim of this study is to investigate the cytotoxic and apoptotic potential of methanol extract of D. psilurus in human promyelocytic leukemia (HL-60) cells and prostate cancer (PC-3) cells.
Cytotoxicity of D. psilurus extract was tested in HL-60 and PC-3 cells using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and flow cytometric methods
The methanol extract of D. psilurus have significant in vitro cytotoxic activity in HL-60 cells and PC-3 cells with IC50 value of 12 ±1.54 μg/ml and 18 ± 0.45 μg/ml respectively after 48 h. The mechanism of antiproliferative activity showed that after 24 h, D. psilurus extract induces apoptosis on HL-60 cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, modification in the DNA distribution and enhance of G2/M phase cell cycle.
The extract induces apoptosis of HL-60 cells associated with ROS production, loss of mitochondrial membrane potential and apoptotic DNA fragmentation.
PMCID: PMC3847675  PMID: 24016040
Dorstenia psilurus; Spice; Apoptosis; HL-60; ROS; Mitochondrial membrane potential
24.  Psychiatric Morbidity, Pain Perception, and Functional Status of Chronic Pain Patients in Palliative Care 
Indian Journal of Palliative Care  2013;19(3):146-151.
Psychological factors, such as that exist when we experience pain, can profoundly alter the strength of pain perception.
The study aims to estimate the prevalence of psychiatric disorders, and its association with perception of pain and functional status in chronic patients in palliative care.
Materials and Methods:
The sample was selected via simple randomisation and post consent were assessed using (1) a semi- structured questionnaire to elicit socio-demographic information and medical data (2) Brief Pain Inventory (3) ICD-10 Symptom Checklist (4) ICD-10-Diagnostic Criteria for Research (DCR) (5) Montgomery Asberg Depression Rating Scale (MADRS) (6) Covi Anxiety Rating Scale (7) Karnofsky Performance Status Scale. Data was analysed using independent sample t test and chi square test.
The psychiatric morbidity was 67% with depression and adjustment disorders being the major diagnosis. There was a significant association between psychiatric morbidity pain variables (P = 0.000). Psychiatric morbidity significantly impaired activity, mood, working, walk, sleep, relationship, and enjoyment. There was no association between aetiology of pain, type of cancer, treatment for primary condition and treatment for pain and psychiatric morbidity. The functional status of cancer patients was also poorer in patients with psychiatric morbidity (P = 0.008).
There is a high prevalence of psychiatric illness in chronic pain patients of any aetiology. Psychiatric morbidity is associated with increased pain perception, impairment in activity and poor functional status.
PMCID: PMC3853392  PMID: 24347904
Cancer; Depression; Functional status; Pain perception; Psychiatric morbidity
25.  Prevalence of Type 2 Diabetes Mellitus in Hepatitis C Virus Infected Population: A Southeast Asian Study 
Journal of Diabetes Research  2013;2013:539361.
Purpose. The study was aimed to investigate the frequency of diabetes mellitus type 2 in patients infected with chronic hepatitis C virus and its association with cirrhosis. Patients and Methods. This prospective case series was conducted at Section of Gastroenterology and Hepatology, Isra University Hospital, Hyderabad, over a period of 4 months from June 2009 to October 2009. Hepatitis C virus seropositive patients who were older than 18 years, diabetic or nondiabetic, were included. Basic demographic data collected by questionnaire and laboratory investigations including fasting blood glucose levels, serum cholesterol, and liver function tests were done. A logistic regression model was used to explore the association between diabetic and nondiabetic HCV seropositives and type 2 diabetes mellitus with cirrhosis. Results. A total of 361 patients with hepatitis C were analyzed; the prevalence of type 2 diabetes mellitus in HCV patients was 31.5%. Out of the total number of the participants, 58.4% (n = 211) were cirrhotics, while 41.6% (n = 150) were noncirrhotic HCV seropositives. In multivariate analysis, cirrhotic patients appeared significantly more likely (P = 0.01) to be diabetic as compared with noncirrhotic patients (OR = 2.005, 95% CI: 1.15, 3.43). Conclusion. Advancing age, increased weight, and HCV genotype 3 are independent predictors of type 2 diabetes in HCV seropositive patients, and there is a statistically significant association of cirrhosis observed with type 2 diabetes mellitus.
PMCID: PMC3747388  PMID: 23984431

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