Publications by authors named "Sonali Sharma"

31 Publications

Association of SARS CoV-2 Cycle Threshold (Ct) with Outcomes in COVID-19: Hospital-Based Study.

J Assoc Physicians India 2021 07;69(7):20-23

Academic Research Development Unit, Rajasthan University of Health Sciences, Jaipur, Rajasthan.

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July 2021

COVID-19 vaccination for cancer patients: Evidence, priority, and practice.

Vaccine 2021 08 24;39(36):5075-5077. Epub 2021 Jul 24.

Department of Surgical Oncology, King George's Medical University, Lucknow, India.

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http://dx.doi.org/10.1016/j.vaccine.2021.07.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302852PMC
August 2021

Efficacy of IVRS-based mHealth intervention in reducing cardiovascular risk in metabolic syndrome: A cluster randomized trial.

Diabetes Metab Syndr 2021 Sep-Oct;15(5):102182. Epub 2021 Jun 21.

Academic Research Development Unit, Rajasthan University of Health Sciences, 302033, Jaipur, India.

Aims: Efficacy of mobile-phone based intervention for reducing cardiovascular risk in metabolic syndrome (MetSyn).

Methods: We screened adults 20-60 years in 10 villages in India for MetSyn using stratified cluster sampling. Lifestyle and biochemical risk factors were assessed. International Harmonized Criteria were used for diagnosis. Villages were randomized with 5 each in control and intervention groups. Interactive voice response system (IVRS) in Hindi was developed. In intervention clusters two messages for promotion of healthy lifestyle and medical treatment were broadcast daily over 12-months and risk factors reassessed.

Results: 1012/1200(84%) persons were screened and MetSyn diagnosed in 286(28.3%). Villages were divided into 5 control(n = 136) and 5 intervention(n = 147) clusters. Baseline characteristics in both clusters were similar. Acceptability of intervention was >60% in 80% participants. At 12 months, significantly greater participants in intervention vs control clusters had healthier lifestyle (healthy diet 28.8vs14.7%, physical activity 25.9vs13.1%, tobacco 13.7vs32.5%), anthropometry (waist circumference 85.7 ± 6.3vs88.6 ± 14.0 cm, body mass index 21.9 ± 2.8vs23.1 ± 2.9 kg/m), systolic BP 123.6 ± 7.7vs128.6 ± 14.1 mmHg, fasting glucose 95.6 ± 19.4vs109.4 ± 43.7 mg/dl, cholesterol 175.5 ± 36.5vs186.4 ± 43.3 mg/dl, and triglycerides 147.6 ± 48.3vs159.5 ± 60.7 mg/dl (p < 0.01). Prevalence of metabolic syndrome declined in intervention group by 22.3%vs3.9%, p < 0.001).

Conclusion: An interactive voice response system based technology significantly reduced multiple cardiovascular risk factors and prevalence of metabolic syndrome.
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http://dx.doi.org/10.1016/j.dsx.2021.06.019DOI Listing
June 2021

IL4-STAT6 signaling induces CD20 in chronic lymphocytic leukemia and this axis is repressed by PI3Kδ inhibitor idelalisib.

Haematologica 2021 Jul 1. Epub 2021 Jul 1.

Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Not available.
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http://dx.doi.org/10.3324/haematol.2021.278644DOI Listing
July 2021

Reply to letter to editor "Cancer patients should be considered as a high-risk priority target in the COVID-19 vaccination process".

J Surg Oncol 2021 09 20;124(3):455. Epub 2021 Apr 20.

Department of Gynecology and Obstetrics, King George's Medical University, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.1002/jso.26507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250936PMC
September 2021

FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia.

Blood 2021 Sep;138(9):758-772

Molecular Medicine, CEITEC Masaryk University, and.

Recirculation of chronic lymphocytic leukemia (CLL) cells between the peripheral blood and lymphoid niches plays a critical role in disease pathophysiology, and inhibiting this process is one of the major mechanisms of action for B-cell receptor (BCR) inhibitors such as ibrutinib and idelalisib. Migration is a complex process guided by chemokine receptors and integrins. However, it remains largely unknown how CLL cells integrate multiple migratory signals while balancing survival in the peripheral blood and the decision to return to immune niches. Our study provided evidence that CXCR4/CD5 intraclonal subpopulations can be used to study the regulation of migration of CLL cells. We performed RNA profiling of CXCR4dimCD5bright vs CXCR4brightCD5dim CLL cells and identified differential expression of dozens of molecules with a putative function in cell migration. GRB2-associated binding protein 1 (GAB1) positively regulated CLL cell homing capacity of CXCR4brightCD5dim cells. Gradual GAB1 accumulation in CLL cells outside immune niches was mediated by FoxO1-induced transcriptional GAB1 activation. Upregulation of GAB1 also played an important role in maintaining basal phosphatidylinositol 3-kinase (PI3K) activity and the "tonic" AKT phosphorylation required to sustain the survival of resting CLL B cells. This finding is important during ibrutinib therapy, because CLL cells induce the FoxO1-GAB1-pAKT axis, which represents an adaptation mechanism to the inability to home to immune niches. We have demonstrated that GAB1 can be targeted therapeutically by novel GAB1 inhibitors, alone or in combination with BTK inhibition. GAB1 inhibitors induce CLL cell apoptosis, impair cell migration, inhibit tonic or BCR-induced AKT phosphorylation, and block compensatory AKT activity during ibrutinib therapy.
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http://dx.doi.org/10.1182/blood.2020008101DOI Listing
September 2021

Impact of COVID-19 pandemic on cancer surgery: Patient's perspective.

J Surg Oncol 2021 Apr 16;123(5):1188-1198. Epub 2021 Feb 16.

Department of Surgical Oncology, King George's Medical University, Lucknow, India.

Background: Coronavirus disease 2019 (COVID-19) has impacted cancer care globally. The aim of this study is to analyze the impact of COVID-19 on cancer healthcare from the perspective of patients with cancer.

Methods: A cross-sectional survey was conducted between June 19, 2020, to August 7, 2020, using a questionnaire designed by patients awaiting cancer surgery. We examined the impact of COVID-19 on five domains (financial status, healthcare access, stress, anxiety, and depression) and their relationship with various patient-related variables. Factors likely to determine the influence of COVID-19 on patient care were analyzed.

Results: A significant adverse impact was noted in all five domains (p =  < 0.05), with the maximal impact felt in the domain of financial status followed by healthcare access. Patients with income levels of INR < 35 K (adjusted odds ratio [AOR] = 1.61, p < 0.05), and 35K- 100 K (AOR = 1.96, p < 0.05), married patients (AOR = 3.30, p < 0.05), and rural patients (AOR = 2.82, p < 0.05) experienced the most adverse COVID-19-related impact.

Conclusion: Delivering quality cancer care in low to middle-income countries is a challenge even in normal times. During this pandemic, deficiencies in this fragile healthcare delivery system were exacerbated. Identification of vulnerable groups of patients and strategic utilization of available resources becomes even more important during global catastrophes, such as the current COVID-19 pandemic. Further work is required in these avenues to not only address the current pandemic but also any potential future crises.
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http://dx.doi.org/10.1002/jso.26429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013664PMC
April 2021

Are Bioceramics the Dernier Cri in the Management of Stage 4 Developed Root? A Finite Element Analysis.

J Contemp Dent Pract 2020 Sep 1;21(9):961-969. Epub 2020 Sep 1.

Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, Delhi, India.

Aim: To compare the stress distribution of four modalities of reinforcing the radicular space of a pulpless central incisor exhibiting stage 4 root development.

Materials And Methods: The model of a pulpless immature central incisor with a stage 4 of root development supporting periodontium was generated based on the properties. The longitudinal growth of the root was completed. Four such models were developed. Then, the radicular space was rehabilitated as follows: Model 1: Ceramicrete; Model 2: Biomimetic Mineralization; Model 3: Biodentine; Model 4: Bioaggregate. They were subjected to three different loading conditions. One was to mimic the mastication by applying a load of 70 N applied at 45° angle. Second loading condition was a vertical load of 100 N to mimic bruxism. The third loading condition was to mirror the impact of a frontal trauma. A load of 100 N was applied labially.

Results: It was observed that during mastication, Model 2 has exhibited the lowest concentration of von Mises stresses, followed by Model 3 and then Model 4 followed by Model 1; this could be because the modulus of elasticity of Model 2 is comparable to that of Dentin. During bruxism and horizontal impact, the maximal stress concentration was found in Model 4, Model 3, Model 2, followed by Model 1.

Conclusion: The closer the elasticity of modulus of the primary endodontic replacement monoblock was to that of dentin, the lower were the stresses generated. However, as the increase in stress values was minimal between groups, these obturating materials can be viable reinforcement materials for the rehabilitation of cases of stage 4 developing root. Biomimetic mineralization strategies can be a viable treatment option for managing cases of the open apex.

Clinical Relevance: Biomimetic mineralization strategies and bioceramics can be used for obturation of root canals with open apex, instead of utilizing these bioceramics as apical plugs.
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September 2020

Amniotic fluid-derived multipotent stromal cells drive diabetic wound healing through modulation of macrophages.

J Transl Med 2021 01 6;19(1):16. Epub 2021 Jan 6.

Hansjörg Wyss Department of Plastic Surgery, New York University School of Medicine, 540 First Avenue, New York, 10016, USA.

Background: Cutaneous wounds in patients with diabetes exhibit impaired healing due to physiological impediments and conventional care options are severely limited. Multipotent stromal cells (MSCs) have been touted as a powerful new therapy for diabetic tissue repair owing to their trophic activity and low immunogenicity. However, variations in sources and access are limiting factors for broader adaptation and study of MSC-based therapies. Amniotic fluid presents a relatively unexplored source of MSCs and one with wide availability. Here, we investigate the potential of amniotic fluid-derived multipotent stromal cells (AFMSCs) to restore molecular integrity to diabetic wounds, amend pathology and promote wound healing.

Method: We obtained third trimester amniotic fluid from term cesarean delivery and isolated and expanded MSCs in vitro. We then generated 10 mm wounds in Lepr diabetic mouse skin, and splinted them open to allow for humanized wound modeling. Immediately after wounding, we applied AFMSCs topically to the sites of injuries on diabetic mice, while media application only, defined as vehicle, served as controls. Post-treatment, we compared healing time and molecular and cellular events of AFMSC-treated, vehicle-treated, untreated diabetic, and non-diabetic wounds. A priori statistical analyses measures determined significance of the data.

Result: Average time to wound closure was approximately 19 days in AFMSC-treated diabetic wounds. This was significantly lower than the vehicle-treated diabetic wounds, which required on average 27.5 days to heal (p < 0.01), and most similar to time of closure in wild type untreated wounds (an average of around 18 days). In addition, AFMSC treatment induced changes in the profiles of macrophage polarizing cytokines, resulting in a change in macrophage composition in the diabetic wound bed. We found no evidence of AFMSC engraftment or biotherapy induced immune response.

Conclusion: Treatment of diabetic wounds using amniotic fluid-derived MSCs encourages cutaneous tissue repair through affecting inflammatory cell behavior in the wound site. Since vehicle-treated diabetic wounds did not demonstrate accelerated healing, we determined that AFMSCs were therapeutic through their paracrine activities. Future studies should be aimed towards validating our observations through further examination of the paracrine potential of AFMSCs. In addition, investigations concerning safety and efficacy of this therapy in clinical trials should be pursued.
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http://dx.doi.org/10.1186/s12967-020-02674-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789548PMC
January 2021

Advancement of nanoscience in development of conjugated drugs for enhanced disease prevention.

Life Sci 2021 Mar 30;268:118859. Epub 2021 Jan 30.

BR Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.

Nanoscience and nanotechnology is a recently emerging and rapid developing field of science and has also been explored in the fields of Biotechnology and Medicine. Nanoparticles are being used as tools for diagnostic purposes and as a medium for the delivery of therapeutic agents to the specific targeted sites under controlled conditions. The physicochemical properties of these nanoparticles give them the ability to treat various chronic human diseases by site specific drug delivery and to use in diagnosis, biosensing and bioimaging devices, and implants. According to the type of materials used nanoparticles can be classified as organic (micelles, liposomes, nanogels and dendrimers) and inorganic (including gold nanoparticles (GNPs), super-paramagnetic iron oxide nanomaterials (SPIONs), quantum dots (QDs), and paramagnetic lanthanide ions). Different types of nanoparticle are being used in conjugation with various types of biomoities (such as peptide, lipids, antibodies, nucleotides, plasmids, ligands and polysaccharides) to form nanoparticle-drug conjugates which has enhanced capacity of drug delivery at targeted sites and hence improved disease treatment and diagnosis. In this study, the summary of various types of nanoparticle-drug conjugates that are being used along with their mechanism and applications are included. In addition, the various nanoparticle-drug conjugates which are being used and which are under clinical studies along with their future opportunities and challenges are also discussed in this review.
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http://dx.doi.org/10.1016/j.lfs.2020.118859DOI Listing
March 2021

miR-29 modulates CD40 signaling in chronic lymphocytic leukemia by targeting TRAF4: an axis affected by BCR inhibitors.

Blood 2021 May;137(18):2481-2494

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

B-cell receptor (BCR) signaling and T-cell interactions play a pivotal role in chronic lymphocytic leukemia (CLL) pathogenesis and disease aggressiveness. CLL cells can use microRNAs (miRNAs) and their targets to modulate microenvironmental interactions in the lymph node niches. To identify miRNA expression changes in the CLL microenvironment, we performed complex profiling of short noncoding RNAs in this context by comparing CXCR4/CD5 intraclonal cell subpopulations (CXCR4dimCD5bright vs CXCR4brightCD5dim cells). This identified dozens of differentially expressed miRNAs, including several that have previously been shown to modulate BCR signaling (miR-155, miR-150, and miR-22) but also other candidates for a role in microenvironmental interactions. Notably, all 3 miR-29 family members (miR-29a, miR-29b, miR-29c) were consistently down-modulated in the immune niches, and lower miR-29(a/b/c) levels associated with an increased relative responsiveness of CLL cells to BCR ligation and significantly shorter overall survival of CLL patients. We identified tumor necrosis factor receptor-associated factor 4 (TRAF4) as a novel direct target of miR-29s and revealed that higher TRAF4 levels increase CLL responsiveness to CD40 activation and downstream nuclear factor-κB (NF-κB) signaling. In CLL, BCR represses miR-29 expression via MYC, allowing for concurrent TRAF4 upregulation and stronger CD40-NF-κB signaling. This regulatory loop is disrupted by BCR inhibitors (bruton tyrosine kinase [BTK] inhibitor ibrutinib or phosphatidylinositol 3-kinase [PI3K] inhibitor idelalisib). In summary, we showed for the first time that a miRNA-dependent mechanism acts to activate CD40 signaling/T-cell interactions in a CLL microenvironment and described a novel miR-29-TRAF4-CD40 signaling axis modulated by BCR activity.
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http://dx.doi.org/10.1182/blood.2020005627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610744PMC
May 2021

Diagnostic Value of Risk of Malignancy Algorithm (ROMA) in Adnexal Masses.

J Obstet Gynaecol India 2020 Jun 23;70(3):214-219. Epub 2019 Dec 23.

1Department of Surgical Oncology, King George's Medical University, Oncology Office, 3rd Floor, Shatabdi Building Phase 2, Lucknow, Uttar Pradesh 226003 India.

Background: Differentiating malignancy from benign diseases is the key to successful management of adnexal masses. Risk of malignancy algorithm (ROMA) has been used for this purpose. We have prospectively studied the diagnostic value of ROMA in patients presented with adnexal masses.

Methods: We prospective calculated ROMA values prior to surgery for adnexal masses. The risk calculated was then correlated with the histological findings, and results were analyzed according to menopausal status. ROMA cutoff value was determined using ROC curve, and sensitivity, specificity and predictive values were calculated. Statistics were performed on SPSS software (version 20.0).

Results: There were 94 patients with adnexal masses included in the study, 65 (69.1%) had epithelial ovarian cancer and 29 (30.9%) were diagnosed benign on histopathology. In both pre- and postmenopausal patients, ROMA values were significantly higher in patients with malignancy compared to those with benign disease (< 0.05). ROMA score was of a significant diagnostic value in both premenopausal (AUC = 0.914, = 10.81, < 0.001) and postmenopausal patients (AUC = 0.975, = 21.51, < 0.001). In premenopausal females, ROMA > 13.3% was able to discriminate malignant from benign patients with 97.06% sensitivity and 85.00% specificity. The positive and negative predictive values were 91.7% and 94.4%. Similarly, in postmenopausal females, ROMA value of > 76% achieved 87.10% sensitivity and 100.00% specificity in discriminating malignant from benign patients with 100% positive and 69.2% negative predictive value. The overall accuracy of ROMA in pre- and postmenopausal patients was 87.0% and 85%, respectively.

Conclusions: ROMA is a useful and accurate test for differentiating epithelial ovarian cancer from benign ovarian masses. Further studies are needed to compare performance of ROMA with the Risk of Malignancy Index (RMI), CA 125 and HE4. Such comparative studies will be helpful to the clinician in deciding the best diagnostic tool for women with adnexal masses.
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http://dx.doi.org/10.1007/s13224-019-01295-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239964PMC
June 2020

A novel Nanoformulation Development of Eugenol and their treatment in inflammation and periodontitis.

Saudi Pharm J 2019 Sep 29;27(6):778-790. Epub 2019 Apr 29.

Department of Epidemic Disease Research, Institutes of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Objective: To prepare a novel nanoemulsion- Carbopol® 934 gel for Eugenol, in order to prevent the periodontitis.

Material And Methods: Spontaneous emulsification method was used for the preparation of nanoemulsion in which it contain Eugenol (oil phase), Tween-80 (surfactant), and PEG (co-surfactant). To the development of best nanoemulsion, three-factor three-level central composite design was used in which %oil; %S and % water were optimized as independent variables. An optimized-nanoemulsion were converted to nanoemulsion-Carbopol® 934 gel.

Results: 5.5% oil, 35.5% S and 59.0% water were optimized as independent and dependent variables. Finally dependent variables optimized as a particle size (nm), PDI and %transmittance were observed 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31% respectively. The values of final results for dependent variables like particle size (nm), PDI and % transmittance were evaluated as 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31%, respectively. TEM and SEM showed a spherical shape of developed nanoemulsion with refractive index (1.63 ± 0.038), zeta potential (-19.16 ± 0.11), pH (7.4 ± 0.06), viscosity (34.28 ± 6 cp), and drug content of 98.8 ± 0.09%. After that a final optimized EUG-NE-Gel was assessed on the basis of their pH measurement, drug content, syringeability, and mucoadhesion on the goat buccal mucosa. Optimized EUG-NE-Gel (Tween-80 and Carbopol® 934 used) showed the results, to improve the periodontal drug delivery of EUG in future.

Conclusion: EUG-NE-Gel showed a significant role in anti-inflammatory activity, analgesic, and anesthetic, antibacterial, and treatment of periodontal disease.
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http://dx.doi.org/10.1016/j.jsps.2019.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733787PMC
September 2019

Risk Factors for Wound Complications Following Transmetatarsal Amputation in Patients With Diabetes.

J Surg Res 2019 11 1;243:509-514. Epub 2019 Aug 1.

Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, New York. Electronic address:

Background: The goal of our study was to evaluate risk factors for wound complications in patients with diabetes mellitus undergoing transmetatarsal amputations (TMAs), given the paucity of research on this subject.

Materials And Methods: We used the American College of Surgeons National Surgical Quality Improvement Program database. In this retrospective analysis, all surgical cases with a primary Current Procedural Terminology code for TMA from 2009 to 2015 were reviewed.

Results: A total of 2316 patients with diabetes mellitus who underwent TMA were identified. Overall wound complications occurred in 276 (11.9%) of patients. Univariate analysis showed that the operative time was significantly longer in patients who developed complications than those who did not (58.3 ± 39.5 versus 50.6 ± 39.4; P = 0.003). Furthermore, the rate of obesity was significantly higher among patients who developed wound complications than those who did not (47.1% versus 41.5%; P = 0.04). Multivariate analysis demonstrated that a longer operative time (odds ratio = 1.02; 95% confidence interval: 1.01-1.04; P = 0.01) and obesity (odds ratio = 1.60; 95% confidence interval: 1.06-2.40; P = 0.03) were independent risk factors for wound complications in our cohort.

Conclusions: These findings emphasize the importance of having heightened clinical vigilance in obese patients with diabetes mellitus undergoing this procedure, close postoperative follow-up, and limiting operative time when possible.
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http://dx.doi.org/10.1016/j.jss.2019.07.003DOI Listing
November 2019

Quasi Prospective Comparative Study on Effect of Yoga among Prediabetics on Progression of Cardiovascular Risk Factors.

Int J Yoga 2019 May-Aug;12(2):114-119

Department of Physiology, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India.

Introduction: Prediabetic patients have higher risk for cardiovascular diseases, which further increases the rate of mortality. Reason for the rate of increase may be lack of observation, follow-up programs, and self-awareness about the conditions of disease. Lifestyle interventions such as yoga can prove to be a beneficial nonpharmacologic intervention in preventing progression of prediabetes to type 2 diabetes. This study highlights importance of short-term intervention, i.e., yoga in prediabetic patients and use it as a tool for primary prevention of diabetes.

Methods: This was an interventional study among adults aged 30-50 years in RUHS college of Medical Sciences and Associated Rukmani Devi Beni Prasad Jaipuria Hospital in Jaipur city. The design of study was quasi prospective comparative study. A total of 102 prediabetic patients of age group 30-50 years were recruited from Jaipuria Hospital. These were divided into two groups: study group (Group A, = 51) were engaged in yoga session and control group (B, = 51) not performed any yoga session.

Results: Yoga intervention resulted in a significant decline in blood glucose ( < 0.001), glycated hemoglobin ( < 0.01), lipid profile cholesterol ( < 0.01), triglyceride ( < 0.01), and low-density lipoprotein ( < 0.01), but high-density lipoprotein ( < 0.02) and very low-density lipoprotein increase ( < 0.03) but not statistically significant relative to the control group.

Conclusion: Short-term yoga intervention is helpful in the control of glycemic parameters like blood glucose, glycated hemoglobin and lipid profile in prediabetic patients. This preliminary study indicates that a yoga program would be a possible risk reduction option for adults at high risk for type 2 diabetes. In addition, yoga holds promise as an approach to reducing cardiometabolic risk factors and increasing exercise self-efficacy for prediabetics performing yoga.
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http://dx.doi.org/10.4103/ijoy.IJOY_49_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521758PMC
May 2019

Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischaemia and its toxicity assessment.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):475-490

h Nanomedicine Lab , Department of Pharmaceutics, School of Pharmaceutical Education and Research , Jamia Hamdard , New Delhi, India.

Objective: Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain.

Methods: Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i.n. in animals.

Results: The developed NPs showed an average particle size, entrapment efficiency with PDI (polydispersity index) of 201.3 ± 4.6 nm, 77.94 ± 5.01% and 0.253 ± 0.019, respectively. Higher mucoadhesive property for CS-GA-PCL-NPs as compared to conventional and homogenized nanoformulations was observed whereas an elution time of 0.37 min and m/z of 821.49/113.41 for GA along with an elution time of 1.94 min and m/z of 363.45/121.40 was observed for hydrocortisone i.e. Internal standard (IS). Similarly, %CV i.e. inter and intra assay i.e. 0.49-4.41%, linear dynamic range (10-2000 ng/mL) and % accuracy of 90.00-99.09% was also observed. AUC with augmented C was noted (**p < .01), in Wistar rat brain as compared to i.v. treated group during pharmacokinetics studies. In MCA-occluded rats, enhanced neurobehavioral activity i.e. locomotor and grip strength along with a decrease in cytokines level (TNF-α and IL-1β) was observed, following i.n. administration.

Conclusions: CS-coated-GA-loaded-PCL-NPs when administered i.n. enhanced the bioavailability of the drug in rat brain as compared to i.v. administration. The observation from toxicity study concludes; the developed NPS are safe and free of any health associated risk.
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http://dx.doi.org/10.1080/21691401.2018.1561458DOI Listing
December 2019

Obesity genetics and cardiometabolic health: Potential for risk prediction.

Diabetes Obes Metab 2019 05 20;21(5):1088-1100. Epub 2019 Mar 20.

Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

The increasing burden of obesity worldwide and its effect on cardiovascular disease (CVD) risk is an opportunity for evaluation of preventive approaches. Both obesity and CVD have a genetic background and polymorphisms within genes which enhance expression of variant proteins that influence CVD in obesity. Genome-based prediction may therefore be a feasible strategy, but the identification of genetically driven risk factors for CVD manifesting as clinically recognized phenotypes is a major challenge. Clusters of such risk factors include hyperglycaemia, hypertension, ectopic liver fat, and inflammation. All involve multiple genetic pathways having complex interactions with variable environmental influences. The factors that make significant contributions to CVD risk include altered carbohydrate homeostasis, ectopic deposition of fat in muscle and liver, and inflammation, with contributions from the gut microbiome. A futuristic model depends on harnessing the predictive power of plausible genetic variants, phenotype reversibility, and effective therapeutic choices based on genotype-phenotype interactions. Inverting disease phenotypes into ideal cardiovascular health metrics could improve genetic and epigenetic assessment, and form the basis of a future model for risk detection and early intervention.
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http://dx.doi.org/10.1111/dom.13641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530772PMC
May 2019

downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels.

Blood 2018 11 13;132(22):2389-2400. Epub 2018 Sep 13.

Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely , which was uniformly downmodulated in all examined tFLs (∼3.5-fold), and observed that high levels of MYC are responsible for repressing in tFL by binding in its upstream region. This MYC-mediated repression of in B cells is not dependent on LIN28A/B proteins, which influence the maturation of precursor () in myeloid cells. We also demonstrated that low levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-κB signaling in malignant B cells. We revealed that low levels of and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of the MYC//FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.
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http://dx.doi.org/10.1182/blood-2018-06-855502DOI Listing
November 2018

Osteo-cutaneous acanthamoebiasis in a non-immunocompromised patient with a favorable outcome.

Parasitol Int 2017 Dec 7;66(6):727-730. Epub 2017 Aug 7.

Department of Medical Parasitology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Osteo-cutaneous form is a rare presentation of acanthamoebiasis. We present the first such case from India in an apparently healthy male who developed cutaneous lesion with bone involvement after traumatic inoculation of Acanthamoeba cysts. The diagnosis was established by routine microbiological techniques and confirmed by 18SrRNA gene sequencing. Aggressive therapy with terbinafine, chlorhexidine, rifampicin and co-trimoxazole was successful in clearing the lesion and preventing encephalitis.
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http://dx.doi.org/10.1016/j.parint.2017.08.003DOI Listing
December 2017

Optimal power settings of aluminum gallium arsenide lasers in caries inhibition - An in vitro study.

J Conserv Dent 2016 Mar-Apr;19(2):175-8

Department of Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, Nitte University, Mangaluru, Karnataka, India.

Context: Incipient carious lesions are characterized by subsurface dissolution due to more fluoride ions in the 50-100 microns of the tooth's outer surface.

Aims: To determine an optimal power setting for 810 nm aluminum gallium arsenide laser for caries inhibition.

Materials And Methods: Fifty-four caries-free extracted teeth were sectioned mesiodistally. The samples were divided into 18 groups for each power setting being evaluated. Each group had six samples. The laser used is 810 nm aluminum gallium arsenide laser with power setting from 0.1 watts to 5 watts. Laser fluorescence based device was used to evaluate the effect of irradiation.

Statistical Analysis Used: Paired "t" test, one-way analysis of variance (ANOVA), Tukey's post hoc test, and the Pearson's correlation test.

Results: The paired t-test showed that there is minimum divergence from the control for 3.5 watts. Tukey's post hoc test also showed statistically significantly results for 3.5 watts. The Pearson's correlation test showed that there was negative correlation between the watts and irradiation.

Conclusions: The power setting that gave statistically significant results was 3.5 watts.
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http://dx.doi.org/10.4103/0972-0707.178704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815549PMC
April 2016

Changing Smiles Through Multidisciplinary Approach with Predictable Aesthetics: A Case Report.

J Indian Prosthodont Soc 2014 Dec 18;14(Suppl 1):168-71. Epub 2012 Jul 18.

Division of Prosthodontics, Army Dental Centre R & R, New Delhi, India.

This clinical report describes a multidisciplinary approach for the rehabilitation of a young patient with mobile and missing front teeth. The objectives of the treatment were to eliminate tooth mobility and replacing missing tooth, while enhancing aesthetics and restoring masticatory function. Treatment included placement of endodontic stabilizer and rehabilitating missing tooth with fixed partial denture and gingival porcelain to satisfy the patient's aesthetic and functional expectations.
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http://dx.doi.org/10.1007/s13191-012-0144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501990PMC
December 2014

Odontometric sexual dimorphism: a sibling correlation.

J Clin Diagn Res 2014 Mar 15;8(3):233-5. Epub 2014 Mar 15.

Lecturer, Department of Preventive Dental Sciences, College of Dentistry, University of Dammam , Saudi Arabia .

Aims And Background: Teeth form an excellent material for anthropological, genetic, odontologic and forensic investigations. The aim of this study was to establish the genetic control of sexual dimorphism in tooth size amongst siblings of Goan children in age range of 14-22 years.

Materials And Methods: Twenty-two sibling pairs were selected (22 males and 22 females) to assess genetic control of sexual dimorphism in tooth size. Alginate impressions were obtained for maxillary and mandibular arches and study models were prepared. Measurements were done using Zoom Digimatic Vernier Calipers with a resolution of 0.01 mm.

Statistical Analysis: Correlation between mesiodistal and buccolingual tooth sizes amongst siblings was calculated using Pearson's correlation coefficient.

Results: A statistically significant association was found between Mesiodistal Widths of Permanent Maxillary Right and Left Second Molars and between Maxillary Right and Left First Premolars amongst sibling pairs. A statistically significant association was also found between Buccolingual Widths of Mandibular Right and Left First Premolars amongst sibling pairs. This statistically significant correlation found amongst siblings establishes a genetic control over sexual dimorphism in these teeth.

Conclusion: The genetic basis of sexual dimorphism in human dentition was ascertained as a significant correlation was found between mesio-distal and bucco-lingual widths of premolars between sibling pairs.
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http://dx.doi.org/10.7860/JCDR/2014/7729.4171DOI Listing
March 2014

Dystrophic epidermolysis bullosa associated with non-syndromic hypodontia.

Indian Dermatol Online J 2013 Oct;4(4):296-9

Department of Pedodontics and Preventive Dentistry, Seema Dental College and Hospital, Rishikesh, Uttarakhand, India.

Epidermolysis bullosa (EB) is a genetic disease associated with fragility and bullous lesions of the skin and mucous membranes. There are various patterns of inheritance and histopathology. The disease is associated with systemic and oral manifestations, among which may be dental decay necessitating oral rehabilitation. The aim of this article is to present the course of the condition in a child with dystrophic EB and also to report an association between EB, hypodontia, and supernumerary teeth which has not been reported earlier in literature.
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http://dx.doi.org/10.4103/2229-5178.120644DOI Listing
October 2013

Community perceptions of mental distress in a post-conflict setting: a qualitative study in Burundi.

Glob Public Health 2013 13;8(8):943-57. Epub 2013 Aug 13.

a Department of Mental Health, Johns Hopkins Bloomberg School of Public Health , Johns Hopkins University , Baltimore , MD , USA.

There is scant documentation of the mental health characteristics of low-income communities recovering from armed conflict. To prepare for quantitative health surveys and health service planning in Burundi, we implemented a qualitative study to explore concepts related to mental distress and coping among adults. Mental distress was defined as problems related to feelings, thinking, behaviour and physical stress. Using free listing and key informant interviews with a range of community members, we triangulated data to identify salient issues. Thirty-eight free list respondents and 23 key informants were interviewed in 5 rural communities in Burundi using 2 interview guides from the WHO Toolkit for Mental Health Assessment in Humanitarian Settings. Based on these interviews, we identified four locally defined idioms/terms relating to mental distress: ihahamuka (anxiety spectrum illnesses), ukutiyemera (a mix of depression and anxiety-like syndrome), akabonge (depression/grief-like syndrome) and kwamana ubwoba burengeje (anxiety-like syndrome). Mental distress terms were perceived as important problems impacting community development. Affected individuals sought help from several sources within the community, including community leaders and traditional healers. We discuss how local expressions of distress can be used to tailor health research and service integration from the bottom up.
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http://dx.doi.org/10.1080/17441692.2013.819587DOI Listing
May 2014

Cell cycle and apoptosis regulatory protein (CARP)-1 is expressed in osteoblasts and regulated by PTH.

Biochem Biophys Res Commun 2013 Jul 11;436(4):607-12. Epub 2013 Jun 11.

Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30min to 5h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1 suggesting that PTH utilized an Extracellular Signal Regulated Kinase (ERK)-independent but p38 dependent pathway to regulate CARP-1 protein expression in osteoblasts. Immunofluorescence staining of differentiated osteoblasts further revealed nuclear to cytoplasmic translocation of CARP-1 protein following PTH treatment. Collectively, our studies identified CARP-1 for the first time in osteoblasts and suggest its potential role in PTH signaling and bone anabolic action.
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http://dx.doi.org/10.1016/j.bbrc.2013.05.136DOI Listing
July 2013

Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment.

PLoS One 2013 2;8(5):e62289. Epub 2013 May 2.

Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America.

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant K a was 1,639 M(-1) as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062289PLOS
December 2013

Congenital Insensitivity to Pain with Anhidrosis (HSAN Type IV), Extremely Rare Syndrome that Can Be Easily Missed by Bone and Joint Surgeons: A Case Report.

Iran J Pediatr 2012 Dec;22(4):559-63

Department of Orthopedics Postgraduate, Govt. Medical College Jammu.

Background: Congenital insensitivity to pain with anhidrosis is an extremely rare disorder in which injuries can often be missed by patient, parents and even by orthopedic surgeon. Pain and tenderness, on which a trauma team so much depends to make a clinical diagnosis and to decide whether to go for radiological evaluation can be misleading in this rare syndrome. So complete clinical examination still forms the corner stone to avoid misdiagnosis and pick up the rare disorders.

Case Presentation: We present a 5 year old girl child, who was brought to us as a case of one and a half month old neglected trauma left leg and was diagnosed to be suffering from congenital insensitivity to pain with anhidrosis (HSAN Type IV).

Conclusion: Congenital insensitivity to pain with anhidrosis is extremely rare entity, in which patients are subjected to repeated injuries which are often neglected. There is no specific treatment but patient training and parent education are key to avoid further neglect and damage.
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December 2012

MKP1-dependent PTH modulation of bone matrix mineralization in female mice is osteoblast maturation stage specific and involves P-ERK and P-p38 MAPKs.

J Endocrinol 2013 Mar 25;216(3):315-29. Epub 2013 Feb 25.

Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Clinical Research Building, 421 East Canfield Avenue, Detroit, Michigan 48201, USA.

Limited information is available on the role of MAPK phosphatase 1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation, and skeletal responsiveness to parathyroid hormone (PTH). As MKP1 regulates the phosphorylation status of MAPKs, we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knockout (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9-14-week-old WT and MKP1 KO male and female mice were examined. Western blot analysis revealed downregulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts and by U in mature KO cells. Changes in matrix Gla protein expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1-dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.
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http://dx.doi.org/10.1530/JOE-12-0372DOI Listing
March 2013

Subclinical hypothyroidism and its association with cardiovascular risk factors.

Clin Lab 2011 ;57(9-10):719-24

Department of Biochemistry, J.L.N. Medical College, Ajmer 305001, Rajasthan, India.

Background: Subclinical hypothyroidism (SH) represents the mildest form of thyroid hormone deficiency and may be associated with adverse consequences [Subclinical hypothyroidism was defined as a TSH level > 4.0 mIU/L and a normal free thyroxine level 0.6-1.8 ng/dL]. The identification of patients with subclinical hypothyroidism having an increased cardiovascular risk (CVR) is important. The aim of the study was to evaluate atherosclerotic risk factors in patients with subclinical hypothyroidism.

Methods: Forty patients with subclinical hypothyroidism and forty healthy euthyroid controls, age and gender matched were included in the study. Serum total triiodothyronine (T3), thyroxine (T4), TSH, free T3 (FT3) and free T4 (FT4) were measured by enzyme linked immunosorbent assay (ELISA). Atherosclerotic risk factors measured were high sensitivity-CRP (hs-CRP), Lipoprotein (a) [Lp (a)] and lipid parameters. Lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were analysed by enzymatic colorimetric, endpoint method whereas the hs-CRP and Lp (a) were measured by quantitative latex turbidimetric method.

Results: Patients with subclinical hypothyroidism had significantly higher levels of serum hs-CRP, Lp (a), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) when compared to same parameters of controls. Further, a significant positive correlation was observed between TSH and hs-CRP, Lp (a), LDL-C and TC in subjects with subclinical hypothyroidism. However, TG levels showed no significant correlation with TSH levels.

Conclusions: We concluded that the SH patients presented increased concentration of some CVR factors. The potential benefits of diagnosis and treatment of subclinical hypothyroidism may have possible advantages firstly by preventing the progression to overt hypothyroidism and secondly decrease the risk of death from cardiovascular disease (CVD) by starting appropriate therapy to improve lipid parameters. Further research is needed on subclinical hypothyroidism and the associated atherosclerotic risk factors.
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November 2011
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