3D assessment of alveolar bone alterations in orthodontic movement among Indians.

Apical root resorption, which is characterised as a biological or abnormal phenomenon that shortens the length of the root apex, is additional typical iatrogenic impact of orthodontic tooth movement that may jeopardise the effectiveness of treatment and tooth lifespan. The main goals of the current retrospective investigation were to assess the dimensions of alveolar bone alterations that come along with orthodontic movement and to look into the frequency and extent of resorption of root in maxillary incisors across categories that were similarly managed with clear aligners (OCA) and fixed appliances (OFA) using CBCT. The study included 50 subjects who were divided into two categories with 25 study subjects in each category. Category OFA: Subjects receiving OFA (n=25). A CBCT scan was used to get three-dimensional pictures at the beginning of therapy as well as at the end of therapy. The overall resorption of root at apical region in OFA group was 0.63±0.21 mm. The overall resorption of root at apical region in OCA group was 0.32 ±0.36 mm. The difference in observation was statistically significant (p= 0.000) with reduced resorption of root at apical region in clear aligners. It was concluded that the decrease in thickness of alveolar bone was greater in orthodontic fixed appliances group as compared to clear aligners. The resorption of root at apical region was lesser in clear aligners group as compared to fixed appliances.

Thirty-day unplanned readmission in hospitalised asthma patients in the USA.

INTRODUCTION: Hospital quality improvement and hospital performance are commonly evaluated using parameters such as average length of stay (LOS), patient safety measures and rates of hospital readmission. Thirty-day readmission (30-DR) rates are widely used as a quality indicator and a quantifiable metric for hospitals since patients are often readmitted for the exacerbation of conditions from index admission. The quality of patient education and postdischarge care can influence readmission rates. We report the 30-DR rates of patients with asthma using a national dataset for the year 2013. OBJECTIVES: The aim of our study was to assess the 30- day readmission (30-DR) rate as well as, the causes and predictors of readmissions. STUDY DESIGNS/METHODS: Using the Nationwide Readmission Database (NRD) (2013), we identified primary discharge diagnoses of asthma by using International Classification of Diseases, Ninth Revision, Clinical Modification code '493'. Categorical and continuous variables were assessed by a χ2 test and a Student's t-test, respectively. The independent predictors of unplanned 30-DR were detected by multivariate analysis. We used sampling weights, which are provided in the NRD, to generate the national estimates. RESULTS: There were 130 490 (weighted N=311 173) inpatient asthma admissions during 2013. The overall 30-DR for asthma was 11.9%. The associated factors for 30-DR were age 45-84 years (40.32% vs 29.05%; p<0.001), enrolment in Medicare (49.33% vs 30.61% p<0.001), extended LOS (mean, 4.40±0.06 vs 3.25±0.04 days; p<0.001), higher mean cost (US$8593.91 vs US$6741.31; p<0.001) and higher disposition against medical advice (DAMA) (4.14% vs 1.51%; p<0.001). The factors that increased the chance of 30-DR were advanced age (≥45-64 vs ≤17 years; OR 4.61, 95% CI 4.04 to 5.27, p<0.0001), male sex (OR 1.19, 95% CI 1.13 to 1.26, p<0.0001), a higher Charlson Comorbidity Index (CCI) (OR 1.16, 95% CI 1.14 to 1.18, p<0.0001), DAMA (OR 2.32, 95% CI 2.08 to 2.59, p<0.0001), non-compliance with medication (OR 1.34, 95% CI 1.24 to 1.46, p<0.0001), post-traumatic stress disorder (OR 1.48, 95% CI 1.22 to 1.79, p<0.0001), alcohol use (OR 1.45, 95% CI 1.27 to 1.65, p<0.0001), gastro-oesophageal reflux disease (OR 1.20, 95% CI 1.14 to 1.27, p<0.0001), obstructive sleep apnoea (OR 1.11, 95% CI 1.03 to 1.18, p<0.0042) and hypertension (OR 1.11, 95% CI 1.06 to 1.17, p<0.0001). CONCLUSIONS: We found that the overall 30-DR rate for asthma was 11.9% all-cause readmission. Major causes of 30-DR were asthma exacerbation (36.74%), chronic obstructive pulmonary disease (11.47%), respiratory failure (6.46%), non-specific pneumonia (6.19%), septicaemia (3.61%) and congestive heart failure (3.32%). One-fourth of the revisits occurred in the first week, while half of the revisits took place in the first 2 weeks. Education regarding illness and the importance of medicine compliance could play a significant role in preventing asthma-related readmission.

Synthesis of 1,4-dihydropyrazolo[4,3-b]indoles via intramolecular C(sp2)-N bond formation involving nitrene insertion, DFT study and their anticancer assessment.

We herein report a new synthetic route for a series of unreported 1,4-dihydropyrazolo[4,3-b]indoles (6-8) via deoxygenation of o-nitrophenyl-substituted N-aryl pyrazoles and subsequent intramolecular (sp2)-N bond formation under microwave irradiation expedite modified Cadogan condition. This method allows access to NH-free as well as N-substituted fused indoles. DFT study and controlled experiments highlighted the role of nitrene insertion as one of the plausible reaction mechanisms. Furthermore, the target compounds exhibited cytotoxicity at low micromolar concentration against lung (A549), colon (HCT-116), and breast (MDA-MB-231, and MCF-7) cancer cell lines, induced the ROS generation and altered the mitochondrial membrane potential of highly aggressive MDA-MB-231 cells. Further investigations revealed that these compounds were selective Topo I (6h) or Topo II (7a, 7b) inhibitors.

Design and Synthesis of Non-Covalent Imidazo[1,2-a]quinoxaline-Based Inhibitors of EGFR and Their Anti-Cancer Assessment.

A series of 30 non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of epidermal growth factor receptor (EGFR) were designed and synthesized. EGFR inhibitory assessment (against wild type) data of compounds revealed 6b, 7h, 7j, 9a and 9c as potent EGFRWT inhibitors with IC50 values of 211.22, 222.21, 193.18, 223.32 and 221.53 nM, respectively, which were comparable to erlotinib (221.03 nM), a positive control. Furthermore, compounds exhibited excellent antiproliferative activity when tested against cancer cell lines harboring EGFRWT; A549, a non-small cell lung cancer (NSCLC), HCT-116 (colon), MDA-MB-231 (breast) and gefitinib-resistant NSCLC cell line H1975 harboring EGFRL858R/T790M. In particular, compound 6b demonstrated significant inhibitory potential against gefitinib-resistant H1975 cells (IC50 = 3.65 µM) as compared to gefitinib (IC50 > 20 µM). Moreover, molecular docking disclosed the binding mode of the 6b to the domain of EGFR (wild type and mutant type), indicating the basis of inhibition. Furthermore, its effects on redox modulation, mitochondrial membrane potential, cell cycle analysis and cell death mode in A549 lung cancer cells were also reported.

Characterization and preparation of Fe3O4 nanoparticles loaded bioglass-chitosan nanocomposite coating on Mg alloy and in vitro bioactivity assessment.

In this study, bioglass (BG)­iron oxide (Fe3O4) nanocomposite coating was developed to produce bioactive and antibacterial coatings. The nanocomposite coating was embedded in chitosan (CS) matrix and coating was fabricated by electrophoretic deposition (EPD) method. The coating was characterized by using SEM/EDX and XRD respectively. The experiment was performed with three varying concentrations (1, 3, 5 (wt%)) of Fe3O4 nanoparticles prepared by the co- precipitation method in the bioactive glass coating. The antibacterial activity was examined in Escherichia coli and Staphylococcus aureus bacteria which determine that the growth of microorganisms was inhibited with the progressive increment of Fe3O4 nanoparticles. The bioactivity assessment was done in PBS for 7 days and it was detected that the composite coatings improve the bone-bonding ability which was again confirmed by SEM-EDX. The corrosion behavior was evaluated in Ringer's solution by electrochemical test. The corrosion analysis revealed that the BG-1% Fe3O4 nanocomposite coating has superior corrosion resistance as compared to the other coatings. The findings of the research have shown that the BG-Fe3O4-CS nanocomposite coating can be widely used as a suitable material for orthopedic applications.

Racial and sex disparities in resource utilization and outcomes of multi-vessel percutaneous coronary interventions (a 5-year nationwide evaluation in the United States).

BACKGROUND: There is a paucity of data regarding the racial and sex disparities in the outcomes of multi-vessel percutaneous coronary interventions (MVPCI). METHODS: The National Inpatient Sample (NIS) was examined for the years 2010 to 2014 to incorporate adult MVPCI-related hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes. We excluded patients with the missing race or gender data from the final scrutiny. Discharge weights were used to obtain the national estimations. The principal outcomes were MVPCI-related racial and gender disparities in terms of the in-hospital mortality and complications, and diagnostic and therapeutic healthcare resource utilization. Secondary outcomes were the length of hospital stay (LOS) and hospitalization charges. We used the Chi-square test and t-test/ANOVA test to equate dichotomous and continuous variables respectively. A two-tailed P of <0.05 was considered clinically significant. RESULTS: An estimated 769,502 MVPCI-related hospitalizations were recorded from 2010 to 2014 after excluding patients with the missing data (70,954; 8.4%). Black male and female were the youngest (62±13, 64±14 years). The highest non-elective admissions (M: 72.8%, F: 71.2%) were reported among Hispanics. Non-whites showed a higher proportion of comorbidities with lower resource utilization than whites. Hispanic males (OR 1.23) showed the highest odds of the in-hospital mortality whereas among females, Asians (OR 1.51), blacks (OR 1.35), followed by Hispanics (OR 1.22) revealed higher odds of in-hospital mortality. Odds of cardiac complications were highest amongst Asians (M: OR 1.19, F: OR 1.40). Black (6±8 days) and Hispanic (7±9 days) showed the highest length of stay among males and females respectively. Total hospitalization charges were highest among Asians. There was a greater increase in the all-cause mortality in non-whites from 2010 to 2014. CONCLUSIONS: This study determines the existence of racial disparities in resource utilization and outcomes in MVPCI. There is an instant need for interventions designed to govern these healthcare discrepancies.

The burden and impact of arrhythmia in chronic obstructive pulmonary disease: Insights from the National Inpatient Sample.

BACKGROUND: We aimed to analyze the burden and predictors of arrhythmias and in-hospital mortality in chronic obstructive pulmonary disease (COPD)-related hospitalizations using the nationwide cohort. METHODS: We queried the National Inpatient Sample (NIS) (2010-2014) databases to identify adult COPD hospitalizations with arrhythmia. Categorical and continuous variables were compared using Chi-square and Student's t-test/ANOVA. Predictors of any arrhythmia including AF and in-hospital mortality were evaluated by multivariable analyses. RESULTS: Out of 21,596,342 COPD hospitalizations, 6,480,799 (30%) revealed co-existent arrhythmias including 4,767,401 AF-arrhythmias (22.1%) and 1,713,398 non AF-arrhythmias (7.9%). The AF or non-AF arrhythmia cohort consisted mostly of older (mean age~ 75.8 & 69.1 vs. 67.5 years) white male (53.3% & 51.9% vs. 46.9%) patients compared to those without arrhythmias (p < 0.001). The all-cause mortality (5.7% & 5.2 vs. 2.9%), mean length of stay (LOS) (6.4 & 6.5 vs. 5.3 days), and hospital charges ($52,699.49 & $58,102.39 vs. $41,208.02) were higher with AF and non AF-arrhythmia compared to the non-arrhythmia group (p < 0.001). Comorbidities such as cardiomyopathy (OR 2.11), cardiogenic shock (OR 1.88), valvular diseases (OR 1.60), congestive heart failure (OR 1.48) and pulmonary circulation disorders (OR 1.25) predicted in-hospital arrhythmias. Invasive mechanical ventilation (OR 6.41), cardiogenic shock (OR 5.95), cerebrovascular disease (OR 3.95), septicemia (OR 2.30) and acute myocardial infarction (OR 2.24) predicted higher mortality (p < 0.001) in the COPD-arrhythmia cohort. CONCLUSIONS: About 30% of COPD hospitalizations revealed co-existent arrhythmias (AF 22.1%). All-cause mortality, LOS and hospital charges were significantly higher with arrhythmias. We observed racial and sex-based disparities for arrhythmias and related mortality.

Thirty-Day Readmissions After Upper and Lower Gastrointestinal Hemorrhage: A National Perspective in the United States.

BACKGROUND: Upper gastrointestinal hemorrhage (UGIH) and lower gastrointestinal hemorrhage (LGIH) are 2 of the most common reasons for hospital admissions across the United States. The 30-day readmission after index admission poses a major burden on the health care infrastructure, and thus, it is important to assess the causes of 30-day readmission for patients with UGIH and LGIH. METHODS: The study cohort was derived from the 2013 National Readmission Database. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) Volume 3 diagnosis codes were utilized to identify UGIH and LGIH patients from this data set. Patients who were readmitted to the hospital within 30 days within the same calendar year were further analyzed. Categorical variables and continuous variables were assessed by the χ test and the student t test, respectively. The independent predictors of unplanned 30-day readmissions were recognized by multivariate logistic regression, adjusting for stratified cluster design of National Readmission Database. SAS 9.4 (SAS Institute Inc., Cary, NC) was used for data analysis. RESULTS: The number of index admissions identified from the National Readmission Data 2013 were 82,290 for UGIH and 133,114 for LGIH. All-cause 30-day readmission rate for UGIH versus LGIH was 14.6% (readmitted N=12,046; 56.64% age 65 y and above) versus 14.4% (readmitted N=19,128; 70.21% age 65 y and above and 49.61% men). Gastrointestinal causes were most common (33.9% vs. 39.6%), followed by cardiac (13.3% vs. 15.3%), infectious (10.4% vs. 9.1%), and respiratory causes (7.8% vs. 7.1%) for 30-day readmission for UGIH and LGIH. Significant predictors of increased 30-day readmission (odds ratio, 95% confidence interval, P-value) included metastatic disease (2.15, 1.75-2.64, P<0.001), discharge against medical advice (1.85, 1.55-2.22, P<0.001), and length of stay >3 days (1.50, 1.38-1.63, P<0.001). Predictors for 30-day readmission for LGIH included metastatic disease (1.75, 1.48-2.06, P<0.001), liver disease (1.59, 1.49-1.71, P<0.001), and drug abuse (1.38, 1.21-1.58, P<0.001). CONCLUSIONS: Most common reason for UGIH and LGIH readmission was related to gastrointestinal disease, followed by cardiac, infectious, and respiratory etiologies. By addressing these etiologies for readmission, it may be possible to reduce adverse outcomes.

Health Risk Assessment of Occupationally Pesticide-Exposed Population of Cancer Prone Area of Punjab.

The alarming health issues especially the unusually high number of cancer cases in agriculture community of Bathinda district of Punjab (India) is a serious concern. There is limited knowledge about the role of gene-environment interactions in oncogenesis prevalent in this area. The aim of this study was to evaluate the association of oxidative stress with CYP1A2, CYP2B6, CYP2C9, CYP3A4, and PON1 genetic variation in the pesticide-exposed (occupationally) population of Bathinda district of Punjab (India). This study demonstrated significantly elevated relative risk (RR) of lower antioxidant defense mechanism (Glutathione, Catalase, Superoxide Dismutase, Glutathione peroxidases, and Glutathione Reductase) in occupationally pesticide-exposed group (n = 120) as compared with unexposed group (n = 84) from Bathinda district of Punjab (India). Our data shows pesticide exposure to be a major risk factor leading to increased oxidative stress inside the body. Gas chromatographic analysis revealed the residues of organophosphates (chlorpyriphos, dichlorvos, ethoprophos) and herbicides (atrazine, butachlor, alachlor, metolachlor) in the blood samples of the exposed population. In vitro results showed a dose dependent decrease in cell viability following treatment of pesticides detected in blood samples in hPBMCs and A549 cell line. Genetic variation analysis revealed missense mutations in CYP2B6 (2 mutations), CY3A4 (1 mutation), and CYP2C9 (2 mutations). The observed mutations have been predicted to cause structural and conformation change in protein structure which could result in altered stability. In first of its kind of study, our data reveal oxidative stress and pesticide residue accumulation inside the body to be the major reasons for health concerns in Bathinda district.

Species differences between rat and human in vitro metabolite profile, in vivo predicted clearance, CYP450 inhibition and CYP450 isoforms that metabolize benzanthrone: Implications in risk assessment.

Benzanthrone (BNZ) is a polycyclic aromatic hydrocarbon found in industrial effluent causing skin, respiratory, gastrointestinal, genitourinary, nervous and hemopoietic toxicity. While its toxicity has been well studied, its metabolism in humans has not been investigated. The aim of this study was to characterize species differences in the in vitro metabolism of BNZ in rat and human liver microsomes and to identify the CYP isoforms involved in its metabolism. Upon incubation in liver microsomes, BNZ was found to be a direct substrate of phase I metabolism in both rat and human, undergoing oxidation and reduction. The Km in rat, 11.62 ± 1.49 µM, was two-fold higher than humans (5.97 ± 0.83 µM) suggesting higher affinity for human CYPs. Further, incubation with human rCYPs, BNZ was found to be substrate of multiple CYPs. The predicted in vivo hepatic clearance was 63.55 and 18.91 mL/min/kg in rat and human, respectively, indicating BNZ to be a high clearance compound. BNZ was found to be a moderate inhibitor of human CYP1A2. BNZ metabolism by multiple CYPs indicates that single enzyme genetic polymorphism is unlikely to have profound effect on the toxicokinetics of BNZ and default uncertainty factor of 3.16 might be sufficient to capture the intraspecies kinetic variability.

Assessment of asymptomatic ischemic heart disease using stress myocardial perfusion imaging in patients with type 2 diabetes mellitus.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in patients with type 2 diabetes mellitus (T2DM) and may be asymptomatic. OBJECTIVE: The objective of this study was to assess the prevalence of asymptomatic myocardial ischemia in patients with T2DM using stress myocardial perfusion imaging. METHODS: We evaluated 97 consecutive patients with T2DM without clinical evidence of CAD presenting to Cardiology and Endocrinology clinics using Tc-99m MIBI gated single-photon emission-computed tomography (SPECT) myocardial perfusion imaging for the presence of asymptomatic CAD. RESULTS: Abnormal myocardial perfusion was observed in 10 patients (10.3%). Of these, one half of patients had reversible myocardial perfusion defects suggestive of inducible myocardial ischemia. The other half had fixed perfusion defects suggestive of previous silent myocardial infarctions. Small and moderate reversible perfusion defects were observed in 3 and 2 patients, respectively. The fixed perfusion defects observed in 5 patients were medium sized. The presence of asymptomatic ischemia was significantly associated with age and smoking but not with other traditional cardiac risk factors. CONCLUSION: Ten percent of patients with T2DM with no clinical evidence of CAD were found to have evidence of asymptomatic ischemia or infarction.

Pharmacokinetics and bioavailability assessment of Miltefosine in rats using high performance liquid chromatography tandem mass spectrometry.

Miltefosine (MFS) is the first effective oral drug for treatment of visceral, mucosal and cutaneous leishmaniasis. In this study, liquid chromatography coupled mass spectrometry (LC-MS/MS) method of MFS was validated in rat plasma and its practical utilization to pharmacokinetic studies in rats for the first time. A rapid, selective and sensitive LC-MS/MS method for MFS in rat plasma was linear over the calibration range of 1-500ng/mL. MFS and Phenacetin (internal standard) were separated on Phenomenex Luna 3µ HILIC 200A (150×4.6mm) column under isocratic condition using methanol: 0.1% formic acid in triple distilled water, 90:10 (v/v) mobile phase at a flow rate of 0.8mL/min. The total chromatographic run time was 4.0min. The intra- and inter-day assay accuracy was observed between 99.45-102.88% and 99.92-101.58%, respectively. The intra- and inter-day assay precision was observed between 2.68-5.54% and 2.35-5.94%, respectively. The validated assay was practically applied to determine the plasma concentrations after oral and intravenous administration of MFS to rats. After oral administration, MFS showed Cmax (3200.00±95.39ng/mL) was observed at 12.00h (tmax) and t1/2 was 102.36±16.65h. The absolute bioavailability of MFS was 60.33±2.32%.

Tele-cytology: An innovative approach for cervical cancer screening in resource-poor settings.

Carcinoma cervix remains a leading cause of cancer mortality among women in countries lacking any screening program. The existing screening policy and approach via conventional cytology centered mainly in Tertiary Care Center, is totally unaffordable to Indian women, especially in the remote areas. This suggests the need of depolarizing the resources via generating the near real time modalities which could be used at the door step of the needy ones. For any screening modality to be effective it should be adequately sensitive, specific, reproducible, cheap, simple, affordable, and the most important is should be real time to ensure wide coverage and curtail loss to follow-up. Incorporating telecytology as a screening tool could make the dream come true. Telecytology is the interpretation of cytology material at a distance using digital images. Use of mobile telecytology unit housed in a van carrying satellite equipment and the automated image capturing systems is the central theme behind this idea. The imaging equipment would be carrying out the imaging of Papanicolaou smears prepared at the screening site and sending the images to the central laboratories situated at some tertiary care level. This concept could overcome the hindrance of trained cytology infrastructure in the resource poor settings and could provide an efficient and economical way of screening patients. There is possibility that the designed approach may not detect the entire women positive for the disease but if the desired objective was to diagnose as many cases as possible in resource poor setting, then this process offers an advantage over no screening at all.