A novel sustainable second-derivative synchronous spectrofluorimetric method for the simultaneous determination of olmesartan medoxomil and rosuvastatin calcium in bulk and formulations: Integrated greenness and whiteness evaluation.

The present research has established a quick and highly sensitive second-derivative synchronous fluorometric technique for the simultaneous quantification of a binary mixture of olmesartan medoxomil and rosuvastatin calcium. Simultaneously, the suggested approach was used to detect the synchronous fluorescence intensity of the cited drugs at Δ λ = 80 nm in ethanol to determine the concentrations of olmesartan medoxomil and rosuvastatin calcium at 265 and 240 nm, respectively. Various experimental conditions were tested, and each variable was analyzed and optimized. The calibration graphs were shown to be linear within ranges of 0.1-2.0 and 0.5-6.0 µg ml-1 for each drug concentration, respectively. The newly developed Green Solvents Selecting Tool (GSST) was utilized to assess the solvent's sustainability. Furthermore, the proposed method was found to be environmentally friendly after being evaluated with three different tools [the Green Analytical Procedure Index (GAPI), the Analytical Greenness Metric (AGREE), and the Analytical Eco-Scale with Eco-score equal to 95]. The whiteness qualities were also studied using the Red-Green-Blue (RGB12) model, which was recently designed and showed a high score equal to 92.9. The proposed method's good findings, as well as its ongoing sustainability, simplicity, and economy, stimulate its application in QC laboratories.

Frailty predicts mortality and complications in chronologically young patients with traumatic orthopaedic injuries.

BACKGROUND: As morbidity and mortality from traumatic orthopaedic injuries continues to rise, increased research is being conducted on how to best predict complications in at risk patients. Recently, frailty indices have been validated in a variety of surgical subspecialties as predictors of morbidity and mortality. However, the vast majority of research has been conducted on geriatric patient populations, with little evidence on patients who are chronologically young. The purpose of this study was to evaluate the role of a modified frailty index (mFI) in predicting mortality and complications after pelvis, acetabulum, and lower extremity trauma in patients of all ages. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2014 for all patients who underwent surgery for pelvis, acetabulum, and lower extremity trauma. The sample size was divided into geriatric (age ≥ 60) and young (age < 60) cohorts. The mFI score was calculated for each patient. Bivariate analysis was performed using logistic regression and a chi-square test to determine the relationship between mFI and both primary and secondary outcomes while adjusting for age. Univariate analysis and multivariate analyses were performed. All analyses were done using SAS 9.4 (Cary, NC) and a p < 0.05 was considered significant. RESULTS: 56,241 patients were identified to have undergone surgery for pelvis, acetabulum, or lower extremity trauma. 28% of patients were identified under the age of 60. In the young cohort, mFI was a strong predictor of thirty-day mortality (OR 11.02, 95% CI 6.26-19.39, p < 0.001). With regards to Clavien-Dindo grade IV complications, MFI is also a strong predictor in the young cohort (OR 28.82, 95% CI 16.05-51.77, p < 0.001). CONCLUSION AND RELEVANCE: The mFI score was a significant predictor of morbidity and mortality in chronologically young orthopaedic trauma patients. The use of the mFI score can provide an individualized risk assessment to interdisciplinary teams for perioperative counseling and to improve outcomes.

Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring.

Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation. Offspring were fed on control diet post-weaning and studied till 30 weeks. Lipid profile, serum glutamate pyruvate transaminase (SGPT), calcium and vitamin D levels were analyzed. Liver fat deposition, omega-3 fatty acids level and mRNA expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α), sterol regulatory element-binding protein 1c (SREBP-1c), interleukin 6 (IL-6), superoxide dismutase 1 (SOD-1) and uncoupling protein 2 (UCP2) were determined. Low serum vitamin D levels with an increase in SGPT and TG levels in CaD and VDD female offspring were observed. Severe liver steatosis with down-regulation of PPAR-α and UCP2 and up-regulation of SREBP-1c, IL-6 and SOD-1 was observed in the female offspring born to deficient dams. CaD and VDD male offspring showed mild steatosis and down-regulation of UCP2 and SOD-1. We conclude that maternal calcium and vitamin D deficiency programs abnormal lipid metabolism and hepatic gene expression in the F1 generation female offspring leading to hepatic steatosis, despite feeding them on control diet post-weaning.

Chronomodulated drug delivery system of urapidil for the treatment of hypertension.

INTRODUCTION: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. MATERIALS AND METHODS: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. RESULTS: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. CONCLUSIONS: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension.

Postoperative cognitive dysfunction, Alzheimer's disease, and anesthesia.

Although aging itself is not a disease, there are many comorbidities that become more common with aging. Heart disease, cancer, and other chronic illnesses are either more common or more severe in aging patients. Approximately 5.5 million people in the United States have Alzheimer's disease (AD), with the principal risk factor being age. It is estimated that the incidence of AD diagnosis doubles every 5 years after the age of 65. Therefore, as the population ages, the impact of AD on the healthcare landscape will increase. Understanding how to manage patients with AD is critical as we begin to care for more elderly patients in the perioperative period. In addition to their other health considerations, aging surgical patients are increasingly more likely to have pre-existing AD or be at risk for developing AD. There is growing interest to determine how anesthesia affects the development or progression of AD. Similarly, a best practice for the anesthetic management of patients with AD is not yet defined. Finally, the relationship between AD and susceptibility to or exacerbation of postoperative cognitive dysfunction (POCD) is not well understood. In this review, we will discuss both the clinical and the preclinical data related to anesthesia and AD, describe the overlapping pathophysiology of neurodegeneration and provide some insight into the anesthetic care of patients with AD.

The value of intermittent point-prevalence surveys of healthcare-associated infections for evaluating infection control interventions at Angkor Hospital for Children, Siem Reap, Cambodia.

BACKGROUND: There are limited data on the epidemiology of paediatric healthcare-associated infection (HCAI) and infection control in low-income countries. We describe the value of intermittent point-prevalence surveys for monitoring HCAI and evaluating infection control interventions in a Cambodian paediatric hospital. METHODS: Hospital-wide, point-prevalence surveys were performed monthly in 2011. Infection control interventions introduced during this period included a hand hygiene programme and a ventilator-associated pneumonia (VAP) care bundle. RESULTS: Overall HCAI prevalence was 13.8/100 patients at-risk, with a significant decline over time. The highest HCAI rates (50%) were observed in critical care; the majority of HCAIs were respiratory (61%). Klebsiella pneumoniae was most commonly isolated and antimicrobial resistance was widespread. Hand hygiene compliance doubled to 51.6%, and total VAP cases/1000 patient-ventilator days fell from 30 to 10. CONCLUSION: Rates of HCAI were substantial in our institution, and antimicrobial resistance a major concern. Point-prevalence surveys are effective for HCAI surveillance, and in monitoring trends in response to infection control interventions.

Power of an effective clinical conversation: improving accrual onto clinical trials.

The National Cancer Institute (NCI) is actively transforming clinical trials to revitalize the clinical trials system and improve patient accrual. For more than 30 years, NCI has provided information and communication resources about cancer clinical trials. The Institute supports a clinical trials Web site (www.cancer.gov/clinicaltrials) that receives nearly a half million page views a month. In addition, NCI's Cancer Information Service (800-4-CANCER, chat and e-mail) responds to 1,750 clinical trial inquiries every month. Although these numbers suggest that a high volume of clinical trial information is being exchanged between NCI, the public, and providers, most patients decide whether to participate in clinical trials during the patient-provider interaction.

Proline-rich cytokine from neurosecretory granules: a new natural substrate for dipeptidyl peptidase IV.

A proline-rich cytokine from neurosecretory granules of bovine neurohypophysis, 15 amino acids containing PRP-1 (Ala-Gly-Ala-Pro-Glu-Pro-Ala-Glu-Pro-Ala-Gln-Pro-Gly-Val-Tyr), had been demonstrated as a unique regulator of activity of neurons, strong antibacterial agent, and mediator of the hypothalamus-neurohypophysis-bone marrow-thymus axis, which participates in hematopoietic stem cells differentiation. In the present work it was shown that this neuropeptide represents a new natural substrate for Dipeptidyl Peptidase IV (DPPIV). The time-dependent increase of primary amines quantity in the assay mixture of PRP-1 and DPPIV has been observed allowing to conclude, that DPPIV catalyses the enzymatic reaction of PRP-1 cleavage. The amount of primary amines in the assay mixtures was evaluated using o-phtaldialdehyde dye. The gel-filtration and paper electrophoresis analyses proved this conclusion. The catalytic parameters of catalyzed by DPPIV enzymatic reaction of PRP-1 cleavage were determined as: V(max) = 1.27 ± 0.11 nmol/min and K(m) = 0.38 ± 0.1 mM.

Rapid detection and characterization of Chikungunya virus by RT-PCR in febrile patients from Kerala, India.

There has been a resurgence and prevalence of fever with symptoms of Chikungunya (CHIK) and increased death toll in Kerala, the southern-most state of India. The objective of this study was to develop a rapid detection method to determine the presence of CHIK- virus in the serum samples collected from febrile patients in Kerala, India. Serum specimens were analyzed for CHIK viral RNA by RT-PCR using primers specific for nsP1 and E1 genes. Five out of twenty clinical samples were positive for CHIK virus. The partial sequences of the E1 and nsP1 genes of the strain, IndKL01 were highly similar to the Reunion strains and the recently isolated Indian strains. A novel substitution, A148V, was detected in the E1 gene of the isolate, IndKL02. The detection procedure used in this study was simple, sensitive and rapid (less than 4 hr). This result suggests that CHIK viruses similar to the Reunion strains, which had resulted in high morbidity and mortality rates, may have caused the recent Chikungunya outbreak in India. The effect of the variant, E1-A148V, in the virulence and the rate of transmission of the virus deserves further investigation.

The role of an absolutely conserved tryptophan residue in octamer formation and stability in mitochondrial creatine kinases.

In most organisms, mitochondrial creatine kinase (MtCK) is present as dimers and octamers with the latter predominating under physiological conditions. An absolutely conserved tryptophan residue (Trp-264 in chicken sarcomeric MtCK) appears to play a key role in octamer stability. Recently, it has been shown that the sponge Tethya aurantia, a member of the most ancient group of living multi-cellular animals, expresses an obligate, dimeric MtCK that lacks this absolutely conserved tryptophan residue, instead possessing a tyrosine in this position. In the present study we confirm that the absolutely conserved tryptophan residue is lacking in other sponge MtCKs where it is instead substituted by histidine or asparagine. Site directed mutations of the Trp-264 in expression constructs of chicken sarcomeric MtCK and the octameric MtCK from the marine worm Chaetopterus destabilized the octameric quaternary structure producing only dimers. A Tyr-->Trp mutation in an expression construct of the Tethya MtCK construct failed to produce octamerization; Tyr-->His and Tyr-->Asn mutations also yielded dimers. These results, in conjunction with analysis of homology models of Chaetopterus and Tethya MtCKs, strongly support the view that while the absolutely conserved tryptophan residue is important in octamer stability, octamer formation involves a complex suite of interactions between a variety of residues.

Cloning, characterization, and expression of a new cry2Ab gene from Bacillus thuringiensis strain 14-1.

Bacillus thuringiensis is the major source for transfer of genes to impart insect resistance in transgenic plants. Cry2A proteins of B. thuringiensis are promising candidates for management of resistance development in insects owing to their difference from the currently used Cry1A proteins, in structure and insecticidal mechanism. The cry2Ab gene was found to lack a functional promoter and, hence, is cryptic in nature. The cry2Ab7 gene was cloned from a new indigenous B. thuringiensis strain, 14-1. Nucleotide sequencing of the cry2Ab gene cloned from B. thuringiensis strain 14-1 revealed an open reading frame of 1902 bp. The deduced amino acid sequence of Cry2Ab of B. thuringiensis strain 14-1 showed a variation in three amino acid residues in comparison to the holotype sequence, Cry2Ab1. Expression of the newly cloned cry2Ab gene was studied in an acrystalliferous strain of B. thuringiensis (4Q7) by fusing the cry2Ab gene downstream of cry2Aa promoter and orf1 + orf2 sequences. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of a spore-crystal mixture obtained from transformants of B. thuringiensis strain 4Q7 showed production of Cry2Ab protein of about 65 kDa. Alkali solubilized Cry2Ab7 protein showed toxicity against Helicoverpa armigera neonates.

ADA2 isoform of adenosine deaminase from pleural fluid.

Adenosine deaminase isoenzyme 2 (ADA2) was isolated from human pleural fluid for the first time. Molecular and kinetic properties were characterized. It was shown that the inhibitors of adenosine deaminase isoenzyme 1 (ADA1), adenosine, and erithro-9-(2-hydroxy-3-nonyl)adenine (EHNA) derivatives are poor inhibitors of ADA2. Comparison of the interaction of ADA2 and ADA1 with adenosine and its derivative, 1-deazaadenosine, indicates that the isoenzymes have similar active centers. The absence of ADA2 inhibition by EHNA is evidence of a difference of these active centers in a close environment. The possible role of Zn2+ ions and the participation of acidic amino acids Glu and Asp in adenosine deamination catalyzed by ADA2 were shown.

Triplets with systemic lupus erythematosus.

We present herein the first case report of identical triplets who developed systemic lupus erythematosus (SLE). The children were diagnosed as having SLE in reverse birth order at ages 8, 9, and 11 years. Although genetically identical, each sibling manifested different clinical signs and symptoms; however, all 3 children did manifest skin rash, fatigue, and biopsy-proven glomerulonephritis at different ages. Findings of laboratory studies were similar, including positivity for antinuclear antibodies, anti-native DNA, and anti-double-stranded DNA, as well as low levels of complement. These findings confirmed SLE in each sibling.

Activity of adenosine deaminase and its isoforms in pleural fluid in tuberculous pleuritis.

BACKGROUND: The problem of tuberculosis is increasing in a number of countries. Adenosine deaminase activity is considered in many clinics to be a valuable biochemical test of this pathology. Considerable research has been devoted to the activity of enzyme isoforms as significant tests for diagnosing tuberculosis. The aim of our study was to compare the significance of different adenosine deaminase dependent parameters in diagnosing tuberculosis. MATERIAL/METHODS: The level of adenosine deaminase and the activity of its two isoenzymes in the pleural fluids of patients with tuberculous and non-tuberculous pleurisy were compared. RESULTS: The adenosine deaminase level in tuberculous pleural effusions was higher than in non-tuberculous pleural effusions. The data we obtained suggest that the enzyme activity level could be a very reliable test in the differential diagnosis of tuberculous pleurisy in the Armenian population. The activity of isoenzymes ADA1 and ADA2, or their ratios to the total ADA activity, though valuable information, has no diagnostic advantage over total ADA activity in diagnosing this pathology. CONCLUSIONS: The results clearly point up the value of using a total ADA activity assay in Armenian clinics for the differential diagnosis of tuberculous pleurisy. Determinations of the activity level of the ADA1 and ADA2 isoenzymes provide no diagnostic advantage over total ADA activity.