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Currently, there is no systematic approach available for the validation, quantitative assessment, and troubleshooting for the in-situ fiber optic/bathless dissolution system (FODS). In this report, a dissolution protocol was developed and validated for a model product, chlorpheniramine maleate (CPM) 4 mg IR tablets. Dissolution runs were conducted at 37 ± 0.2 °C using a USP apparatus II, at 50 rpm in 500 mL of 0.01 N hydrochloric acid. The dissolution system was validated for linearity, accuracy, precision, specificity, and robustness analogously to an HPLC method validation. The linearity determination method was developed using five concentration levels between 25-125 % of the expected concentration, while for accuracy, 80 %, 100 %, and 120 % levels were used, and precision was determined using six runs at the 100 % level. Probe sampling depth, orientation, analytical wavelength, and paddle speed were varied to evaluate the robustness of the system tested. Method equivalence was established by comparing the dissolution results from FODS and the traditional dissolution method using UV spectrophotometry. Based on the statistics generated using the dissolution tests, the results are linear, accurate, precise, and specific. Robustness testing demonstrates that small changes in operating conditions did not significantly change the result. No significant difference in the amount dissolved at Q-timepoint was observed between FODS and traditional testing. Therefore, the FODS is a suitable alternative to traditional dissolution for CPM immediate-release tablets (many other drug products have been tested in the laboratory, and reports are in preparation). Additionally, the current work discusses problems related to media preparation, probe sensitivity, and excipient effects on data collected using FODS. The instrument-specific artifacts and data analysis problems are addressed and troubleshooting with possible solutions to eliminate or mitigate the errors. Although the FODS method was developed and evaluated using CPM in 500 mL dissolution volume, the dissolution method using a more common pharmacopoeial dissolution volume, i.e., 900 mL, was used to demonstrate the troubleshooting experiments for the drug products requiring 900 mL dissolution media., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Ideal pulpectomy for primary dentition demands fast, simple procedures, with short treatment times and minimal appointments. Recently, exclusive pediatric rotary files are available for use in primary teeth. There is a paucity of literature on the clinical efficacy of pediatric rotary files. Hence, this study was planned to evaluate and compare pediatric rotary files and K-files., Aim: The aim of this study was to evaluate and compare instrumentation time, obturation time, and radiographic quality of obturation using rotary systems (Kedo-S; Pro-AF Baby GOLD files) and manual (K-files) technique in primary molar pulpectomies., Materials and Methods: Forty-five primary mandibular molars from 42 children aged 5-9 were selected. Single-visit pulpectomy was performed after dividing selected teeth into three equal groups: (i) K-files, (ii) Kedo-S files, (iii) Pro-AF Baby GOLD files. Instrumentation and obturation times were recorded during the procedure. Immediate postoperative radiographs were taken and evaluated later for obturation quality by two independent evaluators blinded to the instrumentation technique. The results were then statistically analyzed., Results: Kedo-S (Group II) files required the least instrumentation time followed by Pro-AF (Group III) and K-files (Group I). The superior quality of obturation in lesser time was achieved using Pro-AF files (Group III) followed by Kedo-S (Group II) and K-files (Group I)., Conclusion: Pediatric rotary files are efficient alternatives to hand instrumentation and can be considered as the standard of care in pulpectomies of primary teeth., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Contemporary Clinical Dentistry.)

Biorelevant media are increasingly being employed as dissolution media in drug development, including in smaller volumes than 900ml and under non-sink conditions. The objectives were to assess interday repeatability, interanalyst repeatability, and interlaboratory reproducibility of dissolution profiles from biorelevant media, as well as to assess the impacts of biorelevant media production method and biorelevant medium volume on dissolution profiles. Ibuprofen and ketoconazole tablets were subjected to dissolution testing in 500ml, 300ml, and 40ml of fasted state simulated gastric fluid (FaSSGF), fed state simulated gastric fluid (FeSSGF), fasted state simulated intestinal fluid version 2 (FaSSIF-V2), and fed state simulated intestinal fluid version 2 (FeSSIF-V2). f 2 was used to assess repeatability and reproducibility of dissolution profiles. Results indicate favorable interday repeatability (83 of 88 comparisons were similar), favorable interanalyst repeatability (19 of 21 comparisons were similar), and favorable interlaboratory reproducibility (10 of 14 comparisons were similar) of dissolution profiles from biorelevant media, with commercial media showing greater interlaboratory reproducibility than 'from scratch' media. However, biorelevant medium production had low impact on profiles when one analyst conducted all medium preparations and study procedures at one location. Additionally, biorelevant media detected differences when products were not similar. Overall, biorelevant media showed favorable repeatability and reproducibility performance., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Dissolution testing and solubility determinations in different biorelevant media have gained considerable interest in the pharmaceutical industry from early-stage development of new products to forecasting bioequivalence. Among all biorelevant fluids, the preparation of fed-state simulated gastric fluid (FeSSGF) and handling of samples from dissolution/solubility testing in FeSSGF is considered to be relatively challenging. Challenges include maintaining the stability of FeSSGF medium upon sampling, filtration, and mitigating analytical interference of excipients and milk components. To overcome these challenges, standard and uniform working practices are required that are not only helpful in preparation of stable FeSSGF but also serve as a harmonizing guide for the collection of dissolution/solubility samples and their subsequent processing (i.e., handling and assay). The optimization of sample preparation methodology is crucial to reduce method-related variance by ensuring specificity, robustness, and reproducibility with acceptable recovery of the analytes. The sample preparation methodology includes a combination of techniques including filtration, solvent treatment, and centrifugation to remove the interfering media-related components and excipients from the analyte. The analytes of interest were chromatographically separated from the interfering analytes to quantify the drug concentration using the new high-performance liquid chromatography methods with ultraviolet detection. The methods developed allow rapid sample preparation, acceptable specificity, reproducible recoveries (greater than 95% of label claim), and quantification of study drugs (ibuprofen and ketoconazole). The sample preparation technique and method considerations provided here for ibuprofen and ketoconazole can serve as a starting point for solubility and dissolution testing of other small molecules in FeSSGF.

Latinxs in the United States are disproportionately affected by HIV and present with more advanced disease than their non-Latinx peers, due to numerous barriers to care including HIV stigma. We describe the adaptation, implementation, and reach of Sólo Se Vive Una Vez (You Only Live Once), Baltimore's first social marketing campaign promoting HIV screening among Spanish-speaking Latinxs. The 6-month campaign promoted free HIV testing by addressing HIV stigma. The campaign included a website, a social marketing campaign, community outreach events, and advertisements via radio, billboards, local partners, and buses. During the campaign, there were 9,784 unique website users, and ads were served to over 84,592 people on social media platforms. Among Latinx HIV testers at the Baltimore City Health Department, 31.6% reported having seen or heard of Sólo Se Vive Una Vez and 25.3% of Latinx HIV testers reported that the campaign influenced them to get tested.

In the literature, it is reported that eutectics lead to the enhanced dissolution of a poorly soluble compound. However, the solubility theory suggests that since crystal structures of two components are unchanged that all else being equal, the dissolution rates of a fused mixture (FM) should be the same as a physical mixture (PM). The influence of crystal lattice energy on dissolution profiles was investigated using the PM and FM. Experimental phase diagrams constructed using differential scanning calorimetry data were compared with those theoretically derived. Deviation of the experimental phase diagram curves from the theoretical model indicates the nonideal behavior of both systems (ibuprofen/poly(ethylene glycol)-6000 and acetaminophen/caffeine). Both the binary systems showed an increase in the dissolution rate of the PM and FM. However, the dissolution from the PM was comparable with the FM's dissolution profile. The theoretical solubility calculations using the modified solubility equation showed that the use of the eutectic temperature instead of the drug's melting point should give a 3-4-fold increase in drug solubility. However, the correlation between dissolution and solubility calculation showed that the FM did not improve the dissolution when compared with the respective PM's dissolution profile. The proposed explanation is that the unchanged crystal lattice energy in eutectics still limits the solubility and therefore the dissolution rate., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34-0.72), whereas no benefit was observed for other genotypes ( P interaction = 3.7 × 10 -4 ). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD ( N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11-a proinflammatory and atherogenic chemokine also known as eotaxin ( P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia., (© 2020 by the American Diabetes Association.)

Phenytoin sodium, a salt of 5,5-diphenylimidazolidine-2,4-dione, or phenytoin, is commercially available in various dosage forms for its anti-epileptic properties to treat and prevent seizures. The title compound, poly[aquatris(μ 3 -4,4-diphenyl-2,5-dioxoimidazolidin-1-ido)trimethanoltrisodium(I)], [Na 3 (C 15 H 11 N 2 O 2 ) 3 (CH 4 O) 3 (H 2 O) 1.08 ] n , a methanol solvate and hydrate of phenytoin sodium, forms a modulated crystal structure that consists of a supercell made up of three close-to-identical repeat units. Each of the basic fragments consists of one phenytoin anion, a sodium cation, and either a methanol, or a methanol and a water molecule coordinated to the sodium ion, yielding a formula unit of Na(C 15 H 11 N 2 O 2 )(CH 3 OH) x (H 2 O) y for each of the three segments (x, y = 0 or 1; x + y = 1 or 2). Modulation along the b axis is introduced due to the presence or absence of water or methanol molecules at sodium and by the alternating torsion angles of one of the two phenytoin phenyl rings. Individual segments within the asymmetric unit are linked by covalent Na-O and Na-N bonds, with each sodium ion coordinated to one anionic amide N atom and three keto O atoms. The Na-N and one of the Na-O bonds connect (C 15 H 11 N 2 O 2 )·Na units along the modulation direction, creating an infinite [(C 15 H 11 N 2 O 2 )·Na] n chain that is further stabilized by intramolecular N-H...O hydrogen bonding parallel to [010]. The second Na-O bond connects this chain with a symmetry-equivalent copy of itself created by a screw-axis operation, yielding double strands of [(C 15 H 11 N 2 O 2 )·Na] n chains. Two of these double strands, propagating in opposite directions, constitute the content of the unit cell. Neighboring double strands are connected with each other to form layers perpendicular to the a axis, tethered together via O-H...O hydrogen bonds involving the water and methanol molecules. In addition to modulation, each of the repeat units also exhibits disorder of the modulated segments. Phenyl rings of each repeat unit are rotationally disordered, and sodium-coordinated methanol and water molecules are also positionally disordered and/or partially occupied. The solvated structure reported here, while not matching the patterns reported for any of the known forms of phenytoin sodium, does provide a first insight into the complications and complexities involved in resolving the structure of anhydrous phenytoin sodium.

BACKGROUNDIn the Joslin Medalist Study (Medalists), we determined whether significant associations exist between β cell function and pathology and clinical characteristics.METHODSIndividuals with type 1 diabetes (T1D) for 50 or more years underwent evaluation including HLA analysis, basal and longitudinal autoantibody (AAb) status, and β cell function by a mixed-meal tolerance test (MMTT) and a hyperglycemia/arginine clamp procedure. Postmortem analysis of pancreases from 68 Medalists was performed. Monogenic diabetes genes were screened for the entire cohort.RESULTSOf the 1019 Medalists, 32.4% retained detectable C-peptide levels (>0.05 ng/mL, median: 0.21 ng/mL). In those who underwent a MMTT (n = 516), 5.8% responded with a doubling of baseline C-peptide levels. Longitudinally (n = 181, median: 4 years), C-peptide levels increased in 12.2% (n = 22) and decreased in 37% (n = 67) of the Medalists. Among those with repeated MMTTs, 5.4% (3 of 56) and 16.1% (9 of 56) had waxing and waning responses, respectively. Thirty Medalists with baseline C-peptide levels of 0.1 ng/mL or higher underwent the clamp procedure, with HLA-/AAb- and HLA+/AAb- Medalists being most responsive. Postmortem examination of pancreases from 68 Medalists showed that all had scattered insulin-positive cells; 59 additionally had few insulin-positive cells within a few islets; and 14 additionally had lobes with multiple islets with numerous insulin-positive cells. Genetic analysis revealed that 280 Medalists (27.5%) had monogenic diabetes variants; in 80 (7.9%) of these Medalists, the variants were classified as "likely pathogenic" (rare exome variant ensemble learner [REVEL] >0.75).CONCLUSIONAll Medalists retained insulin-positive β cells, with many responding to metabolic stimuli even after 50 years of T1D. The Medalists were heterogeneous with respect to β cell function, and many with HLA+ diabetes risk alleles also had monogenic diabetes variants, indicating the importance of genetic testing for clinically diagnosed T1D.FUNDINGFunding for this work was provided by the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund; the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and the American Diabetes Association (ADA).

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, characterized by motor neuron death in the brain and spinal cord. Mutations in the Cu/Zn superoxide dismutase (SOD1) gene account for ~20% of all familial ALS forms, corresponding to 1%-2% of all ALS cases. One of the suggested mechanisms by which mutant SOD1 (mtSOD1) exerts its toxic effects involves intracellular accumulation of abnormal mtSOD1 aggregates, which trigger endoplasmic reticulum (ER) stress and activate its adaptive signal transduction pathways, including the unfolded protein response (UPR). PERK, an eIF2α kinase, is central to the UPR and is the most rapidly activated pathway in response to ER stress. Previous reports using mtSOD1 transgenic mice indicated that genetic or pharmacological enhancement of the UPR-PERK pathway may be effective in treating ALS. We investigated the response to PERK haploinsufficiency, and the response to deficiency of its downstream effectors GADD34 and CHOP, in five distinct lines of mtSOD1 mice. We demonstrate that, in contrast to a previously published study, PERK haploinsufficiency has no effect on disease in all mtSOD1 lines examined. We also show that deficiency of GADD34, which enhances the UPR by prolonging the phosphorylation of eIF2α, does not ameliorate disease in these mtSOD1 mouse lines. Finally, we demonstrate that genetic ablation of CHOP transcription factor, which is known to be pro-apoptotic, does not ameliorate disease in mtSOD1 mice. Cumulatively, our studies reveal that neither genetic inhibition of the UPR via ablation of PERK, nor genetic UPR enhancement via ablation of GADD34, is beneficial for mtSOD1-induced motor neuron disease. Therefore, the PERK pathway is not a likely target for therapeutic intervention in mtSOD1-induced ALS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthcare system to alleviate them absolutely in future.

Levothyroxine sodium pentahydrate (LEVO) tablets have been on the US market since the mid-twentieth century and remain the most highly prescribed product. Unfortunately, levothyroxine sodium tablets have also been one of the most highly recalled products due to potency and dissolution failures on stability. In 2008, the assay limits were tightened, yet the recalls did not decline, which highlights the serious quality concerns remaining to be elucidated. The aim of the present investigation was to test the hypothesis that the solid-state physical instability of LEVO precedes the chemical instability leading to product failure. The failure mode was hypothesized to be the dehydration of the crystal hydrate, when exposed to certain humidity and temperature conditions, followed by the oxidation of the API through vacated channels. It was previously reported by the authors that LEVO degradation occurred in the presence of oxygen at a low relative humidity (RH). Furthermore, powder X-ray diffractometry shows changes in the crystal lattice of LEVO initially and through the dehydration stages. Storage of LEVO at RT and 40 °C at 4-6% RH for 12 days shows a decrease in d-spacing of the (00 l) planes. Based on a structure solution from the powder data of the dehydrated material, the basic packing motif persists to varying degrees even when fully dehydrated along with disordering. Therefore, the crystal structure changes of LEVO depend on RH and temperature and are now explicable at the structural level for the first time. This exemplifies the dire need for "new prior knowledge" in generic product development.

Anisotropic features with other crystallographic properties like d-spacing, and attachment energy (E att ) can predict material performance during the secondary pharmaceutical processing. A newly developed state-of-the-art compression cell lodged in a powder X-ray diffractometer was used to measure anisotropic Young's moduli (YM) of flufenamic acid (FFA) polymorphs in this study. Methodology is based on the generation of a single crystal deformation in this cell, which reflects as a change in the d-spacing in the PXRD pattern. Anisotropic YM was calculated from such information gathered along different FFA planes. Measured FFA crystallographic molecular features were concatenated to understand macroscopic compaction (Heckel and Shapirao's parameters) and tableting performance. Block shaped crystals of FFA form I, and III after initial characterization with SEM, DSC, PXRD, and FTIR were compressed normal to X, Y, and Z-planes, identified from calculated PXRD pattern using the reported single crystal structure. YM of X and Y planes of form I was significantly higher than corresponding planes of form III. Z plane of form III showed significantly higher YM than that for form I. Low YM of form III can be attributed to its large d-spacing regardless of their high E att than form I, as well as orientation of supramolecular acid dimer (OH⋯O) homosynthon chains in the FFA planes. FFA form I stiffness was further confirmed with lower densification and higher yield pressure of deformation than form III. Clearly, form III exhibited better compressibility, compactibility, and tableting performance than form I due to favorable molecular and macroscopic features. Thus, developed anisotropic measurement approach can be used to distinguish material performance in the early development stage of the pharmaceutical processes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: We evaluated whether the increasing number of genetic loci for coronary artery disease (CAD) identified in the general population could be used to predict the risk of major CAD events (MCE) among participants with type 2 diabetes at high cardiovascular risk., Research Design and Methods: A weighted genetic risk score (GRS) derived from 204 variants representative of all the 160 CAD loci identified in the general population as of December 2017 was calculated in 5,360 and 1,931 white participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Outcome Reduction With Initial Glargine Intervention (ORIGIN) studies, respectively. The association between GRS and MCE (combining fatal CAD events, nonfatal myocardial infarction, and unstable angina) was assessed by Cox proportional hazards regression., Results: The GRS was associated with MCE risk in both ACCORD and ORIGIN (hazard ratio [HR] per SD 1.27, 95% CI 1.18-1.37, P = 4 × 10 -10 , and HR per SD 1.35, 95% CI 1.16-1.58, P = 2 × 10 -4 , respectively). This association was independent from interventions tested in the trials and persisted, though attenuated, after adjustment for classic cardiovascular risk predictors. Adding the GRS to clinical predictors improved incident MCE risk classification (relative integrated discrimination improvement +8%, P = 7 × 10 -4 ). The performance of this GRS was superior to that of GRS based on the smaller number of CAD loci available in previous years., Conclusions: When combined into a GRS, CAD loci identified in the general population are associated with CAD also in type 2 diabetes. This GRS provides a significant improvement in the ability to correctly predict future MCE, which may increase further with the discovery of new CAD loci., (© 2018 by the American Diabetes Association.)

Cholinesterases (ChEs) play a vital role in regulating cholinergic transmission. Inhibition of ChEs is thought to be an emerging and useful therapeutic target for neurodegenerative disorders through restoration of acetylcholine (ACh) levels in the brain (e.g. Alzheimer's disease). To increase the chemical diversity of cholinesterase inhibitors, a series of quinoline chalcones derivatives were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) isoenzymes. All tested compounds (4a-1; 5a-s) exhibited inhibitory activities against AChE and BChE to a considerable extent. Molecular docking studies were performed by using homology models on both AChE and BChE isoenzymes with the aim of exploring probable binding modes of the most potent inhibitor. In order to evaluate drug likeness of newly tested molecules, we carried out in-silico ADME evaluation. All compounds displayed favourable ADME findings which predict good oral bioavailability of these derivatives. Due to an excellent ADME profile the tested compounds were predicted to be safer which can be considered as novel cholinesterase inhibitors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ecto-5'-nucleotidase (e5'NT), a membrane-bound enzyme and an essential member of ecto-nucleotidases which regulates extracellular purinergic signalling. Their upregulation results in various disease conditions, for example, inflammation, hypoxia and cancer. Therefore, efforts have been made to synthesize potent and selective inhibitors of e5'NT. Here we have synthesized, characterized and evaluated six thiazole derivatives (3a-3f) as potent e5'NT inhibitors. Among all derivatives, the compound ( E )-1-(4-methyl-2-(2-(pyridin-3-ylmethylene)hydrazinyl) thiazol-5-yl)ethanone (3a) exhibited maximum inhibition towards both human and rat enzymes. However, their potency against h -e5'NT was 24-fold higher than r -e5'NT. Only two compounds exhibited inhibitory behaviour towards r -e5'NT. The molecular structures of these derivatives were confirmed with the help of solid-state characterization through NMR ( 1 H and 13 C), FTIR and elemental analysis. Additionally, molecular docking was also implemented to explain putative bonding interaction between the active site of an enzyme and potent inhibitors., Competing Interests: We have no competing interests.

Highly progressive neurodegenerative disorder generally known as Alzheimer's disease (AD), is a type of dementia, which is very common in elderly. The most common symptoms may include loss of memory along with disturbed behavioral and cognitive functions. Until now, only 4 cholinesterase (ChE) inhibitors are approved by FDA for symptomatic treatment of AD. Aroyl thiourea derivatives are well known bioactive organic molecules containing carbonyl and thiocarbonyl functional groups. Here, total 14 different thiourea derivatives (3a-3n) were synthesized and characterized by NMR, FTIR and X-ray crystallographic techniques. The synthesized compounds displayed varying inhibition activities on both acetylcholineterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among all compounds, 3b and 3e were potent inhibitors of AChE (IC 50  ± SEM = 8.92 ± 1.03 μM) and BuChE (IC 50  ± SEM = 6.96 ± 0.961 μM) respectively. Enzyme kinetic studies showed that 3b exhibited uncompetitive binding with AChE while 3e demonstrated a mixed inhibition of BuChE. Molecular docking studies on AChE showed that 3b got binding interaction with Trp86 and Tyr337 while 3e showed binding affinity with Trp82 and His438 when docked with BuChE. The obtained results indicated that these thiourea derivatives could be considered as potential candidates to treat AD., (Copyright © 2018. Published by Elsevier B.V.)

Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA 1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively ( P < 5 × 10 -6 ), and meta-analysis in independent cohorts displayed similar associations with metformin response ( P = 1.2 × 10 -8 and P = 0.005, respectively). Previous studies have shown that PRPF31 (+/-) knockout mice have increased total body fat ( P = 1.78 × 10 -6 ) and increased fasted circulating glucose ( P = 5.73 × 10 -6 ). Furthermore, rare variants in STAT3 associated with worse metformin response ( q <0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D., (© 2018 by the American Diabetes Association.)

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Patient activation (the knowledge, confidence, willingness, and skills to manage one's healthcare) and health literacy have well-established associations with health and healthcare outcomes in adults. However, little is known about parent activation on behalf of children and its relation to health literacy. Our objective was to examine relations between parent activation, health literacy, and parent-provider relationship quality. We surveyed 316 Spanish- or English-speaking parents of publicly-insured patients of a general pediatrics clinic. Surveys included the Parent-Patient Activation Measure (P-PAM), the Newest Vital Sign (NVS), and parent-provider relationship measures. We used chi-square analyses and logistic regression to explore associations stratified by survey language. Spanish-speaking parents had significantly lower levels of both parent activation and health literacy compared with English-speaking parents (p<.001). Parent activation was not associated with health literacy, suggesting that they are distinct concepts. Because parent activation is a more easily modifiable trait than health literacy, it may present an opportunity to improve outcomes in less health literate populations. We did not find expected associations between parent activation, health literacy and parent-provider relationship quality. Further study is needed to understand how parent activation relates to pediatric outcomes, and if it is an appropriate intervention target to address child healthcare disparities in populations with limited health literacy.

Objective: A genome-wide association study in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922 and rs9299870) that were significantly associated with cardiovascular mortality during intensive glycemic control and could potentially be used, when combined into a genetic risk score (GRS), to identify patients with diabetes likely to derive benefit from intensive control rather than harm. The aim of this study was to gain insights into the pathways involved in the modulatory effect of these variants., Research Design and Methods: Fasting levels of 65 biomarkers were measured at baseline and at 12 months of follow-up in the ACCORD-Memory in Diabetes (ACCORD-MIND) MRI substudy ( n = 562). Using linear regression models, we tested the association of the GRS with baseline and 12-month biomarker levels, and with their difference (Δ), among white subjects, with genotype data ( n = 351) stratified by intervention arm., Results: A significant association was observed between GRS and ΔGLP-1 (glucagon-like peptide 1, active) in the intensive arm ( P = 3 × 10 -4 ). This effect was driven by rs57922 ( P = 5 × 10 -4 ). C/C homozygotes, who had been found to derive cardiovascular benefits from intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By contrast, T/T homozygotes, who had been found to experience increased cardiac mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No association between ΔGLP-1 and GRS or rs57922 was observed in the standard treatment arm., Conclusions: Differences in GLP-1 axis activation may mediate the modulatory effect of variant rs57922 on the cardiovascular response to intensive glycemic control. These findings highlight the importance of GLP-1 as a cardioprotective factor., (© 2017 by the American Diabetes Association.)

Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To identify genetic determinants of increased cardiovascular mortality among subjects with type 2 diabetes who underwent intensive glycemic therapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial., Research Design and Methods: A total of 6.8 million common variants were analyzed for genome-wide association with cardiovascular mortality among 2,667 self-reported white subjects in the ACCORD intensive treatment arm. Significant loci were examined in the entire ACCORD white genetic dataset (n = 5,360) for their modulation of cardiovascular responses to glycemic treatment assignment and in a Joslin Clinic cohort (n = 422) for their interaction with long-term glycemic control on cardiovascular mortality., Results: Two loci, at 10q26 and 5q13, attained genome-wide significance as determinants of cardiovascular mortality in the ACCORD intensive arm (P = 9.8 × 10 -9 and P = 2 × 10 -8 , respectively). A genetic risk score (GRS) defined by the two variants was a significant modulator of cardiovascular mortality response to treatment assignment in the entire ACCORD white genetic dataset. Participants with GRS = 0 experienced a fourfold reduction in cardiovascular mortality in response to intensive treatment (hazard ratio [HR] 0.24 [95% CI 0.07-0.86]), those with GRS = 1 experienced no difference (HR 0.92 [95% CI 0.54-1.56]), and those with GRS ≥2 experienced a threefold increase (HR 3.08 [95% CI 1.82-5.21]). The modulatory effect of the GRS on the association between glycemic control and cardiovascular mortality was confirmed in the Joslin cohort (P = 0.029)., Conclusions: Two genetic variants predict the cardiovascular effects of intensive glycemic control in ACCORD. Further studies are warranted to determine whether these findings can be translated into new strategies to prevent cardiovascular complications of diabetes., (© 2016 by the American Diabetes Association.)

Background: Transoral endoscopic ENT surgical procedures are a mainstay of treatment for a variety of conditions and are often preferable to open surgery where possible. Cases of micrognathia, prominent incisor teeth or trismus may create difficulties in gaining sufficient access to undertake such procedures. Extraction of the anterior maxillary teeth can help overcome these problems in appropriate cases, with subsequent prosthetic tooth replacement supported by dental implants. To date, this approach has not been reported in the literature., Case Reports: This paper reports on two cases which illustrate this approach; the first case involved pharyngeal pouch management where previous open surgery had failed, and the second case involved glottic carcinoma management where oral access was compromising resection., Conclusion: This technique is recommended to facilitate effective transoral surgical procedures as a low-morbidity alternative to either open surgery or non-surgical therapies.

Diabetes mellitus is a chronic metabolic disorder continuously affecting people all over the world. A common way to treat diabetes mellitus is to limit the conversion of carbohydrates into glucose which is mediated by glucosidase enzymes. Diabetes mellitus is also famous for its life-threatening microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (atherosclerosis) complications. Aldose reductases present in eye lens (ALR1) and kidney (ALR2) are responsible for microvascular complications. The production of advanced glycation end products (AGEs) is involved in the development of atherosclerosis. The present work was aimed at the synthesis and in vitro/in vivo evaluation of different polyoxotungstates against glucosidases (α- and β), aldose reductases (ALR1 and ALR2) and AGEs to discover a new treatment which may limit the complications associated with diabetes mellitus. The polyanion [P6W18O79](20-) was found to be the most potent inhibitor of α-glucosidase (IC50 = 1.33 ± 0.41 μM), ALR1 (IC50 = 0.4 ± 0.009 μM) and ALR2 (IC50 = 0.38 ± 0.02 μM). Animal studies showed that the polyanion [H2W12O40](6-) was very effective in reducing the blood glucose level to 84.25 ± 5.07 mg dL(-1) when compared with standard antidiabetic drug glibenclamide (150.62 ± 9.35 mg dL(-1)) measured after maximum 8 h of dose administration. The data obtained from in vitro and in vivo experiments confirm that [P6W18O79](20-) and [H2W12O40](6-) could be used as a new treatment of diabetes mellitus.

Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeW 6 O 24 ] 6- (TeW 6 ) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeW 6 O 24 ] 6- (CTS-TeW 6 ) was proved to be a potent inhibitor of CIAP with K i value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaP 5 W 30 O 110 ] 14- (CTS-P 5 W 30 ) has showed higher percent cytotoxicity (88 ± 10%) at 10 μM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.

Conversion of nitriles under mild conditions leads to a new class of primary amines, including room temperature ionic liquids, acting as efficient anticancer agents.

Objective: To determine the outcome of patients in terms of wound complications and follow-up, after laparoscopic ventral hernia repair., Study Design: A case series study., Place and Duration of Study: Department of Surgery, Dubai Hospital, Dubai, from January 2007 to December 2011., Methodology: All patients above 13 years of age, who underwent laparoscopic ventral hernia repair, were included. A proceed dual mesh was used for repair of hernia. Multiple parameters were analyzed, including demographic features, presentations, co-morbid conditions, duration of hernia, and defect size. The duration of surgery, postoperative complications, and follow-up of these patients in terms of suture site pain and recurrence of hernia were also analyzed. The data was expressed as frequency, percentages and mean ± standard deviation of values., Results: There were 27 patients with mean age of 47 ± 10.3 years, including 20 female (74.07%) and 7 male (25.95%)patients. All patients presented with abdominal wall swelling. The hernia was partially reducible in 12 patients (44.44%), and completely reducible in 15 patients (55.55%). Seven patients (25.95%) had hypertension, 4 (14.81%) had ischaemic heart disease, and 4 (14.81%) had obesity as co-morbid conditions. All patients underwent laparoscopic hernia repair with proceed dual mesh. The mean defect size of the hernia was 6 cm, and mean duration of surgery was 94 minutes. Early postoperative complications included, seroma in 3 patients (11.11%), and haematoma in one patient (3.70%). The mean follow-up was 23 months. Four patients (14.81) had pain at suture site., Conclusion: Laparoscopic repair is an appropriate approach for ventral hernia repair. It results in good repair and low wound complications in terms of haematoma and wound infection. There was no recurrence of hernia in this study.

Background: Most outbreaks of viral hepatitis in India are caused by hepatitis E. Recently in the year 2009, Modasa town of Sabarkantha district in Gujarat witnessed the outbreak of hepatitis B., Purpose: An attempt was made to study the outbreak clinically and serologically, to estimate the seropositivity of hepatitis B Virus among the cases and their contacts and to know the seroprevalence of hepatitis B envelope antigen (HBeAg) and IgM antibody against hepatitis B core antigen (IgM HBcAb) out of all the Hepatitis B surface Antigen (HBsAg) positive ones., Materials and Methods: Eight hundred and fifty-six (856) cases and 1145 contacts were evaluated for hepatitis B markers namely HBsAg, HBeAg and IgM HBcAb by enzyme-linked immuno Sorbent Assay (ELISA) test., Results: This outbreak of viral hepatitis B in Modasa, Gujarat was most likely due to unsafe injection practices. Evidence in support of this was collected by Government authorities. Most of the patients and approximately 40% of the surveyed population gave history of injections in last 1.5-6 months. Total 664/856 (77.57%) cases and 20/1145 (1.75%) contacts were found to be positive for HBsAg. 53.41% of the positive cases and 52.93% of the positive contacts were HBeAg-positive and thus in a highly infectious stage., Conclusions: Inadequately sterilized needles and syringes are an important cause of transmission of hepatitis B in India. Our data reflects the high positivity rate of a hepatitis B outbreak due to such unethical practices. There is a need to strengthen the routine surveillance system, and to organise a health education campaign targeting all health care workers including private practitioners, especially those working in rural areas, as well as the public at large, to take all possible measures to prevent this often fatal infection.

Purpose: The purpose of this study was to evaluate the effect of submucosal dexamethasone injection to control postoperative pain and swelling in apicectomy of maxillary anterior teeth., Methods: A randomized, controlled trial comprising 60 adult patients (68.3% male, 31.7% female) with no local or systemic problems was conducted. Patients were randomly divided into two groups: Group A was given 4mg dexamethasone injection perioperatively. Group B (control group) was treated conventionally without any steroid injection. Postoperative pain and swelling was evaluated using a visual analog scale (VAS). Objective measurements of facial pain and swelling were performed daily up to six days postoperatively., Results: Dexamethasone group showed significant reduction in pain and swelling postoperatively compared with the control., Conclusion: Submucosal dexamethasone 4mg injection is an effective therapeutic strategy for swift and comfortable improvement after surgical procedure and has a significant effect on reducing postoperative pain and swelling. The treatment offers a simple, safe, painless, noninvasive and cost effective therapeutic option for moderate and severe cases.

Objective: To develop a simple, objective and reproducible quantitative measurement to assess success of posterior urethral valve ablation., Method: In 30 patients with posterior urethral valves the diagnosis was confirmed by voiding cystourethrogram (VCUG). Our protocol was to perform valve ablation, and repeat VCUG at 12 weeks postoperatively. Urethral ratio was calculated by dividing the posterior urethral diameter by the anterior urethral diameter. Thirty males undergoing VCUG for urinary tract infections were evaluated as normative controls., Results: Median age of controls was 12 months (2 days-6 years) and of study group was 13 months (1 day-11 years). Mean urethral ratio in pre-fulguration group was 4.94 (+/-2.97) and in post-fulguration group was 2.134 (+/-1.19) (P<0.001). The mean urethral ratio in the control group of 1.73 (+/-0.577) was significantly different from the pre-fulguration group result (P<0.001), but not significantly different in comparison to the post-fulguration group (P=0.104)., Conclusion: Calculation of urethral ratio on VCUG as a method of assessment of outcome of fulguration is objective, reproducible, and allows preoperative and postoperative VCUG from different facilities to be compared. A post-fulguration urethral ratio of 2.5-3 represents an acceptable result postoperatively.

Background: This study reports our 28 months experience with minimal access surgery (MAS) in children., Materials and Methods: This was a review of all children who underwent MAS between December 2004 and March 2007 at the Departments of Paediatric Surgery, Seth Gordhandas Sunderdas Medical College (GSMC) and King Edward the VII Memorial (KEM) Hospital, India. Results and observations were tabulated and analysed, comparing with observations by various other authors regarding variety of indications such as, operative time, hospital stay, conversion rate, complications, safety, and feasibility of MAS in neonates, in the appropriate operative groups., Results: A total of 199 procedures were performed in 193 children aged between 10 days and 12 years (average age: 5.7 years). One case of each, adrenal mass, retroperitoneoscopic nephrectomy, laparoscopic congenital diaphragmatic hernia (CDH) repair, and abdominoperineal pull-through for anorectal malformation, were converted to open surgeries due to technical difficulty. The overall conversion rate was 3%. Morbidity and mortality were very minimal and the procedures were well tolerated in majority of cases., Conclusion: We concluded that MAS procedures appear to be safe for a wide range of indications in neonates and children. Further development and expansion of its indications in neonatal and paediatric surgery requires further multi-institutional studies and larger cohort of patients, to compare with standards of open surgery.

Aim: To determine diagnostic value of magnetic resonance urography in cases of duplex renal system., Method: Twenty cases between five month to nine years with suspected or known duplex renal system were evaluated by ultrasound (USG), micturating cystourethrography (MCU), intravenous urography (IVU) and magnetic resonance urography (MRU). The findings of these diagnostic imaging studies were then compared with each other and against the results of final diagnosis established at surgery., Results: Duplex renal system could be identified in two of these cases on USG, was diagnosed in four in IVU and could be diagnosed in all cases with MRU., Conclusion: MRU is superior and far accurate than IVU, MCU and USG in diagnosing duplex renal system.

The aim of our study was to evaluate the role of diagnostic and therapeutic laparoscopy for abdominal pain in children. Fifty-four children under the age of 12 years who presented with an acute abdomen with symptoms of duration of less than 72 hours (N = 21), and recurrent abdominal pain (RAP) with duration of symptoms ranging from 2 to 18 months (N = 33) were included in this study. Patients who presented with hemodynamic instability and signs of generalized peritonitis were excluded from this study. All patients were evaluated thoroughly, including a detailed history with relevant investigations and other specific tests, such as the Mantoux test, urinary porphobilinogen, video electroencephalograph, M. tuberculosis polymerase chain reaction, and so on, were taken to rule out rare causes of RAP. The results of the study were assessed, and it is concluded that diagnostic laparoscopy allows for establishing a prompt, accurate diagnosis in the acute abdomen without a therapeutic delay and unnecessary hospital observation. Laparoscopy early in the course of debilitating chronic abdominal pain in children provides economic benefit by eliminating many low-yield imaging studies and also minimizes lost time from school.

Trauma-care systems in India are at a nascent stage of development. Industrialised cities, rural towns and villages coexist, with almost complete lack of organised trauma care. There is gross disparity between trauma services available in various parts of the country. Rural India has inefficient services for trauma care, due to the varied topography, financial constraints and lack of appropriate health infrastructure. There is no national lead agency to co-ordinate various components of a trauma system. No mechanism for accreditation of trauma centres and professionals exists. Education in trauma life-support (TLS) skills has only recently become available. A nation-wide survey encompassing various facilities has demonstrated significant deficiencies in current trauma systems.Although injury is a major public-health problem, the Government of India has failed to recognise it as a priority. Significant efforts to develop trauma-care systems across the country are seen mainly in the private sector. New initiatives under National Health Policy 2002 are expected to result in improvement in the systems, but the allocation of funds remains grossly inadequate for any significant impact on the outcome.

The Antley-Bixler syndrome is a rare multiple congenital anomaly with a high mortality rate. The characteristic manifestations include craniosynostosis, radiohumeral synostosis, midface hypoplasia, joint contractures and arachnodactyly. We report two new cases of this syndrome and address the diagnostic features, associated malformations, inheritance patterns, prenatal findings, and briefly review the literature.

A comparative study of statistical particle model theory of diffuse reflectance has been made. Theories have been applied to six particulate samples having different optical characteristics and average particle sizes that vary from 42 to 106 mum. We made an overall assessment of each theoretical model by determining the CIELAB color difference using experimentally measured and theoretically predicted diffuse reflectance spectra in the visible spectral range. We discuss the performance ratings of the models of other researchers and discovered numerous typographical errors in Fresnel reflection coefficient expressions. We provide the correct versions for these expressions.

The advanced practice, professional nurse in the acute-care setting with autonomy, prescriptive authority, and authority to coordinate care delivery is a role currently evolving. Evaluation data from a small number of individuals on a learning curve from students to novice practitioners were collected over a 2.5-year period. The results show that self-efficacy increases with clinical experience, whereas clinical reasoning and technical competency are challenging to beginning practitioners. Attention to consultative and educational role components should take low priority until these areas become comfortable to students and novice practitioners. Even early in their role development however, acute care nurse practitioners are regarded as highly valuable and contributory members of the patient management team.

Basic nursing education is governed by individual state rules and regulations lacking in uniformity across the United States and based on unstated and perhaps mistaken assumptions. At the same time, there is increasing evidence of problems and difficulties with the current traditional model of nursing education. Before proposing changes in said model, the authors chose to examine what it is that a nursing student does in a clinical area. The perspective of activities and interactions was chosen to illustrate, through a nonparticipant observation study, the patterns and utilization of time during a scheduled clinical experience for baccalaureate nursing students. The goal of the study was to determine who, other than the client/patient, influences the student learning at the clinical site and how learning time is spent. Two schools (one private and one public) and nine clinical sites with 37 observations were used to collect the data for this study. Findings are best summarized in four (overlapping) categories of school time, registered nurse (RN) staff time, hospital staff time, and supervised time. School time, or time spent interacting with the instructor, another student, and/or the student on his/her own in the practice setting (time exclusive of staff input) constituted 84 per cent of all time. RN staff time that was time spent with either the primary nurse or other RNs on the unit used 10 per cent of the student time, Fourteen per cent of student time was spent in hospital staff time, which includes interactions with any nursing staff or other hospital personnel.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this article is to report on a national survey of the 51 state boards of examiners in the United States that govern and regulate nursing education. Data were gathered from the written rules and regulations of each of the state agencies, and content analysis was performed focusing on the following categories: qualifications (State board members, program directors, faculty, and preceptors); roles and responsibilities (state board members, faculty, preceptors, and clinical agencies); and process and content of the nursing education curriculum and program. Findings of the study indicate specific problem areas in the regulating of basic nursing education programs. The following were among the major issues identified: (1) educational qualifications for board membership are virtually nonexistent, (2) in many situations different requirements exist for various types of programs, and (3) there is great disparity from state to state regarding both the content deemed as necessary in nursing education and in the mandated process of that education. The investigators noted that several patterns lend credence to a need for a national plan regarding the state regulation of basic nursing education.

To meet the pressing demands for enhanced quality of patient care in a time of shrinking resources, a cooperative effort between the School of Nursing and the University Hospital (John Dempsey) Department of Nursing was initiated to educate nurses for a new role. Acute care nurse practitioners are master's prepared nurses in advanced practice who are capable of case management. Major functions include creating an initial data base, ordering diagnostic tests, therapeutics interventions, and medications, and monitoring their results in collaboration with attending physicians. Results show promise for unprecedented interdisciplinary patient management and nurse-to-nurse cooperation.

The selection of an ideal semisolid vehicle for growth factors presents a challenge. Some antimicrobial agents are known to delay wound healing. The objective of this investigation was to identify appropriate preservatives and vehicles for TGF-alpha. Criteria for acceptance are noninterference with the mitogenic activity of TGF-alpha as well as adequate product preservation. Vehicles considered were o/w creams, ointments, and a gel. Combinations of six preservatives were tested. Selection was determined using both microbial preservative challenge and TGF-alpha mitogenic assay. In the former, 10 species of microorganisms were inoculated into formulation samples. At selected time intervals, it was determined whether colonies decreased, increased, or remained constant. In the mitogenic assay, samples of either preservatives or formulation prototypes were introduced to TGF-alpha-stimulated fibroblast cell cultures. Mitogenesis was determined by measuring 3H-dThd uptake into newly synthesized DNA. As preservatives, sorbic acid and quaternium-15 appear to satisfy both selection criteria. A thermosetting gel appears most promising as vehicle.

Out of 321 consecutive cases of Percutaneous Transluminal Coronary Angioplasty (PTCA), 28 (8.7%) patients underwent PTCA for nonacute total occlusion with no visible antegrade flow. All patients had evidence of reversible ischaemia in the territory of totally occluded artery. Overall initial success rate was 66% and was mainly related to the duration of the occlusion (85% for occlusion of 1 month or less, 70% for 1-6 months, and nil for more than 6 months duration). In 21 (75%) cases where collateral circulation to the occluded vessel could be demonstrated before PTCA, was not visible after successful PTCA. Failure was mainly due to inability to cross the lesion with the guide wire (8 out of 10 failures). Emergency Coronary Artery Bypass Graft (CABG) surgery was required in 2 cases where dissection of nontarget vessels occurred during manipulation of the guide wire. Acute reocclusion occurred in 2 cases, both were redilated successfully. There was no death. Although the primary success rate is lower than that associated with conventional stenotic lesions, with improvement in the hardware-balloon catheters and guide wires, coronary angioplasty can be performed successfully in majority of the patients with total coronary occlusion.

Nursing educators have struggled to find the optimal solution for students' clinical learning. The authors discuss a potential avenue to address this problem. Through the combined efforts of a hospital-based clinical nurse specialist and a university-based faculty member, the authors promoted effective learning for their students. Their combined strengths resulted in a positive experience for students, staff, and the instructors.

Accurate anatomic diagnosis presents a dilemma in patients with residual shunt after corrective surgery for congenital heart disease. We describe a patient who, after atrial septal defect repair, developed dyspnea and central cyanosis despite normal pulmonary arterial pressures and right heart chamber size. A role for early MRI is suggested.

We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis.

Colorimetric assessment of powder mixtures or pigmented specimens can be made by determining CIE color coordinates from sample spectral reflectance curves. The diffuse reflectance spectra of five particulate systems having different hues are determined using modified particle model theory for wavelengths of 400 (20) 700 nm. Six binary powder mixtures are prepared from these particulate systems. The reflectance spectra of binary powder mixtures are then predicted assuming the contribution of each component to be equal to the product of its reflectance and the total surface area of particles. The theoretically predicted diffuse reflectance spectral curves agree well with experimentally measured ones. The evaluation of the theoretical technique is made by determining the color difference between the measured and predicted color coordinates. The color difference calculated for all the samples is <2 CIELAB units. The study establishes a theoretical aid to predict diffuse reflectance spectra of powder mixtures from the fundamental morphological and optical properties of particulate matter.