279 research outputs found

    Predicting toric soft lens acuity by attenuated cylinder refraction

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    Purpose: As variability in vision with a toric soft contact lens is related to cylinder power, providing the lowest acceptable amount of cylinder correction is sometimes a useful strategy. It would be useful clinically to have a reliable method of testing the acceptability of reduced cylinder correction prior to actually selecting and placing a trial soft toric contact lens on the eye. It would be useful to determine a patient\u27s potential acceptance of a cylinder power and axis that is adjusted to those available in the soft contact lens. Method: 18 myopic subjects (29 eyes), with astigmatism between 0.50D and 1.75D were evaluated. After determining optimal manifest refraction, the cylinder component of the refraction was adjusted to comply with those available in a single use toric soft lens such that the cylinder values and axes in the phoropter were set at -0.75 axis 180 degrees for with-the-rule eyes and -0.75 axis 90 degrees for against-the-rule eyes. Sphere power was then adjusted to best subjective acuity. High and low contrast visual acuity was determined through this attenuated refraction. Focus Dailies Toric lenses with power corresponding to the attenuated refraction were applied and allowed to settle. High and low contrast acuity were determined again, and compared with acuity obtained with the attenuated refraction. Results: Analysis showed a reasonably linear relationship between the visual acuities obtained from the adjusted refraction and the trial contact lens, with a trend to better acuity with the contact lens. Acuity with the contact lens was the same or better than the attenuated refraction for 93% of eyes. Conclusion: Practitioners performing an attenuated cylinder refraction prior to selecting a soft toric contact lens should be able to reliably predict the patient\u27s visual acuity with the contact lenses

    Glucosamine HCl-based solid dispersions to enhance the biopharmaceutical properties of acyclovir

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    The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics

    Office-Based Educational Handout for Influenza Vaccination: A Randomized Controlled Trial

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    This is the author accepted manuscript. The final version is available from American Academy of Pediatrics via the DOI in this recordData sharing statement: De-identified individual participant data will not be made available.OBJECTIVES: To assess the impact of a parent educational intervention about influenza disease on child vaccine receipt. METHODS: A convenience sample of parents of children ≥6 months old with a visit at 2 New York City pediatric clinics between August 2016 and March 2017 were randomly assigned (1:1:1) to receive either usual care, an educational handout about influenza disease that was based on local data, or an educational handout about influenza disease that was based on national data. Parents received the handout in the waiting room before their visit. Primary outcomes were child influenza vaccine receipt on the day of the clinic visit and by the end of the season. A multivariable logistic regression was used to assess associations between intervention and vaccination, with adjustment for variables that were significantly different between arms. RESULTS: Parents who received an intervention (versus usual care) had greater odds of child influenza vaccine receipt by the end of the season (74.9% vs 65.4%; adjusted odds ratio 1.68; 95% confidence interval: 1.06-2.67) but not on the day of the clinic visit. Parents who received the national data handout (versus usual care) had greater odds of child influenza vaccine receipt on the day of the clinic visit (59.0% vs 52.6%; adjusted odds ratio 1.79; 95% confidence interval: 1.04-3.08) but not by the end of the season. CONCLUSIONS: Providing an educational intervention in the waiting room before a pediatric provider visit may help increase child influenza vaccine receipt.European CommissionNIH - Ruth L. Kirschstein National Research Service Awar

    Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

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    Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

    Mycobacteria Exploit Host Hyaluronan for Efficient Extracellular Replication

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    In spite of the importance of hyaluronan in host protection against infectious organisms in the alveolar spaces, its role in mycobacterial infection is unknown. In a previous study, we found that mycobacteria interact with hyaluronan on lung epithelial cells. Here, we have analyzed the role of hyaluronan after mycobacterial infection was established and found that pathogenic mycobacteria can grow by utilizing hyaluronan as a carbon source. Both mouse and human possess 3 kinds of hyaluronan synthases (HAS), designated HAS1, HAS2, and HAS3. Utilizing individual HAS-transfected cells, we show that HAS1 and HAS3 but not HAS2 support growth of mycobacteria. We found that the major hyaluronan synthase expressed in the lung is HAS1, and that its expression was increased after infection with Mycobacterium tuberculosis. Histochemical analysis demonstrated that hyaluronan profoundly accumulated in the granulomatous legion of the lungs in M. tuberculosis-infected mice and rhesus monkeys that died from tuberculosis. We detected hyaluronidase activity in the lysate of mycobacteria and showed that it was critical for hyaluronan-dependent extracellular growth. Finally, we showed that L-Ascorbic acid 6-hexadecanoate, a hyaluronidase inhibitor, suppressed growth of mycobacteria in vivo. Taken together, our data show that pathogenic mycobacteria exploit an intrinsic host-protective molecule, hyaluronan, to grow in the respiratory tract and demonstrate the potential usefulness of hyaluronidase inhibitors against mycobacterial diseases

    Specific Immunoassays Confirm Association of Mycobacterium avium Subsp. paratuberculosis with Type-1 but Not Type-2 Diabetes Mellitus

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    Mycobacterium avium subspecies paratuberculosis (MAP) is a versatile pathogen with a broad host range. Its association with type-1 diabetes mellitus (T1DM) has been recently proposed. Rapid identification of infectious agents such as MAP in diabetic patients at the level of clinics might be helpful in deciphering the role of chronic bacterial infection in the development of autoimmune diseases such as T1DM.We describe use of an ELISA method to identify live circulating MAP through the detection of a cell envelope protein, MptD by a specific M13 phage--fMptD. We also used another ELISA format to detect immune response to MptD peptide. Both the methods were tested with blood plasma obtained from T1DM, type-2 diabetes (T2DM) patients and non-diabetic controls. Our results demonstrate MptD and fMptD ELISA assays to be accurate and sensitive to detect MAP bacilli in a large fraction (47.3%) of T1DM patients as compared to non-diabetic controls (12.6%) and those with confirmed T2DM (7.7%). Comparative analysis of ELISA assays performed here with 3 other MAP antigen preparations, namely HbHA, Gsd and whole cell MAP lysates confirmed comparable sensitivity of the MptD peptide and the fMptD based ELISA assays. Moreover, we were successful in demonstrating positive bacterial culture in two of the clinical specimen derived from T1DM patients.The MptD peptide/fMptD based ELISA or similar tests could be suggested as rapid and specific field level diagnostic tests for the identification of MAP in diabetic patients and for finding the explanations towards the occurrence of type-1 or type-2 diabetes in the light of an active infectious trigger
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