300 Crittenden Blvd Dept Of Psychiatry
Rochester NY 14642
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License #: 020367
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Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation. - Drug delivery and translational research
With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.
MALDI FTICR IMS of Intact Proteins: Using Mass Accuracy to Link Protein Images with Proteomics Data. - Journal of the American Society for Mass Spectrometry
MALDI imaging mass spectrometry is a highly sensitive and selective tool used to visualize biomolecules in tissue. However, identification of detected proteins remains a difficult task. Indirect identification strategies have been limited by insufficient mass accuracy to confidently link ion images to proteomics data. Here, we demonstrate the capabilities of MALDI FTICR MS for imaging intact proteins. MALDI FTICR IMS provides an unprecedented combination of mass resolving power (~75,000 at m/z 5000) and accuracy (<5ppm) for proteins up to ~12kDa, enabling identification based on correlation with LC-MS/MS proteomics data. Analysis of rat brain tissue was performed as a proof-of-concept highlighting the capabilities of this approach by imaging and identifying a number of proteins including N-terminally acetylated thymosin Î²(4) (m/z 4,963.502, 0.6ppm) and ATP synthase subunit Îµ (m/z 5,636.074, -2.3ppm). MALDI FTICR IMS was also used to differentiate a series of oxidation products of S100A8 (m/z 10,164.03, -2.1ppm), a subunit of the heterodimer calprotectin, in kidney tissue from mice infected with Staphylococcus aureus. S100A8 - M37O/C42O(3) (m/z 10228.00, -2.6ppm) was found to co-localize with bacterial microcolonies at the center of infectious foci. The ability of MALDI FTICR IMS to distinguish S100A8 modifications is critical to understanding calprotectin's roll in nutritional immunity.
Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. - PLoS pathogens
Bacterial biofilms account for a significant number of hospital-acquired infections and complicate treatment options, because bacteria within biofilms are generally more tolerant to antibiotic treatment. This resilience is attributed to transient bacterial subpopulations that arise in response to variations in the microenvironment surrounding the biofilm. Here, we probed the spatial proteome of surface-associated single-species biofilms formed by uropathogenic Escherichia coli (UPEC), the major causative agent of community-acquired and catheter-associated urinary tract infections. We used matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) to analyze the spatial proteome of intact biofilms in situ. MALDI-TOF IMS revealed protein species exhibiting distinct localizations within surface-associated UPEC biofilms, including two adhesive fibers critical for UPEC biofilm formation and virulence: type 1 pili (Fim) localized exclusively to the air-exposed region, while curli amyloid fibers localized to the air-liquid interface. Comparison of cells grown aerobically, fermentatively, or utilizing an alternative terminal electron acceptor showed that the phase-variable fim promoter switched to the "OFF" orientation under oxygen-deplete conditions, leading to marked reduction of type 1 pili on the bacterial cell surface. Conversely, S pili whose expression is inversely related to fim expression were up-regulated under anoxic conditions. Tethering the fim promoter in the "ON" orientation in anaerobically grown cells only restored type 1 pili production in the presence of an alternative terminal electron acceptor beyond oxygen. Together these data support the presence of at least two regulatory mechanisms controlling fim expression in response to oxygen availability and may contribute to the stratification of extracellular matrix components within the biofilm. MALDI IMS facilitated the discovery of these mechanisms, and we have demonstrated that this technology can be used to interrogate subpopulations within bacterial biofilms.
Advanced mass spectrometry technologies for the study of microbial pathogenesis. - Current opinion in microbiology
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been successfully applied to the field of microbial pathogenesis with promising results, principally in diagnostic microbiology to rapidly identify bacteria based on the molecular profiles of small cell populations. Direct profiling of molecules from serum and tissue samples by MALDI MS provides a means to study the pathogen-host interaction and to discover potential markers of infection. Systematic molecular profiling across tissue sections represents a new imaging modality, enabling regiospecific molecular measurements to be made in situ, in both two-dimensional and three-dimensional analyses. Herein, we briefly summarize work that employs MALDI MS to study the pathogenesis of microbial infection.Copyright Â© 2014 Elsevier Ltd. All rights reserved.
A proposed model membrane and test method for microneedle insertion studies. - International journal of pharmaceutics
A commercial polymeric film (Parafilm M(Â®), a blend of a hydrocarbon wax and a polyolefin) was evaluated as a model membrane for microneedle (MN) insertion studies. Polymeric MN arrays were inserted into Parafilm M(Â®) (PF) and also into excised neonatal porcine skin. Parafilm M(Â®) was folded before the insertions to closely approximate thickness of the excised skin. Insertion depths were evaluated using optical coherence tomography (OCT) using either a force applied by a Texture Analyser or by a group of human volunteers. The obtained insertion depths were, in general, slightly lower, especially for higher forces, for PF than for skin. However, this difference was not a large, being less than the 10% of the needle length. Therefore, all these data indicate that this model membrane could be a good alternative to biological tissue for MN insertion studies. As an alternative method to OCT, light microscopy was used to evaluate the insertion depths of MN in the model membrane. This provided a rapid, simple method to compare different MN formulations. The use of Parafilm M(Â®), in conjunction with a standardised force/time profile applied by a Texture Analyser, could provide the basis for a rapid MN quality control test suitable for in-process use. It could also be used as a comparative test of insertion efficiency between candidate MN formulations.Copyright Â© 2014 The Authors. Published by Elsevier B.V. All rights reserved.
First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 20 - MMWR. Morbidity and mortality weekly report
Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.
The effect of an emergency department dedicated midtrack area on patient flow. - Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
Emergency department (ED) crowding negatively affects quality of care and disproportionately affects medium-acuity (Emergency Severity Index [ESI] level 3) patients. The effect of a dedicated area in the ED focused on these patients has not been well studied.The objective was to find out the operational effect of a midtrack area dedicated to the evaluation and safe disposition of uncomplicated medium-acuity (ESI 3) patients.This was a 24-month pre-/postintervention study to evaluate the effect of implementation of a dedicated midtrack area at an urban tertiary academic adult ED. The midtrack had three examination rooms and three hallway stretchers for ongoing treatment staffed by an attending physician and two registered nurses (RNs). Besides the two additional RNs representing a 3.4% increase in total daily nursing hours, the intervention required no additional ED resources. The midtrack area was open from 1 p.m. to 9 p.m. on weekdays, corresponding to peak ED arrival rates. All patients presenting during weekdays were included, excluding patients triaged directly to the trauma bay or psychiatric unit or who expired in the ED. The main outcomes were left without being seen (LWBS) rates and ED length of stay (LOS), adjusting for patient volume, daily total patient hours (a proxy for ED crowding), and acuity.A total of 91,903 patients were included for analysis during the study period including 261 pre- and 256 postintervention days. Comparing the pre- and postintervention periods, mean ED daily visits (173 vs. 182) and mean total daily patient hours (889 vs. 942) were all significantly higher in the postintervention period (p<0.0001). There was no significant change in percentage of patients with high triage acuity levels. Despite this increase in volume and crowding, the unadjusted and adjusted LWBS rates decreased from 6.85% to 4.46% (p<0.0001) and from 7.33% to 3.97% (p<0.0001), respectively. The mean LOS for medium-acuity patients also decreased by 39.2 minutes (p<0.0001). For high-acuity patients, there was no significant change in the mean time to room (14.69 minutes vs. 15.21 minutes, p=0.07); however, their mean LOS increased by 24 minutes (331 minutes vs. 355 minutes, p<0.0001).Implementation of a midtrack area dedicated to caring for uncomplicated medium-acuity (ESI 3) patients was associated with a decrease in overall ED LWBS rates and ED LOS for medium-acuity patients.Â© 2014 by the Society for Academic Emergency Medicine.
A comparison of the anti-Staphylococcus aureus activity of extracts from commonly used medicinal plants. - Journal of alternative and complementary medicine (New York, N.Y.)
Resurgences of Staphylococcus aureus infection continue globally, with antibiotic resistance increasing dramatically, making these infections more difficult to treat. S. aureus epidemics impose public health threats, and economic burdens on health care costs worldwide, presenting challenges modern medicine struggles to control.In order to answer today's call for effective treatments against S. aureus, we evaluated and compared various botanical extracts that have historically been suggested as useful for their antimicrobial properties against S. aureus.Briefly, S. aureus cultures were treated with selected botanical extracts and the minimum inhibitory concentration (MIC) determined. In addition, to obtain more quantitative measures on bacterial growth, 24-hour growth studies were done to examine the temporal activity and stability of various botanicals on bacterial replication.The antimicrobial activity observed for the botanical extracts used in this comparative evaluation of efficacy included both bacteriostatic and bacteriocidal activity against S. aureus. Highly effective botanicals including Salvia officinalis, Eucalyptus globulus, Coleus forskohlii, Coptis chinensis, Turnera diffusa, and Larrea tridentata exhibited MIC values ranging from 60 to 300â€‰Î¼g/mL and a 10(6)-fold reduction in bacterial replication. Arctostaphylos uva-ursi and Allium sativum were slightly less effective, exhibiting MIC values ranging from 90 to 400â€‰Î¼g/mL and a 10(5)-fold reduction, while Anemopsis californica gave MIC value of 360â€‰Î¼g/mL and a 10(4)-fold reduction in bacterial replication. Many botanicals, especially at lower doses, had an initial inhibitory effect followed by a recovery in bacterial replication. Such botanicals included E. globulus, C. chinensis, T. diffusa, A. californica, and Berberis vulgaris.Our data demonstrate that S. officinalis, E. globulus, C. forskohlii, A. uva-ursi, C. chinensis, T. diffusa, A. californica, A. sativum, and L. tridentata all show promising direct antimicrobial activity against S. aureus. For many of these botanicals, strong bacteriocidal activity was observed at higher concentrations, but even at lower concentrations, bacteriostatic activity was evident. Other botanicals including B. vulgaris, Baptisia tinctoria, and Glycyrrhiza glabra showed moderate activity against S. aureus, while Schisandra chinensis, Echinacea angustifolia, and Polygonum multiflorum were shown to be ineffective.
Bystander education training for campus sexual assault prevention: an initial meta-analysis. - Violence and victims
The present meta-analysis evaluated the effectiveness of bystander education programs for preventing sexual assault in college communities. Undergraduates trained in bystander education for sexual assault were expected to report more favorable attitudes, behavioral proclivities, and actual behaviors relative to untrained controls. Data from 12 studies of college students (N = 2,926) were used to calculate 32 effect sizes. Results suggested moderate effects of bystander education on both bystander efficacy and intentions to help others at risk. Smaller but significant effects were observed regarding self-reported bystander helping behaviors, (lower) rape-supportive attitudes, and (lower) rape proclivity, but not perpetration. These results provide initial support for the effectiveness of in-person bystander education training. Nonetheless, future longitudinal research evaluating behavioral outcomes and sexual assault incidence is needed.
Ambulatory blood pressure measurements in mid-pregnancy and development of hypertensive pregnancy disorders. - Hypertension in pregnancy
To explore if blood pressure (BP) readings over 24â€‰h is a useful addition to uterine artery Doppler to screen for hypertensive disorders.In a prospective observational study, we invited nulliparous women with abnormal and normal uterine artery Doppler but normal BP at the time of their routine anomaly scan. BP was measured by the woman using automated apparatus at five specified time intervals over 24â€‰h at 22-24 weeks. Pregnancy outcome was retrieved from delivery suite records, discharge summaries, and letters to general practitioners if necessary. Logistic regression was used to explore the contribution of uterine artery Doppler and BP measurements towards the development of pre-eclampsia.Data were available from 52 women with abnormal and 48 women with normal uterine artery Doppler. Thirteen women developed hypertension in pregnancy. Significant difference was found in the BP of women who did or did not develop hypertensive disorders. BP recordings showed the diurnal variation. Both uterine artery Doppler mean PI and BP showed significant correlation with future development of hypertension.Women can self-measure BP at home. BP readings show diurnal variation. There are significant differences in BP of women who do and do not develop hypertension later in the pregnancy. Use of home BP monitoring over 24â€‰h of the day in mid-pregnancy is unlikely to add to the use of uterine artery Doppler and a one-off BP reading for future development of hypertension in pregnancy.
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300 Crittenden Blvd Dept Of Psychiatry Rochester, NY 14642
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