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Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications. - American journal of medical genetics. Part A
We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458â€‰bp (distal) and 53,160,114-53,713,154â€‰bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication.Â© 2015 Wiley Periodicals, Inc.
Rethinking critical care: decreasing sedation, increasing delirium monitoring, and increasing patient mobility. - Joint Commission journal on quality and patient safety
Sedation management, delirium monitoring, and mobility programs have been addressed in evidence-based critical care guidelines and care bundles, yet implementation in the ICU remains variable. As critically ill patients occupy higher percentages of hospital beds in the United States and beyond, it is increasingly important to determine mechanisms to deliver better care. The Institute for Healthcare Improvement's Rethinking Critical Care (IHI-RCC) program was established to reduce harm of critically ill patients by decreasing sedation, increasing monitoring and management of delirium, and increasing patient mobility. Case studies of a convenience sample of five participating hospitals/health systems chosen in advance of the determination of their clinical outcomes are presented in terms of how they got started and process improvements in sedation management, delirium management, and mobility.The IHI-RCC program involved one live case study and five iterations of an in-person seminar in a 33-month period (March 2011-November 2013) that emphasized interdisciplinary teamwork and culture change.Qualitative descriptions of the changes tested at each of the five case study sites demonstrate improvements in teamwork, processes, and reliability of daily work. Improvement in ICU length of stay and length of stay on the ventilator between the pre- and postimplementation periods varied from slight to substantial.Changing critical care practices requires an interdisciplinary approach addressing cultural, psychological, and practical issues. The key lessons of the IHI-RCC program are as follows: the importance of testing changes on a small scale, feeding back data regularly and providing sufficient education, and building will through seeing the work in action.
IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells. - PloS one
The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease.
The relationship of bedside nurses' emotional intelligence with quality of care. - Journal of nursing care quality
Emotional intelligence, a predictor of productivity and success, may impact behaviors responsible for quality of care. This study examined if emotional intelligence of units' bedside nurses is related to the quality of care delivered to the patients. In this study, emotional intelligence was found to be correlated to the number of Clostridium difficile infections, MRSA infections, patient falls with injury, and pressure ulcer screenings (P < .001) in the inpatient acute care setting.
The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. - American journal of rhinology & allergy
Herbal remedies predate written history and continue to be used more frequently than conventional pharmaceutical medications. The novel dry extract BNO 1011 is based on a combination of five herbs that is used to treat acute and chronic rhinosinusitis. We evaluated the pharmacologic effects of the novel dry extract BNO 1011 on human respiratory epithelial cultures specifically addressing electrolyte transport and cilia beat frequency (CBF).Well-differentiated human bronchial epithelial cultures grown at an air-liquid interface were treated on the apical or basolateral surface with varying concentrations of dry extract BNO 1011. Changes in transepithelial sodium and chloride transport were determined in Ussing chambers under voltage-clamped conditions. Changes in CBF were determined using the Sissons-Ammons Video Analysis system (Ammons Engineering, Mt. Morris, MI).When applied to the apical surface, dry extract BNO 1011 activated forskolin-stimulated chloride secretion and ciliary beat in a dose-dependent fashion. Basolateral application of dry extract BNO 1011 did not alter the measured physiological properties.Apical application of dry extract BNO 1011 stimulates both chloride secretion and CBF and therefore may augment mucociliary clearance.
Characterization of 12 polymorphic microsatellite markers in the liverwort Marchantia inflexa (Marchantiaceae). - American journal of botany
Microsatellite markers were developed in Marchantia inflexa, a haploid liverwort with unisexual individuals, to identify clonal genotypes and measure population genetic variability.Twelve polymorphic primer sets were developed from three enriched genomic libraries. Primers were fluorescently labeled, and alleles were identified by fragment analysis. These primers were tested in four natural populations and revealed a moderate level of genetic variation within four populations, as indicated by the number of alleles per locus (range = 1-5).Development of polymorphic markers is crucial to the identification of individuals and will allow additional research into this species, particularly on its population genetics and metapopulation dynamics.
Mechanics of lipid bilayer junctions affecting the size of a connecting lipid nanotube. - Nanoscale research letters
In this study we report a physical analysis of the membrane mechanics affecting the size of the highly curved region of a lipid nanotube (LNT) that is either connected between a lipid bilayer vesicle and the tip of a glass microinjection pipette (tube-only) or between a lipid bilayer vesicle and a vesicle that is attached to the tip of a glass microinjection pipette (two-vesicle). For the tube-only configuration (TOC), a micropipette is used to pull a LNT into the interior of a surface-immobilized vesicle, where the length of the tube L is determined by the distance of the micropipette to the vesicle wall. For the two-vesicle configuration (TVC), a small vesicle is inflated at the tip of the micropipette tip and the length of the tube L is in this case determined by the distance between the two interconnected vesicles. An electrochemical method monitoring diffusion of electroactive molecules through the nanotube has been used to determine the radius of the nanotube R as a function of nanotube length L for the two configurations. The data show that the LNT connected in the TVC constricts to a smaller radius in comparison to the tube-only mode and that tube radius shrinks at shorter tube lengths. To explain these electrochemical data, we developed a theoretical model taking into account the free energy of the membrane regions of the vesicles, the LNT and the high curvature junctions. In particular, this model allows us to estimate the surface tension coefficients from R(L) measurements.
Highly sensitive detection of exocytotic dopamine release using a gold-nanoparticle-network microelectrode. - Analytical chemistry
Here we report a new type of microelectrode sensor for single-cell exocytotic dopamine release. The new microsensor is built by forming a gold-nanoparticle (AuNP) network on a carbon fiber microelectrode. First a gold surface is obtained on a carbon fiber microdisk electrode by partially etching away the carbon followed by electrochemical deposition of gold into the pore. The gold surface is chemically functionalized with a sol-gel silicate network derived from (3-mercaptopropyl)trimethoxysilane (MPTS). A AuNP network is formed by immobilizing Au nanoparticles onto the thiol groups in the sol-gel silicate network. The AuNP-network microelectrode has been characterized by scanning electron microscopy (SEM) and steady-state voltammetry. The AuNP-network microelectrode has been used for amperometric detection of exocytotic dopamine secretion from individual pheochromocytoma (PC12) cells. The results show significant differences in the kinetic peak parameters including shorter rise time, decay time, and half-width as compared to a bare carbon fiber electrode equivalent. These results indicate AuNP-network microelectrodes possess an excellent sensing activity for single-cell exocytotic catecholamine release, specifically dopamine. Moreover, key advantageous properties inherent to bare carbon fiber microelectrodes (i.e., rigidity, flexibility, and small size) are maintained in addition to an observed prolonged shelf life stability and resistance to cellular debris fouling and dopamine polymerization.
Estradiol inhibits depolarization-evoked exocytosis in PC12 cells via N-type voltage-gated calcium channels. - Cellular and molecular neurobiology
Fast neuromodulatory effects of 17-Î²-estradiol (E2) on cytosolic calcium concentration ([Ca(2+)](i)) have been reported in many cell types, but little is known about its direct effects on vesicular neurotransmitter secretion (exocytosis). We examined the effects of E2 on depolarization-evoked [Ca(2+)](i) in PC12 cells using fluorescence measurements. Imaging of [Ca(2+)](i) with FURA-2 revealed that depolarization-evoked calcium entry is inhibited after exposure to 10 nM and 10 Î¼M E2. Calcium entry after exposure to 50 Î¼M E2 decreases slightly, but insignificantly. To relate E2-induced changes in [Ca(2+)](i) to functional effects, we measured exocytosis using amperometry. It was observed that E2 in some cells elicits exocytosis upon exposure. In addition, E2 inhibits depolarization-evoked exocytosis with a complex concentration dependence, with inhibition at both physiological and pharmacological concentrations. This rapid inhibition amounts to 45% at a near physiological level (10 nM E2), and 50% at a possible pharmacological concentration of 50 Î¼M. A small percentage (22%) of cells show exocytosis during E2 exposure ("Estrogen stimulated"), thus vesicle depletion could possibly account (at least partly) for the E2-induced inhibition of depolarization-evoked exocytosis. In cells that do not exhibit E2-stimulated release ("Estrogen quiet"), the E2-induced inhibition of exocytosis is abolished by a treatment that eliminates the contribution of N-type voltage-gated calcium channels (VGCCs) to exocytosis. Overall, the data suggest that E2 can act on N-type VGCCs to affect secretion of neurotransmitters. This provides an additional mechanism for the modulation of neuronal communication and plasticity by steroids.
Nutrition in medicine: nutrition education for medical students and residents. - Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
Proper nutrition plays a key role in disease prevention and treatment. Many patients understand this link and look to physicians for guidance diet and physical activity. Actual physician practice, however, is often inadequate in addressing the nutrition aspects of diseases such as cancer, obesity, and diabetes. Physicians do not feel comfortable, confident, or adequately prepared to provide nutrition counseling, which may be related to suboptimal knowledge of basic nutrition science facts and understanding of potential nutrition interventions. Historically, nutrition education has been underrepresented at many medical schools and residency programs. Our surveys over a decade show that most medical schools in the United States are still not ensuring adequate nutrition education, and they are not producing graduates with the nutrition competencies required in medical practice. Physicians, residents, and medical students clearly need more training in nutrition assessment and intervention. The Nutrition in Medicine (NIM) project, established to develop and distribute a core nutrition curriculum for medical students, offers a comprehensive online set of courses free of charge to medical schools. The NIM medical school curriculum is widely used in the United States and abroad. A new initiative, Nutrition Education for Practicing Physicians, offers an innovative online medical nutrition education program for residents and other physicians-in-training, but with targeted, practice-based educational units designed to be completed in 15 minutes or less. The NIM project is strengthening medical nutrition practice by providing a free, comprehensive, online nutrition curriculum with clinically relevant, evidence-based medical education for undergraduate and postgraduate learners.
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