forward-genetics-screens-using-macrophages-to-identify-toxoplasma

Forward Genetics Screens Using Macrophages to Identify <em>Toxoplasma gondii </em>Genes Important for Resistance to IFN-&#947;-Dependent Cell Autonomous Immunity

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan pathogen. The parasite invades and replicates within ...

New York Medical College

Thyroid dysfunction after pediatric cardiac surgery.

A novel scanning probe microscopy technique has allowed dielectrophoretic force imaging with nanoscale spatial resolution. Dielectrophoresis (DEP) traditionally describes the mobility of polarizable particles in inhomogeneous alternating current (ac) electric fields. Integrating DEP with atomic force microscopy allows for noncontact imaging with the image contrast related to the local electric polarizability. By tuning the ac frequency, dielectric spectroscopy can be performed at solid/liquid interfaces with high spatial resolution. In studies of cells, the frequency-dependent dielectrophoretic force is sensitive to biologically relevant electrical properties, including local membrane capacitance and ion mobility. Consequently, dielectrophoretic force microscopy is well suited for in vitro noncontact scanning probe microscopy of biological systems.

Dielectrophoretic force microscopy of aqueous interfaces.

Dielectrophoretic force microscopy is shown to allow for facile noncontact imaging of systems in aqueous media. Electrokinetic tip-sample forces were predicted from topography measurements of an interface and compared with experimental images. Correlation function and power spectral density analyses indicated that image feedback was maintained without mechanical contact using moderate potentials (e.g., approximately 18 nm off the surface for a 7-Vpp, 100-kHz waveform). The applied dielectrophoretic force and the corresponding increase in effective tip radius were predictably adjusted by changing the peak potential.

Reduction of tip-sample contact using dielectrophoretic force scanning probe microscopy.

Dielectrophoretic force microscopy (DEPFM) and spectroscopy have been performed on individual intact surface-immobilized mammalian red blood cells. Dielectrophoretic force spectra were obtained in situ in approximately 125 ms and could be acquired over a region comparable in dimension to the effective diameter of a scanning probe microscopy tip. Good agreement was observed between the measured dielectrophoretic spectra and predictions using a single-shell cell model. In addition to allowing for highly localized dielectric characterization, DEPFM provided a simple means for noncontact imaging of mammalian blood cells under aqueous conditions. These studies demonstrate the feasibility of using DEPFM to monitor localized changes in membrane capacitance in real time with high spatial resolution on immobilized cells, complementing previous studies of mobile whole cells and cell suspensions.

Nanoscale dielectrophoretic spectroscopy of individual immobilized mammalian blood cells.

We report on the perioperative management of anesthesia and analgesia in a child with sickle cell disease and a congenital myopathy, presenting for corrective orthopedic surgery. The case illustrates two valuable points of interest: the many benefits of regional anesthesia in complex medical cases and the successful use of tourniquets in children with sickle cell disease.

Anesthesia for sickle cell disease and congenital myopathy in combination.

Canalization-the evolutionary loss of the capacity of organisms to develop different phenotypes in different environments-is an evolutionary phenomenon suspected to occur widely, although examples in natural populations are elusive. Because behavior is typically a highly flexible component of an individual's phenotype, it provides fertile ground for studying the evolution of canalization. Here we report how snail populations exposed for different lengths of time to a predatory crab introduced from Europe to America exhibit different degrees of canalization of an adaptive antipredator behavior: soft tissue withdrawal, measured as angular retraction depth. Where crab-snail contact is shortest (60 years), snails showed the highest behavioral flexibility. Where crabs invaded 110 years ago, snails showed significantly less behavioral flexibility, and where the interaction is ancient (Europe), snails exhibited highly canalized behavior. Selection therefore appears to have acted rapidly to increase canalization in wild snail populations, leading ultimately to the hard-wired behavior seen in European conspecifics.

Experimental evidence for the rapid evolution of behavioral canalization in natural populations.

Delays in diagnosing asthma in children are common and are known to delay asthma-specific treatment. Few studies have investigated whether a delay in asthma diagnosis impacts the use of health care services. This study was designed to assess whether a delay in diagnosis of asthma influences the use of health care services. This was a retrospective cohort study with subjects elicited from a convenience sample of 839 healthy children. The criteria for asthma was met in 276 (33%) subjects; of these subjects 179 (65%) had a delay in the diagnosis of asthma and 97 (35%) had a timely diagnosis. Data on health care services (e.g., flu shot, availability of a peak flow meter, hospitalizations, and urgent care or emergency department visits) and the frequency of systemic steroid treatments were collected from medical records during the first 18 years of life. The frequencies of health service and use of systemic steroids were compared using Poisson and logistic regression models in asthmatic children with and without a delay in asthma diagnosis. Children with a delay in asthma diagnosis were more likely to visit urgent care centers at least once (40.8% versus 21.6%; p < 0.001), compared with those with a timely diagnosis. There were no significant differences in other health care service or systemic steroid use. A delay in the diagnosis of asthma was associated with an increase in urgent care visits suggesting suboptimal care. Clinicians should be aware that a delay in the diagnosis of asthma in children may result in the use of suboptimal health care services.

Impact of delay in asthma diagnosis on health care service use.

To evaluate the effect of the timeliness of asthma diagnosis on chest X-ray (CXR) and antibiotic utilization in children.

Impact of delay in asthma diagnosis on chest X-ray and antibiotic utilization by clinicians.

Appropriate use of the child developmental review.

Early recognition and treatment of social and emotional disorders in children is significant for school preparation. These disorders are frequently underdetected without the use of standardized screening instruments. The purpose of our study is to describe the implementation of the Ages and Stages Questionnaire: Social-Emotional (ASQ:SE) in primary care practice by mail when children are 30 months old.

Impact of implementing mental health screening by mail with a primary care management model.

Postpartum depression (PPD) has emerged as an important issue for pediatricians and family practitioners because of detrimental effects on children. PPD occurs in 10% to 22% of women who have recently given birth, but fewer than half of cases are recognized. Despite the impact of PPD, many primary care clinicians do not have systemic screening approaches implemented. This paper will review the development of a screening protocol for PPD in a multispecialty clinic, with the implementation utilizing depression care managers and the preliminary results of our process. Of the 333 screened examinations during the 4-month study, 38.1% (n = 127) were performed for the 2-month well child examination; 33.6% (n = 112) were for the 4-month examination, with 28.2% (n = 94) being performed for the 6-month well child examination. Only 15 (4.5%) were positive for possible depression with a screening compliance rate of 47.9%. No significant difference was noted in the timing of the well child visit with a positive screening test result, nor was there any difference in family medicine versus pediatric colleagues in the utilization of the screening or diagnosis of PPD. Implementation of PPD screening in a multispecialty clinic can be effective, given utilization of depression care managers.

Postpartum depression screening: initial implementation in a multispecialty practice with collaborative care managers.

The transition of Drosophila third instar larvae from feeding, photo-phobic foragers to non-feeding, photo-neutral wanderers is a classic behavioral switch that precedes pupariation. The neuronal network responsible for this behavior has recently begun to be defined. Previous genetic analyses have identified signaling components for food and light sensory inputs and neuropeptide hormonal outputs as being critical for the forager to wanderer transition. Trio is a Rho-Guanine Nucleotide Exchange Factor integrated into a variety of signaling networks including those governing axon pathfinding in early development. Sequoia is a pan-neuronally expressed zinc-finger transcription factor that governs dendrite and axon outgrowth. Using pre-pupal lethality as an endpoint, we have screened for dominant second-site enhancers of a weakly lethal trio mutant background. In these screens, an allele of sequoia has been identified. While these mutants have no obvious disruption of embryonic central nervous system architecture and survive to third instar larvae similar to controls, they retain forager behavior and thus fail to pupariate at high frequency.

An allele of sequoia dominantly enhances a trio mutant phenotype to influence Drosophila larval behavior.

The purpose of our study was to compare the clinical utility of administering 2 recommended developmental screening instruments, the Infant Developmental Inventory (IDI) and the Ages and Stages Questionnaire (ASQ), at 9-month well-child visits in paper format.

Article	Year
Thyroid dysfunction after pediatric cardiac surgery. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 15116015	2004
Dielectrophoretic force microscopy of aqueous interfaces. Langmuir : the ACS journal of surfaces and colloids\| PubMed ID: 15697292	2005
Reduction of tip-sample contact using dielectrophoretic force scanning probe microscopy. Analytical chemistry\| PubMed ID: 16351149	2005
Nanoscale dielectrophoretic spectroscopy of individual immobilized mammalian blood cells. Biophysical journal\| PubMed ID: 16798803	2006
Anesthesia for sickle cell disease and congenital myopathy in combination. Paediatric anaesthesia\| PubMed ID: 16884472	2006
Experimental evidence for the rapid evolution of behavioral canalization in natural populations. The American naturalist\| PubMed ID: 19627238	2009
Impact of delay in asthma diagnosis on health care service use. Allergy and asthma proceedings : the official journal of regional and state allergy societies\| PubMed ID: 20819315	2010
Impact of delay in asthma diagnosis on chest X-ray and antibiotic utilization by clinicians. The Journal of asthma : official journal of the Association for the Care of Asthma\| PubMed ID: 22149172	2012
Appropriate use of the child developmental review. Pediatric annals\| PubMed ID: 22390312	2012
Impact of implementing mental health screening by mail with a primary care management model. Journal of primary care & community health\| PubMed ID: 23799671	2014
Postpartum depression screening: initial implementation in a multispecialty practice with collaborative care managers. Journal of primary care & community health\| PubMed ID: 23804604	2010
An allele of sequoia dominantly enhances a trio mutant phenotype to influence Drosophila larval behavior. PloS one\| PubMed ID: 24376789	2013
Comparing the Clinical Utility of the Infant Developmental Inventory With the Ages and Stages Questionnaire at 9-Month Well-Child Visits. Journal of primary care & community health\| PubMed ID: 25424742	2014

Brian Lynch

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