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1.
Prehosp Emerg Care ; : 1-4, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38551813

ABSTRACT

INTRODUCTION: We report a case of accelerated idioventricular rhythm (AIVR) identified by Emergency Medical Services (EMS) monitoring of an infant presenting with lethargy and respiratory distress. Accelerated idioventricular rhythms are rare ventricular rhythms originating from the His-Purkinje system or ventricular myocytes, consisting of >3 monomorphic beats with gradual onset and termination.1 An AIVR is usually well-tolerated and does not require treatment, though sustained arrythmia may induce syncope, and the rhythm has been seen in newborn infants with congenital heart diseases.1 Monitoring ill children with ECG can identify such dysrhythmias in the prehospital setting. CASE REPORT: An 18-month-old male presented to their pediatrician with lethargy and respiratory distress, prompting activation of EMS. The patient was placed on a 4-lead ECG initially revealing monomorphic QRS complexes at a rate of 170 beats per minute (BPM). A 12-lead ECG was interpreted as sinus tachycardia by the paramedics who noted the QRS complexes were "getting taller and shorter" with a stable rapid heart rate. The clinician then noted a consistently wide tachycardia which spontaneously converted to a narrow complex tachycardia. The QRS pattern remained variable, with notation of variable R-wave height. After arrival to the emergency department, pediatric cardiology was consulted and interpreted the prehospital ECG findings as accelerated idioventricular rhythm. The patient experienced multiple occurrences of accelerated idioventricular rhythm during hospitalization without associated hypoxia or decreased perfusion. DISCUSSION: Accelerated idioventricular rhythm is relatively rare entity without underlying cardiac disease and most cases are asymptomatic or benign. In the pediatric population, AIVR is generally related to congenital heart defects, cardiac tumors, and cardiomyopathies. In the prehospital setting, continuous ECG monitoring should be a part of care by Advanced Life Support personnel in children with altered mental status, respiratory distress, unexplained syncope, or suspected arrhythmias and 12 lead ECG should be considered if there is any abnormality noted. While this patient did not experience persisting morbidity from AIVR, the potentially hazardous rhythm would not have been recognized without the astute observation, clinical management and persistent follow up of the prehospital clinicians.

2.
Pediatr Cardiol ; 44(8): 1808-1814, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37129601

ABSTRACT

Safety and acute outcomes for patients who need catheterization shortly after congenital cardiac surgery has been established; literature on mid-term outcomes is lacking. We sought to evaluate the mid-term outcomes of patients who undergo early postoperative cardiac catheterization. This is a retrospective cohort study of patients who underwent cardiac catheterization within 6 weeks of congenital cardiac surgery with longitudinal follow-up and assessment of mid-term outcomes. Multivariable analysis was utilized to relate variables of interest to outcomes. 99 patients underwent cardiac catheterizations within 6 weeks of cardiac surgery between January 2008 and September 2016. Forty-six (45.5%) interventional procedures were performed at a median age of 41 days (IQR 21-192) and a median weight of 3.9 kg (3.3-6.6). During a median follow-up duration of 4.24 years (1.6-5.6) in study survivors, 61% of patients remained free from the primary endpoint (death and/or transplant). Sixty-nine patients (69.7%) underwent an unplanned surgical or catheter procedure. Renal failure at catheterization (OR 280.5, p 0.0199), inotropic medication at catheterization (OR 14.8, p 0.002), and younger age were all significantly associated with meeting the primary endpoint. Patients requiring surgical intervention as an initial additional intervention underwent more unplanned re-interventions, while patients who survived to hospital discharge demonstrated favorable mortality, though with frequent need for re-intervention. In patients requiring early postoperative cardiac catheterization, renal failure, younger age, and need for inotropic support at catheterization are significantly associated with meeting the primary endpoint.


Subject(s)
Cardiac Surgical Procedures , Heart Defects, Congenital , Child , Humans , Infant , Retrospective Studies , Treatment Outcome , Cardiac Surgical Procedures/adverse effects , Cardiac Catheterization/adverse effects
3.
New Phytol ; 232(1): 418-424, 2021 10.
Article in English | MEDLINE | ID: mdl-33991343

ABSTRACT

A robust understanding of phloem functioning in tall trees evades us because current methods for collecting phloem sap do not lend themselves to measuring actively photosynthesizing canopy leaves. We show that Raman spectroscopy can be used as a quantitative tool to assess sucrose concentration in leaf samples. Specifically, we found that Raman spectroscopy can predict physiologically relevant sucrose concentrations (adjusted R2 of 0.9) in frozen leaf extract spiked with sucrose. We then apply this method to estimate sieve element sucrose concentration in rapidly frozen petioles of canopy red oak (Quercus rubra) trees and found that sucrose concentrations are > 1100 mM at midday and midnight. This concentration is predicted to generate a sieve element turgor pressure high enough to generate bulk flow through the phloem, but is potentially too high to allow for sucrose diffusion from photosynthetic cells. Our findings support the Münch hypothesis for phloem transport once the carbon is in the phloem and challenge the passive-loading hypothesis for carbon movement into the phloem for red oak. This study provides the first ˜in-situ (frozen in the functioning state) source sieve element sucrose concentration characterization in any plant, opening a new avenue for investigation of phloem functioning.


Subject(s)
Phloem , Quercus , Biological Transport , Plant Leaves , Spectrum Analysis, Raman , Sugars , Trees
4.
Plant Physiol ; 183(4): 1612-1621, 2020 08.
Article in English | MEDLINE | ID: mdl-32471810

ABSTRACT

Trees typically experience large diurnal depressions in water potential, which may impede carbon export from leaves during the day because the xylem is the source of water for the phloem. As water potential becomes more negative, higher phloem osmotic concentrations are needed to draw water in from the xylem. Generating this high concentration of sugar in the phloem is particularly an issue for the ∼50% of trees that exhibit passive loading. These ideas motivate the hypothesis that carbon export in woody plants occurs predominantly at night, with sugars that accumulate during the day assisting in mesophyll turgor maintenance or being converted to starch. To test this, diurnal and seasonal patterns of leaf nonstructural carbohydrates, photosynthesis, solute, and water potential were measured, and carbon export was estimated in leaves of five mature (>20 m tall) red oak (Quercus rubra) trees, a species characterized as a passive loader. Export occurred throughout the day at equal or higher rates than at night despite a decrease in water potential to -1.8 MPa at midday. Suc and starch accumulated over the course of the day, with Suc contributing ∼50% of the 0.4 MPa diurnal osmotic adjustment. As a result of this diurnal osmotic adjustment, estimates of midday turgor were always >0.7 MPa. These findings illustrate the robustness of phloem functioning despite diurnal fluctuations in leaf water potential and the role of nonstructural carbohydrates in leaf turgor maintenance.


Subject(s)
Carbon/metabolism , Plant Leaves/metabolism , Quercus/metabolism , Water/metabolism
5.
Oecologia ; 192(3): 671-685, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32052180

ABSTRACT

Warming-induced nutrient enrichment in the Arctic may lead to shifts in leaf-level physiological properties and processes with potential consequences for plant community dynamics and ecosystem function. To explore the physiological responses of Arctic tundra vegetation to increasing nutrient availability, we examined how a set of leaf nutrient and physiological characteristics of eight plant species (representing four plant functional groups) respond to a gradient of experimental nitrogen (N) and phosphorus (P) enrichment. Specifically, we examined a set of chlorophyll fluorescence measures related to photosynthetic efficiency, performance and stress, and two leaf nutrient traits (leaf %C and %N), across an experimental nutrient gradient at the Arctic Long Term Ecological Research site, located in the northern foothills of the Brooks Range, Alaska. In addition, we explicitly assessed the direct relationships between chlorophyll fluorescence and leaf %N. We found significant differences in physiological and nutrient traits between species and plant functional groups, and we found that species within one functional group (deciduous shrubs) have significantly greater leaf %N at high levels of nutrient addition. In addition, we found positive, saturating relationships between leaf %N and chlorophyll fluorescence measures across all species. Our results highlight species-specific differences in leaf nutrient traits and physiology in this ecosystem. In particular, the effects of a gradient of nutrient enrichment were most prominent in deciduous plant species, the plant functional group known to be increasing in relative abundance with warming in this ecosystem.


Subject(s)
Ecosystem , Tundra , Alaska , Arctic Regions , Nutrients
7.
Cornea ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39231626

ABSTRACT

PURPOSE: The purpose of this study was to determine the prevalence of glaucoma and/or ocular hypertension (G/OHTN) in patients with Fuchs endothelial corneal dystrophy (FECD) and correlate with FECD severity and TCF4 cytosine-thymine-guanine18.1 (CTG18.1) trinucleotide repeat expansion genotype. METHODS: We included 167 FECD probands and 110 controls from the University of Texas Southwestern Medical Center FECD Genetics Study to estimate the association between FECD and G/OHTN. Participants underwent slit-lamp microscopy for the assessment of Krachmer grade disease severity of FECD. The diagnosis of G/OHTN was ascertained using a patient-reported history of G/OHTN, previous glaucoma surgery and/or glaucoma laser procedure, and use of glaucoma drops. Genomic DNA from blood of participants was used to genotype the CTG18.1 repeat polymorphism by fragment analysis using short tandem repeat and triplet repeat primed polymerase chain reaction assays. RESULTS: We observed a 19.2% prevalence of G/OHTN in the FECD probands compared with that of 7.3% in controls. The odds ratio of developing G/OHTN in FECD cases compared with controls was estimated to be 3.34 with a 95% confidence interval of 1.42-7.79 adjusting for age and sex. Among FECD cases, the likelihood of developing G/OHTN correlated positively with Krachmer grade (P = 0.043) and age (P = 0.026). There was no statistical difference of the proportions of patients developing G/OHTN between FECD cases with and without TCF4 CTG18.1 repeat expansion (16 out of 94 and 15 out of 72, respectively, P > 0.05). CONCLUSIONS: Patients with clinically significant FECD should be routinely monitored for the development of glaucoma regardless of their TCF4 repeat expansion genotype.

8.
Mil Med ; 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38430524

ABSTRACT

INTRODUCTION: Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. MATERIALS AND METHODS: Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. RESULTS: A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. CONCLUSIONS: The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

9.
J Adolesc Health ; 2024 Aug 11.
Article in English | MEDLINE | ID: mdl-39140928

ABSTRACT

PURPOSE: Pediatric gender-affirming medical care has strong research evidence and support, and transition-related regret is uncommon. Misinformation about regret has nonetheless been used to limit adolescents from accessing this care. This study is the first of a 3-part initiative to clarify long-term satisfaction and regret related to pediatric gender-affirming care (GAC). METHODS: An anonymous survey was distributed to individuals of age 15 and older who participated in at least one prior appointment at a large pediatric gender clinic. The survey questions included (1) demographics; (2) use of gender-affirming interventions; (3) barriers to accessing medical interventions; (4) reasons for any discontinuation of medical interventions; (5) emotions associated with GAC; and (6) intervention-related regret. RESULTS: Participants (N = 150; Mage = 18.6) were predominantly transmasculine-identified and/or assigned female at birth (86%). The most common emotions associated with GAC were satisfaction (88.0%) and confidence (86.7%). A total of 141 participants reported taking hormones, 30 of whom reported ever discontinuing (21.3%). Among these, 11 have already resumed hormones, and 16 might resume. Of the three with no plan to resume hormones, one is fully satisfied with the results, and the remaining two no longer identify as transgender. Only one participant (0.7% of those who ever took hormones) wishes they had never started testosterone or had top surgery, both of which occurred in adulthood. DISCUSSION: Individuals who accessed GAC as adolescents are largely satisfied with this care. Care-related satisfaction and regret are more nuanced than sometimes portrayed and should not be used to limit access.

10.
Cureus ; 15(6): e40944, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37496545

ABSTRACT

Sulfhemoglobin is formed by the irreversible bonding of sulfur atoms to the heme molecule. Oxygen is then unable to bind the heme molecule, rendering the hemoglobin molecule unable to carry oxygen. The most common etiology of sulfhemoglobinemia is the use/misuse of sulfur-containing medications such as AZO. Unlike methemoglobin, sulfhemoglobin, due to its irreversible binding, has no antidote, and the treatment is ultimately supportive. We present a case of a 53-year-old female who presented to the emergency room endorsing dysuria and was noted to have abnormally low oxygen saturation (SpO2) despite having high arterial oxygen pressure (PaO2) on blood gas. History was significant for dysuria developed while traveling and the use of over-the-counter AZO four times daily for the past 10 days. She was diagnosed with a presumed dyshemoglobinemia and, upon return of send-out labs, was confirmed to have sulfhemoglobinemia attributed to phenazopyridine. This case highlights the importance of the recognition of potential dyshemoglobinemias and consideration of sulfhemoglobinemia as a potential causative etiology, especially in patients taking sulfur-containing medications.

11.
Mil Med ; 188(Suppl 6): 400-406, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37948261

ABSTRACT

INTRODUCTION: Evaluation of chronic respiratory symptoms in deployed military personnel has been conducted at Brooke Army Medical Center as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Although asthma and airway hyperreactivity have been the most common diagnoses, the clinical findings in these patients may be multifactorial. This study aims to evaluate the utility of impulse oscillometry (IOS) in diagnosing airway obstruction in patients undergoing multiple pulmonary function testing (PFT) studies. METHODS: Military personnel referred for deployed-related pulmonary symptoms underwent a standardized evaluation at Brooke Army Medical Center and Walter Reed National Military Medical Center over a 5-year span. Initial studies included laboratory tests, high-resolution computed tomography imaging, cardiac evaluation with electrocardiogram, and echocardiography. PFT consisted of full PFTs, forced inspiratory/expiratory pressures, post-spirometry bronchodilator testing, IOS, exhaled nitric oxide, and methacholine challenge testing. RESULTS: A total of 360 patients have completed an evaluation to date. In this cohort, 108 patients (30.0%) have evidence of obstruction by spirometry, whereas 74 (20.6%) had IOS values of both an R5 > 150% and X5 < -1.5. Only 32 (8.9%) had evidence of obstruction by both spirometry and IOS, whereas 210 (57.3%) had neither. A comparison among R5 (resistance at 5 Hz), R20 (resistance at 20 Hz), and X5 (reactance at 5 Hz) was performed in those individuals with and without spirometric obstruction. R5 (% predicted) was 156.2 ± 57.4% (obstruction) vs. 129.1 ± 39.6% (no obstruction) (P < .001); R20 (% predicted) was 138.1 ± 37.7% (obstruction) vs. 125.3 ± 31.2% (no obstruction) (P = .007); and X5 (cmH2O/L/s) was -1.62 ± 1.28 (obstruction) vs. -1.25 ± 0.55 (no obstruction) (P < .001). DISCUSSION: Impulse oscillometry has been advocated as a supplemental pulmonary function test to aid in the diagnosis of airway obstruction. The use of IOS has been primarily used in pediatrics and elderly populations as a validated tool to establish a diagnosis of airway obstruction but is limited in the adult population because of a well-validated set of reference values. Prior studies in adults have most often demonstrated a correlation with an elevated R5 > 150%, elevated resonant frequency, and a negative X5 < -1.5 or a decrease of 30 to 35% in R5 post-bronchodilator. CONCLUSION: Impulse oscillometry may serve as an adjunct to diagnosis but likely cannot replace a standard spirometric evaluation. Our study highlights the future utility for diagnosing early obstructive disease in the symptomatic individual.


Subject(s)
Airway Obstruction , Asthma , Military Personnel , Adult , Humans , Child , Aged , Bronchodilator Agents , Oscillometry/methods , Forced Expiratory Volume , Respiratory Function Tests/methods , Airway Obstruction/diagnosis , Spirometry/methods , Asthma/complications , Asthma/diagnosis
12.
J Trauma Acute Care Surg ; 94(3): 379-384, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36730087

ABSTRACT

BACKGROUND: Ultrasound (US) for the detection of pneumothorax shows excellent sensitivity in the hands of skilled providers. Artificial intelligence may facilitate the movement of US for pneumothorax into the prehospital setting. The large amount of training data required for conventional neural network methodologies has limited their use in US so far. METHODS: A limited training database was supplied by Defense Advanced Research Projects Agency of 30 patients, 15 cases with pneumothorax and 15 cases without. There were two US videos per patient, of which we were allowed to choose one to train on, so that a limited set of 30 videos were used. Images were annotated for ribs and pleural interface. The software performed anatomic reconstruction to identify the region of interest bounding the pleura. Three neural networks were created to analyze images on a pixel-by-pixel fashion with direct voting determining the outcome. Independent verification and validation was performed on a data set gathered by the Department of Defense. RESULTS: Anatomic reconstruction with the identification of ribs and pleura was able to be accomplished on all images. On independent verification and validation against the Department of Defense testing data, our program concurred with the SME 80% of the time and achieved a 86% sensitivity (18/21) for pneumothorax and a 75% specificity for the absence of pneumothorax (18/24). Some of the mistakes by our artificial intelligence can be explained by chest wall motion, hepatization of the underlying lung, or being equivocal cases. CONCLUSION: Using learning with limited labeling techniques, pneumothorax was identified on US with an accuracy of 80%. Several potential improvements are controlling for chest wall motion and the use of longer videos. LEVEL OF EVIDENCE: Diagnostic Tests; Level III.


Subject(s)
Pneumothorax , Thoracic Wall , Humans , Artificial Intelligence , Sensitivity and Specificity , Ultrasonography
13.
Transgend Health ; 7(2): 144-149, 2022 Apr.
Article in English | MEDLINE | ID: mdl-36644517

ABSTRACT

Purpose: Access to early, multidisciplinary, gender-affirming health care significantly improves the psychosocial well-being of transgender and gender diverse youth. The Doernbecher Gender Clinic (DGC) is an interdisciplinary pediatric gender clinic consisting of endocrinology, psychology, and social work. Following the initiation of modified operations in March 2020 due to the COVID-19 pandemic, the DGC converted all interdisciplinary new patient appointments to telehealth. The purpose of this article is to (1) describe the model of care implemented during modified operations, (2) compare the number of new patients seen before and after modified operations, and (3) to contextualize this information with data from a patient satisfaction survey. Method: Retrospective chart review was used to determine how many interdisciplinary new patient appointments occurred before and during modified operations. Additional variables included age, gender, visit modality (phone or video), geographic location, and number of caregivers who participated. In addition, patients and families who attended appointments since modified operations were invited to complete a prospective survey regarding their experience and satisfaction with these appointments, and the narrative responses to questions about advantages and disadvantages were analyzed thematically. Results: Chart review revealed a similar number and make up of new patient appointments before and after the initiation of modified operations. The percentage of patients residing in other urban areas outside of the Portland metro increased over the course of the three time periods, but not to a significant degree. Survey results suggest that both telehealth and in-person visits have advantages and disadvantages with regard to (1) access and (2) comfort. Families appear to differ with regard to their priorities in each area. Conclusion: Telehealth has the potential to provide quality pediatric gender-affirming health care without sacrificing the benefits of an interdisciplinary team-based approach.

14.
PLoS One ; 17(6): e0266483, 2022.
Article in English | MEDLINE | ID: mdl-35771778

ABSTRACT

PURPOSE: Obstructive sleep apnea (OSA) is an established independent risk factor for peripheral neuropathy. Macro and microvascular changes have been documented in OSA, including high levels of potent vasoconstrictors. In diabetes, vasoconstriction has been identified as an underlying risk factor for corneal neuropathy. This study sought to establish a potential relationship between OSA and corneal nerve morphology and sensitivity, and to determine whether changes in corneal nerves may be reflective of OSA severity. DESIGN: Single center cross-sectional study. METHODS: Sixty-seven patients were stratified into two groups: those with OSA and healthy controls. Groups were matched for age, sex, race, smoking, and dry eye status. Outcome measures included serologies, a dilated fundus exam, dry eye testing, anthropometric parameters, corneal sensitivity, subbasal nerve plexus morphology, retinal nerve fiber layer (RNFL) thickness, and the use of questionnaires to assess symptoms of dry eye disease, risk of OSA, and continuous positive airway pressure (CPAP) compliance. RESULTS: No significant differences were observed in corneal nerve morphology, sensitivity, or the number of dendritic cells. In the OSA test group, RNFL thinning was noted in the superior and inferior regions of the optic disc and peripapillary region. A greater proportion of participants in the OSA group required a subsequent evaluation for glaucoma than in the control. In those with OSA, an increase in the apnea hypopnea index was associated with an increase in optic nerve cupping. CONCLUSIONS: OSA does not exert a robust effect on corneal nerves. OSA is however, associated with thinning of the RNFL. Participants with glaucomatous optic nerve changes and risk factors for OSA should be examined as uncontrolled OSA may exacerbate glaucoma progression.


Subject(s)
Dry Eye Syndromes , Glaucoma , Sleep Apnea, Obstructive , Cross-Sectional Studies , Dry Eye Syndromes/complications , Glaucoma/complications , Humans , Nerve Fibers , Retinal Ganglion Cells , Tomography, Optical Coherence
15.
J Struct Funct Genomics ; 12(2): 63-76, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21359640

ABSTRACT

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.


Subject(s)
Bacterial Proteins/chemistry , Burkholderia pseudomallei/enzymology , Phosphorus-Oxygen Lyases/chemistry , Binding Sites , Catalytic Domain , Crystallography, X-Ray , Drug Design , Ligands , Magnetic Resonance Spectroscopy
16.
BMC Struct Biol ; 11: 39, 2011 Oct 13.
Article in English | MEDLINE | ID: mdl-21995815

ABSTRACT

BACKGROUND: Ribose-5-phosphate isomerase is an enzyme that catalyzes the interconversion of ribose-5-phosphate and ribulose-5-phosphate. This family of enzymes naturally occurs in two distinct classes, RpiA and RpiB, which play an important role in the pentose phosphate pathway and nucleotide and co-factor biogenesis. RESULTS: Although RpiB occurs predominantly in bacteria, here we report crystal structures of a putative RpiB from the pathogenic fungus Coccidioides immitis. A 1.9 Å resolution apo structure was solved by combined molecular replacement and single wavelength anomalous dispersion (SAD) phasing using a crystal soaked briefly in a solution containing a high concentration of iodide ions. RpiB from C. immitis contains modest sequence and high structural homology to other known RpiB structures. A 1.8 Å resolution phosphate-bound structure demonstrates phosphate recognition and charge stabilization by a single positively charged residue whereas other members of this family use up to five positively charged residues to contact the phosphate of ribose-5-phosphate. A 1.7 Å resolution structure was obtained in which the catalytic base of C. immitis RpiB, Cys76, appears to form a weakly covalent bond with the central carbon of malonic acid with a bond distance of 2.2 Å. This interaction may mimic that formed by the suicide inhibitor iodoacetic acid with RpiB. CONCLUSION: The C. immitis RpiB contains the same fold and similar features as other members of this class of enzymes such as a highly reactive active site cysteine residue, but utilizes a divergent phosphate recognition strategy and may recognize a different substrate altogether.


Subject(s)
Aldose-Ketose Isomerases/chemistry , Coccidioides/enzymology , Aldose-Ketose Isomerases/genetics , Aldose-Ketose Isomerases/metabolism , Amino Acid Sequence , Binding Sites , Catalytic Domain , Crystallography, X-Ray , Iodides/chemistry , Molecular Sequence Data , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Ribulosephosphates/chemistry , Ribulosephosphates/metabolism , Sequence Alignment , Substrate Specificity
17.
Int J Obes (Lond) ; 35(4): 522-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21386800

ABSTRACT

OBJECTIVE: To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (<6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. DESIGN: Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. METHODS: A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. RESULTS: Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76). CONCLUSION: The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.


Subject(s)
Anti-Bacterial Agents/adverse effects , Cesarean Section/adverse effects , Delivery, Obstetric/methods , Gastrointestinal Tract/microbiology , Obesity/etiology , Adolescent , Adult , Anti-Bacterial Agents/administration & dosage , Body Mass Index , Child , Female , Humans , Infant, Newborn , Longitudinal Studies , Male , Metagenome , Mothers , Pregnancy , Prospective Studies , Risk Factors , Surveys and Questionnaires , Young Adult
18.
Eye Contact Lens ; 37(6): 332-6, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21912260

ABSTRACT

OBJECTIVES: The prevalence of primary open-angle glaucoma (POAG) in patients with corneal endothelial dystrophy has not been previously studied. Prevalence of POAG in patients with endothelial dystrophy was compared with that in the general population to determine the presence of a relationship between the diseases. DESIGN: Retrospective case-control study. METHODS: A study of the prevalence of POAG in 430 eyes of 215 patients with endothelial dystrophy was conducted. Patients followed for less than 6 months were excluded. Relative risk of POAG was calculated using age- and race-matched control data from the Baltimore Eye Survey and the Los Angeles Latino Eye Survey for comparison. Ocular hypertension (OHT) and secondary glaucoma (SG) rates after penetrating keratoplasty (PK) and Descemet stripping endothelial keratoplasty (DSEK) were separately analyzed. RESULTS: Relative risk of POAG in white, African American, and Hispanic patients with endothelial dystrophy was 0.94, 2.59, and 3.7, respectively (P = 0.89, 95% confidence interval [CI], -0.028 to 0.0289; P = 0.13; 95% CI, 0.011-0.274; P = 0.055; 95% CI, 0.0423-0.356). Relative risk of SG and combined OHT/SG in PK versus DSEK was 4.15 and 1.95 (P < 0.001; 95% CI, 0.0654-0.322; P = 0.005; 95% CI, 0.116-0.332), respectively. No differences in OHT/SG rates were found comparing PK-triple with PK, DSEK-triple with DSEK, and repeat with primary PK or DSEK (P = 0.98; P = 0.62; P = 0.95; P = 0.87), respectively. CONCLUSIONS: No increased risk of POAG was found in patients with endothelial dystrophy. Increased prevalence of OHT/SG was shown with PK versus DSEK; possible mechanisms include mechanical closure of Schlemm's canal by running suture and prolonged steroid use.


Subject(s)
Fuchs' Endothelial Dystrophy/complications , Glaucoma, Open-Angle/epidemiology , Black or African American , Case-Control Studies , Female , Fuchs' Endothelial Dystrophy/ethnology , Fuchs' Endothelial Dystrophy/surgery , Glaucoma, Open-Angle/ethnology , Hispanic or Latino , Humans , Male , Ocular Hypertension/epidemiology , Ocular Hypertension/ethnology , Prevalence , Retrospective Studies , Risk Factors , United States/epidemiology
19.
Eye Contact Lens ; 36(4): 223-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20539235

ABSTRACT

PURPOSE: To identify the incidence of and risk factors for intraocular pressure (IOP) elevation after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Retrospective review was conducted of 68 consecutive DSAEK procedures alone, or in combination with phacoemulsification with intraocular lens implantation or exchange, performed by two surgeons at the University of Texas Southwestern Medical Center between 2005 and 2009. Eyes that developed IOP elevation above 21 mm Hg after DSAEK and requiring initiation or escalation of glaucoma therapy were evaluated. RESULTS: Thirty-seven (54%) eyes showed IOP elevation responsive to medical treatment by a mean follow-up of 11.38 +/- 7.81 months. Six (8.8%) eyes required glaucoma surgery. In the eyes, which developed elevated IOP, gonioscopy did not reveal any new peripheral anterior synechiae formation. Prolonged topical steroid usage, rebubbling, combined DSAEK/cataract surgery, or repeat DSAEK were not significant factors (P>0.05) for development of elevated IOP, but history of previous glaucoma or ocular hypertension (OHTN) was significant (P=0.007). CONCLUSIONS: Intraocular pressure elevation is not uncommon in eyes after DSAEK, but most cases can be controlled with conservative management. Intraocular pressure elevation post-DSAEK occurred by mechanisms other than peripheral anterior synechial angle closure. The only significant risk factor for development of elevated IOP in our series was a previous history of glaucoma or OHTN.


Subject(s)
Corneal Diseases/surgery , Corneal Transplantation/adverse effects , Descemet Membrane/surgery , Endothelium, Corneal/transplantation , Intraocular Pressure , Ocular Hypertension/etiology , Adult , Aged , Aged, 80 and over , Corneal Diseases/physiopathology , Corneal Transplantation/methods , Descemet Membrane/pathology , Endothelium, Corneal/pathology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Ocular Hypertension/epidemiology , Ocular Hypertension/physiopathology , Postoperative Complications , Retrospective Studies , Risk Factors , Texas/epidemiology , Tomography, Optical Coherence
20.
Int Med Case Rep J ; 13: 7-10, 2020.
Article in English | MEDLINE | ID: mdl-32021492

ABSTRACT

Charles Bonnet syndrome (CBS) is a condition of visual hallucinations or disturbances occurring in patients with visual pathway pathology not due to underlying psychiatric, metabolic, or neurologic disease. A patient with Parkinson's disease experiencing visual hallucinations was evaluated by the ophthalmology service and found to have decreased vision due to bilateral reversible posterior capsular opacification. The patient's hallucinations did not improve on clozapine, a medication requiring careful monitoring due to potentially severe systemic side effects. However, the hallucinations resolved and vision improved after bilateral treatment of the posterior capsular opacification. Clozapine was then discontinued, and the patient was able to resume his previous Parkinson's disease therapy. This case highlights the importance of considering visual pathway pathology as a contributing factor to visual hallucinations, even in patients with previously diagnosed underlying psychiatric, metabolic, or neurologic disease that could additionally be the etiology of the visual disturbances.

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