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2.
Sci Rep ; 12(1): 13225, 2022 08 02.
Article in English | MEDLINE | ID: mdl-35918463

ABSTRACT

Acute kidney injury (AKI) increases the risk of morbidity, mortality, and progression to chronic kidney disease (CKD). There are few data on the risk of CKD following community-acquired AKI (CA-AKI) and its predictors from developing countries. We evaluated the association of a panel of serum and urine biomarkers at the time of hospital discharge with 4-month renal outcome in CA-AKI. Patients of either sex, aged between 18 and 70 years, with no underlying CKD, and with CA-AKI were recruited at the time of discharge from hospital in this prospective observational study. Levels of serum and urine biomarkers were analyzed and association between these markers and development of CKD, defined as eGFR < 60 ml/min/1.73 m2 or dialysis dependence at 4 month after discharge, were analyzed using multivariate logistic regression analysis and penalized least absolute shrinkage and selection operator logistic regression. Out of a total 126 patients followed up for 4 months, 25 developed CKD. Those who developed CKD were older (p = 0.008), had higher serum creatinine (p < 0.001) and lower serum albumin (p = 0.001) at discharge. Adjusted logistic regression showed that each 10% increase in standardized serum myo-inositol oxygenase (MIOX) level increased the odds of progression to CKD by 13.5%. With 10% increase in standardized urine Neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine and urine protein creatinine ratio (uPCR), increase in the odds of progression to CKD was 10.5%, 9.6% and 8%, respectively. Multivariable logistic model including serum MIOX, discharge serum creatinine and discharge uPCR, was able to predict the progression of CKD [AUC ROC 0.88; (95% CI 0.81, 0.95)]. High level serum MIOX levels at the time of discharge from hospital are associated with progression to CKD in patients with CA-AKI.


Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Acute Kidney Injury/metabolism , Adolescent , Adult , Aged , Biomarkers , Creatinine , Hospitals , Humans , Inositol Oxygenase/metabolism , Lipocalin-2/urine , Middle Aged , Patient Discharge , Renal Dialysis , Renal Insufficiency, Chronic/complications , Young Adult
3.
Cornea ; 41(9): 1094-1102, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35315617

ABSTRACT

PURPOSE: The purpose of this study was to determine longitudinal trends in prevalence and resistance profiles for infectious keratitis at referral centers in Southern California. METHODS: Cultured infectious keratitis cases from January 1, 2006, through December 31, 2009, and January 1, 2016, through December 31, 2019, at the University of California, Los Angeles, were evaluated. Outcome measures included microbial isolate prevalence and antibiotic/antifungal susceptibility and resistance patterns. RESULTS: One hundred thirty-nine and 315 culture-positive isolates were obtained between 2006-2009 and 2016-2019, respectively. Gram-positive organisms accounted for 65% (2006-2009) and 74% (2016-2019) of bacterial isolates ( P = 0.076). Staphylococcus infections, the most common gram-positive and bacterial isolate in both study epochs, demonstrated increased prevalence from 2006-2009 to 2016-2019 (41% vs. 53%, P = 0.019). Although coagulase-negative Staphylococcus (CoNS) increased from 40% to 58% ( P = 0.0012), the prevalence of methicillin-resistant Staphylococcus aureus was unchanged (28% vs. 28%, P = 0.99). Pseudomonas aeruginosa , the most common gram-negative organism, demonstrated decreased prevalence from 18% to 10% ( P = 0.027). Candida species comprised 3.5% of culture-positive isolates in both epochs. All gram-positive isolates were susceptible to vancomycin, and all Staphylococcus isolates were susceptible to linezolid. Pseudomonas aeruginosa remained susceptible to tested fluoroquinolones (>93%) and aminoglycosides (100%) over time. CONCLUSIONS: In southern California between 2006 and 2019, there was a shift toward Staphylococcus species, with increased CoNS, decreased methicillin-sensitive Staphylococcus aureus , and decreased prevalence of P. aeruginosa . Empiric therapy of vancomycin and a fluoroquinolone or aminoglycoside provides effective antibacterial coverage for predominant bacterial species when culture sensitivities are pending.


Subject(s)
Eye Infections, Bacterial , Keratitis , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Eye Infections, Bacterial/microbiology , Fluoroquinolones , Humans , Keratitis/drug therapy , Keratitis/epidemiology , Keratitis/microbiology , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Retrospective Studies , Staphylococcal Infections/drug therapy , Vancomycin
4.
J Clin Neurosci ; 89: 437-447, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34052071

ABSTRACT

Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.


Subject(s)
Diagnostic Imaging/methods , Ophthalmologic Surgical Procedures/adverse effects , Orbit/surgery , Postoperative Complications/diagnostic imaging , Humans , Orbit/diagnostic imaging , Postoperative Complications/etiology
5.
Ophthalmic Surg Lasers Imaging Retina ; 52(2): 84-92, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33626169

ABSTRACT

BACKGROUND AND OBJECTIVE: To identify factors associated with successful treatment discontinuation in eyes with retinal vein occlusions (RVOs) and macular edema (ME) in real-world settings. PATIENTS AND METHODS: Retrospective study of 214 eyes with RVO and ME with 24-month follow-up at five academic centers. Regression analyses identified factors associated with (1) successful treatment discontinuation for at least 6 months without fluid recurrence and (2) best-corrected visual acuity (BCVA) at 24 months. RESULTS: Forty percent of eyes with branch RVO and 35% with central RVO (CRVO) / hemi-retinal RVO (HRVO) successfully discontinued therapy without fluid recurrence, with median time to discontinuation of 6 and 7 months, respectively. Lower 6-month central subfield thickness was associated with greater likelihood of treatment discontinuation within 24 months for eyes with CRVO/HRVO (P = .001), whereas better 6-month BCVA was associated with better 24-month BCVA for all RVO subtypes (P < .001). CONCLUSION: Early anatomic response at 6 months is associated with greater likelihood of stopping treatments. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:84-92.].


Subject(s)
Macular Edema , Retinal Vein Occlusion , Angiogenesis Inhibitors/therapeutic use , Follow-Up Studies , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Retina , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity
6.
J Clin Exp Hepatol ; 10(4): 316-321, 2020.
Article in English | MEDLINE | ID: mdl-32655234

ABSTRACT

BACKGROUND: Renal replacement therapy in the form of either dialysis or transplantation is the only option for end-stage renal disease (ESRD). Blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are of special concern in these patients because of their high incidence. Although there are sufficient data from the developed world, there is scarcity of data from developing countries such as India. METHODS: All newly diagnosed ESRD patients initiated on hemodialysis after attending the Department of Nephrology, PGIMER, Chandigarh between January 2015 and October 2015 were included in the study. All the subjects were initially screened for HCV and HBV serology status and subsequent HCV and HBV status on follow-up at the end of 6 months and evaluated by standardized precoded questionnaires and biochemical examinations. Univariate and multivariate analyses were done to identify the risk factors for seroconversion. RESULTS: A total of 196 patients were recruited for the study after confirming seronegative status. At the end of 6 months, 61 patients lost to follow-up. Anti-HCV antibody had shown moderate association to HCV RNA testing at the end of 6 months by kappa test. Out of 135, 16.3% seroconverted to HCV RNA positive and 0.7% patient became hepatitis B surface antigen positive. Isolation of dialysis machine and nursing staff was associated with lower seroconversion. CONCLUSION: In a real-life scenario, HCV seroconversion is observed in 15% of the patients initiated on hemodialysis. Isolation of both dialysis machine and personnel was associated with lower seroconversion.

7.
Klin Monbl Augenheilkd ; 237(6): 745-753, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32516831

ABSTRACT

Endothelial decompensation can occur from a variety of insults to the endothelium that result in loss of stromal clarity. Direct insults to the endothelium commonly occur in inherited, inflammatory, traumatic, immunological, and infectious etiologies. These injuries may cause transient injury without decompensation, but repetitive injury or severe isolated injury can lead to permanent non-compensatory endothelial cell loss. Elevated intraocular pressure can induce stromal hydration, either primarily or secondarily. With partial and full thickness corneal transplants, chronic endothelial dysfunction can be treated surgically when medical therapy proves inadequate. Practitioners should be aware of the underlying causes for corneal endothelial injury.


Subject(s)
Corneal Diseases , Endothelium, Corneal , Humans
8.
Ophthalmology ; 127(8): 1105-1112, 2020 08.
Article in English | MEDLINE | ID: mdl-32197913

ABSTRACT

PURPOSE: Aggressive posterior retinopathy of prematurity (AP-ROP) is a vision-threatening disease with a significant rate of progression to retinal detachment. The purpose of this study was to characterize AP-ROP quantitatively by demographics, rate of disease progression, and a deep learning-based vascular severity score. DESIGN: Retrospective analysis. PARTICIPANTS: The Imaging and Informatics in ROP cohort from 8 North American centers, consisting of 947 patients and 5945 clinical eye examinations with fundus images, was used. Pretreatment eyes were categorized by disease severity: none, mild, type 2 or pre-plus, treatment-requiring (TR) without AP-ROP, TR with AP-ROP. Analyses compared TR with AP-ROP and TR without AP-ROP to investigate differences between AP-ROP and other TR disease. METHODS: A reference standard diagnosis was generated for each eye examination using previously published methods combining 3 independent image-based gradings and 1 ophthalmoscopic grading. All fundus images were analyzed using a previously published deep learning system and were assigned a score from 1 through 9. MAIN OUTCOME MEASURES: Birth weight, gestational age, postmenstrual age, and vascular severity score. RESULTS: Infants who demonstrated AP-ROP were more premature by birth weight (617 g vs. 679 g; P = 0.01) and gestational age (24.3 weeks vs. 25.0 weeks; P < 0.01) and reached peak severity at an earlier postmenstrual age (34.7 weeks vs. 36.9 weeks; P < 0.001) compared with infants with TR without AP-ROP. The mean vascular severity score was greatest in TR with AP-ROP infants compared with TR without AP-ROP infants (8.79 vs. 7.19; P < 0.001). Analyzing the severity score over time, the rate of progression was fastest in infants with AP-ROP (P < 0.002 at 30-32 weeks). CONCLUSIONS: Premature infants in North America with AP-ROP are born younger and demonstrate disease earlier than infants with less severe ROP. Disease severity is quantifiable with a deep learning-based score, which correlates with clinically identified categories of disease, including AP-ROP. The rate of progression to peak disease is greatest in eyes that demonstrate AP-ROP compared with other treatment-requiring eyes. Analysis of quantitative characteristics of AP-ROP may help improve diagnosis and treatment of an aggressive, vision-threatening form of ROP.


Subject(s)
Diagnostic Imaging/methods , Ophthalmoscopy/methods , Retinopathy of Prematurity/diagnosis , Telemedicine/methods , Disease Progression , Female , Humans , Incidence , Infant, Newborn , Male , North America/epidemiology , Retinopathy of Prematurity/epidemiology , Retrospective Studies , Risk Factors
9.
JAMA Ophthalmol ; 137(9): 1029-1036, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31268499

ABSTRACT

Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but treatment failure and disease recurrence are important causes of adverse outcomes in patients with treatment-requiring ROP (TR-ROP). Objectives: To apply an automated ROP vascular severity score obtained using a deep learning algorithm and to assess its utility for objectively monitoring ROP regression after treatment. Design, Setting, and Participants: This retrospective cohort study used data from the Imaging and Informatics in ROP consortium, which comprises 9 tertiary referral centers in North America that screen high volumes of at-risk infants for ROP. Images of 5255 clinical eye examinations from 871 infants performed between July 2011 and December 2016 were assessed for eligibility in the present study. The disease course was assessed with time across the numerous examinations for patients with TR-ROP. Infants born prematurely meeting screening criteria for ROP who developed TR-ROP and who had images captured within 4 weeks before and after treatment as well as at the time of treatment were included. Main Outcomes and Measures: The primary outcome was mean (SD) ROP vascular severity score before, at time of, and after treatment. A deep learning classifier was used to assign a continuous ROP vascular severity score, which ranged from 1 (normal) to 9 (most severe), at each examination. A secondary outcome was the difference in ROP vascular severity score among eyes treated with laser or the vascular endothelial growth factor antagonist bevacizumab. Differences between groups for both outcomes were assessed using unpaired 2-tailed t tests with Bonferroni correction. Results: Of 5255 examined eyes, 91 developed TR-ROP, of which 46 eyes met the inclusion criteria based on the available images. The mean (SD) birth weight of those patients was 653 (185) g, with a mean (SD) gestational age of 24.9 (1.3) weeks. The mean (SD) ROP vascular severity scores significantly increased 2 weeks prior to treatment (4.19 [1.75]), peaked at treatment (7.43 [1.89]), and decreased for at least 2 weeks after treatment (4.00 [1.88]) (all P < .001). Eyes requiring retreatment with laser had higher ROP vascular severity scores at the time of initial treatment compared with eyes receiving a single treatment (P < .001). Conclusions and Relevance: This quantitative ROP vascular severity score appears to consistently reflect clinical disease progression and posttreatment regression in eyes with TR-ROP. These study results may have implications for the monitoring of patients with ROP for treatment failure and disease recurrence and for determining the appropriate level of disease severity for primary treatment in eyes with aggressive disease.

10.
JAMA Ophthalmol ; 137(9): 1022-1028, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31268518

ABSTRACT

Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but clinical diagnosis is subjective and qualitative. Objective: To describe a quantitative ROP severity score derived using a deep learning algorithm designed to evaluate plus disease and to assess its utility for objectively monitoring ROP progression. Design, Setting, and Participants: This retrospective cohort study included images from 5255 clinical examinations of 871 premature infants who met the ROP screening criteria of the Imaging and Informatics in ROP (i-ROP) Consortium, which comprises 9 tertiary care centers in North America, from July 1, 2011, to December 31, 2016. Data analysis was performed from July 2017 to May 2018. Exposure: A deep learning algorithm was used to assign a continuous ROP vascular severity score from 1 (most normal) to 9 (most severe) at each examination based on a single posterior photograph compared with a reference standard diagnosis (RSD) simplified into 4 categories: no ROP, mild ROP, type 2 ROP or pre-plus disease, or type 1 ROP. Disease course was assessed longitudinally across multiple examinations for all patients. Main Outcomes and Measures: Mean ROP vascular severity score progression over time compared with the RSD. Results: A total of 5255 clinical examinations from 871 infants (mean [SD] gestational age, 27.0 [2.0] weeks; 493 [56.6%] male; mean [SD] birth weight, 949 [271] g) were analyzed. The median severity scores for each category were as follows: 1.1 (interquartile range [IQR], 1.0-1.5) (no ROP), 1.5 (IQR, 1.1-3.4) (mild ROP), 4.6 (IQR, 2.4-5.3) (type 2 and pre-plus), and 7.5 (IQR, 5.0-8.7) (treatment-requiring ROP) (P < .001). When the long-term differences in the median severity scores across time between the eyes progressing to treatment and those who did not eventually require treatment were compared, the median score was higher in the treatment group by 0.06 at 30 to 32 weeks, 0.75 at 32 to 34 weeks, 3.56 at 34 to 36 weeks, 3.71 at 36 to 38 weeks, and 3.24 at 38 to 40 weeks postmenstrual age (P < .001 for all comparisons). Conclusions and Relevance: The findings suggest that the proposed ROP vascular severity score is associated with category of disease at a given point in time and clinical progression of ROP in premature infants. Automated image analysis may be used to quantify clinical disease progression and identify infants at high risk for eventually developing treatment-requiring ROP. This finding has implications for quality and delivery of ROP care and for future approaches to disease classification.

11.
Br J Ophthalmol ; 101(4): 509-513, 2017 04.
Article in English | MEDLINE | ID: mdl-27402970

ABSTRACT

BACKGROUND/AIMS: To report the clinical, histopathological and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the transforming growth factor-B-induced (TGFBI) gene. METHODS: Clinical characterisation was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathological characterisation was performed with light microscopic examination of an excised corneal button and a peripheral blood samples were collected for TGFBI screening. RESULTS: A 42-year-old woman presented with progressive photophobia and decreased visual acuity in both eyes. Slit lamp examination demonstrated punctate and linear branching opacities in the mid and posterior corneal stroma, corresponding to hyper-reflective opacities noted on IVCM and amyloid deposition noted on histopathological examination of an excised corneal button. TGFBI screening revealed two previously reported heterozygous missense mutations: c.337G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12. Screening of an affected sibling with a similar phenotype revealed that she was also heterozygous for both mutations, while screening of another sibling with punctate but not linear stromal opacities revealed that she was heterozygous for only the p.(Leu558Pro) mutation. CONCLUSIONS: The p.(Val113Ile) mutation results in an alteration of the atypical LCD phenotype associated with the p.(Leu558Pro) mutation. This represents only the second report of the alteration of the phenotype of a TGFBI dystrophy by a second, non-homozygous pathogenic mutation, and thus provides insight into the phenotype-genotype correlation of the TGFBI dystrophies.


Subject(s)
Cornea/pathology , Corneal Dystrophies, Hereditary/diagnosis , Corneal Dystrophies, Hereditary/genetics , Microscopy, Confocal , Mutation , Photophobia/physiopathology , Adult , Corneal Dystrophies, Hereditary/physiopathology , Disease Progression , Female , Genetic Association Studies , Humans , Pedigree , Phenotype , Photophobia/etiology , Photophobia/genetics
12.
Graefes Arch Clin Exp Ophthalmol ; 254(7): 1371-8, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26907932

ABSTRACT

PURPOSE: To evaluate the relationship between choroidal melanoma regression rate and its gene expression profile class after iodine-125 brachytherapy at 3 and 6 months, controlling for baseline tumor height. METHODS: Patients from October 2012 to January 2015 at a single Ophthalmic Oncology Center who had undergone iodine-125 brachytherapy for the treatment of choroidal melanoma and who had a gene expression profile test result obtained from intraoperative fine-needle aspiration biopsy at the time of plaque surgery were retrospectively reviewed. Baseline patient and tumor characteristics were obtained, including tumor height and gene expression profile test result. Tumor height at 3 and 6 months following treatment was obtained. Regression rate was analyzed with two-way analysis of variance to class type and baseline pre-operative tumor height. Class 2 patients were matched to class 1 patients by tumor height and resulting distributions of paired regression rate differences were compared. RESULTS: A total of 114 patients were studied. When preoperative tumor height was controlled for in the comparative analysis, neither group of patients at 3 or 6 months had a significant dependency between gene expression profile class and tumor regression rate. Additionally, class 1 and class 2 patients matched for pre-operative tumor height did not express different regression rates. CONCLUSIONS: Our study adds to a growing body of evidence that tumor regression rate does not necessarily depend on gene expression profile class type in choroidal melanoma after brachytherapy at 3 and 6 months when controlling for baseline tumor height.


Subject(s)
Brachytherapy/methods , Choroid Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Genes, Neoplasm/genetics , Iodine Radioisotopes/therapeutic use , Melanoma/pathology , Uveal Neoplasms/pathology , Aged , Biopsy, Fine-Needle , Choroid Neoplasms/genetics , Choroid Neoplasms/radiotherapy , Disease Progression , Female , Follow-Up Studies , Humans , Male , Melanoma/genetics , Melanoma/radiotherapy , Middle Aged , Retrospective Studies , Time Factors , Uveal Neoplasms/genetics , Uveal Neoplasms/radiotherapy , Visual Acuity
14.
Cereb Cortex ; 24(6): 1630-44, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23382518

ABSTRACT

Prior studies of head direction (HD) cells indicate strong landmark control over the preferred firing direction of these cells, with few studies exhibiting shifts away from local reference frames over time. We recorded spiking activity of grid and HD cells in the medial entorhinal cortex of rats, testing correlations of local environmental cues with the spatial tuning curves of these cells' firing fields as animals performed continuous spatial alternation on a T-maze that shared the boundaries of an open-field arena. The environment was rotated into configurations the animal had either seen or not seen in the past recording week. Tuning curves of both cell types demonstrated commensurate shifts of tuning with T-maze rotations during less recent rotations, more so than recent rotations. This strongly suggests that animals are shifting their reference frame away from the local environmental cues over time, learning to use a different reference frame more likely reliant on distal or idiothetic cues. In addition, grid fields demonstrated varying levels of "fragmentation" on the T-maze. The propensity for fragmentation does not depend on grid spacing and grid score, nor animal trajectory, indicating the cognitive treatment of environmental subcompartments is likely driven by task demands.


Subject(s)
Entorhinal Cortex/physiology , Neurons/physiology , Rotation , Space Perception/physiology , Action Potentials , Animals , Cues , Electrodes, Implanted , Environment , Exploratory Behavior/physiology , Head/physiology , Male , Maze Learning/physiology , Orientation/physiology , Rats, Long-Evans , Time Factors
15.
Front Behav Neurosci ; 6: 24, 2012.
Article in English | MEDLINE | ID: mdl-22707936

ABSTRACT

Acetylcholine plays an important role in cognitive function, as shown by pharmacological manipulations that impact working memory, attention, episodic memory, and spatial memory function. Acetylcholine also shows striking modulatory influences on the cellular physiology of hippocampal and cortical neurons. Modeling of neural circuits provides a framework for understanding how the cognitive functions may arise from the influence of acetylcholine on neural and network dynamics. We review the influences of cholinergic manipulations on behavioral performance in working memory, attention, episodic memory, and spatial memory tasks, the physiological effects of acetylcholine on neural and circuit dynamics, and the computational models that provide insight into the functional relationships between the physiology and behavior. Specifically, we discuss the important role of acetylcholine in governing mechanisms of active maintenance in working memory tasks and in regulating network dynamics important for effective processing of stimuli in attention and episodic memory tasks. We also propose that theta rhythm plays a crucial role as an intermediary between the physiological influences of acetylcholine and behavior in episodic and spatial memory tasks. We conclude with a synthesis of the existing modeling work and highlight future directions that are likely to be rewarding given the existing state of the literature for both empiricists and modelers.

16.
Learn Mem ; 19(6): 219-30, 2012 May 15.
Article in English | MEDLINE | ID: mdl-22589278

ABSTRACT

Intrinsic persistent spiking mechanisms in medial entorhinal cortex (mEC) neurons may play a role in active maintenance of working memory. However, electrophysiological studies of rat mEC units have primarily focused on spatial modulation. We sought evidence of differential spike rates in the mEC in rats trained on a T-maze, cued spatial delayed response task. Animals begin at the base of the T-maze where a 1-sec white noise and visual light cue are presented on the left or right side of the maze. Rats are rewarded for responding toward the cued direction. In correct trials, we observed decreased spike rates during the delay period, the time interval between cue presentation and reward delivery. Firing-rate histograms show significant decreases during the delay period compared to 5-sec windows from both pre-cue and post-reward periods. We analyzed how running speed and trajectory specificity correlated to spike rate. Twice as many cells were responsive to cue alone compared to running speed. Trajectory specificity did not relate significantly to firing rate. Decreased spike rate may reflect active maintenance in other structures inhibiting mEC. Alternately, the reduction may reflect decreases in background activity during enhanced attention and cholinergic modulation. Lastly, animals often ran through the T-maze choice-point with varying speed. We calculated the spatial posterior probability density from spike rates during these choice-point passes. Slow passes through the choice point were characterized by greater probability of decoding to the reward locations on correct trials compared to quick passes on the maze consistent with similar "look-ahead" properties previously reported in the hippocampus and ventral striatum.


Subject(s)
Action Potentials/physiology , Cues , Entorhinal Cortex/cytology , Neurons/physiology , Reaction Time/physiology , Space Perception/physiology , Animals , Choice Behavior/physiology , Conditioning, Psychological/physiology , Male , Maze Learning/physiology , Neurons/classification , Orientation/physiology , Photic Stimulation , Rats , Rats, Long-Evans , Wakefulness
17.
Science ; 332(6029): 595-9, 2011 Apr 29.
Article in English | MEDLINE | ID: mdl-21527714

ABSTRACT

Grid cells recorded in the medial entorhinal cortex of freely moving rats exhibit firing at regular spatial locations and temporal modulation with theta rhythm oscillations (4 to 11 hertz). We analyzed grid cell spatial coding during reduction of network theta rhythm oscillations caused by medial septum (MS) inactivation with muscimol. During MS inactivation, grid cells lost their spatial periodicity, whereas head-direction cells maintained their selectivity. Conjunctive grid-by-head-direction cells lost grid cell spatial periodicity but retained head-direction specificity. All cells showed reduced rhythmicity in autocorrelations and cross-correlations. This supports the hypothesis that spatial coding by grid cells requires theta oscillations, and dissociates the mechanisms underlying the generation of entorhinal grid cell periodicity and head-direction selectivity.


Subject(s)
Entorhinal Cortex/physiology , Neurons/physiology , Space Perception , Theta Rhythm , Animals , Entorhinal Cortex/cytology , Male , Membrane Potentials , Motor Activity , Muscimol/pharmacology , Nerve Net/physiology , Neural Pathways , Periodicity , Rats , Rats, Long-Evans , Septum Pellucidum/drug effects , Septum Pellucidum/physiology , Theta Rhythm/drug effects
18.
Hippocampus ; 18(12): 1239-55, 2008.
Article in English | MEDLINE | ID: mdl-19021259

ABSTRACT

As a rat navigates through a familiar environment, its position in space is encoded by firing rates of place cells and grid cells. Oscillatory interference models propose that this positional firing rate code is derived from a phase code, which stores the rat's position as a pattern of phase angles between velocity-modulated theta oscillations. Here we describe a three-stage network model, which formalizes the computational steps that are necessary for converting phase-coded position signals (represented by theta oscillations) into rate-coded position signals (represented by grid cells and place cells). The first stage of the model proposes that the phase-coded position signal is stored and updated by a bank of ring attractors, like those that have previously been hypothesized to perform angular path integration in the head-direction cell system. We show analytically how ring attractors can serve as central pattern generators for producing velocity-modulated theta oscillations, and we propose that such ring attractors may reside in subcortical areas where hippocampal theta rhythm is known to originate. In the second stage of the model, grid fields are formed by oscillatory interference between theta cells residing in different (but not the same) ring attractors. The model's third stage assumes that hippocampal neurons generate Gaussian place fields by computing weighted sums of inputs from a basis set of many grid fields. Here we show that under this assumption, the spatial frequency spectrum of the Gaussian place field defines the vertex spacings of grid cells that must provide input to the place cell. This analysis generates a testable prediction that grid cells with large vertex spacings should send projections to the entire hippocampus, whereas grid cells with smaller vertex spacings may project more selectively to the dorsal hippocampus, where place fields are smallest.


Subject(s)
Action Potentials/physiology , Biological Clocks/physiology , Entorhinal Cortex/physiology , Nerve Net/physiology , Neurons/physiology , Theta Rhythm , Animals , Computer Simulation , Entorhinal Cortex/cytology , Hippocampus/cytology , Hippocampus/physiology , Nerve Net/cytology , Neural Pathways/cytology , Neural Pathways/physiology , Normal Distribution , Rats , Space Perception/physiology , Synaptic Transmission/physiology
19.
Ren Fail ; 29(4): 463-9, 2007.
Article in English | MEDLINE | ID: mdl-17497470

ABSTRACT

Acute renal failure (ARF) occurs in wide range of conditions, making the evaluation of its prognosis a difficult task. Data regarding prognostic factors in ARF in a general population in developing countries are scarce. The objective of the study was to describe predictors of mortality in ARF that are relevant in the developing world. This prospective study was carried out over a one-year period; all hospitalized adults with ARF were included in the study. Predictors of mortality studied included causes of ARF, pre-existing diseases, and severity as well as complications of ARF. Of 33,301 patients admitted during the study period, 294 (0.88%) were either admitted with or developed ARF after hospitalization. Mean age was 43.9 +/- 16.9 (18-86 yrs). Sepsis was the most common cause (63.26%). Pre-existing diseases like cardiovascular disease (CVSD), respiratory system disease (RSD), central nervous system disease (CNSD), hypertension, diabetes mellitus (DM), and malignancy were significantly higher in elderly as compared to younger patients. On univariate analysis sepsis, hypoperfusion as a cause of ARF and hospital-acquired ARF were associated with higher mortality. Pre-existing diseases viz. RSD, CVSD, CNSD, and DM had higher mortality. Among the severity and complications of ARF, oliguria, bleeding and infection during the course of ARF and critical illness were predictors of poor outcome. Age > 60 yrs was associated with significantly higher mortality. However, on multivariate analysis, only critical illness (odds ratio 37.3), age > 60 years (odds ratio of 5.6), and sepsis as cause of ARF (odds ratio of 2.6) were found to be independent predictors of mortality.


Subject(s)
Acute Kidney Injury/mortality , Acute Kidney Injury/etiology , Adult , Critical Illness , Female , Humans , India/epidemiology , Male , Middle Aged , Multiple Organ Failure/epidemiology , Multivariate Analysis , Prospective Studies , Sepsis/complications , Survival Analysis
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