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1.  Bicuspid Aortic Cusp Fusion Morphology Alters Aortic 3D Outflow Patterns, Wall Shear Stress and Expression of Aortopathy 
Circulation  2013;129(6):673-682.
Aortic 3D blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy.
Methods and Results:
4D flow MRI measured in vivo 3D blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4mm; n=15 RN-BAV, 39.6±7.2mm); aorta size controls with tricuspid aortic valves (n=30, 41.1±4.4mm); healthy volunteers (n=15, 24.9±3.0mm). Aortopathy type (0-3), systolic flow angle, flow displacement, and regional wall shear stress (WSS) were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional WSS (p<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV compared to aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV were associated with altered flow displacement in the proximal and mid AAo for type 1 (42-81% decrease versus type 2) and distal AAo for type 3 (33-39% increase versus type 2).
The presence and type of BAV fusion was associated with changes in regional WSS distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiologic mechanism by which valve morphology phenotype can influence phenotypes of BAV aortopathy.
PMCID: PMC3946057  PMID: 24345403
MRI; Bicuspid Aortic Valve; Wall Shear Stress; Hemodynamics; Aortic Disease; 4D flow MRI
3.  Measurement of Intra-abdominal Pressure in Critically-ill Children 
Introduction: It is being increasingly recognized that intra-abdominal hypertension is an important cause of organ dysfunction. This pilot study was done to determine the feasibility of measuring intra-abdominal pressures (IAP) in critically-ill children using simple inexpensive equipment available in the PICU.
Materials and Methods: This was a prospective study done in the paediatric intensive care unit (PICU) of a tertiary care general hospital. Thirty-two consecutive patients admitted to the PICU, staying for more than 24 h and requiring a urinary catheter were studied. IAP was measured by the intravesical method, using a disposable manometer, twice a day for seven days or till discharge/death, Risk factors associated with IAH were recorded.
Results: The majority of the patients had an IAP less than 5 mm Hg. Three patients had grade 1 intra-abdominal hypertension (IAP>12 mm Hg).
Conclusion: It is feasible to measure IAP in paediatric patients without the use of sophisticated equipment.
PMCID: PMC4316304  PMID: 25653998
Intra-abdominal pressure; Intra-abdominal hypertension
4.  The Road To Radiation Protection: A Rocky Path 
Radiation has intrigued us with its magnificent properties of imaging and healing. But this discovery, like many others, came with a heavy price. The pioneers of this form of energy themselves often succumbed to its devastating effects and hence, paved a way for future generations to be wary of it, while continuing to use it. This paper attempts to salute those masters who have helped make the radiation world a safer place to live and work in.
PMCID: PMC4316358  PMID: 25654052
Radiation protection; Rem
5.  Alveolar bone exostoses subsequent to orthodontic implant placement 
BMJ Case Reports  2013;2013:bcr2012007951.
Alveolar bone exostoses (ABE), also known as a buttress bone formation, are not uncommon to the literature. Although, exostoses in response to the trauma from occlusion are a popular concept proposed more than 45 years ago, still the aetiological factors behind this development are unclear. Various risks and complications associated with orthodontic implants have been published, but buttress bone formation subsequent to this procedure has not been reported till date. This article describes a case of ABE, subsequent to the placement of orthodontic mini implants, where after careful evaluation, resective osseous surgery was performed.
PMCID: PMC3604206  PMID: 23355580
6.  Prosthodontic management of an albinism patient-dental implications and management 
BMJ Case Reports  2013;2013:bcr2012008004.
Albinism is a congenital hypopigmentary disorder. Albinism is due to the dysfunction of the melanin-producing cells (melanocytes) resulting in defective production of melanin from tyrosine through a complex pathway of metabolic reactions. Little is known about the varied dental features that albinism presents with. This case report summarises the features encountered in albinism, the different oral findings available in the literature and also presents a case of an albinism patient treated with fixed partial denture and the precautions to be exercised for such patients.
PMCID: PMC3604405  PMID: 23345493
7.  Beneficial Role of Bitter Melon Supplementation in Obesity and Related Complications in Metabolic Syndrome 
Journal of Lipids  2015;2015:496169.
Diabetes, obesity, and metabolic syndrome are becoming epidemic both in developed and developing countries in recent years. Complementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovascular diseases. Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia. The fruits extract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitro. Recent scientific evaluation of this plant extracts also showed potential therapeutic benefit in diabetes and obesity related metabolic dysfunction in experimental animals and clinical studies. These beneficial effects are mediated probably by inducing lipid and fat metabolizing gene expression and increasing the function of AMPK and PPARs, and so forth. This review will thus focus on the recent findings on beneficial effect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanism of actions.
PMCID: PMC4306384  PMID: 25650336
8.  Immature fibrous dysplasia: a mixed radio-opaque radiolucent lesion 
BMJ Case Reports  2013;2013:bcr2012007934.
Fibrous dysplasia is a bone pathology characterised by abnormal differentiation of osteoblasts leading to replacement of normal marrow and cancellous bone by immature bone and fibrous stroma. A case report of a 20-year-old female patient with a chief complaint of a swelling in the right upper back tooth region, of 6 months duration which was diagnosed as an immature fibrous dysplasia is presented.
PMCID: PMC3604024  PMID: 23291823
9.  The Effect of Case Rate and Coinfection Rate on the Positive Predictive Value of a Registry Data-Matching Algorithm 
Public Health Reports  2014;129(Suppl 1):79-84.
Statistical modeling has suggested that the prevalence of false matches in data matching declines as the events become rarer or the number of matches increases. We examined the effect of case rate and coinfection rate in the population on the positive predictive value (PPV) of a matching algorithm for HIV/AIDS and sexually transmitted disease (STD) surveillance registry data.
We used LinkPlus™, a probabilistic data-matching program, to match HIV/AIDS cases diagnosed in New York City (NYC) from 1981 to March 31, 2012, and reported to the NYC HIV/AIDS surveillance registry against syphilis and chlamydia cases diagnosed in NYC from January 1 to June 30, 2010, and reported to the NYC STD registry. Match results were manually reviewed to determine true matches.
With an agreement/disagreement comparison score cutoff value of 10.0, LinkPlus identified 3,013 matches, of which 1,582 were determined to be true by manual review. PPV varied greatly in subpopulations with different case rates and coinfection rates. PPV was the highest (91.6%) in male syphilis cases, who had a relatively low case rate but a high HIV coinfection rate, and lowest (18.0%) in female chlamydia cases, who had a high case rate but a low HIV coinfection rate. When the cutoff value was increased to 15.0, PPVs in male syphilis and female chlamydia cases increased to 98.3% and 90.5%, respectively.
Case rates and coinfection rates have a significant effect on the PPV of a registry data-matching algorithm: PPV decreases as the case rate increases and coinfection rate decreases. Before conducting registry data matching, program staff should assess the case rate and coinfection rate of the population included in the data matching and select an appropriate matching algorithm.
PMCID: PMC3862993  PMID: 24385653
10.  Roles of sensory nerves in the regulation of radiation-induced structural and functional changes in the heart 
International journal of radiation oncology, biology, physics  2014;88(1):10.1016/j.ijrobp.2013.10.014.
Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiotherapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that are not only involved in monitoring of cardiac events such as ischemia/reperfusion, but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD.
Methods and Materials
Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, two weeks before local image-guided heart X-ray irradiation with a single dose of 21 Gy. During the 6-months follow up time, heart function was assessed with high resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western-Blots.
Capsaicin-pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. On the other hand, capsaicin-pretreatment caused a small but significant reduction in cardiac output at 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis.
These results suggest that sensory nerves, while playing a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.
PMCID: PMC3868013  PMID: 24331664
11.  Bicarbonate Availability for Vocal Fold Epithelial Defense to Acidic Challenge 
Bicarbonate is critical for acid-base tissue homeostasis. In this study we investigated the role of bicarbonate ion transport in vocal fold epithelial defense to acid challenges. Acidic insults to the larynx are common in gastric reflux, carcinogenesis and metastasis, and acute inflammation.
Ion transport was measured in viable, porcine vocal fold epithelium. First, 18 vocal folds were exposed to either the carbonic anhydrase antagonist acetazolamide or to vehicle. Second, 32 vocal folds were exposed to either a control buffer or a bicarbonate-free buffer on their luminal or basolateral surface or both. Third, vocal folds were challenged with acid in the presence of bicarbonate-free or control buffer.
The vocal fold transepithelial resistance was greater than 300 Ω*cm2, suggesting robust barrier integrity. Ion transport did not change after exposure to acetazolamide (p > 0.05). Exposure to bicarbonate-free buffer did not compromise vocal fold ion transport (p > 0.05). Ion transport increased after acid challenge. This increase approached statistical significance and was the greatest for the control buffer and for the bicarbonate-free buffer applied to the basolateral surface.
Bicarbonate secretion may contribute to vocal fold defense against acid challenge. Our data offer a potential novel role for bicarbonate as a therapeutic agent to reduce pH abnormalities in the larynx and prevent associated pathological changes.
PMCID: PMC4000062  PMID: 24574427
bicarbonate; ion transport; laryngopharyngeal reflux; vocal fold
12.  Effect of yoga regimen on lung functions including diffusion capacity in coronary artery disease patients: A randomized controlled study 
International Journal of Yoga  2015;8(1):62-67.
Lung functions are found to be impaired in coronary artery disease (CAD), congestive heart failure, left ventricular dysfunction, and after cardiac surgery. Diffusion capacity progressively worsens as the severity of CAD increases due to reduction in lung tissue participating in gas exchange.
Aims and Objectives:
Pranayama breathing exercises and yogic postures may play an impressive role in improving cardio-respiratory efficiency and facilitating gas diffusion at the alveolo-capillary membrane. This study was done to see the effect of yoga regimen on lung functions particularly diffusion capacity in CAD patients.
Materials and Methods:
A total of 80 stable CAD patients below 65 years of age of both sexes were selected and randomized into two groups of 40 each. Group I CAD patients were given yoga regimen for 3 months which consisted of yogic postures, pranayama breathing exercises, dietary modification, and holistic teaching along with their conventional medicine while Group II CAD patients were put only on conventional medicine. Lung functions including diffusion capacity were recorded thrice in both the groups: 0 day as baseline, 22nd day and on 90th day by using computerized MS medisoft Cardio-respiratory Instrument, HYP’AIR Compact model of cardio-respiratory testing machine was manufactured by P K Morgan, India. The recorded parameters were statistically analyzed by repeated measures ANOVA followed by Tukey's test in both the groups. Cardiovascular parameters were also compared before and after intervention in both the groups.
Statistically significant improvements were seen in slow vital capacity, forced vital capacity, peak expiratory flow rate, maximum voluntary ventilation, and diffusion factor/ transfer factor of lung for carbon monoxide after 3 months of yoga regimen in Group I. Forced expiratory volume in 1st sec (FEV1), and FEV1 % also showed a trend toward improvement although not statistically significant. HR, SBP and DBP also showed significant improvement in Group-I patients who followed yoga regimen.
Yoga regimen was found to improve lung functions and diffusion capacity in CAD patients besides improving cardiovascular functions. Thus, it can be used as a complimentary or adjunct therapy along with the conventional medicine for their treatment and rehabilitation.
PMCID: PMC4278137  PMID: 25558135
Coronary artery disease; pulmonary function tests; pranayama; yoga regimen
13.  Eosinophilic panniculitis in a female child: An unusual presentation 
Eosinophilic panniculitis (EP) is characterized by prominent infiltration of subcutaneous fat with eosinophils. The etiology is diverse. This is not a disease but represents a reaction pattern that may occur in a variety of circumstances. The exact pathogenesis of the disease is still unclear. We present the case of a 6-year-old girl child who was diagnosed with EP.
PMCID: PMC4314885  PMID: 25657915
Eosinophilic panniculitis; lower limb; female child
14.  Neuroendocrine Role for VGF 
The vgf gene (non-acronymic) is highly conserved and was identified on the basis of its rapid induction in vitro by nerve growth factor, although can also be induced by brain-derived neurotrophic factor, and glial-derived growth factor. The VGF gene gives rise to a 68 kDa precursor polypeptide, which is induced robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific prohormone convertases in these cells results in the production of a number of smaller peptides. The VGF gene and peptides are widely expressed throughout the brain, particularly in the hypothalamus and hippocampus, in peripheral tissues including the pituitary gland, the adrenal glands, and the pancreas, and in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. VGF peptides have been associated with a number of neuroendocrine roles, and in this review, we aim to describe these roles to highlight the importance of VGF as therapeutic target for a number of disorders, particularly those associated with energy metabolism, pain, reproduction, and cognition.
PMCID: PMC4313783
VGF; energy homeostasis; pain; cognition; reproduction
15.  Spring thaw ionic pulses boost nutrient availability and microbial growth in entombed Antarctic Dry Valley cryoconite holes 
The seasonal melting of ice entombed cryoconite holes on McMurdo Dry Valley glaciers provides oases for life in the harsh environmental conditions of the polar desert where surface air temperatures only occasionally exceed 0°C during the Austral summer. Here we follow temporal changes in cryoconite hole biogeochemistry on Canada Glacier from fully frozen conditions through the initial stages of spring thaw toward fully melted holes. The cryoconite holes had a mean isolation age from the glacial drainage system of 3.4 years, with an increasing mass of aqueous nutrients (dissolved organic carbon, total nitrogen, total phosphorus) with longer isolation age. During the initial melt there was a mean nine times enrichment in dissolved chloride relative to mean concentrations of the initial frozen holes indicative of an ionic pulse, with similar mean nine times enrichments in nitrite, ammonium, and dissolved organic matter. Nitrate was enriched twelve times and dissolved organic nitrogen six times, suggesting net nitrification, while lower enrichments for dissolved organic phosphorus and phosphate were consistent with net microbial phosphorus uptake. Rates of bacterial production were significantly elevated during the ionic pulse, likely due to the increased nutrient availability. There was no concomitant increase in photosynthesis rates, with a net depletion of dissolved inorganic carbon suggesting inorganic carbon limitation. Potential nitrogen fixation was detected in fully melted holes where it could be an important source of nitrogen to support microbial growth, but not during the ionic pulse where nitrogen availability was higher. This study demonstrates that ionic pulses significantly alter the timing and magnitude of microbial activity within entombed cryoconite holes, and adds credence to hypotheses that ionic enrichments during freeze-thaw can elevate rates of microbial growth and activity in other icy habitats, such as ice veins and subglacial regelation zones.
PMCID: PMC4263180  PMID: 25566210
Antarctica; cryoconite; ionic pulse; nitrogen fixation; photosynthesis; bacterial production; McMurdo Dry Valleys; microbial ecology
16.  Malignant Peripheral Nerve Sheath Tumor of the Anterior Mediastinum: A Rare Presentation 
Rare Tumors  2014;6(4):5528.
Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that accounts for 5% of all thoracic neoplasm usually located in the posterior mediastinum and is generally associated with a poor outcome. We present a case of MPNST of the anterior mediastinum presenting in a rare location leading to diagnostic dilemmas and treated primarily by surgical resection.
PMCID: PMC4274440  PMID: 25568746
malignant peripheral nerve sheath tumor; anterior mediastinum; immunohistochemistry
17.  Motor Dual-Task Effect on Gait and Task of Upper Limbs in Older Adults under Specific Task Prioritization: Pilot Study 
Background and Aims
Performing multiple tasks simultaneously may result in reduced performance of subtasks (dual-task cost) particularly among old individuals. Subtask performance during dual-tasking is also known to be affected by task prioritization. However, it has not been well studied how the performance of subtasks is affected during motor dual-task in old adults compared to young when instructed to prioritize one task over the other. This study aims to investigate the dual-task effect on subtasks during motor dual-tasking under specific instruction of task prioritization in old compared to young adults.
Sixteen independent old and 18 young adults performed two single tasks (usual walking, holding a tray as steady as possible while standing) and two dual-tasks (walking while holding a tray focusing attention on keeping tray as steady as possible-WTAT, and walking while holding tray focusing attention on walking -WTAW). Gait parameters [velocity and variability (coefficient of variation; CV) of stride length] and the pitch (forward-backward) and roll (side-to-side) angles of the tray were measured during the four conditions.
During the WTAT compared to single tasks, both young and old groups showed reduced gait velocity (β = -14.0 for old, -34.3 for young), increased gait variability (β = 0.19 for old, 0.51 for young), and increased tray tilt (β =9.4 for old, 7.9 for young in pitch; β =8.8 for old, 5.9 for young in roll). Higher proportion of older individuals showed higher dual-task effect on tray stability, but lower dual-task effect on gait compared to young individuals. During WTAW, there was no difference in dual-task effect between age groups in tray stability or gait performance.
Compared to young, older adults tend to compromise the task involving upper limbs during motor dual-tasking even when instructed to prioritize this task over gait. These findings may have ramifications on developing training strategies to learn or relearn complex motor activities in seniors.
PMCID: PMC4260652  PMID: 23740639
Aged; Task performance and analysis; Attention
18.  Deflections in Mandibular Major Connectors: A FEM Study 
The major connector is the most vital component critically subjected to maximal stress concentration due to various forces acting on it. The main requirement of a major connector is its resistance to deformation by occlusal stresses. This resistance to deformation is a direct consequence of the rigidity of the major connector. Thus rigidity of the major connector is paramount to resist flexing and torquing forces that could be transmitted to the abutment teeth and other structures as destructive forces. The commonly used major connectors for the mandibular arch are lingual bar and lingual plate. In the present study, the deflection of various major connector designs due to occlusal load is assessed by finite element method. They have been analyzed through finite element models. The differences in the deflection behaviour of mandibular major connector used in Kennedy’s Class I, Class II, Class III, and Class IV edentulous situations have been compared. A CT scan of human edentulous mandible was taken and each section from symphysis to condylar region was projected on a graph paper and three-dimensional volumes were created from connected successive profiles to define the final solid geometry of cortical bone. Six framework models with different mandibular major connectors, lingual bar and lingual plate for Kennedy’s Class I, Class II, Class III, and Class IV situations were created. The three dimensional finite element models corresponding to the geometric model were generated using Ansys’s pre-processor. The model was assigned material properties. A vertical biting force of 20 N was applied. The results showed that the maximum deflection was seen in the saddle area when compared to other areas, i.e., major connector and the occlusal rest regions. The lingual bar in Kennedy’s Class III situation and lingual plate in Kennedy’s Class IV situation showed the least deflection when compared to Class I and Class II (distal extensions) situations. Lingual plate is more rigid major connector than lingual bar.
Electronic supplementary material
The online version of this article (doi:10.1007/s13191-012-0191-0) contains supplementary material, which is available to authorized users.
PMCID: PMC3792305  PMID: 24431793
Major connector; Finite element modeling; Lingual bar; Lingual plate
19.  Effectiveness of Mouthrinses and Oral Prophylaxis on Reduction of Microorganisms Count in Irreversible Hydrocolloid Impression: An In Vivo Study 
Dental impressions, contaminated with saliva, blood, plaque, are potential source of infection. All impressions should be disinfected after their removal from mouth to prevent cross contamination. Different methods have been tried to disinfect the commonly used irreversible hydrocolloid impression material, but they have been shown to influence the dimensional stability and surface detail of the impression which ultimately affects the precision of the final prosthesis. The aim of this study was to evaluate the efficacy of pre-procedural oral prophylaxis and mouthrinses in reducing the overall microbial load intraorally as well as on alginate impression surface. A total of 60 positive cases selected from 100 subjects who were partially edentulous and above 18 years of age and without medical or pharmacotherapy histories were studied over a period of 18 months, from outpatient clinic of Department of Prosthodontics, GNIDSR. Alginate impressions, before and after prophylaxis were examined microbiologically for the persistence of test microorganisms on the untreated (control group) and the impressions made after treatment. The data were statistically analyzed by the Student t test to assess the effectiveness of the procedure and also the comparative effectiveness of oral prophylaxis and commonly used mouthrinses. The results showed that the impressions were safer when made after oral prophylaxis and/or mouthrinses
Electronic supplementary material
The online version of this article (doi:10.1007/s13191-012-0222-x) contains supplementary material, which is available to authorized users.
PMCID: PMC3792333  PMID: 24431795
Cross-contamination; Irreversible hydrocolloid impressions; Disinfection; Mouthrinses; Oral prophylaxis
20.  HDAC inhibitor entinostat restores responsiveness of letrozole resistant MCF-7Ca xenografts to AIs through modulation of Her-2 
Molecular cancer therapeutics  2013;12(12):10.1158/1535-7163.MCT-13-0345.
We previously showed that in innately resistant tumors, silencing of the estrogen receptor (ER) could be reversed by treatment with a histone deacetylase (HDAC) inhibitor entinostat (ENT). Tumors were then responsive to aromatase inhibitor (AIs) letrozole. Here, we investigated whether ER in the acquired letrozole resistant tumors could be restored with ENT. Ovariectomized athymic mice were inoculated with MCF-7Ca cells, supplemented with androstenedione (Δ4A), the aromatizable substrate. When the tumors reached ~300mm3, the mice were treated with letrozole. After initial response to letrozole, the tumors eventually became resistant (doubled their initial volume). The mice then were grouped to receive letrozole, exemestane (250μg/day), ENT (50μg/day) or the combination of ENT with letrozole or exemestane for 26 weeks. The growth rates of tumors of mice treated with the combination of ENT with letrozole or exemestane were significantly slower than with the single agent (p<0.05). Analysis of the letrozole resistant tumors showed ENT increased ERα expression and aromatase activity but downregulated Her-2, p-Her-2, p-MAPK and p-Akt.
However, the mechanism of action of ENT in reversing acquired resistance did not involve epigenetic silencing, but rather included post-translational as well as transcriptional modulation of Her-2. ENT treatment reduced the association of the Her-2 protein with HSP-90, possibly by reducing the stability of Her-2 protein. In addition, ENT also reduced Her-2 mRNA levels and its stability. Our results suggest that the HDAC inhibitor may reverse letrozole resistance in cells and tumors by modulating Her-2 expression and activity.
PMCID: PMC3858401  PMID: 24092810
breast cancer; aromatase inhibitors; HDAC inhibitors; Her-2; preclinical studies of endocrine related cancers
21.  The Association between Sarcopenia and the Risk of Serious Infection among Adults Undergoing Liver Transplantation 
While sarcopenia (muscle loss) is associated with increased mortality after liver transplant, its influence on other complications is less well understood. We examined the association between sarcopenia and the risk of severe post-transplant infections among adult liver transplant recipients.
We assessed sarcopenia among 207 liver transplant recipients by calculating total psoas area (TPA) on preoperative computed tomography scans. The presence or absence of severe post-transplant infection was determined by review of the medical chart. The influence of post-transplant infection on overall survival was also assessed.
We identified 196 episodes of severe infections among 111 patients. Fifty-six patients had more than one infection. The median time to development of infection was 27 days (range 13–62). When grouped by tertiles, patients in the lowest tertile had a more than four-fold higher odds of developing severe infection compared to patients in the highest tertile; OR 4.6, CI 95 2.3–9.5). In multivariable analysis, recipient age (hazard ratio 1.04, p=0.02), pre-transplant TPA (hazard ratio 0.38, p<0.01) and pre-transplant total bilirubin level (hazard ratio 1.05, p=0.02) were independently associated with the risk of developing severe infections. Patients with severe post-transplant infections had worse 1-year survival compared to patients without infection (76% vs. 92%, p=0.003).
Among patients undergoing liver transplantation, lower TPA was associated with heightened risk for post-transplant infectious complications and mortality. Future efforts should focus on approaches to assess and mitigate vulnerability among patients undergoing transplantation.
PMCID: PMC3870151  PMID: 24151041
Liver Transplantation; Infections; Frailty; Sarcopenia; LT-13-274
22.  Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are heightened in obese patients 
The American Diabetes Association has called for further research on how patient demographics should determine drug choices for individuals with type 2 diabetes mellitus (T2DM). Here, using in-depth physiology studies, we investigate whether obese patients with T2DM are likely to benefit from thiazolidinediones, medications with a known side effect of weight gain.
Materials and Methods
11 obese and 7 non-obese individuals with T2DM participated in this randomized, placebo-controlled, double-blind, crossover study. Each subject underwent a pair of “stepped” pancreatic clamp studies with subcutaneous adipose tissue biopsies following 21 days of pioglitazone (45 mg) or placebo.
Obese subjects demonstrated significant decreases in insulin resistance and many adipose inflammatory parameters with pioglitazone relative to placebo. Specifically, significant improvements in glucose infusion rates, suppression of hepatic glucose production, and whole fat expression of certain inflammatory markers (IL-6, IL-1b, and iNOS) were observed in obese subjects but not in non-obese subjects. Additionally, adipose tissue from obese subjects demonstrated reduced infiltration of macrophages, dendritic cells, and neutrophils as well as increased expression of factors associated with fat “browning” (PGC-1α and UCP-1).
These findings support the efficacy of pioglitazone to improve insulin resistance and reduce adipose tissue inflammation in obese patients with T2DM.
PMCID: PMC3933072  PMID: 24141239
Type 2 Diabetes; Obesity; Pioglitazone; Adipose Tissue Inflammation; Insulin Resistance
23.  Multicenter Evaluation of the Quidel Lyra Direct C. difficile Nucleic Acid Amplification Assay 
Journal of Clinical Microbiology  2014;52(6):1998-2002.
Clostridium difficile is a Gram-positive bacterium commonly found in health care and long-term-care facilities and is the most common cause of antibiotic-associated diarrhea. Rapid detection of this bacterium can assist physicians in implementing contact precautions and appropriate antibiotic therapy in a timely manner. The purpose of this study was to compare the clinical performance of the Quidel Lyra Direct C. difficile assay (Lyra assay) (Quidel, San Diego, CA) to that of a direct cell culture cytotoxicity neutralization assay (CCNA) and enhanced toxigenic culture. This study was performed at three geographically diverse laboratories within the United States using residual stool specimens submitted for routine C. difficile testing. Residual samples were tested using the Lyra assay on three real-time PCR platforms, and results were compared to those for direct CCNA and enhanced toxigenic culture. The test results for all platforms were consistent across all three test sites. The sensitivity and specificity of the Lyra assay on the SmartCycler II, ABI 7500 Fast DX, and ABI QuantStudio DX instruments compared to CCNA were 90.0% and 93.3%, 95.0% and 94.2%, and 93.8% and 95.0%, respectively. Compared to enhanced toxigenic culture, the sensitivity and specificity of the Lyra assay on the SmartCycler II, ABI 7500, and QuantStudio instruments were 82.1% and 96.9%, 89.3% and 98.8%, and 85.7% and 99.0%, respectively. Overall, the Lyra assay is easy to use and versatile and compares well to C. difficile culture methods.
PMCID: PMC4042815  PMID: 24671790
24.  Urinary Tract Infection: Aetiology and Antimicrobial Resistance Pattern in Infants From A Tertiary Care Hospital in Northern India 
Introduction: Urinary tract infection (UTI) is one of the most common bacterial infections in childhood. Present study was undertaken to determine the occurrence of the uropathogens and their antimicrobial susceptibility pattern in infants (< 1yr) suspected with UTI.
Materials and Methods: This study was conducted in the Microbiology Department on urine samples received from infants for a period of two years from September 2011 to August 2013.
Results: Culture positivity rate was found to be 15.7%. There was an overall male preponderance in cases of UTI (70.1%). Most common bacterial isolate was E.coli (45.4%) followed by Klebsiella (16.7%) and Enterococcus spp (13.2%). Isolation of candida was 21.1%, maximum from ICU (63.1%). Maximum gram negative isolates (50%) showed high resistance to gentamicin, amikacin, cefotaxime and norfloxacin while most of the isolates (5%) were found susceptible to nitrofurantoin and piperacillin-tazobactam. 45.1% of gram negative bacilli were ESBL producer. We recommend continuous monitoring of changes in bacterial pathogens causing UTI and antibiotic sensitivity in each area for effective treatment of UTI.
Conclusion: Since antimicrobial resistance is a major problem, such study will help in formulating a strict antibiotics prescription policy in our country.
PMCID: PMC4253157  PMID: 25478339
Antibiotic sensitivity; Antibiotic prescription policy; Infant UTI
25.  Pulmonary and Ileal Tuberculosis Presenting as Fever of Undetermined Origin 
A 12-year-old girl presented with prolonged fever with no obvious focus on either history or clinical examination. High-resolution computerized tomography of the chest revealed the ‘tree-in-bud’ sign in the right lung and necrotic mediastinal lymph nodes. Barium meal showed multiple ileal strictures. The child was treated with anti-tuberculous therapy for six months. At follow-up six months later, the child had gained weight and had no signs of intestinal obstruction. Tuberculosis is a common cause of fever of undetermined origin and should be investigated for especially in countries with a high prevalence.
PMCID: PMC4253238  PMID: 25478420
Gastro-intestinal; Tuberculosis; Tree-in-bud sign

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