Search

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

Summary This article narrates a robust sensor‐less indirect rotor field‐oriented control (IRFOC) of a six‐phase asymmetrical induction motor (SPAIM) drive with an online estimation of parameters and reduction of common mode voltage (CMV). In comparison to the conventional IRFOC technique, the proposed IRFOC provides the least CMV using modified space vector modulation (SVM). To guarantee proper operation of IRFOC, accurate estimation of rotor time constant is mandatory; any mismatch in the actual and tuned value may lead to poor performance of the IRFOC algorithm. This problem will be further accelerated with encoder‐less control using model‐based estimators. In this manuscript, the problem of simultaneous estimation of speed and machine parameters is investigated, and a model reference adaptive system (MRAS) based speed estimator accompanied by online estimation of parameters is proposed to improve sturdiness against variation of parameters. A Simulink model of the proposed method is developed and a simulation study is carried out. To validate the simulation results, a scaled prototype model of The SPAIM rated for 2 HP, 200 V is developed and encoder‐less IRFOC for the SPAIM drives is implemented using an STM32F407VG controller board. The performance of the proposed observers is tested and verified for all the possible operating conditions and results are presented. [ABSTRACT FROM AUTHOR]

In view of the attractive features like improved torque density, reduction torque pulsation, superior fault tolerance, reduced power rating of voltage source converter, and sterling noise characteristics of six-phase asymmetrical induction motor (SPAIM) as compared to its three-phase counterpart, the SPAIM is considered for the study. In this paper, mathematical modelling of SPAIM is carried out in the synchronous reference frame and then indirect rotor field-oriented control (IRFOC) of SPAIM using a modified carrier wave-based space vector modulation (SVM) scheme is developed. A Simulink model of the proposed system configuration is developed and a simulation study is carried out. In order to validate the simulation results, a scaled prototype model of SPAIM rated for 2 HP, 4-pole, 200V is developed, and closed loop control of SPAIM drive with aforesaid modified SVM technique is implemented using TMS320F28379D controller board. The performance of the system is observed in several operating conditions with simulation studies using MATLAB/Simulink and test setup and various test results are recorded under several operating conditions and presented. Furthermore, the proposed SVM technique is compared with benchmarked SPWM and hysteresis current controller as well and it is observed that it outperforms traditional SPWM and hysteresis-based current controllers in terms of the distortion of stator currents and torque ripples. [ABSTRACT FROM AUTHOR]

Aspergillosis causes invasive pulmonary disease in patients with hematological malignancies. Children with invasive pulmonary aspergillosis (IPA) usually have nonspecific radiographic findings unlike cavitary lesions commonly seen in adults. Pneumothorax due to rupture of peripheral fungal lesionmay be a severe complication in patients with neutropenia. Here, we describe three children during induction chemotherapy for Blymphoblastic leukemia with pneumothorax as a presenting feature of pulmonary aspergillosis. [ABSTRACT FROM AUTHOR]

Increasing the carbon emission in environment has become a major concern for the government. For promoting a clean and green environment with reduction in carbon emission by vehicles, the Government of India aspires with 100 percent electric passenger vehicle mobility by the year 2030 in the country. There is an essential requirements for fast charging stations to meet this demand as large numbers of electric vehicles to be running on the roads. In this paper, we review the state of the art in electric vehicles (EVs) charging topologies which will be necessary to support future EV refueling. Some power converter topologies are also reviewed appropriate to deliver the fast charging. DC-DC universal converter is unified converter for charging the battery and power management on buck/boost plugin operations of EVs. SiC and GaN devices are attractive to be used in the fast charging due to lower switching loss, faster switching frequency and higher operating temperature. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is a leading cause of loss of hearing, vision, and mental retardation in congenitally infected children. It is also associated with complications of organ transplant and opportunistic HIV coinfection. The Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV test is an FDA–approved test that measures CMV DNA viral load in plasma for the diagnosis and management of patients at risk of CMV‐associated diseases. Besides plasma, CMV is often found in bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), and urine. Thus, monitoring of CMV for critical care of patients in these nonplasma samples becomes necessary. The objective of this study was to conduct an analytic and clinical feasibility study of the Roche CMV test in BAL, CSF, and urine. The lower limit of detection, analytic measurement range, assay sensitivity, specificity, and precision were determined. Results of this study showed that the lower limit of detections were 50, 100, and 300 IU/mL for BAL, CSF, or urine, respectively. The analytic measurement ranges were from log10 2.48 to log10 5.48. The assay specificity was 94.4% for BAL and 100% for CSF and urine. The assay precision was all within the acceptable range. The performance of Roche test was further compared with 2 comparators including the RealTime CMV assay (Abbott Molecular) and a CMV Quantitative Polymerase Chain Reaction test (Vela Diagnostics). There was a general positive correlation between the Roche method and the Abbott or the Vela method. Overall, this study suggests that the Roche CMV test is suitable for the quantification of CMV viral load DNA in the described nonplasma samples. [ABSTRACT FROM AUTHOR]

For the remaining treatment applications of bevacizumab: metastatic breast cancer, renal cell carcinoma, and glioblastoma multiforme, various clinical trials have failed to show a significant benefit in overall survival. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factors (VEGF). It is approved for a range of solid cancers such as ovarian cancer, colorectal cancer, glioblastoma multiforme, advanced non-squamous non-small cell lung cancer (NSCLC), cervical cancer, renal cell carcinoma, and metastatic breast cancer. [Extracted from the article]

Background: Over the past decades, the emergence of Methicillin resistant S. aureus (MRSA) has changed the landscape of S. aureus infections around the globe. Aim: Present study was aimed to find out the prevalence of MRSA strains, and evaluate its antibiogram to other common antibiotics. Materials and methods: Total 120 samples were collected from various patients of Dhiraj Hospital, Vadodara. Gujarat. All specimens were inoculated on blood agar and MacConkey agar (HiMedia) and maimitol salt agar Inoculated plates were incubated at 35 °T. After overnight incubation, suspected S. aureus colonies were confirmed by gram staining, catalase test and coagulase (slide and tube) tests, which were performed as per standard guidelines. Disk diffusion method was performed as per Clinical and Laboratory Standards Institute (CLSI) guidelines. A peptone water suspension equivalent to 0.5 McFarland standard was prepared from isolates. A swab was dipped in suspension and streaked over surface of a Mueller-Hinton agar. Sensitivity to Cefoxitin (30 μg) disk was also tested. Results: Out of 120 samples, 73 strains (60.8%) were found to be MRSA with the prevalence higher in males (52/73) compared to females (21/73). Strains were mainly isolated from the pus samples (70%), followed by sputum (11%), blood and urine samples (8%) each. Highest rate of isolation of MRSA was from the orthopedics ward (23%), followed by surgery (22%), medicine (16%), recovery (12%), ICU (11%), pediatrics (10%), obstetrics (5%). Majority of the MRSA strains were resistant to erythromycin (76.7%), Co-trimoxazole (71%) and (61.6%) resistance with Gentamycin and Clindamycin. All strains were resistant to penicillin (100%). The optimistic finding was its 98.6% sensitivity to Linezolid and Vancomycin. Conclusion: The results of the present study showed a high prevalence of (60.8%) MRSA during April to September 2015. The treatment options for MRSA strains have been restricted to potentially toxic antimicrobials like vancomycin, clindamycin. This poses a serious problem for antibiotic therapy of S. aureus infections and leads to high morbidity and mortality. To prevent MRSA infection control measures like hand washing and other aseptic techniques have been implemented strictly. [ABSTRACT FROM AUTHOR]

Background: Staphylococci are ubiquitous being the normal inhabitants of the skin and mucous membranes and the most common cause of human infections all throughout the world, both the community acquired as well as nosocomial infections. Objectives: Objectives of this study were to determine the prevalence of methicillin resistant Staphylococcus aures (MRSA) and detection of emergence of resistance to vancomycin among the Staphylococcus aureus (S. aureus) isolates. Materials and methods: Thus hundred S. aureus isolated from various clinical samples were tested for methicillin resistance by cefoxitin disc (30μg) and vancomycin resistance using Ezy MIC - Vancomycin E-test. Results: The MRSA prevalence was found to be 52%. Of the total MRSA (n=52) 32 were obtained from male and 20 from female; and 36.54% from blood, 28.55%, 15.38%, 11.54% and 3.85% from pus, urine, sputum and body fluids respectively. The MRSA (n=52) were found to be resistant to antibiotics tested routinely but susceptible to levofloxacin (86.54%), doxycycline (92.31%), linezolid (96.15%) and vancomycin (100%). Inducible clindamycin resistance amongst MRSA was found to be 25%. All strains i.e.100% were sensitive to vancomycin indicating zero resistance to vancomycin. Conclusion: Though we did not find any resistance to vancomcyin in our setup, the prevalence of MRSA is high in our set up and calls for strict implementation of hospital infection control measures to prevent the spread of this organism and infections due to it. In this study E-test proved to be useful for detection of vancomycin resistance. [ABSTRACT FROM AUTHOR]

Background Low health literacy ( HL) indicates a limited ability to understand and use basic information to make appropriate health care decisions. Whereas low HL is associated with higher morbidity, mortality, and health care costs in multiple chronic conditions, little is known about HL and its associations in Parkinson's disease ( PD). Methods This was a cross-sectional study of nondemented adults with PD participating in the National Parkinson Foundation Parkinson's Outcomes Project at the University of Pennsylvania. Subjects were administered two brief HL assessments-the Rapid Estimate of Adult Literacy in Medicine-Short Form ( REALM- SF), a word-recognition test, and the Newest Vital Sign ( NVS), a test of literacy, numeracy, and understanding of health information-as well as demographic and clinical questionnaires. Adverse outcomes included falls in the 3 months preceding the study visit and hospital admissions, emergency room visits, infections, or injuries in the preceding year. Caregiver burden was measured using the Multidimensional Caregiver Strain Index. Results A total of 168 subjects completed both HL screens (mean, 65.8 years; 65.5% male; 65.2% H & Y stage 2). Using the REALM- SF, 97.6% of subjects had adequate HL. Using the NVS, however, 29.8% had low HL, which was associated with older age, lower education, male sex, greater disease severity, and poorer cognition. Low HL was associated with hospital admission and increased caregiver burden. Conclusions Low HL is common and associated with greater caregiver burden and a higher likelihood of hospitalization in patients with PD. Because HL is associated with both disease severity and adverse outcomes, it may be an important, modifiable contributor to morbidity. [ABSTRACT FROM AUTHOR]

Background: Infections with pseudomonas have been an important cause of Morbidity and Mortality throughout the history, which makes the treatment challenging every year. The present study was intended to find out the drug resistance pattern of Pseudomonas aeruginosa from various clinical specimens. Materials and methods: The study was conducted during April 2015 to September 2015. One hundred and one strains of Pseudomonas aeruginosa were subjected to antimicrobial susceptibility test by modified Kirby-Bauer disk diffusion method as per CLSI guidelines with Pseudomonas aeruginosa ATCC 27853 as control strain. Results: One hundred and one Strains were isolated from 83 males and 28 females. Majority of the Pseudomonas strains were isolated from ICU (30.63%), followed by Orthopedics (14.41%) and Pediatrics wards (13.51%), Strains were mainly isolated from pus samples (48.65%) followed by urine (20.72%) and sputum sample (13.51%). Majority of the strains were resistant to Aztreonam (70.27%) followed by Ciprofloxacin (54.95%), Amikacin (53.15%), Piperacillin (51.35%), Cefoperazone-sulbactam (50.45%), Gentamycin (49.55%), Cefepime and ceftazidime at 45.95% respectively. While with Piperacillin - Tazobactam we got sensitivity of 63.97% and with Imipenem and Imipenem -EDTA we got sensitivity of 78.38% and 81.08% respectively. Conclusion: We concluded that drug resistance of Pseudomonas was mainly isolated from pus samples of ICU patients, which is therefore an urgent call for the physicians to limit the indiscriminate use of antibiotics. The encouraging finding was its sensitivity to Imipenem and Piperacilin- Tazobactum as an effective antibiotic for the treatment. [ABSTRACT FROM AUTHOR]

Sudden unexplained deaths (SUD) in apparently healthy individuals, for which the causes of deaths remained undetermined after comprehensive forensic investigations and autopsy, present vexing challenges to medical examiners and coroners. Cardiac channelopathies, a group of inheritable diseases that primarily affect heart rhythm by altering the cardiac conduction system, have been known as one of the likely causes of SUD. Adhering to the recommendations of including molecular diagnostics of cardiac channelopathies in SUD investigation, the Molecular Genetics Laboratory of the New York City (NYC) Office of Chief Medical Examiner (OCME) has been routinely testing for six major channelopathy genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RyR2) since 2008. Presented here are the results of cardiac channelopathy testing in 274 well-characterized autopsy negative SUD cases, all with thorough medicolegal death investigation including complete autopsy by NYC OCME between 2008 and 2012. The cohort consisted of 141 infants (92.9% younger than six-month old) and 133 non-infants (78.2% were between 19 and 58 years old). Among the ethnically diverse cohort, African American infants had the highest risks of SUD, and African American non-infants died at significantly younger age (23.7 years old, mean age-at-death) than those of other ethnicities (30.3 years old, mean age-at-death). A total of 22 previously classified cardiac channelopathy-associated variants and 24 novel putative channelopathyassociated variants were detected among the infants (13.5%) and non-infants (19.5%). Most channelopathy-associated variants involved the SCN5A gene (68.4% in infants, 50% in non-infants). We believe this is the first study assessing the role of cardiac channelopathy genes in a large and demographically diverse SUD population drawn from a single urban medical examiner's office in the United States. Our study supports that molecular testing for cardiac channelopathy is a valuable tool in SUD investigations and provides helpful information to medical examiners/coroners seeking cause of death in SUD as well as potentially life-saving information to surviving family members. [ABSTRACT FROM AUTHOR]

Background Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated. Methods We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, > 6 weeks after, and > 6 months after. An untreated control group (n = 14) underwent similar measurement. We combined these data with those of our previous investigation (n = 34 patients and 16 controls) of a very similar design. Results There were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24 mg/dL higher, 95% CI: 17.5–29.9, p < 0.001) and CRP (72% higher, 95% CI: 41%–111%, p < 0.001). The difference between drug treatments was clinically meaningful for atherogenic lipids (16%, 95% CI: 11%–20%, p < 0.001) but small for high-density lipoprotein cholesterol (5%, 95% CI: 1%–9%, p < 0.05). All measures were stable between 6 weeks and 6 months after drug switch. Conclusions We demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is a leading cause of loss of hearing, vision, and mental retardation in congenitally infected children. It is also associated with complications of organ transplant and opportunistic HIV coinfection. The Roche COBAS ® AmpliPrep/COBAS ® TaqMan ® CMV test is an FDA-approved test that measures CMV DNA viral load in plasma for the diagnosis and management of patients at risk of CMV-associated diseases. Besides plasma, CMV is often found in bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), and urine. Thus, monitoring of CMV for critical care of patients in these nonplasma samples becomes necessary. The objective of this study was to conduct an analytic and clinical feasibility study of the Roche CMV test in BAL, CSF, and urine. The lower limit of detection, analytic measurement range, assay sensitivity, specificity, and precision were determined. Results of this study showed that the lower limit of detections were 50, 100, and 300 IU/mL for BAL, CSF, or urine, respectively. The analytic measurement ranges were from log 10 2.48 to log 10 5.48. The assay specificity was 94.4% for BAL and 100% for CSF and urine. The assay precision was all within the acceptable range. The performance of Roche test was further compared with 2 comparators including the RealTime CMV assay (Abbott Molecular) and a CMV Quantitative Polymerase Chain Reaction test (Vela Diagnostics). There was a general positive correlation between the Roche method and the Abbott or the Vela method. Overall, this study suggests that the Roche CMV test is suitable for the quantification of CMV viral load DNA in the described nonplasma samples., (© 2018 Wiley Periodicals, Inc.)

Purpose: This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K)., Patients and Methods: Sixty patients with solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily, initially on days 1 to 21 every 28 days and later, using continuous dosing for selected dose levels. Pharmacodynamic studies incorporated (18)F-FDG-PET, and assessment of phosphorylated AKT and S6 ribosomal protein in platelet-rich plasma (PRP) and tumor tissue., Results: Pictilisib was well tolerated. The most common toxicities were grade 1-2 nausea, rash, and fatigue, whereas the DLT was grade 3 maculopapular rash (450 mg, 2 of 3 patients; 330 mg, 1 of 7 patients). The pharmacokinetic profile was dose-proportional and supported once-daily dosing. Levels of phosphorylated serine-473 AKT were suppressed >90% in PRP at 3 hours after dose at the MTD and in tumor at pictilisib doses associated with AUC >20 h·μmol/L. Significant increase in plasma insulin and glucose levels, and >25% decrease in (18)F-FDG uptake by PET in 7 of 32 evaluable patients confirmed target modulation. A patient with V600E BRAF-mutant melanoma and another with platinum-refractory epithelial ovarian cancer exhibiting PTEN loss and PIK3CA amplification demonstrated partial response by RECIST and GCIG-CA125 criteria, respectively., Conclusion: Pictilisib was safely administered with a dose-proportional pharmacokinetic profile, on-target pharmacodynamic activity at dose levels ≥100 mg and signs of antitumor activity. The recommended phase II dose was continuous dosing at 330 mg once-daily., (©2014 American Association for Cancer Research.)

Background: In-hospital pulmonary embolism (PE) has been extensively studied in large populations; however, out-of-hospital fatal PE studies are rare. Here, we systematically evaluated a large number of decedents who suffered fatal PE outside of hospitals and were subsequently investigated by the New York City Office of Chief Medical Examiner., Methods and Results: A total of 578 consecutive out-of-hospital fatal PE cases were analyzed. All underwent autopsy, toxicology, microbiology, and genetic testing. Incidence rates and baseline characteristics were analyzed. Race-adjusted incidence rates of out-of-hospital fatal PE (per 100 000 people per year) were as follows: blacks, 3.73 (95% confidence interval, 3.31 to 4.11); whites, 1.15 (95% confidence interval, 0.96 to 1.33); and Hispanics, 0.93 (95% confidence interval, 0.72 to 1.10). Overall, obesity (body mass index ≥30 kg/m(2)) was 2.5- to 3-fold higher in fatal PE cases than in the New York City population as a whole. Carrier frequencies for prothrombin G20210A in fatal PE were 2- to 10-fold higher than reported frequencies in ethnically matched controls. Cumulative distribution curves showed that compared with whites, blacks and Hispanics died at significantly younger ages (P<0.001). Univariate and multiple linear regression analyses showed that in addition to nonwhite ethnicity, heterozygous carriers for factor V Leiden (P=0.001) and obesity (P=0.002) are significantly associated with younger age at death., Conclusion: There are unique epidemiological differences in out-of-hospital fatal PE between ethnic groups in New York City.