Δευτέρα 28 Νοεμβρίου 2016

Automated Spike Detection in EEG

For a long time clinicians have wanted a reliable device to analyze EEG records so as to reduce the time needed to review these records. As computers became more accessible to individual clinicians and engineers it became possible in the 1970s to digitize the analog EEG and write programs to detect features such as epileptiform activity ("spikes") in the record. Jean Gotman was one of the first to develop such a program (Gotman et al. 1975). The 70s saw several further refinements to automated EEG analysis, but automated analysis did not get into general use due to a high false positive rate and the lack of a commonly accepted standard as to what an EEG spike is, at least a standard that a computer could understand and implement.

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The importance of electrophysiological assessment of myoclonus

There are very few examples in Neurology, especially in the field of Movement Disorders, where clinical assessment might subside to electrophysiological testing, but myoclonus is one of these. The challenge in the diagnosis of myoclonus is probably reflected by the fact that it can be classified in a number of ways, depending on etiology, presumed source of its generation, activity during which it occurs (i.e., rest, action, etc.) and bodily distribution [Kojovic et al., 2011]. Among all these, the classification based on the putative site of myoclonus origin, or in other words deducing "Where is the lesion?", is of extreme importance, as it will guide therapeutic decisions [Caviness, 2014].

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Ultrasound transducers, angles and modes explained for EMS providers

In this video by Clarius Mobile Health, the basics of ultrasound, the various parts of an ultrasound system and how they can be used on a patient are explained.

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Ultrasound transducers, angles and modes explained for EMS providers

In this video by Clarius Mobile Health, the basics of ultrasound, the various parts of an ultrasound system and how they can be used on a patient are explained.

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Ultrasound transducers, angles and modes explained for EMS providers

In this video by Clarius Mobile Health, the basics of ultrasound, the various parts of an ultrasound system and how they can be used on a patient are explained.

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Brown Location Test

Link to instrument: http://ift.tt/2gcLqF0
Acronym:
BLT
Purpose:
The Brown Location Test is designed to assess visual memory for location of identical objects within a persons visual field.
 
The BLT was originally developed to assess visual memory difficulties that are generally associated with right temporal lobe epilepsy or cortical damage within the right medial temporal lobe.
 
Description:

The BLT as two alternative forms (A & B), has been validated in samples between ages 17 and 89, and can be administered using either a manual or computer version.

 

Instrument instructions are included in the stimulus manual, and the computerized version require only a mouse to click on the correct location.

 

·      12 items per trial are scored as 0 or 1

·      Scores for Learning trials 1-5 are tallied and compared against the mean and standard deviation for their age range

The BLT consists of several learning trials, interference trials, and memory trials:

  • Five learning trials: The same 12 red dot locations are presented for each trial.
  • An interference trial with presentation of black dots.
  • Short delay recall for 12 original dots, a long delay recall (20 min) followed by rotated free recall and recognition
    • Immediate recall (min/max) score: 0/60
    • Short delay (min/max) score: 0/12
    • Long delay(min/max) score: 0/12
Area of Assessment: Attention and Working Memory, Cognition, Vision & Perception
Body Part: Not Applicable
ICF Domain: Body Function
Domain: Cognition, Sensory
Assessment Type: Performance Measure
Length of Test: 31 to 60 Minutes
Time to Administer:
40 Minutes (Includes 20 Minute Delay)
Number of Items: 12 items are presented per trial.
Equipment Required: For the hand administered version, a test booklet, red chips, and response forms are required. For the computer program administration, a computer and working mouse are required.
Training Required:
Yes. Reading an Article/Manual.
Type of training required: Reading an Article/Manual
Cost: Not Free
Actual Cost:

The BLT is not free; however, it can be purchased for a significantly reduced price for research purposes.

  • BLT Kits Hand Admin $175 USD
  • BLT Computer Admin $175 USD
  • Both Hand and Comp $250 USD
  • Research Kit (Pre-Approved) $80 USD
Age Range: Adult: 18-64 years, Elderly adult: 65+
Administration Mode: Computer
Diagnosis: Acquired Brain Injury, Traumatic Brain Injury
Populations Tested: Epilepsy
Standard Error of Measurement (SEM):
Not Established
Minimal Detectable Change (MDC):
Not Established
Minimally Clinically Important Difference (MCID):
Not Established
Cut-Off Scores:
Not Established
Normative Data:

Brown et al., 2007 (n= 110; 79 females, 31 males. 84% Caucasian, 11% African American, 4% Asian American, and 1% Hispanic. The average age was 33.15 years (SD= 16.1); average education was 14.8 years (SD = 2.43).

 

Mean Scores for the two forms of the BLT

 

BLT-A (n=105)

BLT-B (n=46)

Subtest Score

Mean

Standard Deviation

Mean

Standard Deviation

Trial 1

5.02

1.87

5.17

2.28

Trial 2

6.80

2.21

6.63

2.11

Trial 3

8.06

2.45

8.15

1.99

Trial 4

9.24

2.15

9.46

2.00

Trial 5

10.17

1.92

10.43

1.72

Trials 1-5

39.28

8.57

39.85

8.35

Interference

4.58

2.13

4.59

1.64

Short Delay

8.80

2.50

9.00

2.40

Long Delay

8.81

2.59

8.93

2.48

Rotated Long Delay

7.56

2.71

8.33

2.33

Recognition Total

19.02

2.73

19.41

2.68

True Hits

9.87

1.57

10.04

1.30

False Positives

2.70

1.75

2.46

1.95

 

Brown et al. 2015 (n=29; 12 males and 17 females; Mean Age= 36.65, SD= 14.23)

 

Scores provided in standard z-scores:

  • BLT Learning Trial for LTLE (mean = -0.31; SD = 1.12)
  • BLT Long Delay for LTLE (mean = -0.25; SD = 1.02)
  • BLT Learning Trial for RTLE (mean = -1.45; SD = 0.86)
  • BLT for Long Delay for RTLE (mean = -1.75; SD = 0.84)
Test-retest Reliability:

(Brown et al. 2007)

  • Excellent split-half reliabilities for Learning Trials 1-5
    • .82 for the BLT-A (N = 110) and .78 for the BLT-B (N = 41)
  • Excellent alternate form test-retest reliabilities
    • r= .84 for Trials 1-5
    • Pearson correlation coefficients significant (p < .01) for each subtest of the BLT and are comparable to those reported for the CVLT-II standardization sample
Interrater/Intrarater Reliability:
Not Applicable
Internal Consistency:

Brown et al., 2015 references Brown et al., 2007 saying it showed good internal consistency.

Criterion Validity (Predictive/Concurrent):
Not Established
Construct Validity (Convergent/Discriminant):

Construct Validity: (Brown et al., 2007)

 

  • Demonstrated Evidence for construct validity via a Factor analysis of a brief neuropsychological test battery that revealed that all of the BLT subtests loaded on a single visual memory factor.
  • Factor Analysis:
    • 3 factors accounted for 59% of the variance
    • First factor accounted for 31.31% of total variance, consisted of all the BLT subtest scores.
    • The second factor accounted for 19.65% of variance, consisted of all the CVLT-II subtest scores.
    • The third factor accounted for 8.17% of variance and consisted of the Vocabulary, Matrix Reasoning, Estimated Intellectual Functioning standardized scores
    • Cancellation test loaded minimally on each of the three factors.
Content Validity:
Not Statistically Assessed
Face Validity:
Not Statistically Assessed
Floor/Ceiling Effects:
Not Established
Responsiveness:
Not Established
Considerations:
There is currently limited research on the BLT as it is a relatively new measure. Additional research is necessary to established the validity and reliability of the BLT across various patient populations.
Bibliography:

Abrahams, S., Morris, R. G., Polkey, C. E., Jarosz, J. M., Cox, T. C. S., Graves, M., & Pickering, A. (1999). Hippocampal involvement in spatial and working memory: a structural MRI analysis of patients with unilateral mesial temporal lobe sclerosis. Brain and cognition, 41(1), 39-65.

 

Abrahams, S., Pickering, A., Polkey, C. E., & Morris, R. G. (1997). Spatial memory deficits in patients with unilateral damage to the right hippocampal formation. Neuropsychologia, 35(1), 11-24.

 

Bornstein, R. A., & Chelune, G. J. (1988). Factor structure of the wechsler memory scale-revised. The Clinical Neuropsychologist, 2(2), 107-115.

 

Benton, A. L. (1974). Visual retention test. Psychological Corporation.

 

Brown, F. C., Hirsch, L. J., & Spencer, D. D. (2015). Spatial memory for asymmetrical dot locations predicts lateralization among patients with presurgical mesial temporal lobe epilepsy. Epilepsy & Behavior, 52, 19-24.

 

Brown, F. C., Roth, R. M., & Katz, L. J. (2015). Allocentric but not egocentric visual memory difficulties in adults with ADHD may represent cognitive inefficiency. Psychiatry research, 228(3), 649-658.

 

Brown, F. C., Roth, R. M., Saykin, A. J., & Beverly-Gibson, G. (2007). A new measure of visual location learning and memory: development and psychometric properties for the Brown Location Test (BLT). The Clinical Neuropsychologist, 21(5), 811-825.

 

Brown, F. C., Tuttle, E., Westerveld, M., Ferraro, F. R., Chmielowiec, T., Vandemore, M., ... & Spencer, D. D. (2010). Visual memory in patients after anterior right temporal lobectomy and adult normative data for the Brown Location Test. Epilepsy & Behavior, 17(2), 215-220.

 

Conroy, S. K., McDonald, B. C., Ahles, T. A., West, J. D., & Saykin, A. J. (2013). Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates. Brain imaging and behavior, 7(4), 491-500.

 

Golby, A. J., Poldrack, R. A., Brewer, J. B., Spencer, D., Desmond, J. E., Aron, A. P., & Gabrieli, J. D. (2001). Material-specific lateralization in the medial temporal lobe and prefrontal cortex during memory encoding. Brain, 124(9), 1841-1854.

 

Heinly, M., Vitelli, K., Murah, J., Mangini, D., Stryjewski, A., Brown, C., & Brown, F. (2015, September). An Alternate Forms Reliability Study of the Brown Location Test Paper vs. Computer-Based Versions within a Single Testing Session. In Archives of Clinical Neuropsychology (Vol. 30, No. 6, pp. 586-586). Great Clarendon St., Oxford OX2 6DP, England: Oxford University Press.

 

Lee, T., Yip, J. T., & JonesGotman, M. (2002). Memory deficits after resection from left or right anterior temporal lobe in humans: a metaanalytic review. Epilepsia, 43(3), 28

 

Moye, J. (1997). Nonverbal memory assessment with designs: Construct validity and clinical utility. Neuropsychology review, 7(4), 157-170.

 

Osterrieth, P. A. (1944). The test of copying a complex figure: A contribution to the study of perception and memory. Archives de Psychologie, 30, 286-356.

 

Parslow, D. M., Rose, D., Brooks, B., Fleminger, S., Gray, J. A., Giampietro, V., ... & Vythelingum, G. N. (2004). Allocentric spatial memory activation of the hippocampal formation measured with fMRI. Neuropsychology, 18(3), 450.

 

Wechsler, D. (1945). A standardized memory scale for clinical use. The Journal of Psychology, 19(1), 87-95.

Year published: 2004
Instrument in PDF Format: No


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Ultrasound transducers, angles and modes explained for EMS providers

In this video by Clarius Mobile Health, the basics of ultrasound, the various parts of an ultrasound system and how they can be used on a patient are explained.

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Pa. patrol car, ambulance transporting patient collide

The ambulance sustained minor damage, and the patient was transferred to another ambulance for the remainder of the transport.

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Comparison of the efficacy and safety of 2 different antiretroviral regimens in tertiary care hospital: A retrospective observational study

2016-11-28T12-22-25Z
Source: National Journal of Physiology, Pharmacy and Pharmacology
Reshma S R, Mangala Gowri S R, Vaneeth Agarwal, Narendranath Sanji, Navin Patil, Dinakar KR, Keerthisagar J.
Background: Highly active retroviral therapy has reduced the morbidity and mortality of HIV infection. Although many regimens have reduced the plasma virus load in patients, there are many cases of long-term toxicity, adverse effects, and drug resistance. Aims and Objective: To compare the efficacy and safety between combination of stavudine lamivudine nevirapine (SLN) and stavudine lamivudine efavirenz (SLE) (antiretroviral regimens) in tertiary care hospital. Materials and Methods: A retrospective cohort study was conducted in the anti-retroviral therapy (ART) center of CG Hospital, a tertiary care center at Davangere. Data were collected for the duration of 12 months (June 2012 to May 2013). The study was conducted after obtaining the permission from the institutional ethical committee and incharge officer. Prescriptions of the patients were collected, and relevant information was entered in the preformed pro forma and analyzed. Results: In total of 144 cases, 94 patients received combination therapy of SLN whereas 50 patients received combination therapy of SLE. To compare the baseline parameters such as CD4 counts, weight and hemoglobin with post-treatment values Dunns multiple comparison test was applied. To compare the changes in the parameters between the 2 therapies unpaired t-test was applied. There was a statistically significant improvement in CD4 counts in both the therapies but between group comparisons showed no statistical difference, inspite of clinical improvement more pronounced in patients receiving SLN combination. Hemoglobin levels have improved significantly post therapy in both the groups. Conclusion: In this study, there was clinically significant improvement in all the parameters considered for analyses in patients receiving SLN compared to SLE therapy but fails to show statistical significance.


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The anxiolytic effect of bee pollen hydroalcoholic extract in mice

2016-11-28T12-22-25Z
Source: National Journal of Physiology, Pharmacy and Pharmacology
Neda Sistani Karampour, Ali Asghar Hemmati, Azam Malmir.
Background: Anxiety is a common human mental disorder. Medicinal therapy of this disease is associated with many side-effects. Thus, search for new medication with fewer side-effects seems inevitable. Bee pollen (often referred to as a life-giving dust) has various therapeutic properties. Aims and Objectives: In this study, potential anxiolytic effects of hydroalcoholic extract of bee pollen was examined in mice. Materials and Methods: This study was conducted on 20-25 g male mice in three groups of eight. Animals received intraperitoneal injections of hydroalcoholic extract of bee pollen at 200, 400, 800, and 1600 mg/kg doses, diazepam at 1 mg/kg dose, and saline at 10 ml/kg dose. 30 min after injection, animals were studied in elevated plus maze device for 5 min. Results: The results obtained showed significantly longer presence in open arms of elevated plus maze device of animals that received 800 and 1600 mg/kg doses of hydroalcoholic extract of bee pollen compared to animals that received diazepam. However, no significant difference was observed between 1600 and 800 mg/kg doses. Conclusion: The above results confirmed anxiolytic effect of hydroalcoholic extract of bee pollen on mice.


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Manganese induced hematological alteration in Wistar rats

2016-11-28T11-36-56Z
Source: Journal of Environmental and Occupational Science
Milan Chandel, Gyan Chand Jain.
Aim: Manganese (Mn) is an essential trace metal that act as cofactor in many cellular enzymes. The present study was designed to evaluate toxic effects of manganese chloride (MnCl2.4H2O) on marker hematological parameters in rats after sub chronic exposure and after 60 days of treatment withdrawal. Method: Adult male Wistar rats were randomly divided into five groups. In group I, the rats were treated with vehicle (0.5 ml distilled water) and served as control. The rats in group II, III and IV were exposed to MnCl2 (50, 100 and 150 mg/kg b.wt./day, p.o. respectively) for 120 days. Half of the rats of group IV were followed by 60 days post exposure recovery period and served as group V. Results: The results of the study showed significant dose dependent decrease in red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Hct) value, platelet count and significant increase in white blood cell (WBC) count after MnCl2 exposure, Whereas no significant changes were observed in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) after treatment. Scanning electron microscopic study of blood showed a dose dependent increase in abnormal shaped RBCs in MnCl2 treated rats. Most of the effects in these parameters were recovered after 60 days of treatment withdrawal. Conclusion: The results of the study reveals that MnCl2 exposure resulted in hematological toxicity in rats and most of the changes in these parameters recovered when Mn exposure was ceased.


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Methods of Power-Force-Velocity Profiling During Sprint Running: A Narrative Review

Abstract

The ability of the human body to generate maximal power is linked to a host of performance outcomes and sporting success. Power-force-velocity relationships characterize limits of the neuromuscular system to produce power, and their measurement has been a common topic in research for the past century. Unfortunately, the narrative of the available literature is complex, with development occurring across a variety of methods and technology. This review focuses on the different equipment and methods used to determine mechanical characteristics of maximal exertion human sprinting. Stationary cycle ergometers have been the most common mode of assessment to date, followed by specialized treadmills used to profile the mechanical outputs of the limbs during sprint running. The most recent methods use complex multiple-force plate lengths in-ground to create a composite profile of over-ground sprint running kinetics across repeated sprints, and macroscopic inverse dynamic approaches to model mechanical variables during over-ground sprinting from simple time-distance measures during a single sprint. This review outlines these approaches chronologically, with particular emphasis on the computational theory developed and how this has shaped subsequent methodological approaches. Furthermore, training applications are presented, with emphasis on the theory underlying the assessment of optimal loading conditions for power production during resisted sprinting. Future implications for research, based on past and present methodological limitations, are also presented. It is our aim that this review will assist in the understanding of the convoluted literature surrounding mechanical sprint profiling, and consequently improve the implementation of such methods in future research and practice.



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Md. paramedic haunted by call helps raise funds for injured toddlers

By EMS1 Staff

PRINCE GEORGE'S COUNTY, Md. — After an emotionally heavy call, one paramedic decided to take an extra step in helping two children in need. 

Prince George's County  paramedic Lt. Pamela Graham responded to a call of two toddlers who had been stabbed by their father Nov. 11. 

"We got the call as 'children stabbed,' so you think, 'No, this cannot be. Something's wrong,'" Graham told NBC Washington

The 2- and 3-year-old boys were transported by first responders to the hospital, where they were treated for non-life threatening injuries. The boys' father, Christian Diller, was arrested and charged with first-degree murder and assault. 

Weeks after the call, Graham set up a YouCaring page in order to raise funds for the family, who is trying to relocate and move forward. She also set up a Christmas party for the family, which Graham plans to hold at her house with members of the fire and police department. 

"Two-year-olds and 3-year-olds are supposed to be running around, jumping off the couch and playing with the toys," Graham said. 

Almost $3,000 of a $10,000 goal has been raised for the family. 



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An epidemiological study of self-medication among urban adults of Aligarh

2016-11-28T09-58-41Z
Source: International Journal of Medical Science and Public Health
Anees Ahmad, Mohd Tabish Khan, Najam Khalique, Mohd Athar Ansari, Mohd Maroof.
Background: Self prescribing is usually defined as medication that is taken on the patients own initiative or on the advice of a pharmacist or lay person. In developing countries like India, private pharmacies are the predominant drug dispensers and prescription only drugs are available for sale in official pharmacies without a prescription. Modern medicament though of prime importance to humanity is potentially hazardous when administered indiscriminately in the form of self-medication. Objectives: To study the prevalence and pattern of self-medication among urban adults. Materials and Methods: A cross-sectional study was done among 424 adults aged 18 years and above residing in registered field practice area of Urban Health Training Centre. The sample was drawn using systematic random sampling with probability proportionate to size. The interview was taken using predesigned and pre-tested questionnaire. Out of 424, 395 adults responded to the questionnaire. Results were analyzed using SPSS version 20. Tests of proportion were used. Results: The prevalence of self-medication was found to be 83%. Pain was the most common symptom for self-medication. The source of drugs was mainly medical store. Lack of time, mild illnesses were the most common reason for not seeking medical advice. The majority of them were unaware of the adverse effects related to self-medication. Conclusion: Higher prevalence, as well as low awareness of side effects of self-medication, was seen. Awareness regarding the adverse consequence related to self-medication should be raised to lower the prevalence of self-medication.


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Profile of Human Immunodeficiency Virus seropositives attending Integrated Counseling and Testing Center of a Medical College in Chhattisgarh

2016-11-28T09-58-41Z
Source: International Journal of Medical Science and Public Health
Srishti Dixit, Divya Sahu, Aditi Chandrakar, Prem Sagar Panda, Shanta P Khes, Somen Kumar Pradhan.
Background: Acquired immune deficiency syndrome (AIDS) is one of the most important public health problems of the late 20th and early 21st centuries. Hence, it is necessary to understand the sociodemographic profile and risk behavior pattern of human immunodeficiency virus (HIV)-infected individuals for better implementation of interventions. Objective: The objective of this study was to assess sociodemographic profile, risk behavior pattern, and source of referral of HIV seropositive clients attending Integrated Counseling and Testing Center (ICTC). Materials and Methods: A crosssectional study was done on all HIV-seropositive attendees who attended ICTC from July 2015 to October 2015. Results: Out of all 274 individuals, 61.31% were male, 58.39% were of 20-39 years age, 77.01% were married, and 34.39% had completed primary education. Most common occupation among males is government or private service (20.83%) and almost half of the females were homemakers (49.06%). 174 (63.50%) individuals stated heterosexual transmission as the risk behavior. 3.66% of individuals got infected because of parent to child transmission. 37.23% of individuals visited ICTC voluntarily. Conclusion: Epidemiological studies should be carried out in various settings to understand the role and complex relations of social and demographic and behavioral factors, which will help, interrupt, and control the transmission of HIV/AIDS.


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Refractive errors among school-going children in Hyderabad

2016-11-28T09-58-41Z
Source: International Journal of Medical Science and Public Health
Mohammed Zain Ur-Rehman, Sultan Rizwan Ahmad, Mariya Syed.
Background: Uncorrected refractive error is the leading cause of eye problem worldwide. Children are more vulnerable because it starts in school age and can hinder the learning process and educational achievement. Objectives: The objectives of the study were to assess the prevalence of known case of refractive error among school-going children and its socioeconomic characteristics, and attitude of the students toward corrective measure. Materials and Methods: A study was conducted among school-going children from 6th to 10th standard from three schools. Permission was taken from the respective schools authority and consent was taken from parents through school. Each school had about 300 students, making a total of 900. Students are known to have refractive errors were included in the study. Out of 900, 190 were known to be affected. Data were collected using predesigned questionnaire and analyzed by appropriate statistical tests. Results: The prevalence of known case of refractive error was 21%. Maximum (51%) were between 11 and 12 years of age. About 95% of affected students had myopia. Majority of the students (54.2%) had blurring of vision as their initial complaint. Regarding family history of refractive errors, 65% of the students fathers were affected, 49% mothers were affected, and 43% of the siblings were affected. Almost 100% of the students used glasses and only 50% of the students get their eyes checked every 6 months. About 48% of students spent >2 h in front of screen and 47% students spent


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XCI-escaping gene KDM5C contributes to ovarian development via downregulating miR-320a

Abstract

Mechanisms underlying female gonadal dysgenesis remain unclarified and relatively unstudied. Whether X-chromosome inactivation (XCI)-escaping genes and microRNAs (miRNAs) contribute to this condition is currently unknown. We compared 45,X Turner Syndrome women with 46,XX normal women, and investigated differentially expressed miRNAs in Turner Syndrome through plasma miRNA sequencing. We found that miR-320a was consistently upregulated not only in 45,X plasma and peripheral blood mononuclear cells (PBMCs), but also in 45,X fetal gonadal tissues. The levels of miR-320a in PBMCs from 45,X, 46,XX, 46,XY, and 47,XXY human subjects were inversely related to the expression levels of XCI-escaping gene KDM5C in PBMCs. In vitro models indicated that KDM5C suppressed miR-320a transcription by directly binding to the promoter of miR-320a to prevent histone methylation. In addition, we demonstrated that KITLG, an essential gene for ovarian development and primordial germ cell survival, was a direct target of miR-320a and that it was downregulated in 45,X fetal gonadal tissues. In conclusion, we demonstrated that downregulation of miR-320a by the XCI-escaping gene KDM5C contributed to ovarian development by targeting KITLG.



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Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

Abstract

Parkinson's disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual's genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a "systems biology" overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.



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Anomalies in human sex-determination provide unique insights into the complex genetic interactions of early gonad development

Abstract

Human sex-determination (SD) involves complex mutually antagonistic genetic interactions of testis- and ovary-determining pathways. For many years both male and female sex-determination was considered to be regulated by a linear cascade of pro-male and pro-female genes respectively, however it has become clear that male and female development is achieved through the repression of the alternative state. A gene determining the formation of a testis may function by repressing the female state and vice-versa. Uniquely in development, SD is achieved by suppression of the alternate fate and maintained in adulthood by a mutually antagonistic double-repressive pathway. Here, we review genetic data generated through large scale sequencing approaches that are changing our view of how this system works, including the recently described recurrent NR5A1 p.R92W mutation associated with testis development in 46,XX children. We also review some of the unique challenges in the field to establish that mutations, such as this are pathogenic. The impending surge of new genetic data on human sex-determination from sequencing projects will create opportunities for the development of mechanistic models that will clarify how the system operates and importantly provide data to understand how selection and developmental processes interact to direct the evolution of SD across species.

Thumbnail image of graphical abstract

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Reinforcement in removable prosthodontics: a literature review

Abstract

Background

Removable prothodontics are often associated with mechanical troubles in daily use, such as fracture or deformation. These troubles render prostheses unusable and reduce wearers' QOL. Various reinforcements are used to prevent such problems, but consensus on reinforcement has not been reached.

Objective

This review aimed to summarize the effects of reinforcement, and to propose favorable reinforcement based on material, design, and position in the prostheses.

Methods

Initially, 139 articles were selected by electronic and manual searches. After exclusion of 99 articles based on the exclusion criteria, 40 articles were finally included in the review. Electronic searches were performed for articles published from 2005 to 2015 in PubMed, EMBASE, Medline, and Cochrane Library and manual searches were performed in 10 journals relevant to the topic of removable prosthodontics.

Results

For in vitro studies, certain dental alloys and fibers were mainly used. Their forms were different, including complicated forms in dental alloys and various forms in fibers. The materials were examined for mechanical properties like fracture strength, flexural strength, and elastic modulus, and compared with one another or without reinforcement. There were a few clinical studies and one longitudinal study.

Conclusion

Cast metal reinforcement seemed to be most favorable in terms of fracture toughness and stiffness. The most favorable forms differed depending on the prostheses, but placement around thin and deformable areas was effective. However, randomized or longitudinal clinical reports and comparative clinical studies on the use of reinforcement were still lacking and such studies are necessary in the future.

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Effects of low-level laser therapy on burning mouth syndrome

Abstract

Objectives

To investigate low-level laser therapy (LLLT) applied to treat burning mouth syndrome (BMS).

Materials and methods

This prospective. comparative. partially-blinded. single-centre. clinical trial of GaAlAs Laser. with 815 nm wavelength. included 44 BMS patients divided randomly into three groups: Group I (n=16): GaAlAs laser 815 nm wave-length. 1W output power. continuous emissions. 4 seconds .4 Joules and fluence rate is 133.3 joules/cm2.

Group II (n=16): GaAlAs infrared laser. 815 nm wavelength. 1W output power. continuous emissions. 6 seconds. 6 Joules and fluence rate 200 joules/cm2 Group III (n=12) placebo group. sham laser. All groups received a weekly dose for 4 weeks. Pain intensity was recorded using a 10-cm visual analog scale; patients responded to the oral health impact profile (OHIP-14). xerostomia severity test and the hospital anxiety-depression scale (HAD). These assessments were performed at baseline, 2 weeks and 4 weeks.

Results

LLLT decreased pain intensity and improved OHIP-14 scores significantly from baseline to 2 weeks in Groups I and II compared with the placebo group. No statistically significant differences were found from 2 weeks to 4 weeks. Overall improvements in VAS scores from baseline to the end of treatment were: Group I 15.7%; Group II 15.6%; Group III placebo 7.3%.

Conclusions

LLLT application reduces symptoms slightly in BMS patients.

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Assessment of cardiovascular risk factors among youths in Bengaluru urban district, India

2016-11-28T06-02-34Z
Source: International Journal of Medical Science and Public Health
Naveen Ramesh, Dwayne Mascarenhas, Roger Manuel, Rathnaprabha GK, Pretesh R Kiran.
Background: Cardiovascular disease (CVD) is one among the leading causes of death world over and in India. Risk factors for CVD have their beginnings early in life, and early detection and correction could have far-reaching implications in arresting the rising trend of mortality and morbidity due to CVD. Objectives: This study was done with the objective of assessing the prevalence of cardiovascular risk factors among college attending youths in Bengaluru urban district and to study the factors associated with these risks. Materials and Methods: A cross-sectional study among 1267 college students, aged 15-24 years in five colleges of Bengaluru urban district. Modified National Health and Nutrition Examination Survey questionnaire and glazer stress scale were administered to elicit prevalence of risk factors. Height, weight, and blood pressure were measured. Data were analyzed for frequencies, means and standard deviations and proportions compared using Chi-square test. Results: The prevalence of physical inactivity was 82%, stress was 56%, and that of unhealthy dietary habits was 42%. Alcohol consumption was reported by 25% of the students, tobacco consumption by 14%, both in the smoked and smokeless forms. On examination, 11.4% of the students were hypertensive, 24.9% underweight, and 6.1% overweight of them 0.4% were obese. A positive family history of CVD or death was positive among 50.4% of young adults. Conclusions: The present study shows the presence of several cardiovascular risk factors among college students. Interventions in the form of health education among youth adults regarding the need for adopting healthy lifestyles as well as regarding the ill effects of smoking, alcohol, physical inactivity, unhealthy dietary habits, and managing stress could help address the burden of modifiable risk factors.


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Barriers and Facilitators to Sustainment of an Evidence-Based Supported Employment Program

Abstract

Large-scale initiatives to expand evidence-based practices are often poorly implemented and rarely endure. The purpose of this study was to identify the perceived barriers and facilitators to sustainment of an evidence-based supported employment program, Individual Placement and Support (IPS). Within a 2-year prospective study of sustainment among 129 IPS programs in 13 states participating in a national learning community, we interviewed IPS team leaders and coded their responses to semi-structured interviews using a conceptual framework adapted from another large-scale implementation study. Leaders in 122 agencies (95%) that sustained their IPS programs identified funding, prioritization, and workforce characteristics as both key facilitators and barriers. Additional key factors were lack of local community supports as a barrier and leadership and structured workflow as facilitators. Within the IPS learning community, team leaders attributed the sustainment of their program to funding, prioritization, workforce, agency leadership, and structured workflow. The actions of the learning community's leadership, state governments, and local programs together may have contributed to the high sustainment rate.



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Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous vasoconstriction in human hypertension

Abstract

Despite ample evidence of dysregulated sympathetic control of the peripheral vasculature in hypertension, no studies have examined integrated neurovascular function during cold stress in hypertensive adults (HTN). We hypothesized that (1) whole-body cooling would elicit greater cutaneous vasoconstriction and greater increases in skin sympathetic nervous system activity (SSNA) in HTN (n = 14; 56 ± 2 yrs) compared to age-matched normotensive adults (NTN; n = 14; 55 ± 2 yrs) and (2) augmented reflex vasoconstriction in HTN would be mediated by an increase in cutaneous vascular adrenergic sensitivity and a greater contribution of non-adrenergic sympathetic co-transmitters. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (water-perfused suit). Sympathetic adrenergic- and non-adrenergic-dependent contributions to reflex cutaneous vasoconstriction and vascular adrenergic sensitivity were pharmacologically assessed using intradermal microdialysis. Cooling elicited greater increases in SSNA (NTN: +64 ± 13 vs. HTN: +194 ± 26 %baseline; P < 0.01) and greater reductions in skin blood flow (NTN: −16 ± 2 vs. HTN: −28 ± 3 %baseline; P < 0.01) in HTN compared to NTN, reflecting an increased response range for sympathetic reflex control of cutaneous vasoconstriction in HTN. Norepinephrine (NE) dose-response curves showed no HTN-related difference in cutaneous adrenergic sensitivity (logEC50; NTN: −7.4 ± 0.3 vs. HTN: −7.5 ± 0.3 log M; P = 0.84); however, non-adrenergic sympathetic co-transmitters mediated a significant portion of the vasoconstrictor response to cold stress in HTN. Collectively, these findings indicate that hypertension increases the peripheral cutaneous vasoconstrictor response to cold via greater increases in skin sympathetic outflow coupled with an increased reliance on non-adrenergic neurotransmitters.

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Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring

Promoting beige/brite adipogenesis and thermogenic activity is considered as a promising therapeutic approach to reduce obesity and metabolic syndrome. Maternal obesity impairs offspring brown adipocyte function and correlates with obesity in offspring. We previously found that dietary resveratrol (RES) induces beige adipocyte formation in adult mice. Here we further evaluated the effect of resveratrol supplementation to pregnant mice on offspring thermogenesis and energy expenditure. Female C57BL/6 J mice were fed a control diet (CON) or a high fat diet (HFD) with/without 0.2% (w/w) RES during pregnancy and lactation. Male offspring were weaned onto a HFD and maintained on this diet for 11 weeks. The offspring thermogenesis and related regulatory factors in adipose tissue were evaluated. At weaning, HFD offspring had lower thermogenesis in brown and white adipose tissues compared to CON offspring, which was recovered by maternal RES supplementation, along with the appearance of multiocular brown/beige adipocytes and elevated thermogenic gene expression. Adult offspring of RES-treated mothers showed increased energy expenditure and insulin sensitivity when on an obesogenic diet compared to HFD offspring. The elevated metabolic activity was correlated with enhanced brown adipose function and white adipose tissue browning in HFD+RES compared to HFD offspring. In conclusion, RES supplementation to HFD-fed dams during pregnancy and lactation promoted white adipose browning and thermogenesis in offspring at weaning accompanied by persistent beneficial effects in protecting against HFD-induced obesity and metabolic disorders.

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DNA elements: The ins and outs of enhancer validation

Nature Reviews Genetics. doi:10.1038/nrg.2016.155

Author: Linda Koch



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Cancer genomics: Single-cell RNA-seq to decipher tumour architecture

Nature Reviews Genetics. doi:10.1038/nrg.2016.151

Author: Ross Cloney



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Cortical and reticular contributions to human precision and power grip

Abstract

It is well accepted that the corticospinal tract contributes to the control of finger muscles during precision and power grip in humans but the neural mechanisms involved remain poorly understood. Here, we examined motor evoked potentials elicited by cortical and subcortical stimulation of corticospinal axons (MEPs and CMEPs, respectively) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in an intrinsic hand muscle during index finger abduction (control task), precision grip, and power grip. We found that the size of MEPs, but not CMEPs, were more suppressed during power grip compared with precision grip and index finger abduction, suggesting a cortical origin for these effects. Notably, intracortical inhibition was more reduced during power grip compared with the other tasks. To further examine the origin of changes in intracortical inhibition we assessed the contribution of the reticular system, which projects to cortical neurons and it is involved in these gripping configurations. An acoustic startle cue, which engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks and this positively correlated with changes in intracortical inhibition. A startle cue decreased intracortical inhibition, but not CMEPs, during power grip. F-waves remained unchanged across conditions. Our novel findings show that changes in corticospinal excitability present during power grip compared with finer finger manipulations are largely cortical in origin and suggest that the ascending reticular system contributed, at least in part, to these effects.

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Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn+/- transgenic mouse model of mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by SMN defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at eleven months of age, with a significant loss of 19% at seven months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in three fast-twitch and one slow-twitch hindlimb muscle innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn+/- transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die-back of motoneurons that innervate both fast- and slow-twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA.

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Does trans-spinal and local DC polarization affect presynaptic inhibition and post-activation depression?

Abstract

Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans-spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation (tDCS), and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feed-back systems, presynaptic inhibition and post-activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans-spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity-dependent actions on presynaptic inhibition and post-activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post-activation depression in a polarity-independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans-spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post-activation depression because they indicate that some common DC-sensitive mechanisms contribute to them.

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