Σάββατο 23 Φεβρουαρίου 2019
Parent Report of Amplification Use in Children with Mild Bilateral or Unilateral Hearing Loss
from #Audiology via ola Kala on Inoreader https://ift.tt/2BSv8eK
The Effects of Nonlinear Frequency Compression and Digital Noise Reduction on Word Recognition and Satisfaction Ratings in Noise in Adult Hearing Aid Users
from #Audiology via ola Kala on Inoreader https://ift.tt/2U9FwWE
Bilingualism and Speech Understanding in Noise: Auditory and Linguistic Factors
from #Audiology via ola Kala on Inoreader https://ift.tt/2BQRtsX
An Evaluation of Hearing Aid Beamforming Microphone Arrays in a Noisy Laboratory Setting
from #Audiology via ola Kala on Inoreader https://ift.tt/2U44INZ
Can Self-Reported Personal Audio System Volume Predict Actual Listening Levels in Young Adults?
from #Audiology via ola Kala on Inoreader https://ift.tt/2TZZT8q
Capillary versus Serum β-hydroxybutyrate in Pediatric Diabetic Ketoacidosis
Abstract
Objective
To find the strength of agreement between point-of-care and serum β-hydroxybutyrate.
Methods
236 paired samples (capillary β-hydroxybutyrate by a point of care device and serum β-hydroxybutyrate by colorimetric enzymatic estimation) samples were collected from 26 children aged <13 years admitted with diabetic ketoacidosis. Inborn errors of metabolism and septic shock were excluded.
Results
Capillary ß-hydroxybutyrate showed excellent agreement with serum â-hydroxybutyrate with mean (SD) bias of 0.027 (0.78); 95% limit of agreement -1.51, 1.56 and intraclass correlation 96.1% (95%CI 95%–97%, P<0.001). An increase in the bias noted for value above 5 mmol/L (P<0.001) (serum measurements were higher than capillary point-of-care measurements). Capillary âhydroxybutyrate correlated significantly with blood pH, anion gap,bicarbonate and carbon dioxide levels on blood gas analysis (P<0.05).
Conclusion
Capillary β-hydroxybutyrate estimation is a valid method for monitoring of ketonemia in pediatric diabetic ketoacidosis.
https://ift.tt/2SWatRj
Extended Sick Neonate Score (ESNS) for Clinical Assessment and Mortality Prediction in Sick Newborns referred to Tertiary Care
Abstract
Objective
To evaluate utility of a new Extended Sick Neonate Score (ESNS). to predict 'inhospital mortality' and compare with Score for Neonatal Acute Physiology – Perinatal Extension II (SNAPPE II) and Sick Neonate Score (SNS).
Design
Prospective observational study.
Methods
All extramural sick newborns transported to the neonatology unit of a tertiary care teaching hospital over a period of one year. Correlation between ESNS, SNAPPE-II and SNS scoring, and sensitivity/specificity of each score to predict mortality were determined.
Results
961 newborns were enrolled in the study. ESNS, SNAPPE II and SNS were strongly correlated, even when stratified by gestation. ESNS of ≤11 had the best sensitivity (85.9%) and specificity (89.8%). For preterms, ESNS ≤12 had the best sensitivity (92.3%) and specificity (76.7%).
Conclusion
ESNS can predict 'in-hospital mortality' outcome with satisfactory sensitivity and specificity.
https://ift.tt/2SUXI9S
Adolescent Immunization Schedule: Need for a Relook
Abstract
Adolescent immunization is one of the important yet a neglected field in India. There is no adolescent-specific schedule in the government's Universal Immunization Program. Though a separate adolescent immunization schedule exists for the private sector, there is almost no data on the coverage rates of the adolescent vaccines. With the changing epidemiology of certain vaccine preventable diseases, rapid development in the field of vaccinology and the advent of some new vaccines, there is a need to revisit the adolescent vaccination schedule. Common vaccine preventable diseases like dengue, mumps, hepatitis A and typhoid should be given higher priority whereas an alternate strategy should be adopted on the use of the vaccine against diphtheria, tetanus and pertussis.
https://ift.tt/2E6XbYb
Glanzmann Thrombasthenia in a Newborn with Heterozygous Factor V Leiden and Heterozygous MTHFR C677T Gene Mutations
Abstract
Introduction
Glanzmann thrombasthenia is a rare congenital platelet dysfunction.
Case characteristics
A 2-day-old male neonate delivered at 35 weeks' gestation was referred with extensive bruising and jaundice. His elder sibling had Glanzmann thrombasthenia, and his mother had thrombophilic risk factors. Flow cytometric analysis revealed absent CD41/ CD61. A molecular thrombophilia panel revealed the presence of heterozygous factor V Leiden G1691A and methylenetetrahydrofolate reductase C677T gene mutations.
Outcome
General precautions to avoid injuries and spontaneous bleeding were advised.
Message
Life-threatening bleeding may not be the first finding in cases of thrombasthenia accompanied by thrombophilic risk factors.
https://ift.tt/2T0NYe3
Skilled Counseling in Enhancing Early and Exclusive Breastfeeding Rates: An Experimental Study in an Urban Population in India
Abstract
Objective
The study was conducted to evaluate the effect of breastfeeding counseling and breastfeeding support by trained counselors during the ante-natal period at health facility and postnatal period at home on breastfeeding practices during the first six months of life.
Design
This was a randomized controlled study that compared the effect of counseling on breastfeeding during the first 6 months of life.
Setting
study was done in a government medical college in northern India, which is situated in an urban area.
Participants
300 healthy pregnant women from an urban population attending the antenatal clinic at Jawaharlal Nehru Medical College, Aligarh Muslim University were recruited for the study.
Intervention
Subjects were equally assigned randomly to the intervention (2 antenatal and 8 postpartum home counseling visits by the counselors) and control (non-counseling) group.
Main Outcome Measures
Infant feeding practices including rates of initiation of the breastfeeding within one hour of birth; exclusive breastfeeding and bottle-feeding during the first 6 months of life.
Results
Initiation of breastfeeding within one hour of birth was 73.4% in intervention group as compared to 33.6% in control group (P=0.001). More mothers in the intervention group (88.1%) were able to sustain exclusive breastfeeding rates at 6 months of age in comparison to the control group (50%) (OR 7.44, 95% CI 3.98-13.92).
Conclusions
This study substantiates positive role of skilled counseling by a trained dedicated breastfeeding counselor during the antenatal and post-natal periods on breastfeeding practices during the first six months of life.
https://ift.tt/2E6CE5X
Profile of Dengue Fever in Hospitalized Children in Saurashtra, Gujarat, 2013-2017
Abstract
Objective
To study the five year trend of epidemiological and demographic characteristics of dengue infections from year 2013 to 2017 among children upto 15 years.
Methods
This study presents data from review of microbiology department records of samples for dengue testing with information supplied by clinicians on the investigation request form. Patients were tested for NS1 Ag, IgM Ab or both.
Results
Out of 4216 samples, 1072 (25.4%) were positive for dengue. Positivity ranged from 44.1% in year 2013, 25.8% in 2015 to 16.1% in year 2017. Most cases reported were among male (57.9%), from urban areas (77.9%) and Rajkot district (75.7%). Reporting of dengue cases increased from July to November with peak during October every year.
Conclusion
Serum samples for dengue serology were more commonly positive in July-September months during the study period, and in male children, and those from urban areas.
https://ift.tt/2SSLo9U
An Infant with Interstitial Lung Disease
Abstract
Interstitial lung disease in infants, unlike older children and adults, has diverse etiology, including infective, metabolic, autoimmune, genetic, malignant and idiopathic causes. Clinical recognition of the interstitial pattern of lung involvement is important as the etiology and management is entirely different from that of recurrent or chronic lung parenchymal pathologies. We discuss the clinical and pathological findings of an infant with interstitial pneumonia, who succumbed to hospital-acquired sepsis.
https://ift.tt/2Eb1Atb
Aquagenic Wrinkling of Skin: A Screening Test for Cystic Fibrosis
Abstract
Objective
To study the utility of aquagenic wrinkling as screening test for children with cystic fibrosis.
Design
Evaluation of diagnostic test.
Setting
Pediatric Chest Clinic, and Pediatric Wards of a tertiary care hospital in New Delhi.
Participants
Three groups (children with cystic fibrosis, carriers of cystic fibrosis, and controls).
Methods
Time taken to develop aquagenic wrinkling was measured. The test was performed by asking the enrolled subject to put their one hand in water and was checked for development of wrinkling every minute, and a photograph was also taken every minute.
Results
A total of 64 children with cystic fibrosis, 64 controls and 64 carriers were enrolled in the study. Median (IQR) time to develop aquagenic wrinkling in the three groups was 2 (1.5,3) minutes, 4 (3,5) minutes and 8 (5,11) minutes, respectively. The optimal cut-off was calculated as 3 minutes by Receiver operating characteristic curve with a sensitivity and specificity for identification of children with cystic fibrosis as 81% and 57%, respectively. The area under curve was 76.5%. The 3 minute cut-off for development of aquagenic wrinkling was applied to 54 children referred for sweat test. 20 children had sweat chloride values of ≥60 mEq/l and diagnosed as cystic fibrosis. 15 of these developed aquagenic wrinkling at ≤3 minutes, giving a sensitivity of 75%.
Conclusions
In places with no facility for sweat test, children with phenotype compatible with cystic fibrosis who develop aquagenic wrinkling in 3 minutes may be diagnosed as probable cystic fibrosis and referred for confirmation by sweat test.
https://ift.tt/2E7K1Kk
Profile of Acute Kidney Injury in Hospitalized Children with Idiopathic Nephrotic Syndrome
Abstract
Objective
To determine the incidence, risk factors and outcome of acute kidney injury (AKI) in hospitalized children with nephrotic syndrome.
Methods
All consecutive hospitalized children (aged 1–14 years) with diagnosis of nephrotic syndrome between February 2016 and January 2017 were enrolled for the study. Children (aged 1–14 years) with features of nephritis, underlying secondary causes of nephrotic syndrome as well as children admitted for diagnostic renal biopsy and intravenous cyclophosphamide or rituximab infusion were excluded.
Results
A total of 73 children (81 admissions) were enrolled; incidence of AKI was 16% (95% CI, 9-23). On multivariate logistic regression analysis, furosemide infusion was observed as an independent risk factor for acute kidney injury (OR 23; 95% CI, 3-141; P<0.001). Out of 13 children with AKI, three died.
Conclusions
Acute kidney injury in hospitalized children with nephrotic syndrome has high risk of mortality. Children receiving furosemide infusion should be closely monitored for occurrence of acute kidney injury.
https://ift.tt/2E6GQCQ
Procrastination and Rational/Irrational Beliefs: A Moderated Mediation Model
Abstract
The present study focuses on the integrated effect of self-doubt, rational and irrational beliefs, and fear of failure on procrastination in a sample of Turkish undergraduate students (N = 293). The results confirm prior evidence indicating that self-doubt, fear of failure, and rational/irrational beliefs were important predictors of procrastination. The results show that (a) both self-doubt and irrational beliefs have direct and interactive effects on fear of failure, (b) fear of failure mediates the relationship between self-doubt and procrastination, (c) rational beliefs moderated the predictive effect of fear of failure on procrastination, and (d) the indirect effect of self-doubt on procrastination via fear of failure may vary depending on the level of rational and irrational beliefs. These findings suggest that future intervention attempts should focus on modifying irrational beliefs and enhancing rational beliefs to cope with procrastination.
https://ift.tt/2TiFqhU
Predictors of abatacept retention over 2 years in patients with rheumatoid arthritis: results from the real-world ACTION study
Abstract
Objectives
Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study.
Method
ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. Crude abatacept retention rates over 2 years were estimated using Kaplan–Meier analyses in biologic-naive and -failure patients. Clinically relevant risk factors and significant prognostic factors for retention were evaluated using a Cox proportional hazards multivariable model.
Results
Overall, 2350/2364 enrolled patients were evaluable; 673 (28.6%) were biologic naive and 1677 (71.4%) had prior biologic failure (1 biologic, 728/1677 [43.4%]; ≥ 2 biologics, 949/1677 [56.6%]). Abatacept retention rate (95% confidence interval [CI]) at 2 years was 47.9% (45.7, 50.0): 54.5% (50.4, 58.3) for biologic-naive vs 45.2% (42.7, 47.7) for biologic-failure patients (log-rank P < 0.001). For patients with 1 and ≥ 2 prior biologic failures, respectively, retention rates (95% CI) were 50.2% (46.3, 53.9) vs 41.3% (38.0, 44.6; log-rank P < 0.001). Main reasons for discontinuation (biologic-naive vs biologic-failure, respectively) were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) double positivity versus negativity were predictive of higher retention in both biologic-naive (hazard ratio [HR] [95% CI] 0.71 [0.53, 0.96]; P = 0.019) and biologic-failure patients (HR [95% CI] 0.76 [0.62, 0.94]; P = 0.035).
Conclusions
Abatacept initiation as earlier vs later line of therapy in RA may achieve higher 2-year retention rates. RF and anti-CCP seropositivity could predict increased abatacept retention, irrespective of treatment line.
Trial registration
NCT02109666
https://ift.tt/2XikjeU
Correction to: Proposal for a simple algorithm to differentiate adult-onset Still’s disease with other fever of unknown origin causes: a longitudinal prospective study
The author regrets that the original version of this article contained error. Figure 1 was shown in the wrong version, thus corrected figure is shown in this article.
https://ift.tt/2SqvK0E
Efficacy of mycophenolate mofetil in Japanese patients with systemic lupus erythematosus
Abstract
Objectives
To assess the renal and non-renal efficacy of mycophenolate mofetil (MMF) in Japanese patients with systemic lupus erythematosus (SLE).
Methods
We conducted a retrospective study to assess the renal and non-renal efficacies of MMF in Japanese patients with systemic lupus erythematosus (SLE). We analyzed 14 patients with lupus nephritis (LN) who were given MMF, and 13 patients who received monthly intravenous cyclophosphamide (IVCY) as induction therapy, and a further 19 patients without LN who were treated with MMF, and 13 patients who took tacrolimus (TAC) to reduce glucocorticoid dosages. We assessed the therapeutic effects of each therapeutic regime on renal and non-renal disease manifestations over a six-month period after treatment initiation.
Results
Median urine protein to creatinine ratios in the MMF and IVCY groups significantly decreased from 2.2 to 0.7 g/gCr and from 3.3 to 0.5 g/gCr, respectively. Significant improvements in serum immunological variables (serum complements C3 and C4 and the anti-double stranded DNA antibody) and reductions in the SLE disease activity index (SLEDAI) and daily prednisolone dosages were observed in each group with LN. MMF and TAC significantly improved SLEDAI and serum immunological variables and reduced daily prednisolone dosages in patients without LN.
Conclusion
The present results demonstrated that MMF might be an effective treatment for renal and non-renal manifestations in Japanese patients with SLE and has potential as a good therapeutic alternative and steroid-sparing agent.
https://ift.tt/2Xmsnv2
Efficacy of ω-3 supplementation in patients with psoriasis: a meta-analysis of randomized controlled trials
Abstract
Several studies have been conducted with the aim of investigating the effect of Omega(ω)-3 on different psoriasis indices including Psoriasis Area and Severity Index (PASI) score, erythema, scaling, itching, area involved, and infiltration. Nevertheless, a pooled analysis of trials that evaluated these variables has not been conducted. Therefore, the aim of this meta-analysis was to assess the efficacy of ω-3 fatty acids in treating patients with psoriasis. We searched through different electronic, references of retrieved articles, and previous related reviews databases up to November 2018. Both combined and stratified analyzes were conducted. A fixed-effects or random effects model was used to assess the mean effect sizes. An eventual 10 studies involving 560 participants were considered as eligible for inclusion in the present meta-analysis. The meta-analysis indicated a significant reduction in PASI score by − 1.58 (95% confidence interval (CI), − 2.24, − 0.92; P < 0.001) in favor of ω-3 polyunsaturated fatty acid (PUFA) group. The random effects model showed a statistically significant beneficial effect of ω-3 PUFA supplementation on reducing erythema by − 1.66 unit and reducing scaling (weighted mean difference (WMD), − 0.69; 95% CI, − 1.26, − 0.13; P = 0.02). Significant improvements in erythema, itching, and scale were observed in the trials which used the higher dosage of ω-3 supplementation. The results of current meta-analysis study support the use of ω-3 PUFA supplementation for the improvement of the evaluated parameters in psoriatic patients. However, well-controlled and randomized studies are needed to confirm the veracity of non-significant and/or equivocal findings.
https://ift.tt/2SnqMBD
Upregulated expression of STAT3/IL-17 in patients with systemic lupus erythematosus
Abstract
Elevated IL-17 levels with higher Th17 numbers are identified in systemic lupus erythematosus (SLE). STAT3 signaling plays a crucial role in the Th17 generation, and SOCS3 negatively regulates their formation. We investigated IL-17, STAT3, and SOCS3 expression, and analyzed their correlations to elucidate the regulatory mechanisms of IL-17 production in SLE. This study enrolled 32 patients, and venous mononuclear cells (MNCs) were isolated with further purification of CD4-positive T cells. IL-17 and SOCS3 levels were measured by real-time quantitative PCR, and pSTAT3/STAT3 expression was analyzed by immunoblot. Elevated IL-17 and SOCS3 levels were identified in lupus patients. There were higher IL-17 levels in lupus nephritis (class IV) than in SLE without renal involvement. Positive correlations were found between IL-17 levels and SOCS3 expression, lupus activity (SLEDAI-2K), or daily proteinuria. There were higher intensities of pSTAT3/β-actin and STAT3/β-actin in SLE, and a positive correlation between IL-17 expression and pSTAT3/β-actin or STAT3/β-actin intensity. Lupus nephritis (class IV) had higher STAT3/β-actin intensity than SLE without renal involvement. These results suggest upregulated STAT3/IL-17 expression in lupus patients. Such findings might facilitate the development of novel compounds and the application of existing therapeutics targeting the STAT3/IL-17 signal in SLE.
https://ift.tt/2Xmsl6o
The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients—a 6-month follow-up prospective study
Abstract
Introduction
Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications.
Aim
The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response.
Methods
One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3–5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3–5 weeks. Sera were collected before vaccination, 18–90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA.
Results
Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future.
Conclusion
Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.
https://ift.tt/2SnqIBT
Venous vessel wall thickness in lower extremity is increased in male patients with Behcet’s disease
Abstract
Vascular involvement, especially in young males, is seen in up to 40% of the patients with Behcet's disease (BD) and is a major cause of mortality and morbidity. In this study, we investigated vessel wall thickness (VWT) and dilatation in lower extremity veins with Doppler ultrasound (US) in male BD patients. Sixty-one male patients with BD, 37 healthy male controls (HC) and 27 male patients, with ankylosing spondylitis (AS), were included in the study. Venous Doppler US was performed by an experienced radiologist blinded to cases. Bilateral common femoral vein (CFV) wall thickness and great/small saphenous vein (SV) dilatations were assessed. All venous measurements were significantly higher in BD compared to AS and HC (p < 0.001 for all). Both right and left extremity CFV thicknesses had a high area under the ROC curve (> 0.8). Cut-off values for right and left CFV thicknesses for BD was 0.49 and 0.48 mm, respectively. High sensitivity and specificities are observed for both measurements (right CFV: sensitivity 81%, specificity 78.4%; left CFV: sensitivity 82.8%, specificity 81.1%). We found increased CFV thickness in BD patients independent of vascular involvement. As a similar change was not observed in controls, increased CFV thickness may be a specific sign of venous inflammation in BD. Our acceptable sensitivity and specificity values of CFV measurements suggest that assessment of femoral vein thickness with US may be a candidate diagnostic tool, especially in young males suspected of BD.
https://ift.tt/2XnUOsu
Clinical and MRI response to dose reduction of an etanercept-biosimilar for hip arthritis in patients with ankylosing spondylitis: an observational, retrospective cohort study
Abstract
Objectives
Hip arthritis plays a critical role in the prognosis of ankylosing spondylitis (AS). Dose reduction of tumor necrosis factor inhibitors preserves general improvement of AS, so this study attempted to examine the equivalence between Yisaipu® tapering and conventional therapy for hip arthritis in AS patients, using clinical parameters and magnetic resonance image (MRI).
Methods
AS patients received this etanercept-biosimilar injections (50 mg/week) in the first 12 weeks. Participants in the tapering group were treated with this reagent 50 mg every other week from week 13 to week 24, while the control group kept undergoing full-dose therapy. Clinical and laboratory parameters were assessed at baseline, week 12 and week 24. MRI examination of hip was performed at baseline and week 24.
Results
One hundred and thirty-six patients were enrolled, and 80 of them were in the tapering group. Linear mixed model revealed that main effects of tapering group with control group as reference in disease activity parameters were insignificant (p > 0.05). Main effects of baseline with week 24 as reference were significant (p < 0.05), but main effects of week 12 with week 24 as reference were not (p > 0.05). Prevalence of acute inflammatory change in MRI significantly decreased in the tapering group (76.88% vs 20.00%, p < 0.05) and control group (76.79% vs 19.64%, p < 0.05). Influence of both treatments on acute inflammatory change was equivalent (p > 0.05).
Conclusion
Efficacy of Yisaipu® tapering treatment is comparable to the full-dose therapy for hip arthritis in AS patients. Both treatments maintain remission of hip arthritis after patients achieved low disease activity.
https://ift.tt/2Xmsgj6
Effective serum level of etanercept biosimilar and effect of antidrug antibodies on drug levels and clinical efficacy in Chinese patients with ankylosing spondylitis
Abstract
Objectives
To investigate the effective serum level of etanercept biosimilar in Chinese patients with ankylosing spondylitis (AS) who achieve AS Disease Activity Score-C-reactive protein (ASDAS-CRP) < 2.1, and the effect of antidrug antibodies on drug levels and clinical efficacy.
Methods
Our study enrolled 60 patients with AS who were treated with etanercept biosimilar. Serum and clinical data were collected at baseline and treatment weeks 4, 12, and 24. Drug levels and antidrug antibody levels were measured using an enzyme-linked immunosorbent assay while tumour necrosis factor (TNF)-α levels were measured using cytometric bead array. A receiver operating characteristic (ROC) curve was used to analyse effective serum level of etanercept biosimilar.
Results
Patients with ASDAS-CRP ≥ 2.1 exhibited significantly lower drug levels than those with ASDAS-CRP < 2.1 did. The cut-off values of effective serum level of patients with AS who achieved ASDAS-CRP < 2.1 at weeks 4, 12, and 24 were 2.32, 2.12, and 2.36 μg/mL, respectively. Patients with drug levels above the cut-off value had lower Bath AS Disease Activity Index (BASDAI) and TNF-α levels. Antidrug antibodies had no effect on the Assessment of Spondylosis Arthritis International Society (ASAS) remission rates, but patients with antidrug antibodies had lower drug levels and higher TNF-α levels.
Conclusions
Detecting serum drug levels and antidrug antibody levels might facilitate estimation of the clinical efficacy and adjustment of medication regimen during etanercept biosimilar therapy in Chinese patients with AS.
https://ift.tt/2SmHely
Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile
Abstract
Introduction
Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms − 794 CATT5–8 (rs5844572) and − 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the − 794 CATT5–8 and − 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc.
Materials and methods
A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively.
Results
An association between the − 794 CATT7 and − 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p = 0.03) in SSc. In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles.
Conclusion
The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc.
https://ift.tt/2XmsdUs
Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years
Abstract
Objective
To evaluate ultrasonographic subclinical inflammatory synovitis and enthesitis in psoriasis patients, without clinical arthritis or enthesitis compared with healthy controls, with a 2-year follow-up to study the associated incidence of psoriatic arthritis (PsA).
Methods
A total of 109 consecutive psoriasis vulgaris patients without clinical signs of PsA and 90 healthy controls were included from two tertiary medical centers. Subjects underwent dermatological examination, PASI score evaluation for severity of psoriasis, musculoskeletal examination using 68/66 joints count for tenderness and swollen joints. Patients were assessed for CRP, musculoskeletal ultrasound (MSUS) in the form of grayscale ultrasound (GSUS), and power Doppler ultrasound (PDUS) for eight entheses and 34 joints to detect MSUS subclinical enthesitis and synovitis. All patients were followed-up for 2 years to detect evolving PsA.
Results
Subclinical enthesitis and synovitis were detected in 39.5% of psoriasis patients and 10% of controls (P < 0.001). CRP was significantly higher in psoriasis patients with MSUS manifestations (P < 0.01). PDUS and GSUS subclinical synovitis and/or enthesitis were detected at least in one site in psoriatic patients more than in controls (P < 0.05). During a 2-year follow-up of patients, the annual PsA incidence was 4.3%. Psoriasis patients who developed PsA showed a higher prevalence of baseline enthesitis, higher PDUS and GSUS synovitis scores, and higher baseline CRP level than those who did not develop PsA.
Conclusions
MSUS subclinical synovitis and enthesitis are quite common in psoriasis patients. The incidence of PsA in Saudi's psoriasis patients was slightly higher than worldwide reports. Subclinical enthesitis, PDUS, and GSUS synovitis could predict PsA development.
https://ift.tt/2SnqsTr
Incidence and prevalence of granulomatosis with polyangiitis and microscopic polyangiitis in health management organization in Argentina: a 15-year study
Abstract
Background/objective
Our objective was to estimate incidence and prevalence rates of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) using data from a university hospital-based health management organization (HIMCO) in Latin America.
Methods
Multiple methods for case finding were used to ensure complete ascertainment. GPA was diagnosed if fulfilling ACR 1990 criteria or a clinical diagnosis was made by an experienced rheumatologist. For MPA, a clinical diagnosis made by an experienced rheumatologist in concordance with Chapel Hill 2012 consensus. Renal limited vasculitis (RLV) ANCA-P positive was considered along with MPA. Global, age-specific, and sex-specific incidence and prevalence rates were calculated for members of the HIMCO with continuous affiliation ≥ 1 year from January 2000 to January 2015. Each person was followed up until GPA or MPA were diagnosed, voluntarily withdraw of the HIMCO, death, or study finalization. Prevalence was calculated on January 1, 2015.
Results
Nineteen incident cases of GPA and 28 of MPA were identified from January 2000 to January 2015. During this period, a total of 349,775 HIMCO persons contributed a total of 2,073,438 person-years. GPA and MPA overall incidence rate per 1,000,000 person-years were 9 (95% CI 5–13) and 14 (95% CI 9–19), respectively. Age-specific incidence rates in both female and male patients peaked in the seventh decade of life in our population. On January 1, 2015, prevalence rates were 7.4 per 100,000 (95% CI 2.8–12) for GPA and 5.2 per 100,000 (95% CI 1.3–9) for MPA. Prevalence rates were higher in ages over 70 for both genders and both diseases.
Conclusion
In this first study from Latin America, incidence and prevalence rates were in ranges of previous reports from other sites of the world. In our population, GPA and MPA were more frequent in women and in older ages, and the incidence of MPA was higher than that of GPA.
| Key points • In Argentina, MPA incidence was higher than GPA, similar to that reported in other parts of the world. • Prevalence and incidence rates were higher in ages over 70 for both sexes and both diseases. |
https://ift.tt/2Xmsc2Q
Utilize lung ultrasound B-lines and KL-6 to monitor anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis-associated interstitial lung disease: a case report and literature review
Abstract
In the past decade, lung ultrasound (LUS) B-lines and serum Krebs von den Lungen-6 (KL-6) antigen have been recognized as biomarkers of the connective tissue disease-associated interstitial lung diseases (CTD-ILDs). Robust data have demonstrated that B-lines total numbers and KL-6 levels are correlated with high-resolution computed tomography findings, pulmonary function test, and some clinical parameters in CTD-ILDs. However, limited data are available regarding the use of these two biomarkers to follow CTD-ILDs. Herein, we report a case with anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis-associated ILD, successfully treated with high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, pirfenidone, and followed using lung ultrasound and KL-6.
https://ift.tt/2Snqmv3
Time is the Enemy.
| Related Articles |
Time is the Enemy.
J Am Acad Audiol. 2019 Feb;30(2):92
Authors: Jacobson GP
PMID: 30789340 [PubMed - in process]
from #Audiology via ola Kala on Inoreader https://ift.tt/2E9AFO2
Time is the Enemy.
| Related Articles |
Time is the Enemy.
J Am Acad Audiol. 2019 Feb;30(2):92
Authors: Jacobson GP
PMID: 30789340 [PubMed - in process]
from #Audiology via ola Kala on Inoreader https://ift.tt/2E9AFO2
via IFTTT
In vitro schistosomicidal activity of tamoxifen and its effectiveness in a murine model of schistosomiasis at a single dose
Abstract
Schistosomiasis is a neglected tropical disease affecting 220 million people worldwide. Praziquantel has proven to be effective against this parasitic disease, though there are increasing concerns regarding tolerance/resistance that calls for new drugs. Repurposing already existing and well-known drugs has been a desirable approach since it reduces time, costs, and ethical concerns. The anti-cancer drug tamoxifen (TAM) has been used worldwide for several decades to treat and prevent breast cancer. Previous reports stated that TAM affects Schistosoma hormonal physiology; however, no controlled schistosomicidal in vivo assays have been conducted. In this work, we evaluated the effect of TAM on female and male Schistosoma mansoni morphology, motility, and egg production. We further assessed worm survival and egg production in S. mansoni-infected mice. TAM induced morphological alterations in male and female parasites, as well as in eggs in vitro. Furthermore, in our in vivo experiments, one single dose of intraperitoneal TAM citrate reduced the total worm burden by 73% and led to a decrease in the amount of eggs in feces and low percentages of immature eggs in the small intestine wall. Eggs obtained from TAM citrate-treated mice were reduced in size and presented hyper-vacuolated structures. Our results suggest that TAM may be repurposed as a therapeutic alternative against S. mansoni infections.
https://ift.tt/2SnTzpE
Evaluation of connectivity estimates using spiking neuronal network models
Abstract
The flow of information between different regions of the cortex is fundamental for brain function. Researchers use causality detection techniques, such as Granger causality, to infer connectivity among brain areas from time series. Generalized partial directed coherence (GPDC) is a frequency domain linear method based on vector autoregressive model, which has been applied in electroencephalography, local field potential, and blood oxygenation level-dependent signals. Despite its widespread usage, previous attempts to validate GPDC use oversimplified simulated data, which do not reflect the nonlinearities and network couplings present in biological signals. In this work, we evaluated the GPDC performance when applied to simulated LFP signals, i.e., generated from networks of spiking neuronal models. We created three models, each containing five interacting networks, and evaluated whether the GPDC method could accurately detect network couplings. When using a stronger coupling, we showed that GPDC correctly detects all existing connections from simulated LFP signals in the three models, without false positives. Varying the coupling strength between networks, by changing the number of connections or synaptic strengths, and adding noise in the times series, altered the receiver operating characteristic (ROC) curve, ranging from perfect to chance level retrieval. We also showed that GPDC values correlated with coupling strength, indicating that GPDC values can provide useful information regarding coupling strength. These results reinforce that GPDC can be used to detect causality relationships over neural signals.
https://ift.tt/2ErOj0p
A process account of the uncontrolled manifold structure of joint space variance in pointing movements
Abstract
In many situations, the human movement system has more degrees of freedom than needed to achieve a given movement task. Martin et al. (Neural Comput 21(5):1371–1414, 2009) accounted for signatures of such redundancy like self-motion and motor equivalence in a process model in which a neural oscillator generated timed end-effector virtual trajectories that a neural dynamics transformed into joint virtual trajectories while decoupling task-relevant and task-irrelevant combinations of joint angles. Neural control of muscle activation and the biomechanical dynamics of the arm were taken into account. The model did not address the main signature of redundancy, however, the UCM structure of variance: Many experimental studies have shown that across repetitions, variance of joint configuration trajectories is structured. Combinations of joint angles that affect task variables (lying in the uncontrolled manifold, UCM) are much more variable than combinations of joint angles that do not. This finding has been robust across movement systems, age, and tasks and is often preserved in clinical populations as well. Here, we provide an account for the UCM structure of variance by adding four types of noise sources to the model of Martin et al. (Neural Comput 21(5):1371–1414, 2009). Comparing the model to human pointing movements and systematically examining the role of each noise source and mechanism, we identify three causes of the UCM effect, all of which, we argue, contribute: (1) the decoupling of motor commands across the task-relevant and task-irrelevant subspaces together with "neural" noise at the level of these motor commands; (2) "muscle noise" combined with imperfect control of the limb; (3) back-coupling of sensed joint configurations into the motor commands which then yield to the sensed joint configuration within the UCM.
https://ift.tt/2VcM3Qg
Emergence of cognitive priming and structure building from the hierarchical interaction of canonical microcircuit models
Abstract
The concept of connectionism states that higher cognitive functions emerge from the interaction of many simple elements. Accordingly, research on canonical microcircuits conceptualizes findings on fundamental neuroanatomical circuits as well as recurrent organizational principles of the cerebral cortex and examines the link between architectures and their associated functionality. In this study, we establish minimal canonical microcircuit models as elements of hierarchical processing networks. Based on a combination of descriptive time simulations and explanatory state-space mappings, we show that minimal canonical microcircuits effectively segregate feedforward and feedback information flows and that feedback information conditions basic processing operations in minimal canonical microcircuits. Further, we derive and examine two prototypical meta-circuits of cooperating minimal canonical microcircuits for the neurocognitive problems of priming and structure building. Through the application of these findings to a language network of syntax parsing, this study embodies neurocognitive research on hierarchical communication in light of canonical microcircuits, cell assembly theory, and predictive coding.
https://ift.tt/2ErVt4O
Extracellular GABA assisting in organizing dynamic cell assemblies to shorten reaction time to sensory stimulation
Abstract
Until recently, glia, which exceeds the number of neurons, was considered to only have supportive roles in the central nervous system, providing homeostatic controls and metabolic supports. However, recent studies suggest that glia interacts with neurons and plays active roles in information processing within neuronal circuits. To elucidate how glia contributes to neuronal information processing, we simulated a sensory neuron–glia (neuron–astrocyte) network model. It was investigated in association with ambient (extracellular) GABA level, because the astrocyte has a major role in removing extracellular GABA molecules. In the network model, transporters, embedded in plasma membranes of astrocytes, modulated local ambient GABA levels by actively removing extracellular GABA molecules which persistently acted on receptors in membranes outside synapses and provided pyramidal cells with inhibitory currents. Gap-junction coupling between astrocytes mediated a concordant decrease in local ambient GABA levels, which solicited a prompt population response of pyramidal cells (i.e., activation of an ensemble of pyramidal cells) to a sensory stimulus. As a consequence, the reaction time of a motor network, to which axons of pyramidal cells of the sensory network project, to the sensory stimulus was shortened. We suggest that the astrocytic gap-junction coupling may assist in organizing dynamic cell assemblies by coordinating a reduction in local ambient GABA levels, thereby shortening reaction time to sensory stimulation.
https://ift.tt/2Vhxsmv
Time is the Enemy.
| Related Articles |
Time is the Enemy.
J Am Acad Audiol. 2019 Feb;30(2):92
Authors: Jacobson GP
PMID: 30789340 [PubMed - in process]
from #Audiology via ola Kala on Inoreader https://ift.tt/2E9AFO2
via IFTTT
Bridging vein and tentorial sinus in the subtemporal corridor during the anterior transpetrosal approach
Abstract
Background
The bridging vein (BV) and the tentorial sinus (TenS) are important venous structures in neurological surgery. These venous structures during the anterior transpetrosal approach (ATPA) have not been reported. The objective of this study is to examine the BV and the TenS in the subtemporal corridor during the ATPA and propose a technique to identify the BV preoperatively.
Methods
This study included 126 patients treated via the ATPA. The BV and the TenS located in the operative fields were analyzed. Furthermore, in the preoperative evaluation, the cross-sectional shapes of the intradural vein and the interdural sinus were analyzed by curved planar reconstruction (CPR), and the flattening rate was calculated. Flattening rate = (a-b)/a = 1-b/a (a: long radius, b: short radius).
Results
Seventeen BVs and 18 TenS were identified. The bridging site was divided into two groups: tentorial and middle fossa. The middle fossa group was divided into three subgroups: cavernous sinus, middle fossa dural sinus, and middle fossa dural adherence. Five isolated TenS were sacrificed and no venous complications were observed. The mean flattening rate was 0.13 in the intradural vein and 0.51 in the interdural sinus, respectively (P = 0.0003).
Conclusions
We showed classification of the BV, and preservation of the BV and TenS during the ATPA. Furthermore, we found that the interdural sinus was significantly flatter than the intradural veins. Measuring the flattening rate by CPR may be useful to identify BVs preoperatively.
https://ift.tt/2IzRRSt
Combination of “quadratic adaptive algorithm” and “hybrid operator splitting” or uniformization algorithms for stability against acceleration in the Markov model of sodium ion channels in the ventricular cell model
Abstract
The Markovian model has generally been used for cardiac electrophysiological simulations. However, the Markovian model is so stiff that speeding up the computation of the algorithms with variable time-steps always results in simulation instability. In particular, the unstable simulations always occur at a low voltage rate or current change, while transition rates in the Markovian model are changing markedly. The uniformization (UNI) method allows for a Markovian model simulation with high stability but also a high computation cost. To save computation costs with variable time-steps, we propose a speed increasing idea that is a compromise to the trade-off between stability and acceleration by combining Chen-Chen-Luo's "quadratic adaptive algorithm" (CCL) method with "hybrid operator splitting" (HOS) into the solver (CCL + HOS solver). The computation cost of this CCL + HOS solver is approximately 24 times lower than the CCL + UNI solver, and the CCL + HOS solver can function 295 times faster in comparison to the HOS solver with a fixed time-step (DT). The suggested optimal solver should be CCL + HOS solver with a maximum time-step at 0.1 ms due to its high speed with low error. Additionally, the CCL method has much better performance and stability than the hybrid method in this single-cell model simulation.
https://ift.tt/2TjaCOp
Transferrin-functionalised microemulsion co-delivery of β-elemene and celastrol for enhanced anti-lung cancer treatment and reduced systemic toxicity
Abstract
In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries β-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that β-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of β-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with β-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.
https://ift.tt/2IvpRzr
Difficult Conversations in Cancer Care: Lessons from a Student-Led Initiative
Abstract
With the rising global burden of cancer, healthcare professionals will inevitably be involved directly or indirectly in the care of cancer patients. Although medical education has recently evolved to emphasise the biopsychosocial model, current training regarding difficult communication skills and breaking bad news remains inadequate. Our aim was to utilise a novel method of teaching communication skills through public engagement. This was achieved by setting up a local network of cancer patients who were willing to share their stories to aid student learning. A group of medical students from years one to four interviewed a total of 48 cancer patients about their illness experiences. Student reflections were collated, producing three common themes: (1) knowing what to say, (2) seeing the person in the patient, and (3) understanding the consequences of poor communication. The experiences allowed students to develop their communication skills, learn from patient experiences, and reflect on their future practice. Patient stories, including art, drawings, and poems, were collated in the form of a book and disseminated to promote further learning. We hope our reflections and public engagement initiative will identify key areas of difficult communication, enhance learning, and prepare students for meaningful and often difficult conversation in cancer care. Similar principles could be used in other areas of medical education to allow students to develop safe and effective interpersonal skills.
https://ift.tt/2U5eJKM
Analysis of Predictors of Type 2 Diabetes Mellitus Remission After Roux-en-Y Gastric Bypass in 101 Chinese Patients
Abstract
Background
To investigate prognostic factors for complete remission in type 2 diabetes mellitus (T2DM) patients who underwent gastric bypass (GBP) and to establish a prognostic model for risk stratification.
Methods
We evaluated the baseline clinical features of patients with T2DM who received at Beijing Tian Tan Hospital from April 2012 to December 2015. Complete remission of T2DM was defined as meeting the following criteria: HbA1c < 6.5%, fasting plasma glucose (FPG) < 100 mg/dL, and absence of hypoglycemic drugs for 1 year following GBP.
Results
A total of 101 patients were enrolled in our study, and the complete remission rate of T2DM was 70.3% (71/101). Compared with patients with incomplete remission, patients with complete remission of T2DM had higher C-peptide levels, lower HbA1c, shorter disease duration, better β cell function, and an absence of insulin therapy. HbA1c level, fasting C-peptide, duration of T2DM, and history of medical therapy were important prognostic factors for complete remission of T2DM (P = 0.001, 0.002, 0.01, 0.028, respectively). Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, fasting C-peptide higher than 1.2 ng/mL, and absence of insulin therapy before GBP achieved a higher complete remission rate of T2DM after GBP (AUC of the model was 0.825, 95% CI, 0.741–0.910; P = 0.001).
Conclusions
The duration of T2DM, history of medical therapy, and levels of HbA1c and fasting C-peptide are independent predictors for the prognosis of T2DM patients undergoing GBP. Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, a fasting C-peptide higher than 1.2 ng/mL, and an absence of insulin therapy may have a higher complete remission rate of T2DM after GBP.
https://ift.tt/2EtNNPP
Colorectal Cancer Knowledge and Awareness Among University Students in a Caribbean Territory: a Cross-sectional Study
Abstract
Introduction
The burden of colorectal cancer (CRC) has been on the rise globally over the last decade. Several studies point to the fact that there is a lack of knowledge and awareness for CRC which may be attributed to the increase in the burden over time. Therefore, we aimed to assess the level and predictors for knowledge of CRC and its risk factors.
Methods
This study was a cross-sectional study conducted on the student population of the University of the West Indies, St. Augustine Campus, Trinidad. We assessed CRC knowledge using scales examining their level of knowledge for CRC and its risk factors. Lifestyle behaviors (smoking, physical activity, dietary behaviors, and alcohol consumption) and perceived risk for developing CRC were also collected using a standard survey. Predictors for CRC knowledge were assessed using forward stepwise linear and logistic regression models.
Results
The overall CRC knowledge was 54.740% ± 19.721%. Poor knowledge levels were seen among 36.23% while satisfactory/good knowledge was seen among 63.77%. Predictors of poor CRC knowledge were males (OR = 1.559; p = 0.003), frequent/excessive alcoholic drinkers (OR = 1.924; p = 0.029), and low physical activity (OR = 1.331; p = 0.042). Predictors of satisfactory/good CRC knowledge were those with higher scores for the prudent dietary pattern (OR = 0.893; p = 0.016), and compared with those who reported no risk, participants reporting low risk had an increased likelihood of obtaining good CRC knowledge scores (OR = 0.526; p = < 0.001) and high risk (0.310; p = < 0.001).
Conclusion
The level of awareness/knowledge on CRC and its risk factors is low. Improvement of CRC awareness and healthy lifestyle campaigns among young adults is needed for the Caribbean region.
https://ift.tt/2BODMLh
Host–pathogen interaction in Toxoplasma gondii -infected mixed chicken blood cell cultures
Abstract
Toxoplasma gondii has the ability to infect various nucleated cell types in different hosts. The aim of the present study was to investigate which chicken blood cells were targeted by T. gondii in a mixed blood cell culture similar to in vivo conditions and to evaluate parasite–host cell interactions. The study consisted of two subsequent experiments. In experiment 1, we applied T. gondii tachyzoites (ME49) at a multiplicity of infection of 1 tachyzoite per blood cell and examined parasite replication, cytokine, and inducible nitric oxide synthase (iNOS) mRNA expression between 1 h and 48 h post-infection (p.i.) by quantitative PCR. By using T. gondii RH-GFP tachyzoites expressing the green fluorescent protein (GFP) in experiment 2, we aimed for visualizing infected cells by confocal laser scanning microscopy (CLSM) and flow cytometric analysis at 24 h p.i. The parasite replication curve showed a massive decrease of parasite stages until 24 h p.i. followed by an approximately plateau phase. We observed mainly significantly increased iNOS mRNA expression levels in T. gondii-infected culture compared to uninfected cells. Flow cytometry and CLSM data confirmed monocytes/macrophages as main target cells for T. gondii. Moreover, different lymphocytes like B cells and cytotoxic T cells seem to be targeted to a low extent. Our findings indicate that monocytes/macrophages play a key role during T. gondii infection in chicken as host cells and triggering of immune response. To the best of our knowledge, this is the first report of a mixed chicken blood cell culture experimentally infected with T. gondii.
https://ift.tt/2SV7ngG
Characterization of new polyether-diols with different molar masses and modality prepared by ring opening polymerization of oxiranes initiated with anhydrous potassium hydroxide
Abstract
Several new polyether-diols were prepared by ring-opening polymerization of monosubstituted oxiranes in the presence of anhydrous potassium hydroxide. 1,2-Butylene oxide (BO), styrene oxide (SO), isopropyl glycidyl ether (IPGE), allyl glycidyl ether (AGE), phenyl glycidyl ether (BGE), p-methoxyphenyl glycidyl ether (MPGE) and benzyl glycidyl ether (BGE) were chosen as monomers. Macrocyclic ligands complexing metal cations, i.e. coronand 18C6 or cryptand C222 were used as activators in these systems. All polymerizations were carried out in tetrahydrofuran solution at room temperature. Molar mass (Mn) and dispersity (Mw/Mn) of the polymers obtained with KOH depends on the kind of monomer, initial concentration of the initiator and the presence and kind of ligand or water. For example, PBO-diols prepared without ligand are bimodal and for the main fraction Mn > Mcalc. However, after addition of 18C6 polymers are unimodal and unexpectedly have much higher Mn = 13,700–15,800 and very low dispersity (Mw/Mn = 1.04–1.08). Mn of PBO-diols decrease with increase of [KOH]o and do not change at [BO]o = 2.0–9.0 mol/dm3. Addition of C222 results in Mn decrease of PBO-diols. Similar effects were observed in the polymerization of PAGE-diols and PPGE-diols. In the polymerization of SO, PGE, MPGE and BGE initiator efficiency (f) is high and Mn < Mcalc. Polymodality of some polymers obtained was discussed in term of the formation of various species propagating with different rate constants.
Graphical abstract
Polyether-diols synthesized using anhydrous hydroxide as initiator.
https://ift.tt/2U4eVKx
Progressive decline in pulmonary function 5 years post-operatively in patients who underwent anterior instrumentation for surgical correction of adolescent idiopathic scoliosis
Abstract
Purpose
To evaluate changes in pulmonary function tests (PFT) at 5 years post-operatively in patients with adolescent idiopathic scoliosis (AIS) and to determine whether these changes are progressive or static after 2 years.
Methods
AIS surgical patients with pre-operative and 5 year post-operative forced expiratory volume (FEV) and forced vital capacity (FVC) were included. The percentage of patients with pulmonary impairment at 5 years was calculated. Repeated measures ANOVA was used to evaluate changes between pre-operative PFT and 5 years post-operative PFT and to determine whether the changes differed between curve types and approach. A sub-analysis of patients with 2 year data was performed to determine whether PFT changes were static or progressive.
Results
Two hundred and sixty-two patients had undergone pre-operative and 5 year post-operative PFTs. At 5 years, 42% were normal, 41% had mild impairment, and 17% had moderate-severe impairment. Overall, there was a decline in % predicted FVC (p < 0.05); FEV remained stable. There was no difference based on major curve type (p > 0.05). Anterior instrumentation cases declined significantly between pre-operative PFT and 5 years post-operative PFT (FEV: − 10% open, − 6% thoracoscopic; FVC: − 13% open, − 8% thoracoscopic) (p ≤ 0.02). The posterior cases remained stable (2% FEV, p = 0.7; − 0.6% FVC, p = 0.06). A subgroup of 90 patients with 2 year post-operative PFTs demonstrated that changes were progressive between 2 and 5 years post-operatively. The average change in FVC from 2 to 5 years was significantly different between the anterior open (− 9%) and posterior-only (0.7%) groups (p = 0.015).
Conclusion
In patients who underwent anterior instrumentation, PFTs declined from the pre-operative to the 5 years post-operative time point. There was a progressive decline of 4–10% beyond 2 years post-operatively. Patients who underwent posterior instrumentation remained stable.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material. 
https://ift.tt/2BPBhbw
Classification of breast mass in mammography using anisotropic diffusion filter by selecting and aggregating morphological and textural features
Abstract
In this paper, we describe a novel mammogram classification framework for classifying breast tissues as normal, benign or malignant. First, we establish a set of symbolic rules for mammograms pre-classification from the particularities of a tissue (the background, class and severity of abnormality) taking into account the different forms of breast according to their abnormality. A decision tree reflecting a preliminary attribution from the region of interest (ROI) of a mammogram represents this pre-classification. The images obtained by this technique are processed with an anisotropic diffusion filter to reduce the noise and preserve edges. Then, a feature matrix is generated using: on the one hand, textural features from both a Gray Level Co-occurrence Matrix (GLCM) and a Gray Level Run Lengths Matrix (GLRLM) applied to all the filtered regions of interest (ROI) of a mammogram; and on the other, after mass region is segmented out, the features extracted from the mass boundary and the margin region between the mass and background for classification. To derive the relevant features from the feature matrix, we resort to RELIEF and MRMR feature selection method separately. The key point of our proposal is the modeling of Back Propagation Neural Network (BPNN) by a network of queues for representing the textural and morphological properties of the masses. The relevant and ordered features are injected in BPNN classifier using queuing network. The standard database MIAS is used for validation of the proposed scheme. In any case, we observed that the opening of closed neural network improves the performance. However, the MRMR feature selection method outperforms RELIEF one the point of view of precision and area under curve of receiver operating characteristic. These measures are respectively 98.1% and0.9650 for normal vs. abnormal classification, whereas, they are respectively 95.2% and 0.9200 for benign vs. malignant classification.
https://ift.tt/2EpZLKf
Preventive effects of seat belts on traumatic brain injury in motor vehicle collisions classified by crash severities and collision directions
Abstract
Purpose
This study aimed to measure the preventive effect of seat belt on traumatic brain injury (TBI) and to compare the effect according to the crash severities and collision directions.
Methods
Korea In-Depth Accident Study (KIDAS) has collected vehicle and demographic data on injured occupants involved in motor vehicle collisions (MVCs) who visited three emergency medical centers for calendar years 2011–2016. Primary and secondary end points were TBI (abbreviated injury score 2+) and in-hospital mortality. Crush extent (CE) was classified into 1–2, 3–4, 5–6, and 7–9 according to the crash severity. We calculated adjusted odds ratios (ORs) of seat belts and CE for study outcomes and developed an interaction model in each collision direction using multivariate logistic regression analysis.
Results
Of the 2,245 occupants who were injured in MVCs, 295 (13.1%) occupants sustained TBI. In univariate analysis, old age, unbelted status, lateral collision, and higher CE were factors associated with TBI in MVCs. Occupants with belted status was less likely to have TBI and in-hospital mortality compared with those with unbelted status [AORs (95% CI) 0.48 (0.37–0.62) and 0.49 (0.30–0.81), respectively]. In interaction analysis, preventive effects of seat belts on TBI from MVCs were retained within CE 5–6 in frontal MVCs and within CE 1–2 in near side lateral MVCs, and those of seat belts on in-hospital mortality were reserved within CE 3–4 in frontal and rollover MVCs.
Conclusions
The preventive effects of seat belts on TBI and in-hospital mortality are preserved within a limited crash severity in each collision direction.
https://ift.tt/2T4TdZF
Objective sleep quality and metabolic risk in healthy weight children results from the randomized Childhood Adenotonsillectomy Trial (CHAT)
Abstract
Background
We hypothesized that cardiopulmonary coupling (CPC) sleep quality reflects cardiovascular and cardiometabolic health, in healthy weight children.
Methods
Retrospective signal analysis of existing ECG data utilizing CPC, FDA cleared, software as medical device (SaMD). ECG signals were extracted from baseline polysomnography studies in the prospective Childhood Adenotonsillectomy Trial database, multicenter, single-blind, randomized controlled trial of 5.0–9.9-year-old children identified with obstructive sleep apnea syndrome without severe hypoxemia. Healthy weight was defined as age- and gender-specific BMI in the 5th–85th percentile range and overweight above the 85th percentile. The cohort was stratified based on CPC sleep quality Index (SQI) defined as high sleep quality (SQI ≥ 80) or low sleep quality (SQI < 60). Cardiovascular, cardiometabolic, quality of life, and cognition were compared between the sleep quality groups.
Results
Healthy weight children with low sleep quality had more fragmented sleep with significantly higher arousal index (10.0 ± 4.3 vs.7.2 ± 3.1; p = 0.00) and eLFCBB (12.4 ± 4.9 vs. 0.9 ± 1.0; p < 0.001) CPC indicator of sleep fragmentation, higher average heart rate during sleep (84.5 ± 10.6 vs. 79.4 ± 7.1; p = 0.03) and worse insulin/glucose ratio (1.7 ± 1.6 vs. 1.1 ± 1.1; p = 0.03) and fasting insulin levels (7.9 ± 7.2 vs.5.3 ± 5.5; p = 0.05) when compared to healthy weight children with high sleep quality. SQI significantly correlates with average heart rate during sleep, insulin and triglyceride levels; for a unit increase in SQI, there is 0.154 unit decrease in average heart rate during sleep, 0.109 unit in insulin levels and 0.332 unit in triglyceride levels, respectively.
Conclusion
CPC sleep quality offers insights into pediatric sleep and how it affects cardiovascular and cardiometabolic health. ECG is simple signal to collect, which makes this method practical for testing sleep, over multiple nights, and on multiple occasions providing information on sleep dynamics not possible before.
Trial registration
https://ift.tt/2TiBbTT
Prognostic factors and survival in Ewing’s sarcoma treated by limb salvage surgery
Abstract
Purpose
Survival in Ewing's sarcoma (ES) has increased with the use of chemotherapy. Surgical techniques such as limb salvage (LS) have been developed. Survival and adverse events have been widely studied in general series of ES, but there are few specific series of ES cases treated by LS, despite this being the most commonly used (surgical) approach. The aim of this study was to determine survival and prognostic factors in ES patients undergoing LS.
Patients and methods
We analysed all ES patients treated between January 1984 and May 2008 and selected all those treated by systemic multimodal therapy and LS. We assessed the influence of patient characteristics, tumour parameters and therapeutic results in event-free survival (EFS).
Results
Ninety patients were included. Fifty of them were treated by systemic multimodal therapy and locally by LS. ean age was 20 years. Overall survival (OS) was 68.8% and EFS was 60.6% at years. In the univariate analysis, pelvic location, age and response to chemotherapy were associated with poor prognosis. After multivariate analysis, poor response to treatment, pelvis location and age between 12 and 17 years were found to be independent prognostic factors. Dissemination at diagnosis was not a prognostic factor.
Conclusions
OS and EFS in ES treated by LS were similar to findings in previous ES studies. factors are no different, except for the presence of metastasis at diagnosis.
https://ift.tt/2SUEq49
Supplementation of organ culture medium with dextran is not required in pre-stripped human donor tissue for DMEK surgery
Abstract
To assess corneal endothelial cell (CEC) quantity and quality in eye-bank prepared lamellar grafts for Descemet Membrane Endothelial Keratoplasty (DMEK) from organ cultured donor corneas that have not undergone de-swelling by media supplementation with dextran. Prior to graft preparation, corneas that had not undergone de-swelling (n = 30) were placed into fresh storage medium without dextran (KMI). Corneas in the control group (n = 30) were placed in dehydration medium containing 5% dextran (KMII). Subtotal stripping of Descemet's membrane (DM) was performed manually. Following graft preparation, 10 corneas of each group were cultured further in their respective medium for 24 h, 72 h, or 120 h, respectively. Before and after DM stripping, as well as at the end of culture, CEC numbers were obtained. At the end of culture, CEC morphology was graded using a scoring system and CEC metabolism was assessed by detection of adenosine triphosphate. At 24 h after DM stripping, mean CEC counts (in cells/mm2) were 2204 in corneas stored in KMII, and 2391 in corneas stored in KMI (p = 0.003). This corresponds to a mean relative CEC loss of 12.4% with dextran versus 9.7% without dextran (p = 0.04). At 72 h, CEC counts were 1946 in KMII, and 2289 in KMI (p = 0.004). This corresponds to CEC loss of 23% with dextran versus 14% without dextran (p = 0.009). At 120 h, CEC counts were 2047 in KMII, and 2230 in KMI (p = 0.14). This corresponds to CEC loss of 22.7% with dextran versus 17.2% without dextran (p = 0.14). Also, at 120 h after DM stripping, 6/10 corneas fell below a threshold of 2000 cells/mm2 if stored in medium containing dextran, versus 1/9 corneas if stored without dextran (p = 0.003). Morphological assessment of CEC quality revealed equal scores for cell polymorphism (median = 1), granulation (median = 0) and segmentation (median = 1) in all groups. Lower ATP/protein ratios were observed in corneas stored in medium without dextran at 24 h (p < 0.001), 72 h (p < 0.001), and 120 h (p = 0.02). Abandoning the use of dextran in corneas destined for DMEK surgery leads to increased CEC counts and thereby serves to reduce tissue loss.
https://ift.tt/2SlHVeP
Temporal enhancement of 2D color Doppler echocardiography sequences by fragment-based frame reordering and refinement
Abstract
Purpose
The goal of this study was to develop an algorithm that enhances the temporal resolution of two-dimensional color Doppler echocardiography (2D CDE) by reordering all the acquired frames and filtering out the frames corrupted by out-of-plane motion and arrhythmia.
Methods
The algorithm splits original frame sequence into the fragments based on the correlation with a reference frame. Then, the fragments are aligned temporally and merged into a resulting sequence that has higher temporal resolution. We evaluated the algorithm with 10 animal epicardial 2D CDE datasets of the right ventricle and compared it with the existing approaches in terms of resulting frame rate, image stability and execution time.
Results
We identified the optimal combination of alternatives for each step, which resulted in an increase in frame rate from 14 ± 0.87 to 238 ± 93 Hz. The average execution time was 7.23 ± 0.48 s in comparison with 0.009 ± 0.001 s for ECG gating and 1167.37 ± 587.85 s for flow reordering. Our approach demonstrated a significant (p < 0.01) increase in image stability compared with ECG gating and flow reordering.
Conclusion
This work presents an offline algorithm for temporal enhancement of 2D CDE. Unlike previous frame reordering approaches, it can filter out-of-plane or corrupted frames, increasing the quality of the results, which substantially increases diagnostic value of 2D CDE. It can be used for high-frame-rate intraoperative imaging of intraventricular and valve regurgitant flows and is potentially modifiable for real-time use on ultrasound machines.
https://ift.tt/2tDWKiV
Factors Impacting Adherence to Diabetes Medication Among Urban, Low Income Mexican-Americans with Diabetes
Abstract
Mexican-Americans carry a high burden of type 2 diabetes and are disproportionately affected by diabetes related mortality and morbidity. Poor adherence to medication is an important barrier to achieving metabolic control and contributes to adverse health outcomes and health disparities. Little is known about barriers and facilitators to medication adherence among Mexican-Americans with diabetes. This is a qualitative study of semi-structured interviews with a sample of 27 adults (25 Mexican-Americans and 2 Latinos of other origin) with self-reported type 2 diabetes who were recruited as part of a church-based, randomized controlled trial for diabetes self-management education in a low-income, immigrant neighborhood of Chicago. Face-to-face, in-depth interviews were conducted (one in English and 26 in Spanish), audio-recorded, transcribed verbatim, and professionally translated. Systematic qualitative methods were used to analyze interviews. All 27 participants were Latino, and 25 were of Mexican descent. Participants' mean age was 57 years, 81% were female, 69% had an annual income less than $20,000 and 48% had no health insurance. Mean A1C level was 8.6% and mean systolic blood pressure was 125 mmHg. The majority of participants (85%) reported using oral diabetes medication and 35% reported taking insulin. 76% reported being affiliated with one of the two partnering catholic churches based in the South Lawndale neighborhood of Chicago, also known as Little Village. Concerns regarding effectiveness and negative impact of diabetes medication were prevalent and expressed by 13 (48%) of 27 participants. Dissatisfaction with ineffective provider communication and not being able to pay for medication were other important barriers to adherence and were expressed by 7% and 11% of participants, respectively. Family support, for example, family members assisting in organizing medications in boxes and reminding participants to take them, was reported by 15% of participants and emerged as an important facilitator to medication adherence. There is a gap in research on factors influencing adherence to diabetes medication among Mexican-Americans. Our study suggests that concerns regarding negative impact of diabetes medication and concerns regarding effectiveness are prevalent barriers to adherence. These barriers can be addressed through educational efforts targeting patients and clinicians by specifically including content on beliefs that lead to poor adherence in diabetes self-management interventions for patients and continuing medical education for providers and by developing interventions that engage family members as a support system for medication adherence.
https://ift.tt/2tyfbpn
Fast local SAR image despeckling by edge-avoiding wavelets
Abstract
In this paper, a local despeckling algorithm based on á trous version of edge-avoiding wavelets for synthetic aperture radar images is proposed. Edge-avoiding wavelets provide the decomposition of the input image into several detail layers and a residual image which corresponds to the despeckled result by means of weighted á trous wavelet transform. The weight function is similar to the range kernel of the well-known bilateral filter and is determined by enhancing evaluation indexes. Visual and quantitative comparisons validate the performance of the proposed method in terms of both speckle reduction and edge preservation ability.
https://ift.tt/2GYPy94
Usher Syndrome and Non-syndromic Deafness: Functions of Different Whirlin Isoforms in the Cochlea, Vestibular Organs, and Retina
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Pranav Dinesh Mathur, Jun Yang
Abstract
Usher syndrome (USH) is the leading cause of inherited combined vision and hearing loss. However, mutations in most USH causative genes lead to other diseases, such as hearing loss only or vision loss only. The molecular mechanisms underlying the variable disease manifestations associated with USH gene mutations are unclear. This review focuses on an USH type 2 (USH2) gene encoding whirlin (WHRN; previously known as DFNB31), mutations in which have been found to cause either USH2 subtype USH2D or autosomal recessive non-syndromic deafness type 31 (DFNB31). This review summarizes the current knowledge about different whirlin isoforms encoded by WHRN orthologs in animal models, the interactions of different whirlin isoforms with their partners, and the function of whirlin isoforms in different cellular and subcellular locations. The recent findings regarding the function of whirlin isoforms suggest that disruption of different isoforms may be one of the mechanisms underlying the variable disease manifestations caused by USH gene mutations. This review also presents recent findings about the vestibular defects in Whrn mutant mouse models, which suggests that previous assumptions about the normal vestibular function of USH2 patients need to be re-evaluated. Finally, this review describes recent progress in developing therapeutics for diseases caused by WHRN mutations.
from #Audiology via ola Kala on Inoreader https://ift.tt/2ViEvM3
Standardized questions in English for estimating tinnitus prevalence and severity, hearing difficulty and usage of healthcare resources, and their translation into 11 European languages
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Roshni Biswas, Alessandra Lugo, Silvano Gallus, Michael A. Akeroyd, Deborah A. Hall
Abstract
Introduction
Prevalence estimates depend largely on the nature of the question asked to define the presence of the health condition, and the literature on the population burden of tinnitus and hearing difficulties is no different in this respect. The lack of standardized questions for data collection limits comparison across studies and across countries. The purpose of this short Technical Note is to report the first attempt to establish a set of standard questions developed for use in population-based surveys, and their adaptation and translation from English into 11 European languages.
Methods
Four questions and their corresponding response options were adapted from existing population-based surveys to assess tinnitus prevalence, tinnitus symptom severity, use of healthcare resources for tinnitus and hearing difficulty. The translated versions (Bulgarian, French, German, Greek, Italian, Latvian, Polish, Portuguese, Romanian, Russian, and Spanish) were generated using recognized methods to achieve a "world-for-world" translation.
Results
Translated versions were produced with acceptable functional equivalence to the original English-language version, as judged by a small panel of bilingual speakers who participated in the online field testing.
Conclusion
This work is the first of its kind to promote multi-national standardization by creating a set of tools that can readily be used across countries. These are currently being used in a European-wide study of tinnitus prevalence, and have wider application across English- and Spanish speaking countries including the Americas and Oceania.
Graphical abstract
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An optimized, clinically relevant mouse model of cisplatin-induced ototoxicity
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): K. Fernandez, T. Wafa, T.S. Fitzgerald, L.L. Cunningham
Abstract
Cisplatin-induced ototoxicity results in significant, permanent hearing loss in pediatric and adult cancer survivors. Elucidating the mechanisms underlying cisplatin-induced hearing loss as well as the development of therapies to reduce and/or reverse cisplatin ototoxicity have been impeded by suboptimal animal models. Clinically, cisplatin is most commonly administered in multi-dose, multi-cycle protocols. However, many animal studies are conducted using single injections of high-dose cisplatin, which is not reflective of clinical cisplatin administration protocols. Significant limitations of both high-dose, single-injection protocols and previous multi-dose protocols in rodent models include high mortality rates and relatively small changes in hearing sensitivity. These limitations restrict assessment of both long-term changes in hearing sensitivity and effects of potential protective therapies. Here, we present a detailed method for an optimized mouse model of cisplatin ototoxicity that utilizes a multi-cycle administration protocol that better approximates the type and degree of hearing loss observed clinically. This protocol results in significant hearing loss with very low mortality. This mouse model of cisplatin ototoxicity provides a platform for examining mechanisms of cisplatin-induced hearing loss as well as developing therapies to protect the hearing of cancer patients receiving cisplatin therapy.
from #Audiology via ola Kala on Inoreader https://ift.tt/2ViE5Ft
Usher Syndrome and Non-syndromic Deafness: Functions of Different Whirlin Isoforms in the Cochlea, Vestibular Organs, and Retina
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Pranav Dinesh Mathur, Jun Yang
Abstract
Usher syndrome (USH) is the leading cause of inherited combined vision and hearing loss. However, mutations in most USH causative genes lead to other diseases, such as hearing loss only or vision loss only. The molecular mechanisms underlying the variable disease manifestations associated with USH gene mutations are unclear. This review focuses on an USH type 2 (USH2) gene encoding whirlin (WHRN; previously known as DFNB31), mutations in which have been found to cause either USH2 subtype USH2D or autosomal recessive non-syndromic deafness type 31 (DFNB31). This review summarizes the current knowledge about different whirlin isoforms encoded by WHRN orthologs in animal models, the interactions of different whirlin isoforms with their partners, and the function of whirlin isoforms in different cellular and subcellular locations. The recent findings regarding the function of whirlin isoforms suggest that disruption of different isoforms may be one of the mechanisms underlying the variable disease manifestations caused by USH gene mutations. This review also presents recent findings about the vestibular defects in Whrn mutant mouse models, which suggests that previous assumptions about the normal vestibular function of USH2 patients need to be re-evaluated. Finally, this review describes recent progress in developing therapeutics for diseases caused by WHRN mutations.
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Standardized questions in English for estimating tinnitus prevalence and severity, hearing difficulty and usage of healthcare resources, and their translation into 11 European languages
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Roshni Biswas, Alessandra Lugo, Silvano Gallus, Michael A. Akeroyd, Deborah A. Hall
Abstract
Introduction
Prevalence estimates depend largely on the nature of the question asked to define the presence of the health condition, and the literature on the population burden of tinnitus and hearing difficulties is no different in this respect. The lack of standardized questions for data collection limits comparison across studies and across countries. The purpose of this short Technical Note is to report the first attempt to establish a set of standard questions developed for use in population-based surveys, and their adaptation and translation from English into 11 European languages.
Methods
Four questions and their corresponding response options were adapted from existing population-based surveys to assess tinnitus prevalence, tinnitus symptom severity, use of healthcare resources for tinnitus and hearing difficulty. The translated versions (Bulgarian, French, German, Greek, Italian, Latvian, Polish, Portuguese, Romanian, Russian, and Spanish) were generated using recognized methods to achieve a “world-for-world” translation.
Results
Translated versions were produced with acceptable functional equivalence to the original English-language version, as judged by a small panel of bilingual speakers who participated in the online field testing.
Conclusion
This work is the first of its kind to promote multi-national standardization by creating a set of tools that can readily be used across countries. These are currently being used in a European-wide study of tinnitus prevalence, and have wider application across English- and Spanish speaking countries including the Americas and Oceania.
Graphical abstract
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An optimized, clinically relevant mouse model of cisplatin-induced ototoxicity
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): K. Fernandez, T. Wafa, T.S. Fitzgerald, L.L. Cunningham
Abstract
Cisplatin-induced ototoxicity results in significant, permanent hearing loss in pediatric and adult cancer survivors. Elucidating the mechanisms underlying cisplatin-induced hearing loss as well as the development of therapies to reduce and/or reverse cisplatin ototoxicity have been impeded by suboptimal animal models. Clinically, cisplatin is most commonly administered in multi-dose, multi-cycle protocols. However, many animal studies are conducted using single injections of high-dose cisplatin, which is not reflective of clinical cisplatin administration protocols. Significant limitations of both high-dose, single-injection protocols and previous multi-dose protocols in rodent models include high mortality rates and relatively small changes in hearing sensitivity. These limitations restrict assessment of both long-term changes in hearing sensitivity and effects of potential protective therapies. Here, we present a detailed method for an optimized mouse model of cisplatin ototoxicity that utilizes a multi-cycle administration protocol that better approximates the type and degree of hearing loss observed clinically. This protocol results in significant hearing loss with very low mortality. This mouse model of cisplatin ototoxicity provides a platform for examining mechanisms of cisplatin-induced hearing loss as well as developing therapies to protect the hearing of cancer patients receiving cisplatin therapy.
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via IFTTT
Usher Syndrome and Non-syndromic Deafness: Functions of Different Whirlin Isoforms in the Cochlea, Vestibular Organs, and Retina
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Pranav Dinesh Mathur, Jun Yang
Abstract
Usher syndrome (USH) is the leading cause of inherited combined vision and hearing loss. However, mutations in most USH causative genes lead to other diseases, such as hearing loss only or vision loss only. The molecular mechanisms underlying the variable disease manifestations associated with USH gene mutations are unclear. This review focuses on an USH type 2 (USH2) gene encoding whirlin (WHRN; previously known as DFNB31), mutations in which have been found to cause either USH2 subtype USH2D or autosomal recessive non-syndromic deafness type 31 (DFNB31). This review summarizes the current knowledge about different whirlin isoforms encoded by WHRN orthologs in animal models, the interactions of different whirlin isoforms with their partners, and the function of whirlin isoforms in different cellular and subcellular locations. The recent findings regarding the function of whirlin isoforms suggest that disruption of different isoforms may be one of the mechanisms underlying the variable disease manifestations caused by USH gene mutations. This review also presents recent findings about the vestibular defects in Whrn mutant mouse models, which suggests that previous assumptions about the normal vestibular function of USH2 patients need to be re-evaluated. Finally, this review describes recent progress in developing therapeutics for diseases caused by WHRN mutations.
from #Audiology via ola Kala on Inoreader https://ift.tt/2ViEvM3
via IFTTT
Standardized questions in English for estimating tinnitus prevalence and severity, hearing difficulty and usage of healthcare resources, and their translation into 11 European languages
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): Roshni Biswas, Alessandra Lugo, Silvano Gallus, Michael A. Akeroyd, Deborah A. Hall
Abstract
Introduction
Prevalence estimates depend largely on the nature of the question asked to define the presence of the health condition, and the literature on the population burden of tinnitus and hearing difficulties is no different in this respect. The lack of standardized questions for data collection limits comparison across studies and across countries. The purpose of this short Technical Note is to report the first attempt to establish a set of standard questions developed for use in population-based surveys, and their adaptation and translation from English into 11 European languages.
Methods
Four questions and their corresponding response options were adapted from existing population-based surveys to assess tinnitus prevalence, tinnitus symptom severity, use of healthcare resources for tinnitus and hearing difficulty. The translated versions (Bulgarian, French, German, Greek, Italian, Latvian, Polish, Portuguese, Romanian, Russian, and Spanish) were generated using recognized methods to achieve a “world-for-world” translation.
Results
Translated versions were produced with acceptable functional equivalence to the original English-language version, as judged by a small panel of bilingual speakers who participated in the online field testing.
Conclusion
This work is the first of its kind to promote multi-national standardization by creating a set of tools that can readily be used across countries. These are currently being used in a European-wide study of tinnitus prevalence, and have wider application across English- and Spanish speaking countries including the Americas and Oceania.
Graphical abstract
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via IFTTT
An optimized, clinically relevant mouse model of cisplatin-induced ototoxicity
Publication date: Available online 22 February 2019
Source: Hearing Research
Author(s): K. Fernandez, T. Wafa, T.S. Fitzgerald, L.L. Cunningham
Abstract
Cisplatin-induced ototoxicity results in significant, permanent hearing loss in pediatric and adult cancer survivors. Elucidating the mechanisms underlying cisplatin-induced hearing loss as well as the development of therapies to reduce and/or reverse cisplatin ototoxicity have been impeded by suboptimal animal models. Clinically, cisplatin is most commonly administered in multi-dose, multi-cycle protocols. However, many animal studies are conducted using single injections of high-dose cisplatin, which is not reflective of clinical cisplatin administration protocols. Significant limitations of both high-dose, single-injection protocols and previous multi-dose protocols in rodent models include high mortality rates and relatively small changes in hearing sensitivity. These limitations restrict assessment of both long-term changes in hearing sensitivity and effects of potential protective therapies. Here, we present a detailed method for an optimized mouse model of cisplatin ototoxicity that utilizes a multi-cycle administration protocol that better approximates the type and degree of hearing loss observed clinically. This protocol results in significant hearing loss with very low mortality. This mouse model of cisplatin ototoxicity provides a platform for examining mechanisms of cisplatin-induced hearing loss as well as developing therapies to protect the hearing of cancer patients receiving cisplatin therapy.
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Biosynthesis of resveratrol and piceatannol in engineered microbial strains: achievements and perspectives
Abstract
Resveratrol (3,5,4′-trihydroxystilbene) and piceatannol (3,5,3′,4′-tetrahydroxystilbene) are well-known natural products that are produced by plants. They are important ingredients in pharmaceutical industries and nutritional supplements. They display a wide spectrum of biological activity. Thus, the needs for these compounds are increasing. The natural products have been found in diverse plants, mostly such as grapes, passion fruit, white tea, berries, and many more. The extraction of these products from plants is quite impractical because of the low production in plants, downstream processing difficulties, chemical hazards, and environmental issues. Thus, alternative production in microbial hosts has been devised with combinatorial biosynthetic systems, including metabolic engineering, synthetic biology, and optimization in production process. Since the biosynthesis is not native in microbial hosts such as Escherichia coli, Saccharomyces cerevisiae, and Corynebacterium glutamicum, genetic engineering and manipulation have made it possible. In this review, the discussion will mainly focus on recent progress in production of resveratrol and piceatannol, including the various strategies used for their production.
https://ift.tt/2Xky3WA
Triclosan in Treated Wastewater from a City Wastewater Treatment Plant and its Environmental Risk Assessment
Abstract
Triclosan (TCS) is a potential endocrine-disrupting compound (EDC), which produces an adverse impact on aquatic life and human beings. Wastewater discharge is considered as the primary source of triclosan in water bodies. The study is aimed to investigate the occurrence and environmental risk of triclosan released by municipal wastewater treatment plants (WWTP). An analytical protocol was developed and validated to determine the presence of TCS in the samples through offline solid-phase extraction (SPE) and liquid chromatography - electron spray ionization (ESI)—quadrupole mass spectrum (LC/ESI/MS). The limit of detection and quantification of protocol was estimated as 2.8 ng/L and 6.25 ng/L, respectively. The season-wise influent and effluent samples from two WWTP in Chennai, India, were monitored. The TCS concentrations in samples were found in the range of 443 to 1757 ng/L. The Risk Quotient (RQ) method was performed to evaluate the environmental (ecotoxicological and human health) risk associated with the exposure of TCS-containing wastewater. The results of the study revealed that primary producer (algae) was highly vulnerable to exposure of TCS in the aquatic environment. The estimated daily intake of TCS was much lower than the reference dosage, and this indicates that TCS did not produce any considerable risk to human health. Also, it suggested that additional treatment was required for complete removal of triclosan residues.
https://ift.tt/2ThLlUq
Lifetime alcohol intake and pancreatic cancer incidence and survival: findings from the Melbourne Collaborative Cohort Study
Abstract
Purpose
Pancreatic cancer has one of the worst prognoses with 5-year survival below 10%. There is some evidence that alcohol consumption might increase the risk of pancreatic cancer. We examined associations of pre-diagnostic alcohol intake with (i) incidence of pancreatic cancer, and (ii) overall survival following pancreatic cancer.
Methods
Usual alcohol intake was estimated at recruitment in 1990–1994 for 38,472 participants in the Melbourne Collaborative Cohort Study using recalled frequency and quantity of beverage-specific intake for 10-year periods from age 20. Pancreatic cancer incidence (C25 according to International Classification of Diseases for Oncology) and vital status were ascertained through to 30 September 2015. Cox regression was performed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with lifetime, age 20–29, and baseline alcohol intakes.
Results
By the end of follow-up (average 20.2 years), 239 incident cases of pancreatic cancer were diagnosed, of which 228 had died. No evidence of an association was observed between alcohol intake and risk of pancreatic cancer. Higher lifetime alcohol intake was associated with lower overall survival following a diagnosis of pancreatic cancer (mortality HR 1.09 per 10 g/day increment, 95% CI 1.00–1.19; p value = 0.04). A similar finding was observed for age 20–29 intake (HR 1.09 per 10 g/day increment, 95% CI 1.02–1.18; p value = 0.01) but not with baseline intake.
Conclusions
We observed an association between lower alcohol use from an early age and improved survival following pancreatic cancer, but this finding needs to be confirmed by other studies.
https://ift.tt/2Np2BSg
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