scholarly journals A Pharmacophore-Based Approach to Demonstrating the Scope of Alcohol Dehydrogenases

2020 ◽  
Author(s):  
Katrina Madden ◽  
Peter M.T. Todd ◽  
Kouji Urata ◽  
Angela Russell ◽  
Kylie Vincent ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Screening Tool ◽  
Early Stage ◽  
Model Reaction ◽  
Screening Tools ◽  
High Tolerance ◽  
Alcohol Dehydrogenases ◽  
Ketone Reduction ◽  
Culture Shift ◽  
Chemical Groups

<p>Barriers to the ready adoption of biocatalysis into asymmetric synthesis for early stage medicinal chemistry are addressed, using ketone reduction by alcohol dehydrogenase as a model reaction. An efficient substrate screening approach is used to show the wide substrate scope of commercial alcohol dehydrogenase enzymes, with a high tolerance to chemical groups employed in drug discovery (heterocycle, trifluoromethyl and nitrile/nitro groups) observed. We use our screening data to build a preliminary predictive pharmacophore-based screening tool using Forge software, with a precision of 0.67/1, demonstrating the potential for developing substrate screening tools for commercially available enzymes without publically available structures. We hope that this work, combined with our simple protocols for scaleable H<sub>2</sub>-driven biocatalytic ketone reduction, will facilitate a culture shift towards adopting biocatalysis alongside traditional chemical catalytic methods.</p>

scholarly journals A Pharmacophore-Based Approach to Demonstrating the Scope of Alcohol Dehydrogenases

2020 ◽  
Author(s):  
Katrina Madden ◽  
Peter M.T. Todd ◽  
Kouji Urata ◽  
Angela Russell ◽  
Kylie Vincent ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Screening Tool ◽  
Early Stage ◽  
Model Reaction ◽  
Screening Tools ◽  
High Tolerance ◽  
Alcohol Dehydrogenases ◽  
Ketone Reduction ◽  
Culture Shift ◽  
Chemical Groups

<p>Barriers to the ready adoption of biocatalysis into asymmetric synthesis for early stage medicinal chemistry are addressed, using ketone reduction by alcohol dehydrogenase as a model reaction. An efficient substrate screening approach is used to show the wide substrate scope of commercial alcohol dehydrogenase enzymes, with a high tolerance to chemical groups employed in drug discovery (heterocycle, trifluoromethyl and nitrile/nitro groups) observed. We use our screening data to build a preliminary predictive pharmacophore-based screening tool using Forge software, with a precision of 0.67/1, demonstrating the potential for developing substrate screening tools for commercially available enzymes without publically available structures. We hope that this work, combined with our simple protocols for scaleable H<sub>2</sub>-driven biocatalytic ketone reduction, will facilitate a culture shift towards adopting biocatalysis alongside traditional chemical catalytic methods.</p>

scholarly journals Early Stage in Identifying Autism Spectrum Disorder (ASD) Through Screening and Diagnosis

2018 ◽  
Vol 8 (4) ◽  
pp. 660-663
Keyword(s):  
Screening Tool ◽  
Early Stage ◽  
Treatment Method ◽  
Development Stage ◽  
Autism Spectrum ◽  
Screening Tools ◽  
Early Screening ◽  
Positive Score ◽  
Screening And Diagnosis

The objective of the paper was to evaluate developed screening tools on autism students’ as early detection detect early signs especially on visual for ASD children. The outcomes of early intervention in ASD can be improved but it depends types of the treatment. Method of collecting data was using tool, observation and interview. In design, flowchart and storyboard are produced. While in development stage, learning media and materials are presented with visualization in the form of sound, text, videos and pictures. The results of this study are a positive score and feedback from children with ASD. They are easy to focus in using this tool instead of conventional screening tool. The students really attract to something that related to technology. However, the suggestion of a screening for ASD when concerning from their parents or family. The quality of the instruments and screening procedure are the challenges faced during the process. The advantages of early screening and detection among ASD is very to avoid parents unnecessary worry among parents.

scholarly journals Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee
Keyword(s):  
Kidney Disease ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Screening Tools ◽  
Tubular Injury ◽  
Current Standard ◽  
Diabetic Kidney ◽  
Wide Range

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

scholarly journals Malnutrition and cancer, diagnosis and treatment

2021 ◽  
Author(s):  
Angelika Beirer
Keyword(s):  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Screening Tool ◽  
Psychological Treatment ◽  
Early Stage ◽  
Nutritional Therapy ◽  
German Society ◽  
Fat Free Mass ◽  
Nutritional Risk

Summary Background The prevalence of malnutrition in cancer patients ranges from about 20% to more than 70%. However, 10–20% of cancer patients’ deaths are related to malnutrition, not the malignancy itself. To reverse the pattern of weight loss, improve the patients’ quality of life, reduce the treatment toxicity, the psychological stress and the risk of mortality, the diagnosis of malnutrition should be made as early as possible to facilitate the best possible treatment. Methods A systematic literature search was conducted following guidelines of ESPEN (European Society for Clinical Nutrition), DGEM (German Society for Nutritional Medicine) and ASPEN (American Society for Parenteral and Enteral Nutrition). Results and conclusion To assess the risk of malnutrition, all cancer patients should be screened regularly with a valid screening tool (e.g., MUST [Malnutrition Universal Screening Tool], NRS [Nutritional Risk Screening] or PG-SGA [Scored Patient-Generated Subjective Global Assessment]). If risk of malnutrition is present, adequate nutritional therapy is recommended to stop involuntary weight loss. Patients should engage in exercise to maintain and improve muscle mass, strength and function. They should be offered regular dietetic counselling, and their muscle depletion should be monitored by determining fat-free mass. As cachectic patients in particular are at risk, the presence of cachexia should also be recognized at an early stage. Three consensus-based definitions are widely accepted: Fearon et al. and the EPCRC (European Palliative Care Research Collaborative) propose definitions specifically for cancer cachexia, while Evans et al. put forward a definition for cachexia associated with all types of underlying chronic diseases. However, if there is a cancer cachexia diagnosis, additional pharmacological and psychological treatment should be considered.

scholarly journals Healthcare Provider Perspectives on Bipolar I Disorder Screening and the Rapid Mood Screener (RMS), a Pragmatic, New Tool

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 181-183
Author(s):  
Michael E. Thase ◽  
Stephen M. Stahl ◽  
Roger S. McIntyre ◽  
Tina Matthews-Hayes ◽  
Mehul Patel ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Nurse Practitioners ◽  
Primary Care Physicians ◽  
Screening Tool ◽  
Positive Impact ◽  
Screening Tools ◽  
Predictive Values ◽  
Bipolar I Disorder ◽  
Provider Perspectives ◽  
Patient Reported

AbstractIntroductionAlthough mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed (“yes”), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.MethodsA nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.ResultsAmong HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.DiscussionThe RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.FundingAbbVie Inc.

scholarly journals An ADH toolbox for raspberry ketone production from natural resources via a biocatalytic cascade

2021 ◽  
Author(s):  
Aileen Becker ◽  
Dominique Böttcher ◽  
Werner Katzer ◽  
Karsten Siems ◽  
Lutz Müller-Kuhrt ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Genetically Modified Organisms ◽  
Optical Purity ◽  
High Yield ◽  
Alcohol Dehydrogenases ◽  
Flavor Compound ◽  
Raspberry Ketone ◽  
Cofactor Recycling ◽  
Cosmetic Industry ◽  
Key Points

Abstract Raspberry ketone is a widely used flavor compound in food and cosmetic industry. Several processes for its biocatalytic production have already been described, but either with the use of genetically modified organisms (GMOs) or incomplete conversion of the variety of precursors that are available in nature. Such natural precursors are rhododendrol glycosides with different proportions of (R)- and (S)-rhododendrol depending on the origin. After hydrolysis of these rhododendrol glycosides, the formed rhododendrol enantiomers have to be oxidized to obtain the final product raspberry ketone. To be able to achieve a high conversion with different starting material, we assembled an alcohol dehydrogenase toolbox that can be accessed depending on the optical purity of the intermediate rhododendrol. This is demonstrated by converting racemic rhododendrol using a combination of (R)- and (S)-selective alcohol dehydrogenases together with a universal cofactor recycling system. Furthermore, we conducted a biocatalytic cascade reaction starting from naturally derived rhododendrol glycosides by the use of a glucosidase and an alcohol dehydrogenase to produce raspberry ketone in high yield. Key points • LB-ADH, LK-ADH and LS-ADH oxidize (R)-rhododendrol • RR-ADH and ADH1E oxidize (S)-rhododendrol • Raspberry ketone production via glucosidase and alcohol dehydrogenases from a toolbox Graphical abstract

scholarly journals The effective screening tools for detecting hearing loss in elderly population: HHIE-ST Versus TSQ

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nichtima Chayaopas ◽  
Pornthep Kasemsiri ◽  
Panida Thanawirattananit ◽  
Patorn Piromchai ◽  
Kwanchanok Yimtae
Keyword(s):  
Older Adults ◽  
Hearing Loss ◽  
Screening Tool ◽  
Diagnostic Value ◽  
Screening Tools ◽  
Effective Screening ◽  
Hearing Disability ◽  
Test Study ◽  
Combined Test ◽  
Single Question

Abstract Background Globally increasing number of elders is concerned. Hearing loss process in older adults cannot be avoided. An effective screening tool for hearing loss is essential for proper diagnosis and rehabilitation, which can improve QOL in older adults. Methods This prospective-diagnostic test study evaluates the diagnostic value of Thai version of the Hearing Handicap Inventory for Elderly Screening (HHIE-ST) and the Thai Single Question (TSQ) surveys in screening hearing disability in 1109 Thai participants aged 60 years and older in communities in four provinces in Thailand. The HHIE-ST consisted of 10 selected questions from the validated HHIE-Thai version. A TSQ survey was developed to have the same meaning as an English Single Question survey. The participants answered both questionnaires, and a standard audiometry test assessed with air conduction from 250 to 8000 Hz was included as a gold standard. Results The prevalence of hearing disability was 38.34%. The HHIE-ST achieved a sensitivity of 88.96% (95% CI 85.77–91.64) and specificity of 52.19% (95% CI 48.24–56.13) for diagnosis hearing disability in Thai older adults, whereas the TSQ yielded a sensitivity of 88.73% and a specificity of 55.93%. A combined test including the HHIE-ST and TSQ achieved better performance with sensitivity of 85.29% and specificity of 60.13%. Conclusions Either the HHIE-ST or the TSQ is a sensitive and useful tool for screening hearing disability in Thai older adults. Using the HHIE-ST together with the TSQ resulted in a better screening tool for detecting moderate hearing loss older adults who will benefit and recommended for hearing rehabilitation. Trial registration The study is registered with the following number in the Thai Clinical Trials Registry: TCTR20151015003. Date of registration October 14, 2015.

scholarly journals Predicting Polysomnography Parameters from Anthropometric Features and Breathing Sounds Recorded during Wakefulness

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 905
Author(s):  
Ahmed Elwali ◽  
Zahra Moussavi
Keyword(s):  
Primary Outcome ◽  
Screening Tool ◽  
Correlation Coefficients ◽  
Random Forest Classifier ◽  
Screening Tools ◽  
Apnea Hypopnea Index ◽  
Bilinear Model ◽  
Arousal Index ◽  
Obstructive Sleep ◽  
Anthropometric Features

Background: The apnea/hypopnea index (AHI) is the primary outcome of a polysomnography assessment (PSG) for determining obstructive sleep apnea (OSA) severity. However, other OSA severity parameters (i.e., total arousal index, mean oxygen saturation (SpO2%), etc.) are crucial for a full diagnosis of OSA and deciding on a treatment option. PSG assessments and home sleep tests measure these parameters, but there is no screening tool to estimate or predict the OSA severity parameters other than the AHI. In this study, we investigated whether a combination of breathing sounds recorded during wakefulness and anthropometric features could be predictive of PSG parameters. Methods: Anthropometric information and five tracheal breathing sound cycles were recorded during wakefulness from 145 individuals referred to an overnight PSG study. The dataset was divided into training, validation, and blind testing datasets. Spectral and bispectral features of the sounds were evaluated to run correlation and classification analyses with the PSG parameters collected from the PSG sleep reports. Results: Many sound and anthropometric features had significant correlations (up to 0.56) with PSG parameters. Using combinations of sound and anthropometric features in a bilinear model for each PSG parameter resulted in correlation coefficients up to 0.84. Using the evaluated models for classification with a two-class random-forest classifier resulted in a blind testing classification accuracy up to 88.8% for predicting the key PSG parameters such as arousal index. Conclusions: These results add new value to the current OSA screening tools and provide a new promising possibility for predicting PSG parameters using only a few seconds of breathing sounds recorded during wakefulness without conducting an overnight PSG study.

scholarly journals Psoriatic arthritis screening: a systematic review and meta-analysis

Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 692-707 ◽  
Author(s):  
Nicolas Iragorri ◽  
Glen Hazlewood ◽  
Braden Manns ◽  
Vishva Danthurebandara ◽  
Eldon Spackman
Keyword(s):  
Systematic Review ◽  
Psoriatic Arthritis ◽  
Sensitivity And Specificity ◽  
Screening Tool ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Screening Tools ◽  
Screening Questionnaire ◽  
Psa Screening ◽  
Early Psoriatic Arthritis

Abstract Objective To systematically review the accuracy and characteristics of different questionnaire-based PsA screening tools. Methods A systematic review of MEDLINE, Excerpta Medical Database, Cochrane Central Register of Controlled Trials and Web of Science was conducted to identify studies that evaluated the accuracy of self-administered PsA screening tools for patients with psoriasis. A bivariate meta-analysis was used to pool screening tool-specific accuracy estimates (sensitivity and specificity). Heterogeneity of the diagnostic odds ratio was evaluated through meta-regression. All full-text records were assessed for risk of bias with the QUADAS 2 tool. Results A total of 2280 references were identified and 130 records were assessed for full-text review, of which 42 were included for synthesis. Of these, 27 were included in quantitative syntheses. Of the records, 37% had an overall low risk of bias. Fourteen different screening tools and 104 separate accuracy estimates were identified. Pooled sensitivity and specificity estimates were calculated for the Psoriatic Arthritis Screening and Evaluation (cut-off = 44), Psoriatic Arthritis Screening and Evaluation (47), Toronto Psoriatic Arthritis Screening (8), Psoriasis Epidemiology Screening Tool (3) and Early Psoriatic Arthritis Screening Questionnaire (3). The Early Psoriatic Arthritis Screening Questionnaire reported the highest sensitivity and specificity (0.85 each). The I2 for the diagnostic odds ratios varied between 76 and 90.1%. Meta-regressions were conducted, in which the age, risk of bias for patient selection and the screening tool accounted for some of the observed heterogeneity. Conclusions Questionnaire-based tools have moderate accuracy to identify PsA among psoriasis patients. The Early Psoriatic Arthritis Screening Questionnaire appears to have slightly better accuracy compared with the Toronto Psoriatic Arthritis Screening, Psoriasis Epidemiology Screening Tool and Psoriatic Arthritis Screening and Evaluation. An economic evaluation could model the uncertainty and estimate the cost-effectiveness of PsA screening programs that use different tools.

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