Pathway optimization and key enzyme evolution of N-acetylneuraminate biosynthesis using an in vivo aptazyme-based biosensor.

Abstract: N-acetylneuraminate (NeuAc) biosynthesis has drawn much attention owing to its wide applications in many aspects. Previously, we engineered for the first time an artificial NeuAc biosynthetic pathway in Escherichia coli using glucose as sole substrate. However, rigorous requirements for the flux and cofactor balance make subsequent strain improvement rather difficult. In this study, an in vivo NeuAc biosensor was designed and applied for genetic screening the mutant library of NeuAc producer. Its NeuAc responsive manner was demonstrated using sfgfp as a reporter and a Ni2+-based selection system was developed to couple the cell growth with in vivo NeuAc concentration. Employing this selection system, the NeuAc biosynthesis pathway was optimized and the key enzyme NeuAc synthase was evolved, which improved the titer by 34% and 23%, respectively. The final strain produced up to 8.31g/L NeuAc in minimal medium using glucose as sole carbon source. This work demonstrated the effectiveness of NeuAc biosensor in genetic screening and great potential in metabolic engineering of other organisms.

Yang|Peng|P| Wang|Jing|J| Pang|Qingxiao|Q| Zhang|Fengyu|F| Wang|Junshu|J| Wang|Qian|Q| Qi|Qingsheng|Q|

D052157:Aptamers, Nucleotide
D015374:Biosensing Techniques
D019020:Directed Molecular Evolution
D004926:Escherichia coli
D029968:Escherichia coli Proteins
D019158:N-Acetylneuraminic Acid
D007652:Oxo-Acid-Lyases

Pathway optimization
N-acetylneuraminate
Biosensor
NeuAc synthase
Genetic selection


Blood Group Typing: From Classical Strategies to the Application of Synthetic Antibodies Generated by Molecular Imprinting.

Abstract: Blood transfusion requires a mandatory cross-match test to examine the compatibility between donor and recipient blood groups. Generally, in all cross-match tests, a specific chemical reaction of antibodies with erythrocyte antigens is carried out to monitor agglutination. Since the visual inspection is no longer useful for obtaining precise quantitative information, therefore there is a wide variety of different technologies reported in the literature to recognize the agglutination reactions. Despite the classical methods, modern biosensors and molecular blood typing strategies have also been considered for straightforward, accurate and precise analysis. The interfacial part of a typical sensor device could range from natural antibodies to synthetic receptor materials, as designed by molecular imprinting and which is suitably integrated with the transducer surface. Herein, we present a comprehensive overview of some selected strategies extending from traditional practices to modern procedures in blood group typing, thus to highlight the most promising approach among emerging technologies.

D001788:Blood Grouping and Crossmatching

molecular imprinting
agglutination
synthetic receptors
ABO-blood group typing


Could Neurotracker be used as a clinical marker of recovery following pediatric mild traumatic brain injury? An exploratory study.

Abstract:
PRIMARY OBJECTIVE
This study aimed to explore the potential for the Neurotracker, a perceptual-cognitive, multiple-object tracking test, and train paradigm, as a marker of functional recovery after mild traumatic brain injury (mTBI). It is hypothesized that Neurotracker could serve as a proxy for assessing cerebral functioning.

RESEARCH DESIGN
A comparative, 6 time points, longitudinal study design was used to compare Neurotracker performance between children and adolescents who were clinically recovered from mTBI and healthy controls.

METHODS AND PROCEDURES
Clinical measures were collected at the initial and final visits. Neurotracker trainings were performed at each of the 6 visits. Speed thresholds (Neurotracker performance) were recorded at each visit.

MAIN OUTCOMES AND RESULTS
A two-way repeated measures ANOVA suggested no differences between the groups but a significant time effect was apparent.

CONCLUSIONS
Clinically recovered children and adolescents exhibit similar training abilities to control subjects on this task. These results support further investigations using Neurotracker as a marker of recovery following mTBI.

three-dimensional multiple object tracking


The course of major depressive disorder from childhood to young adulthood: Recovery and recurrence in a longitudinal observational study.

Abstract:
BACKGROUND
The episodic nature of major depressive disorder (MDD) in clinically referred adults has been well-characterized, particularly by the NIMH Collaborative Depression Study. Previous work has established that MDD also is episodic prior to adulthood, but no study has yet provided comprehensive information on the actual course of MDD in clinically referred juveniles. Thus, the present investigation sought to characterize recovery, recurrence, and their predictors across multiple episodes of MDD in initially 8- to 13-year-old outpatients (N=102), and to estimate freedom from morbidity ("well-time") across the years.

METHOD
Clinically referred youngsters with MDD were repeatedly assessed in an observational study across two decades (median follow up length: 15 years). Survival analytic techniques served to model recovery from the 1st, 2nd and 3rd lifetime episodes of MDD, the risk of developing the 2nd, 3rd, and 4th episodes, and the effects of traditional psychosocial and clinical predictors of outcomes. "Well-time" across the follow-up and its predictors also were examined.

RESULTS
Recovery rates ranged from 96% to 100% across MDD episodes; episode lengths ranged from 6 to 7 months. Up to 72% of those recovered from the first episode of MDD had a further episode; median inter-episode intervals were about 3-5 years. No single demographic, social, or clinical variable, nor treatment, consistently predicted recovery/recurrence. Psychiatric morbidity over time derived mostly from non-affective disorders, which, however, did not alter the course of MDD.

LIMITATIONS
The sample was relatively small and power to detect small effects further declined with each MDD episode recurrence.

CONCLUSIONS
Echoing findings on adults, the course of pediatric-onset MDD in this clinical sample was unequivocally episodic. Traditional course predictors had limited temporal stability, highlighting the need to examine novel predictor variables. The ongoing risk of depression episodes into the second and third decades of life suggests that prevention efforts should start in late childhood.

Recovery and recurrence
Course predictors
Childhood depression
Clinical course
Longitudinal follow-up
Major depressive disorder/episode


Metabolic Acidosis in CKD: A Review of Recent Findings.

Abstract: Metabolic acidosis is fairly common in patients with chronic kidney disease (CKD). The prevalence of metabolic acidosis increases with worsening kidney function and is observed in ∼40% of those with stage 4 CKD. For the past 2 decades, clinical practice guidelines have suggested treatment of metabolic acidosis to counterbalance adverse effects of metabolic acidosis on bone and muscle. Studies in animal models of CKD also demonstrated that metabolic acidosis causes kidney fibrosis. During the past decade, results from observational studies identified associations between metabolic acidosis and adverse kidney outcomes, and results from interventional studies support the hypothesis that treating metabolic acidosis with sodium bicarbonate preserves kidney function. However, convincing data from large-scale, double-blinded, placebo-controlled, randomized trials have been lacking. This review discusses findings from recent interventional trials of alkali therapy in CKD and new findings linking metabolic acidosis with cardiovascular disease in adults and CKD progression in children. Finally, a novel agent that treats metabolic acidosis in patients with CKD by binding hydrochloric acid in the gastrointestinal tract is discussed.

Melamed|Michal L|ML|
Raphael|Kalani L|KL|

metabolic acidosis
chronic kidney disease
observational studies
sodium bicarbonate
bicarbonate
interventional trials
end-stage kidney disease
total CO2
veverimer


Machine Learning Prediction of Death in Critically Ill Patients With Coronavirus Disease 2019.

Abstract:
OBJECTIVES
Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019.

DESIGN
This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration.

SETTING
Sixty-eight U.S. ICUs.

PATIENTS
Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020.

INTERVENTIONS
None.

MEASUREMENTS AND MAIN RESULTS
The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model.

CONCLUSIONS
eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

Churpek|Matthew M|MM|
Gupta|Shruti|S|
Spicer|Alexandra B|AB|
Hayek|Salim S|SS|
Srivastava|Anand|A|
Chan|Lili|L|
Melamed|Michal L|ML|
Brenner|Samantha K|SK|
Radbel|Jared|J|
Madhani-Lovely|Farah|F|
Bhatraju|Pavan K|PK|
Bansal|Anip|A|
Green|Adam|A|
Goyal|Nitender|N|
Shaefi|Shahzad|S|
Parikh|Chirag R|CR|
Semler|Matthew W|MW|
Leaf|David E|DE|

machine learning
coronavirus disease 2019
artificial intelligence
intensive care unit


New polymer-supported mono- and bis-Cinchona alkaloid derivatives: synthesis and use in asymmetric organocatalyzed reactions.

Abstract: The straightforward synthesis of polystyrene-supported Chinchona alkaloids and their application in the asymmetric dimerization of ketenes is reported. Six different immobilized derivatives, consisting of three dimeric and two monomeric 9-O ethers, were prepared by "click" anchoring of soluble alkaloid precursors on to azidomethyl resins. The resulting insoluble polymer-bound (IPB) organocatalysts were employed for promoting the dimerization of in-situ generated ketenes. After opening of the ketene dimer intermediates with N,O-dimethylhydroxylamine, valuable Weinreb amides were eventually obtained in good yield (up to 81 %) and excellent enantiomeric purity (up to 96 % ee). All of the IPB catalysts could be recycled effectively without significant loss of activity and enantioselectivity. The extension to other asymmetric transformations (meso-anhydride desymmetrization and α-amination of 2-oxindoles) is also briefly discussed.

Jumde|Ravindra P|RP|
Di Pietro|Anila|A|
Manariti|Antonella|A|
Mandoli|Alessandro|A|

ketenes
desymmetrization
Cinchona alkaloids
asymmetric catalysis
click chemistry
supported catalysts


Variations in Pu isotopic composition in soils from the Spitsbergen (Norway): Three potential pollution sources of the Arctic region.

Abstract: Although the polar regions have not been industrialised, numerous contaminants originating from human activity are detectable in the Arctic environment. This study reports evidence of 240Pu/239Pu atomic ratios in the tundra and initial soils from different parts of west and central Spitsbergen and recognizes possible environmental inputs of non-global fallout Pu. The average atomic ratio of 240Pu/239Pu equal to 0.179 (ranging between 0.129 and 0.201) in tundra soils are comparable to the characteristic ratio for global fallout (0.180). However, the 240Pu/239Pu atomic ratios in the initial soils from proglacial zone of glaciers change within wide range between 0.1281 and 0.234 with the mean value of 0.169. By combining alpha and mass spectrometry, the three-sources model was used to identify the Pu sources in initial soils. Our study indicated that the main source of Pu is nuclear tests and that a second source with lower Pu ratio may come from weapons grade Pu (unexploded weapons grade Pu ie. material from bomb which didn't undergo nuclear explosions for example for security tests). Additionally, we found samples with high 238Pu/239+240Pu activity ratios and with typical global fallout 240Pu/239Pu atomic ratios, which are associated with separate sources of pure 238Pu from the SNAP-9A satellite burn up in the atmosphere.

Łokas|E|E|
Anczkiewicz|R|R|
Kierepko|R|R|
Mietelski|J W|JW|

Arctic
Atomic ratio
Tundra
Initial soil
(240)Pu/(239)Pu
Source identification


Sociocultural Influences on Arab Women's Participation in Breast Cancer Screening in Qatar.

Abstract: Breast cancer, the most common cancer among Arab women in Qatar, significantly affects the morbidity and mortality of Arab women largely because of low participation rates in breast cancer screening. We used a critical ethnographic approach to uncover and describe factors that influence Arab women's breast cancer screening practices. We conducted semistructured interviews with 15 health care practitioners in Qatar. Through thematic analysis of the data, we found three major factors influencing breast cancer screening practices: (a) beliefs, attitudes, and practices regarding women's bodies, health, and illness; (b) religious beliefs and a culturally sensitive health care structure; and (c) culturally specific gender relations and roles. Arab women's health practices cannot be understood in isolation from the sociocultural environment. The problem of low rates of breast cancer screening practices and supportive interventions must be addressed within the context and not be limited to the individual.

Hwang|Jasmine J|JJ|
Donnelly|Tam T|TT|
Ewashen|Carol|C|
McKiel|Elaine|E|
Raffin|Shelley|S|
Kinch|Janice|J|

D007722:Health Knowledge, Attitudes, Practice

illness and disease, social construction


Acute cerebellar ataxia as the first manifestation of Imerslund-Gräsbeck syndrome.

Abstract: Imerslund-Gräsbeck syndrome is a rare condition caused by vitamin B12 deficiency and proteinuria. In this article, we reported the case of a 10-year-old girl with imbalance and urinary incontinence. The case had cerebellar ataxia as the primary manifestation. The disequilibrium had progressed gradually within three weeks and was consistent with the symptoms of cerebellar involvement and urinary incontinence. Brain and cervico-thoraco-lumbar magnetic resonance imaging were normal. The patient had elevated lactate dehydrogenase (LDH=4775), in addition to macrocytic anemia, on laboratory examinations; thus, the possibility of malignancy was raised. Then, bone marrow aspiration was performed, showing hypercellular marrow with megaloblastic changes. This finding proved megaloblastic anemia. Regarding the low prevalence of vitamin B12 deficiency in healthy individuals, extensive studies were performed to find out the cause. The serum level of vitamin B12 was found to be lower than the normal range. Although urinalysis revealed significant proteinuria, further nephrological investigations did not indicate any abnormalities. No evidence of serious problems was observed in the gastrointestinal tract study, and metabolic studies were normal. Finally, based on the obtained data, Imerslund-Gräsbeck syndrome was recognized. Patient was treated by vitamin B12 injection, leading to improved balance, and in one-month follow-up, she was able to walk independently, and the cerebellar symptoms had greatly disappeared; however, proteinuria persisted.

Cerebellar ataxia
Urinary incontinence
Megaloblastic anemia
Vitamin B12 deficiency


Aged parents' experiences during a critical illness trajectory and after the death of an adult child: a review of the literature.

Abstract:
BACKGROUND
Given the growing life expectancy, the likelihood increases that health-care providers are confronted with older people having an adult child with a life-limiting disease.

AIM
This literature review aimed to (1) explore the experiences of aged parents with regard to their position and role as a parent of an adult child with a life-limiting illness, (2) detect gaps in the existing literature and (3) make recommendations for future research.

DESIGN
A literature search of English articles, including both quantitative and qualitative designs.

DATA SOURCES
Four electronic databases and the reference lists of included studies.

RESULTS
In total, 19 studies (7 quantitative and 12 qualitative) were included. Few studies describe the experiences of older people whose adult child has cancer or has died of cancer. Existing studies are merely descriptive and give no concrete recommendations for health-care providers in daily practice. The studies suggest that aged parents carry deep burdens from the prospect of losing their adult child. Aged parents want to stay involved but need to reconfigure their parent role. As soon as the cancer diagnosis is disclosed, parents are confronted with a re-awakening of parental nurturing, which clashes with the autonomy of the adult child. Even after the adult child is deceased, older parents retain the image of themselves as parents.

CONCLUSIONS
There is a need for more in-depth research to understand the lived experience of these parents and what health-care providers can do to assist them.

Van Humbeeck|Liesbeth|L|
Piers|Ruth D|RD|
Van Camp|Sigrid|S|
Dillen|Let|L|
Verhaeghe|Sofie T L|ST|
Van Den Noortgate|Nele J|NJ|

aged
parents
critical illness
death
review
Adult children
grief


The impact of calcium supplementation on methane fermentation and ammonia inhibition of fish processing wastewater.

Abstract: The effect of trace metal supplementation on the methane fermentation of fish processing wastewater (FPW) was studied in both batch and continuous experiments using a self-agitated anaerobic baffled reactor (SA-ABR). In the batch experiments, a single supplementation of Ca2+, Co2+ and Fe2+ was show to have a significant positive impact on the performance of methane fermentation. The continuous experiment results showed that supplementation with 1.5 g-Ca2+/L-substrate remarkably enhanced the performance of methane fermentation of the SA-ABR in treating FPW with the optimal organic loading rate achieved at 7.62 g-COD/L/d. During the steady states (stages 2 to 5), the average removal efficiencies of COD, protein, carbohydrate and lipid were 89, 85, 80 and 91%, respectively. The biogas conversion rates were in the range of 0.39 to 0.45 L-biogas/g-COD with a high methane content of 74%. Besides, Ca2+ supplementation also improved the resistance of the methane fermentation system to ammonia inhibition.

Sanjaya|Eli Hendrik|EH|
Cheng|Hui|H|
Qin|Yu|Y|
Kubota|Kengo|K|
Li|Yu-You|YY|

Calcium supplementation
Methane fermentation
Ammonia inhibition
Trace metal supplementation
fish processing wastewater (FPW)


Community-Based Needs Assessment of Neurodevelopment, Caregiver, and Home Environment Factors in Young Children Affected by HIV in Lima, Peru.

Abstract:
BACKGROUND
In many resource-poor settings such as Peru, children affected by HIV have a high prevalence of neurodevelopmental delays (NDDs) and remain excluded from adequate treatment.

METHODS
Community health workers (CHWs) administered NDD screening instruments to assess child development and associated caregiver and household factors in 14 HIV-affected parent-child dyads. Focus group discussion with caregivers was conducted to explore their needs and behaviors around early child stimulation and to assess their perceptions of the screening experience.

RESULTS
Over 70% of the children had abnormal classification in at least 1 (out of 5) developmental domains according to Ages and States Questionnaire-provided cutoff scores. Caregiver depression and stress were associated with abnormal development as were some parenting behavior factors. Knowledge about child development was low. Caregivers felt testing and discussing results with a CHW were very insightful. Reported caregiver behavior differed between caregivers with HIV-infected children and those with uninfected children.

CONCLUSION
Taken together, these exploratory quantitative data suggest that parenting behaviors associated with low child development scores may be modifiable and that community-based testing is well received and informative to these HIV-infected caregivers.

Muñoz|Maribel|M| Nelson|Adrianne|A| Johnson|Maureen|M| Godoy|Nancy|N| Serrano|Esther|E| Chagua|Engerid|E| Valdivia|Jesica|J| Santacruz|Janeth|J| Wong|Milagros|M| Kolevic|Lenka|L| Kammerer|Betsy|B| Vega|Clemente|C| Vibbert|Martha|M| Lundy|Shannon|S| Shin|Sonya|S|

D017028:Caregivers
D002657:Child Development
D002675:Child, Preschool
D003150:Community Health Workers
D015658:HIV Infections
D006801:Humans
D007223:Infant
D020380:Needs Assessment
D011446:Prospective Studies
D011634:Public Health
D012111:Residence Characteristics
D011795:Surveys and Questionnaires

children affected by HIV
community health
community health workers
child development
training


An averaging technique for the P300 spatial distribution.

Abstract:
INTRODUCTION
This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and Images".

OBJECTIVES
The main objectives of the paper regard the analysis of amplitude spatial distribution of the P300 evoked potential over a scalp of a particular subject and finding an averaged spatial distribution template for that subject. This template, which may differ for two different subjects, can help in getting a more accurate P300 detection for all BCIs that inherently use spatial filtering to detect P300 signal. Finally, the proposed averaging technique for a particular subject obtains an averaged spatial distribution template through only several epochs, which makes the proposed averaging technique fast and possible to use without applying any prior training data as in case of data enhancement technique.

METHODS
The method used in the proposed framework for the averaging of spatial distribution of P300 evoked potentials is based on the statistical properties of independent components (ICs). These components are obtained by using independent component analysis (ICA) from different target epochs.

RESULTS
This paper gives a novel averaging technique for the spatial distribution of P300 evoked potentials, which is based on the P300 signals obtained from different target epochs using the ICA algorithm. Such a technique provides a more reliable P300 spatial distribution for a subject of interest, which can be used either for an improved spatial selection of ICs, or more accurate P300 detection and extraction. In addition, the experiments demonstrate that the values of spatial intensity computed by the proposed technique for P300 signal converge after only several target epochs for each electrode allocation. Such a speed of convergence allows the proposed algorithm to easily adapt to a subject of interest without any additional artificial data preparation prior the algorithm execution such in case of data enhancement technique.

CONCLUSION
The proposed technique averages the P300 spatial distribution for a particular subject over all electrode allocations. First, the technique combines P300-like components obtained by the ICA run within a target epoch in order to obtainan averaged P300 spatial distribution. Second, the technique averages spatial distributions of P300 signals obtained from different target epochs in order to get the final averaged template. Such an template can be useful for any BCI technique where spatial selection is used to detect evoked potentials.

P300
P300 spatial distribution
ICA
BCI Competition Dataset


An Integrated miRNA-lncRNA Signature Predicts the Survival of Stage II Colon Cancer.

Abstract:
OBJECTIVE
By in silico analysis of colon cancer data from the Cancer Genome Atlas (TCGA) database, we develop a prognostic signature to improve the stratification of high-risk stage II colon cancer patients.

METHOD
RNA sequencing (RNA-Seq) data from 187 stage II colon cancer patients was obtained from the TCGA data portal. We excluded cases without a sufficient amount of survival data (n=21), leaving 166 stage II colon cancer patients to be selected for further survival analysis. Differentially expressed lncRNAs and miRNAs were unveiled by the edgeR package of R. A comprehensive ceRNAs regulatory network was constructed using the Cytoscape. Cox regression analysis was performed to screen prognostic RNAs and develop a prognostic signature. The Multi Experiment Matrix and Gene Ontology were undertaken to assess the prognostic lncRNA MIR31HG function.

RESULTS
The multivariate analysis indicates that 2 lncRNAs (WASIR2 and MIR31HG) and 2 miRNAs (hsa-mir-200a and hsa-mir-155) exhibited an independently significant prognostic value for stage II colon cancer. The 4 lncRNA-miRNA signatures for predicting the overall survival (OS) was constructed with the formula: Risk score=exp WASIR2*(0.213)+exp MIR31HG*(0.152)+exp hsa-mir-200a*(-0.329)+exp hsa-mir-155*(0.300). The area under the curve in the receiver operating characteristic analysis was 0.810. Kaplan-Meier survival curves confirm that the low-risk group had a low death rate, with a 5-year OS rate at 87.7%. However, the high-risk group had a low 5-year OS of 23.1% (P=0.000). The correlative genes of MIR31HG were found to be enriched in the epithelial-to-mesenchymal transition pathway, and the VEGFR3 signaling in lymphatic endothelium pathways.

CONCLUSIONS
These findings indicate that the 4 lncRNA-miRNA prognostic signature could be a marker for survival of stage II colon cancer patients.

Wang|Xiao-Jie|XJ| Zeng|Bing|B| Lin|Shuangming|S| Chen|Min|M| Chi|Pan|P|

D015972:Gene Expression Regulation, Neoplastic


Unestable knee osteochondritis dissecans: arthroscopic fixation with bio-absorbable device.

Abstract:
INTRODUCTION
Knee ostheochondritis dissecans is an osteochondral disease, whose treatment is still debated. The purpose this study was to analyze the patients attached with bioabsorbable nail, assisted by arthroscopy.

MATERIAL AND METHOD
Analysis was performed using median and interquartile range (P25-P75), with a follow-up of 9 patients (10 knees) operated for stage III osteochondral lesions. After a minimum of 12 months, the KOOS, IKDC, satisfaction questionnaires were evaluated and a MR control was perfomed.

RESULTS
Bone healing was observed in 80% of patients in the first year, with a delay in union in 20%. The median for age was 15 years. The average follow-up was 5.93 years. All cases were located in the internal condyle. The OCD lesions did not show comminution or necrosis. The 40% of stable lesions, according to preoperative MR, were unestable in arthroscopy and it were attached with internal nail. Two groups of osteochondral lesions were differentiated: juvenile OCD (60%) and adult OCD (40%); all of them were stage III lesions. IKDC questionnaire results were an improvement of 29.5 (22.25, 37.52). In the KOOS questionnaire, an improvement was obtained in symptoms of 18.07, in pain of 29.12, in daily living 25.53, in function (sports, recreational activities) of 35 and in quality of life of 34.42.

CONCLUSIONS
The bioabsorbable nail is a valid, reproducible option for unestable lesions with lesion integrity, with great improvement in function, quality of life and with few complications.

Bogallo|J M|JM|
Godino Izquierdo|M|M|
Dalla-Rosa|J|J|
Ramos González|L|L|
Arjona Díaz|M|M|
Guerado|E|E|

Knee
Osteochondritis dissecans
Fixation
Bioabsorbable
Bioabsorbable
Juvenil
Bioabsorbible
Fijación
Osteocondritis disecante
Rodilla


Age-related differences in metacognition for memory capacity and selectivity.

Abstract: Background: We compared two types of metacognitive monitoring in younger and older adults: metacognitive accuracy for their overall memory performance and their ability to selectively remember high-value information. Method: Participants studied words paired with point values and were asked to maximise their point score. In Experiment 1, they predicted how many words they would remember while in Experiment 2, they predicted how many points they would earn. Results: In Experiment 1, while younger adults were accurate in their predictions, older adults were overconfident in the number of words they would recall throughout the task. In Experiment 2, however, both younger and older adults were equally accurate when predicting the amount of points they would earn after some task experience. Conclusions: While younger adults may have higher metacognitive accuracy for their capacity, older adults can accurately assess their ability to selectively remember information, suggesting potentially separate metacognitive mechanisms that are differentially affected by aging.

metacognition
Memory
selectivity
predictions
value-directed remembering


Brain dopamine neurone 'damage': methamphetamine users vs. Parkinson's disease - a critical assessment of the evidence.

Abstract: The objective of this review is to evaluate the evidence that recreational methamphetamine exposure might damage dopamine neurones in human brain, as predicted by experimental animal findings. Brain dopamine marker data in methamphetamine users can now be compared with those in Parkinson's disease, for which the Oleh Hornykiewicz discovery in Vienna of a brain dopamine deficiency is established. Whereas all examined striatal (caudate and putamen) dopamine neuronal markers are decreased in Parkinson's disease, levels of only some (dopamine, dopamine transporter) but not others (dopamine metabolites, synthetic enzymes, vesicular monoamine transporter 2) are below normal in methamphetamine users. This suggests that loss of dopamine neurones might not be characteristic of methamphetamine exposure in at least some human drug users. In methamphetamine users, dopamine loss was more marked in caudate than in putamen, whereas in Parkinson's disease, the putamen is distinctly more affected. Substantia nigra loss of dopamine-containing cell bodies is characteristic of Parkinson's disease, but similar neuropathological studies have yet to be conducted in methamphetamine users. Similarly, it is uncertain whether brain gliosis, a common feature of brain damage, occurs after methamphetamine exposure in humans. Preliminary epidemiological findings suggest that methamphetamine use might increase risk of subsequent development of Parkinson's disease. We conclude that the available literature is insufficient to indicate that recreational methamphetamine exposure likely causes loss of dopamine neurones in humans but does suggest presence of a striatal dopamine deficiency that, in principle, could be corrected by dopamine substitution medication if safety and subject selection considerations can be resolved.

Kish|Stephen J|SJ|
Boileau|Isabelle|I|
Callaghan|Russell C|RC|
Tong|Junchao|J|

D000697:Central Nervous System Stimulants

D050483:Dopamine Plasma Membrane Transport Proteins

dopamine
methamphetamine
Parkinson's disease
substantia nigra
levodopa
striatum


Dung-associated arthropods influence foraging ecology and habitat selection in Black-necked Cranes (Grus nigricollis) on the Qinghai-Tibet Plateau.

Abstract: Variation in grassland vegetation structure influences the habitat selection of insectivorous birds. This variation presents a trade-off for insectivorous predators: Arthropod abundance increases with vegetation height and heterogeneity, but access to arthropod prey items decreases. In contrast, grazing by large herbivores reduces and homogenizes vegetation, decreasing total arthropod abundance and diversity. However, the presence of livestock dung may help counteract the overall reduction in invertebrates by increasing arthropods associated with dung. It is unclear, however, how the presence of arthropod prey in dung contributes to overall habitat selection for insectivorous birds or how dung-associated arthropods affect trade-offs between vegetation structure, arthropod abundance, and access to prey. To explore these relationships, we studied habitat selection of the Black-necked Crane (Grus nigricollis), a large omnivorous bird that breeds on the Qinghai-Tibet Plateau. We assessed the relationships between habitat selection of cranes and vegetation structure, arthropod abundance, and the presence of yak dung. We found that Black-necked Cranes disproportionately foraged in grassland patches with short sward height, low sward height heterogeneity, and high numbers of dry yak dung, despite these habitats having lower total arthropod abundance. Although total arthropod abundance is lower, these habitats are supplemented with dry yak dung, which are associated with coleopteran larvae, making dung pats an indicator of food resources for breeding Black-necked Cranes. Coleopteran adults and larvae in yak dung appear to be an important factor influencing the habitat selection of Black-necked Cranes and should be considered when assessing grassland foraging trade-offs of insectivorous birds. This research provides new insights into the role of livestock dung in defining foraging habitats and resources for insectivorous predators.

grassland
birds
foraging availability
grazing activity
invertebrate prey accessibility


In vitro effects of bufotenine against RNA and DNA viruses.

Abstract: Bufotenine, an alkaloid that can be found in plant extracts and skin secretions of amphibians, is reported to have potential antiviral activity. The present study evaluated the antiviral activity of bufotenine against different genetic lineages of rabies virus (RABV, a single-stranded, negative-sense RNA virus), canine coronavirus (CCoV, a positive-sense RNA virus) and two double-stranded DNA viruses (two strains of herpes simplex virus type 1/HSV-1 [KOS and the acyclovir-resistant HSV-1 strain 29R] and canine adenovirus 2, CAV-2). The maximal non-toxic bufotenine concentrations in Vero and BHK-21 cells were determined by MTT assays. The antiviral activity of bufotenine against each virus was assessed by examination of reductions in infectious virus titres and plaque assays. All experiments were performed with and without bufotenine, and the results were compared. Bufotenine demonstrated significant RABV inhibitory activity. No antiviral action was observed against CCoV, CAV-2 or HSV-1. These findings indicate that the antiviral activity of bufotenine is somewhat linked to the particular infectious dose used and the genetic lineage of the virus, although the mechanisms of its effects remain undetermined.

de Carvalho Ruthner Batista|Helena Beatriz|HB|

Bufotenine Alkaloid Rabies Coronavirus Adenovirus Herpesvirus


Hematopoietic Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria in the Age of Eculizumab.

Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematopoietic cell disease characterized by the destruction of hematopoietic cells through activation of the complement system with manifestations that can be life-threatening including hemolysis, thrombosis, and marrow failure. Allogeneic hematopoietic cell transplantation (HCT) remains the sole cure for PNH, but eculizumab, a terminal complement inhibitor of C5, has been used to prevent complement-mediated hemolysis in patients with PNH since its approval by the Food and Drug Administration in 2007. We examined outcomes of HCT in patients with PNH to evaluate the effects of disease subtype, conditioning intensity, and eculizumab use either pre-HCT or post-HCT. Fifty-five patients with a diagnosis of PNH underwent at least 1 HCT, with 4 patients requiring a second HCT for graft failure. The median age at the time of first HCT was 30.0 years (range, 4.2 to 66.9 years). Seventeen patients (30.9%) had classical PNH, and the remaining 38 patients had PNH associated with another marrow disorder (aplastic anemia in 26 of the 38). Indications for HCT included pancytopenia in 47.3% of the patients, myeloid malignancy (myelodysplastic syndrome, myeloproliferative neoplasm, or acute myelogenous leukemia) in 21.8%, recurrent hemolysis in 20.0%, and thrombosis in 10.9%. Of the 55 first HCTs, 26 were performed with myeloablative conditioning, 27 were performed with reduced-intensity conditioning, and 2 sets of identical twins underwent HCT without any conditioning. Donor types included HLA-matched related in 38.2%, HLA-matched unrelated in 34.5%, single HLA-allele mismatched unrelated in 16.4%, umbilical cord blood in 5.5%, syngeneic in 3.6%, and HLA-haploidentical in 1.8%. The median duration of follow-up in surviving patients was 6.1 years (range, 2.1 to 46.1 years) after first HCT. The median time to neutrophil and platelet engraftment was 17 days and 19 days, respectively; all but 2 patients (96.3%) had sustained engraftment. Overall survival was 70% at 5 years. Neither the choice of conditioning intensity nor PNH subtype affected survival. Nineteen patients died during follow-up, including 12 patients before day +365. Six patients received treatment with eculizumab before HCT, and 2 were treated after HCT. All patients treated with eculizumab were alive at a median follow-up of 2.3 years (range, .2 to 6.9 years). Both patients treated with eculizumab after HCT had minimal to no acute GVHD (aGVHD), with grade I skin aGVHD in 1 patient and no aGVHD in the other patient, and no chronic GVHD at 2.1 and 4.1 years post-HCT, respectively. With the approval of eculizumab, the indications for HCT include persistent hemolysis, persistent thrombosis, and associated marrow failure. Administration of eculizumab before and after HCT warrants further study, particularly considering our observation of minimal to no GVHD in 2 patients who received eculizumab after HCT.

Cooper|Jason P|JP|
Farah|Rafic J|RJ|
Stevenson|Philip A|PA|
Gooley|Ted A|TA|
Storb|Rainer|R|
Scott|Bart L|BL|

D018380:Hematopoietic Stem Cell Transplantation

Paroxysmal nocturnal hemoglobinuria
PNH
Allogeneic transplantation
E eculizumab


Effects of anemia and iron deficiency on quality of life in women with heavy menstrual bleeding.

Abstract:
OBJECTIVE
To assess the impact of anemia and iron deficiency on health-related quality of life (HRQoL) in women treated for heavy menstrual bleeding (HMB).

DESIGN
Secondary analysis of a randomized controlled trial.

SETTING
Five university hospitals in Finland.

SAMPLE
A total of 236 women referred for HMB.

METHODS
Women were randomized to treatment with hysterectomy or a levonorgestrel-releasing intrauterine system. We defined groups based on women's pretreatment hemoglobin [hemoglobin <120 g/L (anemic) vs. hemoglobin ≥120 g/L (nonanemic)] and serum ferritin (ferritin <15 μg/L vs. ≥15 μg/L) concentrations. HRQoL was compared between groups at baseline, 6 and 12 months after treatment. Hemoglobin and ferritin were followed for 5 years.

MAIN OUTCOME MEASURES
HRQoL was measured by the RAND 36-item health survey (RAND-36), 5-Dimensional EuroQol and two questionnaires of mental wellbeing.

RESULTS
At baseline, 63 women (27%) were anemic and 140 (60%) were severely iron deficient (ferritin <15 μg/L). Only 8% of the anemic women had taken iron supplementation. Twelve months after treatment hemoglobin had increased in both hemoglobin groups, but was still significantly lower (p < 0.001) in initially anemic women (128 g/L) compared with nonanemic women (136 g/L). Twelve months after treatment three domain scores of RAND-36 increased more (energy, p = 0.002; physical functioning, p = 0.04; social functioning, p = 0.05), and anxiety (p = 0.02) and depression scores (p = 0.002) decreased more in anemic compared with nonanemic women. Serum ferritin took 5 years to reach normal levels.

CONCLUSIONS
Improved HRQoL after treatment of HMB is associated with correction of anemia. Clinicians should actively screen for anemia in women with HMB and emphasize early iron substitution as an integral part of treatment.

Peuranpää|Pirkko|P| Heliövaara-Peippo|Satu|S| Fraser|Ian|I| Paavonen|Jorma|J| Hurskainen|Ritva|R|

Anemia
iron deficiency
quality of life
heavy menstrual bleeding
menorrhagia


Closed-Form Algorithm for 3-D Near-Field OFDM Signal Localization under Uniform Circular Array.

Abstract: Due to its widespread application in communications, radar, etc., the orthogonal frequency division multiplexing (OFDM) signal has become increasingly urgent in the field of localization. Under uniform circular array (UCA) and near-field conditions, this paper presents a closed-form algorithm based on phase difference for estimating the three-dimensional (3-D) location (azimuth angle, elevation angle, and range) of the OFDM signal. In the algorithm, considering that it is difficult to distinguish the frequency of the OFDM signal's subcarriers and the phase-based method is always affected by errors of the frequency estimation, this paper employs sparse representation (SR) to obtain the super-resolution frequencies and the corresponding phases of subcarriers. Further, as the phase differences of the adjacent sensors including azimuth angle, elevation angle and range parameters can be expressed as indefinite equations, the near-field OFDM signal's 3-D location is obtained by employing the least square method, where the phase differences are based on the average of the estimated subcarriers. Finally, the performance of the proposed algorithm is demonstrated by several simulations.

Su|Xiaolong|X|0000-0002-4015-6531 Liu|Zhen|Z| Chen|Xin|X| Wei|Xizhang|X|

near-field OFDM signal
uniform circular array (UCA)
phase difference
sparse representation (SR)
parameter estimation


Environmental effects on the bioaccumulation of PAHs in marine zooplankton in Gaoping coastal waters, Taiwan: Concentration, distribution, profile, and sources.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are toxic and ubiquitous in the environment and pose great risks. Bioaccumulation by plankton is the outset for PAHs entering marine food web. The long-term driving environmental factors for bioaccumulation of PAHs in zooplankton have not been well investigated. In this study, high variation of PAH concentrations in zooplankton (5 to 5440 ng g-1 dry weight) was found, with the highest PAH levels near the transect Kaohsiung Harbor. Precipitation significantly enhances the PAH concentration in zooplankton and affects the PAH distribution in the water column, indicating PAH input from terrestrial runoff. The sources of PAHs in the coastal waters are a mixture of petroleum and combustion. Biomass dilution dominates bioaccumulation of PAHs in zooplankton, especially for the dominant species, copepods. This study provides the first information on PAH bioaccumulation in zooplankton to understand PAH transport in the plankton food web in subtropical coastal waters.

Hsieh|Hung-Yen|HY| Huang|Kuang-Ching|KC| Cheng|Jing-O|JO| Lo|Wen-Tseng|WT| Meng|Pei-Jie|PJ| Ko|Fung-Chi|FC|

PAHs
Zooplankton
Food web
Isomer ratios
Pyrogenic origin


Cardiac autonomic function and insulin resistance for the development of hypertension: a six-year epidemiological follow-up study.

Abstract:
BACKGROUND AND AIMS
To explore the impact of cardiac autonomic function (CAF) and insulin resistance (IR) on incident hypertension.

METHODS AND RESULTS
In 1996, 1638 subjects finished baseline examination, which included anthropometry, blood pressures, CAF, blood biochemistry, plasma insulin, urine examination and electrocardiogram. CAF included standard deviation of normal-to-normal intervals or RR intervals (SDNN), low- and high-frequency power spectrum (LF and HF), and LF/HF ratio at supine for 5 min, the RR interval changes during lying-to-standing maneuver, and the ratio between the longest RR interval during expiration and the shortest RR interval during inspiration (E/I ratio). We used homeostasis model assessment to define beta cell function (HOMA-B) and insulin resistance (HOMA-IR). In total, 992 non-hypertensive participants completed the follow-up assessment in 2003 and 959 participants were included for the final analysis. Incident hypertension was determined by blood pressure status at follow-up. In unadjusted model, both square root of HOMA-IR (OR:3.37, 95%CI: 2.10-6.64) and HOMA-B (OR:0.996, 95%CI: 0.992-0.999) were related to incident hypertension. In multivariate model, square root of HOMA-IR (OR:1.97, 95%CI: 1.05-3.70), but not HOMA-B, was associated with incident hypertension. After further adjustment for baseline CAF, the positive relationship between the square root of HOMA-IR and incident hypertension disappeared. In contrast, LF/HF ratio (OR:1.18, 95%CI: 1.01-1.37), HF power (OR:0.98, 95%CI: 0.96-0.999), and E/I ratio (OR:0.71, 95%CI: 0.54-0.95) were each independently associated with incident hypertension after further adjustment for HOMA measures.

CONCLUSION
Sympathovagal imbalance with an apparently decreased parasympathetic tone is an important predictor of incident hypertension independent of IR.

Wu|J S|JS|
Yang|Y C|YC|
Lu|F H|FH|
Lin|T S|TS|
Chen|J J|JJ|
Huang|Y H|YH|
Yeh|T L|TL|
Chang|C J|CJ|

a ratio between the RR intervals during expiration and inspiration

a ratio between the longest RR interval around the 30th beat and the shortest RR interval around the 15th beat after standing

homeostasis model assessment for insulin resistance

P P P P P P P P P P P P P P P M R M P U R P U


Antibacterial evaluation of silver nanoparticles synthesized from lychee peel: individual versus antibiotic conjugated effects.

Abstract: This paper describes the extracellular synthesis of silver nanoparticles from waste part of lychee fruit (peel) and their conjugation with selected antibiotics (amoxicillin, cefixim, and streptomycin). FTIR studies revealed the reduction of metallic silver and stabilization of silver nanoparticles and their conjugates due to the presence of CO (carboxyl), OH (hydroxyl) and CH (alkanes) groups. The size of conjugated nanoparticles varied ranging from 3 to 10 nm as shown by XRD. TEM image revealed the spherical shape of biosynthesized silver nanoparticles. Conjugates of amoxicillin and cefixim showed highest antibacterial activity (147.43 and 107.95%, respectively) against Gram-negative bacteria i.e. Alcaligenes faecalis in comparison with their control counterparts. The highest reduction in MIC was noted against Gram-positive strains i.e. Enterococcus faecium (75%) and Microbacterium oxydans (75%) for amoxicillin conjugates. Anova two factor followed by two-tailed t test showed non-significant results both in case of cell leakage and protein estimation between nanoparticles and conjugates of amoxicillin, cefixime and streptomycin. In case of MDA release, non-significant difference among the test samples against the selected strains. Our study found green-synthesized silver nanoparticles as effective antibacterial bullet against both Gram positive and Gram negative bacteria, but they showed a more promising effect on conjugation with selected antibiotics against Gram negative type.

Perveen|Shaghufta|S| Safdar|Naila|N| Chaudhry|Gul-E-Saba|GE| Yasmin|Azra|A|

Antibacterial evaluation
Silver nanoparticles
Lychee peel
Antibiotics conjugates
Protein estimation
Malondialdehyde contents


Responding to aid volatility: government spending on district health care in Zambia 2006-2017.

Abstract: Background: A corruption event in 2009 led to changes in how donors supported the Zambian health system. Donor funding was withdrawn from the district basket mechanism, originally designed to pool donor and government financing for primary care. The withdrawal of these funds from the pooled financing mechanism raised questions from Government and donors regarding the impact on primary care financing during this period of aid volatility.Objectives: To examine the budgets and actual expenditure allocated from central Government to the district level, for health, in Zambia from 2006 to 2017 and determine trends in funding for primary care.Methods: Financial data were extracted from Government documents and adjusted for inflation. Budget and expenditure for the district level over the period 2006 to 2017 were disaggregated by programmatic area for analysis.Results: Despite the withdrawal of donor funding from the district basket after 2009, funding for primary care allocated to the district level more than doubled from 2006 to 2017. However, human resources accounted for this increase. The operational grant, on the other hand, declined.Conclusion: The increase in the budget allocated to primary care could be an example of 'reverse fungibility', whereby Government accounted for the gap left by donors. However, the decline in the operational grant demonstrates that this period of aid volatility continued to have an impact on how primary care was planned and financed, with less flexible budget lines most affected during this period. Going forward, Government and donors must consider how funding is allocated to ensure that primary care is resilient to aid volatility; and that the principles of aid effectiveness are prioritised to continue to provide primary health care and progress towards achieving health for all.

corruption
Primary care
fungibility
aid effectiveness
aid coordination
decentralisation
health financing
official development assistance


Long-Term Effect of Daily Chemical Disinfection on Surface Topography and Candida Albicans Biofilm Formation on Denture Base and Reline Acrylic Resins.

Abstract:
PURPOSE
This study investigated the effect of long-term daily chemical disinfection on the topographic and Candida albicans biofilm formation on a denture base resin and a reline acrylic resin.

MATERIAL AND METHODS
Circular samples (14 × 1.2 mm) were fabricated from a denture base (Vipi Wave) and reline acrylic resins (Tokuyama Rebase Fast II). Samples were kept in 50 ml of distilled water (48 h at 37°C). Subsequently, the samples were immersed in five different solutions: 0.5% sodium hypochlorite; 3.8% sodium perborate; 2% chlorhexidine gluconate; apple vinegar containing 4% maleic acid; and distilled water (control group). The specimen was immersed in the solutions for 8 h daily and transferred to distilled water at 37°C for more 16 h. The surface topographic and Candida albicans (ATCC 90028) biofilm formation were evaluated at baseline (before chemical disinfection) and after 1, 3 and 6 months of immersion. The surface topographic was evaluated by arithmetical roughness average (Ra) and scanning electron microscope (SEM), while the biofilm formation was evaluated by colony-forming units (CFU/ml) method and Alamar Blue assay (cell metabolism). The results were evaluated by three-way analysis of variance (ANOVAs) and post-hoc tests (α = 0.05).

RESULTS
The results showed statistically significant effects from the type of acrylic resin (p = 0.029) and time (p <0.001) on the roughness of the specimen. In general, the reline resin had higher roughness than the denture base resin. In addition, the roughness of the samples after 1, 3 and 6 months of immersion in the cleaning solutions was higher than at baseline. In relation to the microbiological assays, there were no statistically significant differences (p >0.055) in the CFU/ml values of the biofilms among the different resins, periods of time and cleaning solutions. Considering the metabolism of the cells within the biofilms, the results showed that, at baseline, it was statistically significantly higher (p <0.05) than after 1, 3 and 6 months of storage. The SEM images showed that all disinfectant solutions provided surface changes of both acrylic resins (base and reline) after 1, 3 and 6 months of immersion.

CONCLUSIONS
The roughness of both acrylic resins was affected by the disinfection in all cleaning agents, increasing over time, and this effect was more evident in the reline acrylic resin group. This surface change was also observed in the SEM images. While the number of cells within the biofilms was not affected by immersion in the cleaning agents, their metabolism was lower after 1, 3 and 6 months of immersion.

Amaya Arbeláez|Maria Isabel|MI|
Vergani|Carlos Eduardo|CE|
Barbugli|Paula Aboud|PA|
Pavarina|Ana Claudia|AC|
Sanitá|Paula Volpato|PV|
Jorge|Janaina Habib|JH|

D000180:Acrylic Resins
D018441:Biofilms
D002176:Candida albicans
D003819:Denture Bases
D003820:Denture Cleansers
D004203:Disinfection
D008422:Materials Testing
D013499:Surface Properties

biofilm
roughness
acrylic base resin
denture cleansers
hard relines


Atypical or Incomplete Kawasaki Disease in a Young Child: A Case Report.

Abstract: This case report describes an atypical or incomplete presentation of Kawasaki Disease. Kawasaki Disease is an inflammatory process that can affect all blood vessels and result in cardiac complications; particularly coronary artery aneurysms. Patients are typically young children, usually younger than 5 years of age, who initially present with a high fever and nonspecific rash. The child in this case presented with an atypical or incomplete presentation, and was diagnosed with Kawasaki disease after multiple provider encounters. Signs and symptoms of Kawasaki disease versus atypical or incomplete Kawasaki disease, differential diagnoses, and potential complications from Kawasaki disease are discussed in this case report.

D009080:Mucocutaneous Lymph Node Syndrome

Atypical
incomplete Kawasaki disease
fever
rash/exanthema illness


The role of voice rest after micro-laryngeal surgery for benign vocal fold lesions.

Abstract:
PURPOSE
To compare post-operative vocal outcomes of a voice rest regimen versus no voice restrictions following micro-laryngeal surgery for benign glottic lesions.

METHODS
This was a combined prospective and retrospective cohort study on 167 patients who underwent micro-laryngeal surgery for benign focal fold lesion removal. Participants were divided into two regimens: standard voice rest (n = 92) or no voice restriction (n = 75). The primary outcome was post-operative vocal improvement, evaluated using voice handicap index questionnaire (VHI-10), GRBAS scale, and computerised acoustic analysis (shimmer, jitter, and the harmonic-to-noise ratio). The secondary outcome was emergence of vocal fold mucosal abnormalities in the immediate post-operative period. Parameters were collected at baseline and at the last clinical visit.

RESULTS
There was no statistically significant difference between the voice rest and no-voice rest groups regarding baseline parameters of age, gender, laryngeal pathology, and voice use. Improvement in GRBAS scale values and VHI-10 scores between pre- and post-operative periods between groups did not demonstrate any statistically significant differences (P = 0.5303 and P = 0.1457, respectively). Similarly, the results of computerized voice analysis also showed no differences between groups in terms of shimmer (P = 0.9590), jitter (P = 0.5692), and harmonic-to-noise ratio (P = 0.1871). No correlation was found between the post-operative vocal fold's mucosal abnormalities and the type of voice rest regimen.

CONCLUSION
Voice quality and wound healing were similar regardless of the type of voice rest regimen applied. No voice rest at all was as good as voice rest after micro-laryngeal surgery.

Vocal fold
Benign lesion
Phonosurgery
Voice disorders
Voice therapy


Inhibition of Trigeminal Nociception by Non-invasive Vagus Nerve Stimulation: Investigating the Role of GABAergic and Serotonergic Pathways in a Model of Episodic Migraine.

Abstract: Migraine is a prevalent neurological disease that is characterized by unpredictable episodic attacks of intense head pain. The underlying pathology involves sensitization and activation of the trigeminal system. Although non-invasive vagus nerve stimulation (nVNS) is recommended for the treatment of migraine, the abortive mechanism of action is not well-understood. The goal of this study was to compare the ability of nVNS and sumatriptan to inhibit trigeminal activation in two animal models of episodic migraine and to investigate the receptor mechanism of action of nVNS. Nocifensive head withdrawal response was investigated in adult male Sprague Dawley rats using von Frey filaments. To induce trigeminal nociceptor sensitization, complete Freund's adjuvant was injected in the trapezius muscle and trigeminal neurons were activated by exposure to a pungent odor or injection of the nitric oxide donor sodium nitroprusside. Some animals received nVNS or sumatriptan as treatment. Some animals were injected intracisternally with antagonists of GABAA, 5-HT3 or 5-HT7 receptors prior to nVNS since these receptors are implicated in descending modulation. While unsensitized animals exposed to the pungent odor or nitric oxide alone did not exhibit enhanced mechanical nociception, sensitized animals with neck muscle inflammation displayed increased trigeminal nocifensive responses. The enhanced nociceptive response to both stimuli was attenuated by nVNS and sumatriptan. Administration of antagonists of GABAA, 5-HT3, and 5-HT7 receptors in the upper spinal cord suppressed the anti-nocifensive effect of nVNS. Our findings suggest that nVNS inhibits trigeminal activation to a similar degree as sumatriptan in episodic migraine models via involvement of GABAergic and serotonergic signaling to enhance central descending pain modulation.

Cornelison|Lauren E|LE|
Woodman|Sara E|SE|
Durham|Paul L|PL|

vagus nerve
pain
sensitization
sumatriptan
nitric oxide
neck inflammation


The cytotoxicity of 8-O-4' neolignans from the seeds of Crataegus pinnatifida.

Abstract: Nine new 8-O-4' neolignans, named pinnatifidanin B I-IX (1-9), together with 9 known analogs (10-18) were isolated from the seeds of Crataegus pinnatifida. The structures of 1-18 were determined by spectroscopic methods, including 1D, 2D NMR, CD and HRESIMS analysis. Compounds 8-11, 17 and 18 displayed potent cytotoxic activities against human cancer cell lines, and most interestingly, none of the 6 compounds displayed inhibitory activity against human lung cell line (Mrc5). The 6 cytotoxic compounds are considered to be potential as antitumor agents, which could significantly inhibit the cancer cell growth in a dose-dependent manner and are probably safer than positive control drug.

Huang|Xiao-Xiao|XX| Zhou|Chen-Chen|CC| Li|Ling-Zhi|LZ| Li|Fei-Fei|FF| Lou|Li-Li|LL| Li|Dian-Ming|DM| Ikejima|Takshi|T| Peng|Ying|Y| Song|Shao-Jiang|SJ|

D004354:Drug Screening Assays, Antitumor

Cytotoxicities
Crataegus pinnatifida
8-O-4′ Neolignans


Music-Assisted Training for Dart Throwing Novices: Post-Training Effects on Heart Rate and Performance Accuracy.

Abstract: While previous research has suggested that lowering athletes' heart rates can enhance sports performance, it is unknown whether slow-paced music might induce a lower heart rate and thereby improve some types of motor performance. In this study, we investigated the effects of different types of music during dart-throw training on both heart rate and dart-throwing performance in 45 (M age = 19.7, SD = 0.31 years) novice dart throwers who were randomly assigned to either a Slow Music Group (SMG), a Fast Music Group (FMG), or a Control Group (CG). All participants completed three dart-throwing blocks - Pre-Test, Practice, and Post-Test. During the Practice block, participants practiced dart-throwing with either slow-paced, fast-paced or no music according to their assigned group. We recorded the participants' heart rates and total dart-throwing accuracy scores during Pre-Test and Post-Test. Music-assisted dart-throw training with slow-paced music was effective in significantly inhibiting a performance-related increase in heart rate and was associated with the greatest dart throwing improvement after training.

heart rate
sport performance
music
dart-throwing
psychomotor training


Nephrectomy and inferior vena cava thrombectomy for renal cell carcinoma among patients with impaired renal function: defining predictors of outcomes.

Abstract:
BACKGROUND
Management of renal cell carcinoma (RCC) with inferior vena cava thrombus (IVCT) is associated with high morbidity. Chronic kidney disease (CKD) is a known risk factor for perioperative complications in many surgical procedures. The objective of this study was to review the association between preoperative CKD (eGFR < 60 mL/min) and post-operative outcomes in patients with RCC and IVCT undergoing radical nephrectomy (RN) and tumour thrombectomy (TT).

METHODS
A retrospective review of patients with RCC and IVCT treated with RN and TT was carried out. Complications were recorded according to the Clavien-Dindo classification. Multivariable models were fitted using logistic regression analyses for high-grade complications and salvage therapies and linear-regression for intraoperative blood loss (IBL).

RESULTS
One hundred and one patients with RCC and IVCT, treated with RN and TT, were identified. Forty per cent of patients had preoperative CKD. Median IBL was higher in CKD arm (2.5 versus 1.6 L, P = 0.04). In a multivariate linear regression analysis, CKD (beta 1.34, P = 0.01) remained an independent predictor of IBL. High-grade complications were more frequent in the CKD group (34% versus 16%, P = 0.09) and in logistic regression analysis, CKD was an independent predictor of high-grade complications (OR 3.33, 95% CI 1.01-10.9). Furthermore, CKD patients were less likely to be considered for salvage therapies (62% versus 38%, P = 0.02).

CONCLUSIONS
In patients treated with RN and TT, CKD is an independent predictor of perioperative morbidity. This clinical variable should be considered when selecting patients and subsequent efforts should be made to optimize other competing risk factors in order to reduce the incidence of perioperative adverse events in this patient population.

Zargar-Shoshtari|Kamran|K|
Ashouri|Kenan|K|
Sharma|Pranav|P|
Baumgarten|Adam|A|
Sexton|Wade J|WJ|
Pow-Sang|Julio|J|
Spiess|Philippe E|PE|

inferior vena cava
thrombectomy
renal cell carcinoma
complication


Prevalence of alcohol use disorder among individuals who binge eat: a systematic review and meta-analysis.

Abstract:
BACKGROUND AND AIMS
Binge eating disorder (BED) is correlated with substance use. This study aimed to estimate the life-time prevalence of alcohol use disorder (AUD) among individuals with non-compensatory binge eating and determine whether their life-time prevalence of AUD is higher than in non-bingeing controls.

DESIGN
A systematic search of databases (PubMed, Embase and Web of Science) for studies of adults diagnosed with BED or a related behavior that also reported the life-time prevalence of AUD was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was followed. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO).

SETTING
Studies originating in Canada, Sweden, the United Kingdom and the United States.

PARTICIPANTS
Eighteen studies meeting the inclusion criteria were found, representing 69 233 individuals.

MEASUREMENTS
Life-time prevalence of AUD among individuals with binge eating disorder and their life-time relative risk of AUD compared with individuals without this disorder.

RESULTS
The pooled life-time prevalence of AUD in individuals with binge eating disorder was 19.9% [95% confidence interval (CI) = 13.7-27.9]. The risk of life-time AUD incidence among individuals with binge eating disorder was more than 1.5 times higher than controls (relative risk = 1.59, 95% CI = 1.41-1.79). Life-time AUD prevalence was higher in community samples than in clinical samples (27.45 versus 14.45%, P = 0.041) and in studies with a lower proportion of women (β = -2.2773, P = 0.044).

CONCLUSIONS
Life-time alcohol use disorder appears to be more prevalent with binge eating disorder than among those without.

alcohol use disorder
systematic review
meta-analysis
binge eating disorder
Alcohol abuse
alcohol dependence


Parallel diurnal fluctuation of testosterone, androstenedione, dehydroepiandrosterone and 17OHprogesterone as assessed in serum and saliva: validation of a novel liquid chromatography-tandem mass spectrometry method for salivary steroid profiling.

Abstract:
BACKGROUND
Salivary androgen testing represents a valuable source of biological information. However, the proper measurement of such low levels is challenging for direct immunoassays, lacking adequate accuracy. In the last few years, many conflicting findings reporting low correlation with the serum counterparts have hampered the clinical application of salivary androgen testing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) makes it possible to overcome previous analytical limits, providing new insights in endocrinology practice.

METHODS
Salivary testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA) and 17OHprogesterone (17OHP) were extracted from 500µL of saliva, separated in 9.5 min LC-gradient and detected by positive electrospray ionization - multiple reaction monitoring. The diurnal variation of salivary and serum androgens was described by a four paired collection protocol (8 am, 12 am, 4 pm and 8 pm) in 19 healthy subjects.

RESULTS
The assay allowed the quantitation of T, A, DHEA and 17OHP down to 3.40, 6.81, 271.0 and 23.7 pmol/L, respectively, with accuracy between 83.0 and 106.1% for all analytes. A parallel diurnal rhythm in saliva and serum was observed for all androgens, with values decreasing from the morning to the evening time points. Salivary androgen levels revealed a high linear correlation with serum counterparts in both sexes (T: R>0.85; A: R>0.90; DHEA: R>0.73 and 17OHP: R>0.89; p<0.0001 for all).

CONCLUSIONS
Our LC-MS/MS method allowed a sensitive evaluation of androgen salivary levels and represents an optimal technique to explore the relevance of a comprehensive androgen profile as measured in saliva for the study of androgen secretion modulation and activity in physiologic and pathologic states.


Follicle-Stimulating Hormone Receptor: Advances and Remaining Challenges.

Abstract: Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs). FSH is a large naturally heterogeneous heterodimeric glycoprotein. The FSHR is characterized by a very large NH2-terminal extracellular domain, which binds FSH and participates to the activation/inactivation switch of the receptor. Once activated, the FSHR couples to Gαs and, in some instances, to other Gα-subunits. GPCR kinases and β-arrestins are also recruited to the FSHR and account for its desensitization, the control of its trafficking and its intracellular signaling. Of note, the FSHR internalization and recycling are very fast and involve very early endosomes (EE) instead of EE. All the transduction mechanisms triggered upon FSH stimulation lead to the activation of a complex signaling network that controls gene expression by acting at multiple levels. The integration of these mechanisms not only leads to context-adapted responses from the target gonadal cells but also indirectly affects the fate of germ cells. Depending on the physiological/developmental stage, FSH elicits proliferation, differentiation, or apoptosis in order to maintain the homeostasis of the reproductive system. Pharmacological tools targeting FSHR recently came to the fore and open promising prospects both for basic research and therapeutic applications. This chapter provides an updated review of the most salient aspects and peculiarities of FSHR biology and pharmacology.

De Pascali|Francesco|F|
Tréfier|Aurélie|A|
Landomiel|Flavie|F|
Bozon|Véronique|V|
Bruneau|Gilles|G|
Yvinec|Romain|R|
Poupon|Anne|A|
Crépieux|Pascale|P|
Reiter|Eric|E|

Follicle-stimulating hormone
Reproduction
GPCR
β-arrestin
Signaling
Pharmacology
Bias
Fertility
G protein
Glycoprotein hormones
Modeling


LED control of gene expression in a nanobiosystem composed of metallic nanoparticles and a genetically modified E. coli strain.

Abstract:
BACKGROUND
Within the last decade, genetic engineering and synthetic biology have revolutionized society´s ability to mass-produce complex biological products within genetically-modified microorganisms containing elegantly designed genetic circuitry. However, many challenges still exist in developing bioproduction processes involving genetically modified microorganisms with complex or multiple gene circuits. These challenges include the development of external gene expression regulation methods with the following characteristics: spatial-temporal control and scalability, while inducing minimal permanent or irreversible system-wide conditions. Different stimuli have been used to control gene expression and mitigate these challenges, and they can be characterized by the effect they produce in the culture media conditions. Invasive stimuli that cause permanent, irreversible changes (pH and chemical inducers), non-invasive stimuli that cause partially reversible changes (temperature), and non-invasive stimuli that cause reversible changes in the media conditions (ultrasound, magnetic fields, and light).

METHODS
Opto-control of gene expression is a non-invasive external trigger that complies with most of the desired characteristics of an external control system. However, the disadvantage relies on the design of the biological photoreceptors and the necessity to design them to respond to a different wavelength for every bioprocess needed to be controlled or regulated in the microorganism. Therefore, this work proposes using biocompatible metallic nanoparticles as external controllers of gene expression, based on their ability to convert light into heat and the capacity of nanotechnology to easily design a wide array of nanostructures capable of absorbing light at different wavelengths and inducing plasmonic photothermal heating.

RESULTS
Here, we designed a nanobiosystem that can be opto-thermally triggered using LED light. The nanobiosystem is composed of biocompatible gold nanoparticles and a genetically modified E. coli with a plasmid that allows mCherry fluorescent protein production at 37 °C in response to an RNA thermometer.

CONCLUSIONS
The LED-triggered photothermal protein production system here designed offers a new, cheaper, scalable switchable method, non-destructive for living organisms, and contribute toward the evolution of bioprocess production systems.

Mathematical model opto-thermal conversion


Nephrotoxicity after radionuclide therapies.

Abstract: Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50-60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.

Parihar|Ashwin Singh|AS|
Chopra|Sejal|S|
Prasad|Vikas|V|

Renal toxicity
177Lu
90Y
Acute kidney injury
CKD
Chronic
DOTATATE
DOTATOC
PRRT
PSMA
RLT
Radioimmunotherapy
Theranostics


Oral health knowledge and awareness among pregnant women in India: A systematic review.

Abstract: Pregnancy is a unique period during a woman's life and is characterized by complex physiological changes, which may adversely affect oral health. The present systematic review was conducted to assess knowledge and awareness regarding oral health among pregnant women in India. Relevant cross-sectional observational studies were included in the systematic review to assess the level of knowledge and awareness regarding oral health among pregnant women in India. Seven studies out of 255 were finally included in the present review after conducting both electronic and manual search of scientific databases. Potential biases were reported and appropriate data were extracted by the concerned investigators. Almost 67% of the subjects had good knowledge and awareness regarding oral health in one of the study findings. Knowledge regarding effect of decayed teeth on the appearance of the people was significantly related to the parity status of the subjects (P = 0.024) in other study reports. Very few subjects (17.1% and 37.5%) felt the need for visiting a dentist during pregnancy in two studies. The results of the present review showed that pregnant women had poor knowledge and awareness regarding oral health. Therefore, there is an urgent need for education and motivation of expectant mothers regarding oral health through various health promotion interventions.

Gambhir|Ramandeep Singh|RS|
Nirola|Ashutosh|A|
Gupta|Tarun|T|
Sekhon|Tegbir Singh|TS|
Anand|Samir|S|

Adverse pregnancy outcomes
low-birth weight baby
oral health awareness
oral hygiene
premature delivery


Association between actigraphy-derived physical activity and cognitive performance in patients with schizophrenia.

Abstract:
BACKGROUND
An association between low levels of physical activity and impaired cognitive performance in schizophrenia has been proposed, but most studies have relied on self-report measures of activity. This study examined the association between actigraphy-derived physical activity and cognitive performance adjusting for multiple covariates in patients with schizophrenia.

METHOD
Patients with schizophrenia (n = 199) were recruited from chronic psychiatric wards, and 60 age-, sex- and body mass index-matched comparison participants were recruited from the staff of two hospitals and universities. Physical activity was assessed objectively for 7 days using an ActiGraph. Cognitive performance was assessed with the Cognitrone test from the Vienna Test System and the Grooved Pegboard Test. Demographic variables, metabolic parameters, positive and negative symptoms, duration of illness and hospitalization, and medication use were included as covariates. Pearson correlations and multivariable linear regressions were conducted to examine the associations between physical activity levels and cognitive performance.

RESULTS
Patients with schizophrenia were less physically active and had poorer performance on attention/concentration and speed of processing than the comparison group. Patients with schizophrenia who spent more time in light physical activity showed better performance on attention/concentration (β = 0.198, p = 0.020) and speed of processing (β= -0.169, p = 0.048) tasks than those who were less active. Cognitive performance was also associated with moderate-vigorous physical activity, but the effect was no longer significant once light physical activity had been taken into account.

CONCLUSIONS
This study provides evidence for a positive association between objectively measured light physical activity and cognitive performance in people with schizophrenia, after adjustment for multiple confounders.

Chen|L-J|LJ| Steptoe|A|A| Chung|M-S|MS| Ku|P-W|PW|

cognition
Accelerometry
actigraphy
inactivity
psychiatric disorders


Hepatitis A in Poland in 2017 - epidemic increase cases

Abstract:
AIM
The aim of this article is to describe and assess changes in epidemiological situation of Hepatitis A in Poland in 2017.

MATERIALS AND METHODS
The assessment was based on the information from the individual case questionnaires, aggregated data from the bulletins “Infectious diseases and poisonings in Poland in 2017” and reports from epidemiological investigations in outbreaks of hepatitis A, submitted by the sanitary-epidemiological stations to the Department of Epidemiology of Infectious Diseases and Surveillance in NIPH-NIH.

RESULTS
In 2017 a large increase of HAV cases and hepatitis A incidence was observed in Poland (3006 cases, incidence 7.8 per 100 000) in comparison to 2016 (35; 0.09). Majority of the cases were registered in large cities, where incidence was 3 times higher than in rural areas. Among reported there were 501 cases (16.6% of all cases) selfdeclaring as man who have sex with man (MSM). In course of the year an increasing trend in the number of cases was observed until September and the increase of male to female ratio (m/f) until May. Moreover 251 HAV outbreaks were reported, number of which increased until October and with the increase of m/f ratio in these outbreaks until April. From July to October there was an increase in the number of small outbreaks with m/f ratio equal 1. There were 178 imported cases reported, most of them from European countries- especially Germany and Spain.

SUMMARY AND CONCLUSIONS
In 2017 over 80-fold increase of HAV cases and hepatitis A incidence was observed in comparison to previous years. Available epidemiological data indicate that ongoing HAV outbreak among MSM in Europe reached also Poland, and data from the second part of the year suggest infection spreading in non-MSM part of the population. It is therefore highly indicated that the list of risk groups for which vaccination against hepatitis A is recommended should also be expanded for MSM. To avoid such increase in the number of cases in future it is recommended to introduce vaccinations in risk groups as soon as large international outbreak occurs.

Polański|Piotr|P| Kucharczyk|Bożena|B| Kondej|Barbara|B| Cielebąk|Ewa|E| Kucharczyk|Agata|A| Sadkowska-Todys|Małgorzata|M|

hepatitis A
Poland
2017
epidemiology
HAV
MSM


Butyrylcholinesterase identification in a phenylvalerate esterase-enriched fraction sensitive to low mipafox concentrations in chicken brain.

Abstract: Multiple epidemiological and experimental studies have demonstrated that exposure to organophosphorus compounds (OPs) is associated with a variety of neurological disorders. Some of these exposure symptoms cannot be precisely correlated with known molecular targets and mechanisms of toxicity. Most of the known molecular targets of OPs fall in the protein family of serine esterases. We have shown that three esterase components in the soluble fraction of chicken brain (an animal model frequently used in OP neurotoxicity assays) can be kinetically distinguished using paraoxon, mipafox and phenylmethyl sulfonyl fluoride as inhibitors, and phenyl valerate as a substrate; we termed them Eα, Eβ and Eγ. The Eα-component, which is highly sensitive to paraoxon and mipafox and resistant to PMSF, has shown sensitivity to the substrate acetylthiocholine, and to ethopropazine and iso-OMPA (specific inhibitors of butyrylcholinesterase; BChE) but not to BW 284C51 (a specific inhibitor of acetylcholinesterase; AChE). In this work, we employed a large-scale proteomic analysis B with a LC/MS/MS TripleTOF system; 259 proteins were identified in a chromatographic fractionated sample enriched in Eα activity of the chicken brain soluble fraction. Bioinformatics analysis revealed that BChE is the only candidate protein identified to be responsible for almost all the Eα activity. This study demonstrates the potential information to be gained from combining kinetic dissection with large-scale proteomics and bioinformatics analyses for identification of proteins that are targets of OP toxicity and may be involved in detoxification of phosphoryl and carbonyl esters.

Mangas|Iris|I| Radić|Zoran|Z| Taylor|Palmer|P| Ghassemian|Majid|M| Candela|Héctor|H| Vilanova|Eugenio|E| Estévez|Jorge|J|

Butyrylcholinesterase
Brain
Organophosphorus compounds
LC-MSMS
Neuropathy Target Esterase
Phenyl valerate esterases


Tuberous sclerosis complex-mediated mTORC1 overactivation promotes age-related hearing loss.

Abstract: The underlying molecular mechanisms of age-related hearing loss (ARHL) in humans and many strains of mice have not been fully characterized. This common age-related disorder is assumed to be closely associated with oxidative stress. Here, we demonstrate that mTORC1 signaling is highly and specifically activated in the cochlear neurosensory epithelium (NSE) in aging mice, and rapamycin injection prevents ARHL. To further examine the specific role of mTORC1 signaling in ARHL, we generated murine models with NSE-specific deletions of Raptor or Tsc1, regulators of mTORC1 signaling. Raptor-cKO mice developed hearing loss considerably more slowly than WT littermates. Conversely, Tsc1 loss led to the early-onset death of cochlear hair cells and consequently accelerated hearing loss. Tsc1-cKO cochleae showed features of oxidative stress and impaired antioxidant defenses. Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo. In addition, we identified the peroxisome as the initial signaling organelle involved in the regulation of mTORC1 signaling in cochlear hair cells. In summary, our findings identify overactive mTORC1 signaling as one of the critical causes of ARHL and suggest that reduction of mTORC1 activity in cochlear hair cells may be a potential strategy to prevent ARHL.

Fu|Xiaolong|X| Sun|Xiaoyang|X| Zhang|Linqing|L| Jin|Yecheng|Y| Chai|Renjie|R| Yang|Lili|L| Zhang|Aizhen|A| Liu|Xiangguo|X| Bai|Xiaochun|X| Li|Jianfeng|J| Wang|Haibo|H| Gao|Jiangang|J|

D000076222:Mechanistic Target of Rapamycin Complex 1

D000076223:Regulatory-Associated Protein of mTOR

D000077004:Tuberous Sclerosis Complex 1 Protein

Aging
Neurodegeneration
Neurological disorders
Neuroscience


The Mechanistic Impact of N-Glycosylation on Stability, Pharmacokinetics, and Immunogenicity of Therapeutic Proteins.

Abstract: N-glycosylation is one of major post-translational modifications in nature, and it is essential for protein structure and function. As hydrophilic moieties of glycoproteins, N-glycans play important roles in protein stability. They protect the proteins against proteolytic degradation, aggregation, and thermal denaturation through maintaining optimal conformations. There are extensive evidences showing the involvement of N-glycans in the pharmacodynamics and pharmacokinetics of recombinant therapeutic proteins and antibodies. Highly sialylated complex-type glycans enable the longer serum half-lives of proteins against uptake through hepatic asialoglycoprotein receptor and mannose receptor for degradation in lysosomes. Moreover, the presence of nonhuman glycans results in clearance through pre-existing antibodies from serum and induces IgE-mediated anaphylaxis. N-glycans also facilitate or reduce the adverse immune responses of the proteins through interacting with multiple glycan-binding proteins, including those specific for mannose or mannose 6-phosphate. Due to the glycan impacts, a few therapeutic proteins were glycoengineered to improve the pharmacokinetics and stability. Thus, N-glycosylation should be extensively investigated and optimized for each individual protein for better efficacy and safety.

stability
pharmacokinetics
immunogenicity
protein structures
glycoproteins
clearance
immune responses
glycan-binding proteins
glycosylation
monoclonal antibodies


The Evolving Role of Ophthalmology Clinics in Screening for Early Alzheimer's Disease: A Review.

Abstract: Alzheimer's disease (AD) is the leading cause of dementia, which is a growing public health concern. Although there is no curative treatment for established AD, early recognition and modification of the known risk factors can reduce both severity and the rate of progression. Currently, an early diagnosis of AD is rarely achieved, as there is no screening for AD. The cognitive decline in AD is gradual and often goes unnoticed by patients and caregivers, resulting in patients presenting at later stages of the disease. Primary care physicians (general practitioners in the UK) can administer a battery of tests for patients presenting with memory problems and cognitive impairment, however final diagnosis of AD is usually made by specialised tertiary level clinics. Recent studies suggest that in AD, visuospatial difficulties develop prior to the development of memory problems and screening for visuospatial difficulties may offer a tool to screen for early stage AD. AD and cataracts share common risk and predisposing factors, and the stage of cataract presentation for intervention has shifted dramatically with early cataract referral and surgical intervention becoming the norm. This presentation offers an ideal opportunity to administer a screening test for AD, and visuospatial tools can be administered at post-operative visits by eye clinics. Abnormal findings can be communicated to primary care physicians for further follow up and assessment, or possible interventions which modify risk factors such as diabetes, hypertension and obesity can be undertaken. We propose that eye clinics and ophthalmology facilities have a role to play in the early diagnosis of AD and reducing the burdens arising from severe dementia.

screening
dementia
cataracts
eye
Alzheimer’s disease


Serum interferon levels associated with the disease activity in women with overt Graves' disease.

Abstract:
BACKGROUND
Inflammatory cytokines participate in immune reactions and the pathogenesis of autoimmunity. Herein, we quantified four groups of inflammatory cytokines, including interferons (IFNs), the tumor necrosis factor (TNF) superfamily (TNFSF), interleukin (IL)-related cytokines, and bone and extracellular matrix remodeling-related cytokines to determine their contributions in women with overt Graves' disease (GD).

METHODS
Forty-three women with GD were enrolled in this cross-sectional study. Thirty-seven cytokines, thyroid-stimulating hormone (TSH), free thyroxine, and TSH receptor antibody (TSHRAb) were quantified. GD patients with a low TSH level at the time of sample collection were defined as having active GD.

RESULTS
Patients with active GD had higher IFN-α2, IFN-γ, IFN-λ1, and IFN-λ2 levels than those with inactive GD. In addition, certain TNFSF cytokines, including soluble cluster of differentiation 30 (sCD30), TNFSF member 14 (TNFSF14), pentraxin (PTX)-3, soluble TNF receptor 2 (sTNF-R2), and thymic stromal lymphopoietin (TSLP) were higher in active GD than in inactive GD. Moreover, active GD patients had higher IL-2, IL-12(p40), osteocalcin (OCN), and matrix metalloproteinase (MMP)-3 than inactive GD patients. All IFNs except IFN-λ1 were correlated with TSHRAb titers. Moreover, TNFSF cytokines, consisting of B-cell-activating factor, sCD30, TNFSF14, PTX-3, sTNF-R2, and TSLP, were associated with TSHRAb levels.

CONCLUSIONS
Serum IFNs could be the most remarkable cytokines in modulating the disease severity and TSHRAb titers in women with full-blown GD. Further molecular-based research to clarify the actual role of IFNs in the disease progression of GD is needed.

Cheng|Chao-Wen|CW| Fang|Wen-Fang|WF| Tang|Kam-Tsun|KT| Lin|Jiunn-Diann|JD|

Thyroid-stimulating hormone receptor antibody


Quality of Life Experienced by Major Lower Extremity Amputees.

Abstract: Lower extremity amputations and diabetic foot-related complications in the Caribbean population have been previously reported. However, there is a lack of evidence that assess the quality of life experienced in such amputees. This study aimed to determine the health-related quality of life (HRQoL) in patients after a major lower limb amputation. Data collection was performed for all major lower limb amputations undertaken at a tertiary care institution in Trinidad and Tobago, between January 2012 to December 2016. The quality of life for patients who were accessible, alive, and willing to participate was assessed using the EuroQol 5D-5L tool. Statistical analysis was performed using the Mann-Whitney U and Kruskal-Wallis tests comparing medians across various subgroups. A total of 134 individuals were still alive and willing to participate in the study. The average EQ-5D-5L index value for the cohort was (0.598), which was significantly lower compared to EQ-5D-5L population norms for Trinidad and Tobago p < 0.05. Statistically significant differences were also seen in median EQ-5D-5L index value for patients who ambulated with a prosthesis (0.787) compared to those who used another device for mobilization (0.656), p < 0.05, and to those patients who did not ambulate (0.195), p < 0.05. A comparable Quality of life was seen between the level of amputation (transtibial versus transfemoral) and gender (males versus females), p-values were 0.21 and 1.0, respectively. Overall quality of life after major amputation, as well as independent mobilization with a prosthesis, continues to be problematic in the Caribbean population. Factors adversely related to the quality of life post major amputation include increasing age, problems related to mobility, and non-ambulatory patients.

Pran|Lemuel|L| Baijoo|Shanta|S| Harnanan|Dave|D| Slim|Hani|H| Maharaj|Ravi|R| Naraynsingh|Vijay|V|

quality of life
major lower limb amputation
prosthesis
trans-femoral amputation
trans-tibial amputation


Using existing questionnaires in latent class analysis: should we use summary scores or single items as input? A methodological study using a cohort of patients with low back pain.

Abstract:
BACKGROUND
Latent class analysis (LCA) is increasingly being used in health research, but optimal approaches to handling complex clinical data are unclear. One issue is that commonly used questionnaires are multidimensional, but expressed as summary scores. Using the example of low back pain (LBP), the aim of this study was to explore and descriptively compare the application of LCA when using questionnaire summary scores and when using single items to subgrouping of patients based on multidimensional data.

MATERIALS AND METHODS
Baseline data from 928 LBP patients in an observational study were classified into four health domains (psychology, pain, activity, and participation) using the World Health Organization's International Classification of Functioning, Disability, and Health framework. LCA was performed within each health domain using the strategies of summary-score and single-item analyses. The resulting subgroups were descriptively compared using statistical measures and clinical interpretability.

RESULTS
For each health domain, the preferred model solution ranged from five to seven subgroups for the summary-score strategy and seven to eight subgroups for the single-item strategy. There was considerable overlap between the results of the two strategies, indicating that they were reflecting the same underlying data structure. However, in three of the four health domains, the single-item strategy resulted in a more nuanced description, in terms of more subgroups and more distinct clinical characteristics.

CONCLUSION
In these data, application of both the summary-score strategy and the single-item strategy in the LCA subgrouping resulted in clinically interpretable subgroups, but the single-item strategy generally revealed more distinguishing characteristics. These results 1) warrant further analyses in other data sets to determine the consistency of this finding, and 2) warrant investigation in longitudinal data to test whether the finer detail provided by the single-item strategy results in improved prediction of outcomes and treatment response.

Nielsen|Anne Molgaard|AM|
Vach|Werner|W|
Kent|Peter|P|
Hestbaek|Lise|L|
Kongsted|Alice|A|

questionnaire
low back pain
subgrouping
classification
clinical interpretability
data mining


Cardiovascular disease and its management among Pacific people: a systematic review by ethnicity and place of birth.

Abstract:
BACKGROUND
Pacific people experience a disproportionate burden of cardiovascular disease (CVD), whether they remain in their country of origin or migrate to higher-income countries, such as Australia, Aotearoa New Zealand or the United States of America. We sought to determine whether the CVD health needs of Pacific people vary according to their ethnicity or place of birth.

METHODS
We conducted a systematic review of medical research databases and grey literature to identify relevant data published up to 2020. Texts were included if they contained original data stratified by Pacific-specific ethnicity or place of birth on the burden or management of CVD, and were assessed as having good quality using a National Heart, Lung, and Blood Institute quality assessment tool. The protocol for this review was registered with the Open Science Forum ( https://doi.org/10.17605/OSF.IO/X7NR6 ).

RESULTS
Of 3679 texts identified, 310 full texts were reviewed and the quality of 23 of these assessed, using the pre-defined search strategy. Six items (four reports, one article, one webpage) of good quality met the review eligibility criteria. All included texts provided data on epidemiology but only one reported on the management of CVD. Four texts were of Pacific populations in Pacific Island countries and two were of Pacific diaspora in other countries. Data from the Global Burden of Disease study, which provided estimates for the greatest number of Pacific countries, showed substantial differences in mortality rates between Pacific countries for every CVD type. For example, the mortality rate per 100,000 for ischemic heart disease (IHD) ranged from 103.41 in the Cook Islands to 430.35 in the Solomon Islands. A New Zealand-based report showed differences in CVD rates by Pacific ethnicity (e.g. the age-standardised prevalence of IHD per 1,000 population in Auckland ranged from 107.8 (Niuean) to 138 among Cook Islands Māori (p < 0.001)).

CONCLUSIONS
This review of published studies reveals that the epidemiology of CVD among Pacific people varies by specific ethnic groups, place of birth, and country of residence. There is a critical need for high-quality contemporary ethnic-specific Pacific data to respond to the diverse CVD health needs in these underrepresented groups.

Cardiovascular disease
Management
Pacific
Epidemiology
Atherosclerosis
Equity
Migrant


Factors associated with induced abortion over time: secondary data analysis of five waves of the Australian Longitudinal Study on Women's Health.

Abstract:
OBJECTIVE
A trend analysis of associations with induced abortion.

METHODS
Secondary analysis of the 1973/78 cohort of the Australian Longitudinal Study of Women's Health of women responding to two or more consecutive surveys out of five (N=9,042), using generalised estimating equations.

RESULTS
New abortions dropped from 7% to 2% at surveys 4 and 5. By survey 5, 16% of respondents reported abortions, only 2% of them new. Women aged in their twenties were more likely to terminate a pregnancy if they reported less-effective contraceptives (aOR2.18 CI 1.65-2.89); increased risky drinking (aOR1.65 CI 1.14-2.38); illicit drugs ≤12 months (aOR3.09 CI 2.28-4.19); or recent partner violence (aOR2.42 CI 1.61-3.64). By their thirties, women were more likely to terminate if they reported violence (aOR2.16 CI 1.31-3.56) or illicit drugs <12 months (aOR2.69 CI 1.77-4.09). Women aspiring to be fully- (OR1.58 CI 1.37-1.83) or self-employed (OR1.28 CI 1.04-1.57), with no children (OR1.41 CI 1.14-1.75) or further educated (OR 2.08 CI 1.68-2.57) were more likely to terminate than other women.

CONCLUSIONS
Abortion remains strongly associated with factors affecting women's control over reproductive health such as partner violence and illicit drug use. Implications for public health: Healthcare providers should inquire about partner violence and illicit drug use among women seeking abortion, support women experiencing harm and promote effective contraception.

Taft|Angela J|AJ|
Powell|Rhonda L|RL|
Watson|Lyndsey F|LF|
Lucke|Jayne C|JC|
Mazza|Danielle|D|
McNamee|Kathleen|K|

Australian Longitudinal Study of Women’s Health