Improved production of 1-deoxynojirymicin in Escherichia coli through metabolic engineering.

Abstract: Azasugars, such as 1-deoxynojirymicin (1-DNJ), are associated with diverse pharmaceutical applications, such as antidiabetic, anti-obesity, anti-HIV, and antitumor properties. Different azasugars have been isolated from diverse microbial and plant sources though complicated purification steps, or generated by costly chemical synthesis processes. But the biosynthesis of such potent molecules using Escherichia coli as a heterologous host provides a broader opportunity to access these molecules, particularly by utilizing synthetic biological, metabolic engineering, and process optimization approaches. This work used an integrated approach of synthetic biology, enzyme engineering, and pathway optimization for rational metabolic engineering, leading to the improved production of 1-DNJ. The production of 1-DNJ in recombinant E. coli culture broth was confirmed by enzymatic assays and mass spectrometric analysis. Specifically, the pathway engineering for its key precursor, fructose-6-phosphate, along with optimized media condition, results in the highest production levels. When combined, 1-DNJ production was extended to ~ 273 mg/L, which is the highest titer of production of 1-DNJ reported using E. coli.

D017485:1-Deoxynojirimycin
D001426:Bacterial Proteins
D053898:Biosynthetic Pathways
D003001:Cloning, Molecular
D003470:Culture Media
D004269:DNA, Bacterial
D004926:Escherichia coli
D005285:Fermentation
D005636:Fructosephosphates
D005798:Genes, Bacterial
D060847:Metabolic Engineering
D058615:Synthetic Biology

1-Deoxynojirymicin
Metabolic engineering
Azasugars
Pathway optimization


The global epidemiology of emerging Histoplasma species in recent years.

Abstract: Histoplasmosis is a serious infectious disease in humans caused by Histoplasma spp. (Onygenales), whose natural reservoirs are thought to be soil enriched with bird and bat guano. The true global burden of histoplasmosis is underestimated and frequently the pulmonary manifestations are misdiagnosed as tuberculosis. Molecular data on epidemiology of Histoplasma are still scarce, even though there is increasing recognition of histoplasmosis in recent years in areas distant from the traditional endemic regions in the Americas. We used multi-locus sequence data from protein coding loci (ADP-ribosylation factor, H antigen precursor, and delta-9 fatty acid desaturase), DNA barcoding (ITS1/2+5.8s), AFLP markers and mating type analysis to determine the genetic diversity, population structure and recognise the existence of different phylogenetic species among 436 isolates of Histoplasma obtained globally. Our study describes new phylogenetic species and the molecular characteristics of Histoplasma lineages causing outbreaks with a high number of severe outcomes in Northeast Brazil between 2011 and 2015. Genetic diversity levels provide evidence for recombination, common ancestry and clustering of Brazilian isolates at different geographic scales with the emergence of LAm C, a new genotype assigned to a separate population cluster in Northeast Brazil that exhibited low diversity indicative of isolation. The global survey revealed that the high genetic variability among Brazilian isolates along with the presence of divergent cryptic species and/or genotypes may support the hypothesis of Brazil being the center of dispersion of Histoplasma in South America, possibly with the contribution of migratory hosts such as birds and bats. Outside Brazil, the predominant species depends on the region. We confirm that histoplasmosis has significantly broadened its area of occurrence, an important feature of emerging pathogens. From a practical point of view, our data point to the emergence of histoplasmosis caused by a plethora of genotypes, and will enable epidemiological analysis focused on understanding the processes that lead to histoplasmosis. Further, the description of this diversity opens avenues for comparative genomic studies, which will allow progress toward a consensus taxonomy, improve understanding of the presence of hybrids in natural populations of medically relevant fungi, test reproductive barriers and to explore the significance of this variation.

de Souza Collares Maia Castelo-Branco|D|D|

Epidemiology
Histoplasmosis
Genetic diversity
Population structure
Emerging pathogens
Histoplasma capsulatum


Association of Adolescent- and Parent-Reported Relationship Functioning with HIV Sexual Risk Among Adolescents in Botswana.

Abstract: Globally, adolescents in sub-Saharan Africa are the youth most affected by HIV. Parent-adolescent relationships can be protective in child and adolescent development and may be implicated in lowered adolescent HIV sexual risk. However, the importance of parental and adolescent perceptions of their relationship and assessing the implications of family functioning in adolescents' risk for HIV or other sexually transmitted infections are not well established in the research literature. This dyadic study simultaneously assessed both parents' and adolescents' perceptions of family functioning and their relationships with adolescent sexual behaviors in Botswana. Seventy-two parent-adolescent dyads completed audio computer-assisted self-interview surveys. Surveys, independently completed by parents and their adolescent, assessed multiple indicators of their relationship and is the first such study in Botswana to collect the perspectives of both the parents and their adolescents. The results highlight significantly discrepant views of their relationships and revealed that the magnitude of those discrepancies was associated with greater adolescent HIV sexual risk behavior across multiple measures of family relationships. Parents' inaccurate perceptions of their adolescents' sexual activity were also associated with greater adolescent sexual risk. These findings elucidate the importance of improving parent-adolescent communications and relationships, which may subsequently assist in lowering adolescents' sexual risk for HIV and other negative sexual health outcomes.

HIV
Adolescent
Family functioning
Dyads
Parent–adolescent relationship


Feeding methods, sleep arrangement, and infant sleep patterns: a Chinese population-based study.

Abstract:
BACKGROUND
Findings from prior research into the effect of feeding methods on infant sleep are inconsistent. The objectives of this study were to examine infants' sleep patterns by feeding methods and sleep arrangement from birth to eight months old.

METHODS
This longitudinal cohort study enrolled 524 pregnant women at 34-41 weeks of gestation and their infants after delivery in 2006 and followed up until eight months postpartum. The study subjects were recruited from nine women and children hospitals in nine cities in China (Beijing, Chongqing, Wuhan, Changsha, Nanning, Xiamen, Xi'an, Jinan, and Hailin). Participating infants were followed up weekly during the first month and monthly from the second to the eighth month after birth. Twenty-four hour sleep diaries recording infants' sleeping and feeding methods were administered based on caregiver's self-report. Multivariable mixed growth curve models were fitted to estimate the effects of feeding methods and sleep arrangement on infants' sleep patterns over time, controlling for maternal and paternal age, maternal and paternal education level, household income, supplementation of complementary food, and infant birth weight and length.

RESULTS
Exclusively formula fed infants had the greatest sleep percentage/24 h, followed by exclusively breast milk fed infants and partially breast milk fed infants (P<0.01). Night waking followed a similar pattern. However, the differences in sleep percentage and night waking frequency between exclusively formula and exclusively breast milk fed infants weakened over time as infants developed. In addition, compared to infants with bed-sharing sleep arrangement, those with room sharing sleep arrangement had greater daytime and 24-hour infant sleep percentage, whereas those with sleeping alone sleep arrangement had greater nighttime sleep percentage.

CONCLUSIONS
Our data based on caregiver's self-report suggested that partial breastfeeding and bed-sharing may be associated with less sleep in infants. Health care professionals need to work with parents of newborns to develop coping strategies that will help prevent early weaning of breastfeeding.

Huang|Xiao-Na|XN| Wang|Hui-Shan|HS| Chang|Jen-Jen|JJ| Wang|Lin-Hong|LH| Liu|Xi-Cheng|XC| Jiang|Jing-Xiong|JX| An|Lin|L|

feeding method
sleep arrangement
infant sleep
breast feeding


Physiological levels of folic acid reveal purine alterations in Lesch-Nyhan disease.

Abstract: Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media. Thus, physiological levels of folic acid induce accumulation of 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP), an intermediary of de novo purine biosynthetic pathway, and depletion of ATP. Additionally, Z-nucleotide derivatives (AICAr, AICA) are detected at high levels in the urine of patients with LND and its variants (hypoxanthine-guanine phosphoribosyltransferase [HGprt]-related neurological dysfunction and HGprt-related hyperuricemia), and the ratio of AICAr/AICA is significantly increased in patients with neurological problems (LND and HGprt-related neurological dysfunction). Moreover, AICAr is present in the cerebrospinal fluid of patients with LND, but not in control individuals. We hypothesize that purine alterations detected in LND fibroblasts may also occur in the brain of patients with LND.

folic acid
purines
Lesch-Nyhan disease
ZMP
AICAr


Assessment of human telomeric G-quadruplex structures using surface-enhanced Raman spectroscopy.

Abstract: G-Quadruplex (G4) structures of a human telomeric 24-mer (5'-TTAGGGTTAGGGTTAGGGTTAGGG-3') sequence (Tel24) stabilized by sodium and potassium ions have been assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The distinctive SERS spectra of Tel24 in the presence of 100 mM Na+ and 100 mM K+ were obtained and the SERS bands characteristic of the antiparallel basket-type and the mixed hybrid (3+1) structures, respectively, were identified and assigned. The influence of the SERS - active substrate on the scattering enhancement was studied using citrate- and chloride-covered silver nanoparticles, in the absence and presence of the aggregating agent (0.1 M Na2SO4 and 0.1 M K2SO4). The highly reproducible SERS spectra of Tel24 obtained in various SERS active media indicated the same adsorption mechanism of the cation - stabilized G-quadruplexes onto the metal surface, regardless of the silver colloid. The remarkable resemblance between the circular dichroism (CD) spectra of the Tel24 structures with and without the colloid confirmed that interaction with the enhancing silver surface did not affect the stability of the formed G4 structures. The presented study pointed to a great potential of the SERS spectroscopy for the sensitive structural analysis of various G4 topologies. Graphical Abstract SERS spectroscopy allowed identification of Na+ stabilized antiparallel basket-type and K+ stabilized hybrid (3+1) structures of the same 24-mer human telomeric sequence.

Miljanić|Snežana|S| Ratkaj|Marina|M| Matković|Marija|M| Piantanida|Ivo|I| Gratteri|Paola|P| Bazzicalupi|Carla|C|

Human telomere
G-Quadruplex
Surface-enhanced Raman spectroscopy
Silver colloid
DNA structure


Novel fatty acid chain modified GLP-1 derivatives with prolonged in vivo glucose-lowering ability and balanced glucoregulatory activity.

Abstract: Glucagon-like peptide-1 is a potent hypoglycemic hormone with beneficial properties for the treatment of diabetes. However, its half-life is short because the rapid metabolic degradation. This study aims to prolong the half-life of glucagon-like peptide-1 through conjugation with the fatty acid side chain which helps the conjugates to interact with the albumin. Firstly, we chose two optimized polypeptide chains which have tremendous hypoglycemic effect named Cys17-Gly8-GLP-1(7-36)-NH2 and Cys37-Gly8-GLP-1(7-37)-NH2, and various fatty acid chains were modified. All conjugates preserved relatively strong GLP-1R activation and I-6 behaved best in glucose-lowering ability. The prolonged antidiabetic effects of I-6 were further confirmed by hypoglycemic efficacy test in vivo. Meanwhile, once daily injection of I-6 to diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. It is concluded that I-6 is a promising agent for further investigation of its potential to treat obese patients with diabetes.

Cai|Xingguang|X| Sun|Lidan|L| Dai|Yuxuan|Y| Avraham|Yosefa|Y| Liu|Chunxia|C| Han|Jing|J| Liu|Yuan|Y| Feng|Dazhi|D| Huang|Wenlong|W| Qian|Hai|H|


Selective weighting of cutaneous receptor feedback and associated balance impairments following short duration space flight.

Abstract: The present study investigated the perception of low frequency (3 Hz) vibration on the foot sole and its relationship to standing balance following short duration space flight in nine astronauts. Both 3 Hz vibration perception threshold (VPT) and standing balance measures increased on landing day compared to pre-flight. Contrary to our hypothesis, a positive linear relationship between these measures was not observed; however astronauts with the most sensitive skin (lowest 3 Hz VPT) were found to have the largest sway on landing day. While the change in foot sole sensitivity does not appear to directly relate to standing balance control, an exploratory strategy may be employed by astronauts whose threshold to pressure information is lower. Understanding sensory adaptations and balance control has implications to improve balance control strategies following space flight and in sensory impaired populations on earth.

Strzalkowski|Nicholas D J|ND|
Lowrey|Catherine R|CR|
Perry|Stephen D|SD|
Williams|David R|DR|
Wood|Scott J|SJ|
Bent|Leah R|LR|

Balance
Space flight
Foot sole
Skin
Tactile perception


Serum CD203c+ Extracellular Vesicle Serves as a Novel Diagnostic and Prognostic Biomarker for Succinylated Gelatin Induced Perioperative Hypersensitive Reaction.

Abstract:
Background
Perioperative hypersensitivity reaction (HR) is an IgE-FcϵRI-mediated hypersensitivity reaction with degranulation and activation of mast cells and basophils. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. However, it is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activation in vivo could potentially have high diagnostic and prognostic values. In the present study, we investigated EVs pelleted from serum in patients with succinylated gelatin induced HR.

Methods
Extracellular vesicles (EVs) were isolated using a total exosome isolation kit and ultracentrifugation, characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. Basophils were isolated from fresh peripheral blood by negative selection using Basophil Isolation Kit II. Human mast cell line was stimulated with IL4. The expression levels of proteins related to the hypersensitive response were evaluated by Western blotting and flow Cytometer. Histamine and tryptase levels were tested using a commercial ELISA kit, and gene expression of inflammatory mediators was evaluated by qRT-PCR. The receiver operating characteristic (ROC) curve was used to evaluate the specificity and sensitivity of biomarker in predicting HR.

Results
The concentration of EVs and protein expression level of CD63, FcϵRI, CD203c and tryptase were significantly (p< 0.05) increased in HR samples. The expression level of mast cell/basophil specific CD203c were significantly increased in EVs derived from serum and basophils of HR patients, and the CD203c+-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators. Moreover, the ROC curve of EVs concentration and CD203c expression indicated that CD203c+-EVs had a strong diagnostic ability for HR.

Conclusion
Serum CD203c+-EVs serves as a novel diagnostic and prognostic biomarker for HR.

Qi|Zheng|Z| Xue|Qiong|Q| Wang|Haitao|H| Cao|Bin|B| Su|Yu|Y| Xing|Qinghe|Q| Yang|Jian-Jun|JJ|

extracellular vesicle
biomarker
perioperative hypersensitive reaction
mast cells
basophils


Changes in T helper cell-related factors in patients with type 2 diabetes mellitus after empagliflozin therapy.

Abstract: The immune factors related to T helper (Th) 1 (T-bet, STAT1, and IFN-γ), Th17 (ROR-γt, STAT3, and IL-17), and Treg (FOXP3, STAT5, and IL-10) cells, and SOCS1/3 and the proliferation of Th cells were investigated in type 2 diabetes mellitus patients before (baseline) and after empagliflozin therapy. A total of 56 patients on metformin and gliclazide were separated into two groups: Group 1 did not receive empagliflozin (EMPA-) and the Group 2 received 10 mg/day of empagliflozin for 6 months (EMPA+). The expressions of T-bet, ROR-γt, FOXP3, STAT1/3/5 and SOCS1/3 were evaluated in CD4+ T cells with real-time PCR. The production of IFN-γ, IL-17, and IL-10 from CD4+ T cells was measured using ELISA. The proliferation of Th cells was assessed with flow cytometry. Six months of empagliflozin therapy significantly reduced the expression of ROR-γt and increased FOXP3 and STAT5 expression, compared to baseline. Production of IL-17 decreased after empagliflozin treatment, while IL-10 was enhanced in the EMPA+ group. Oral administration of empagliflozin or the addition of empagliflozin to the cell cultures diminished the proliferation of Th cells. Empagliflozin showed anti-inflammatory effects on Th cells by decreasing Th17-related factors, reducing proliferation capacity, and increasing Treg cell properties.

Borzouei|Shiva|S| Moghimi|Hamid|H| Zamani|Alireza|A| Behzad|Mahdi|M|

D057132:Nuclear Receptor Subfamily 1, Group F, Member 3

Type 2 diabetes mellitus
Empagliflozin
Cytokine
T helper cell


Abstract:
BACKGROUND
Attachment and intimacy play an important role in shaping sexual and relational experiences. Yet, their interrelation has rarely been investigated in the context of sexual problems and never been tested in Saudi Arabian women.

AIM
The present study examined the interrelations of attachment orientation and sexual function, distress, satisfaction, and relational satisfaction in a sample of Saudi Arabian women and explored whether this link can be explained by 2 important aspects of (sexual) intimacy, namely perceived partner responsiveness (PPR) and sexual assertiveness.

METHOD
This is a cross-sectional, observational study in a sample of 50 heterosexual women with sexual problems and 50 control women without problems, who completed an Arabic version of questionnaires on attachment orientation, sexual assertiveness, PPR, relationship satisfaction, sexual satisfaction, sexual distress, and sexual function.

RESULTS
We found that both attachment anxiety and sexual refusal showed a significant association with the level of sexual function, sexual distress, and sexual satisfaction (P < .01) in the clinical group. No mediating effects of sexual refusal were found. In the control group, sexual function, sexual distress, and sexual satisfaction were predicted by attachment avoidance (P < .01). Level of sexual function was also predicted by sexual initiation (P < .05). PPR fully mediated the association between attachment anxiety and relational satisfaction in the clinical group (P < .01), while in the control group the link between attachment avoidance and relational satisfaction was only partially mediated by PPR (P < .01).

STRENGTHS & LIMITATIONS
This study offers unique information on relational and sexual functioning in a culture in which sexual expression and intimate behavior are restricted, particularly in women.

CLINICAL IMPLICATIONS
Perceiving the partner as being more responsive is an important target of intervention to increase satisfaction with the relationship.

CONCLUSIONS
Our results suggest that attachment anxiety and low sexual assertiveness, as indicated by lower tendencies to refuse sex when not desired, play a significant role in predicting negative sexual experiences in women who cope with sexual difficulties. Attaky A, Kok G, Dewitte M. Attachment Insecurity and Sexual and Relational Experiences in Saudi Arabian Women: The Role of Perceived Partner Responsiveness and Sexual Assertiveness. J Sex Med 2020;17:1383-1394.

D001242:Assertiveness
D003430:Cross-Sectional Studies
D005260:Female
D006801:Humans
D007398:Interpersonal Relations
D010549:Personal Satisfaction
D012529:Saudi Arabia
D012725:Sexual Behavior
D012747:Sexual Partners
D011795:Surveys and Questionnaires

Attachment
Perceived Partner Responsiveness
Sexual Assertiveness
Sexual Function
Relationships
Interpersonal
Saudi Arabia


Does functional assessment predict everyday visual functioning? Visual function testing and quality of life in mild/moderate age-related macular degeneration.

Abstract:
PURPOSE
To prospectively assess correlations between self-reported vision-related quality of life (VR-QoL) and clinical functional assessments in mild/moderate age-related macular degeneration (AMD).

METHODS
Cross-sectional analysis of 64 participants with bilateral mild/moderate AMD. Microperimetry (MP), flicker perimetry (FP), multifocal electroretinogram (mfERG) findings, best-corrected visual acuity (BCVA) and the National Eye Institute Visual-Function Questionnaire-25 (NEI VFQ-25) were assessed for correlation between clinical testing results and NEI VFQ-25 findings.

RESULTS
MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p < 0.05 and R2 < 0.3 for all). FP findings and mfERG response density were not correlated with any subscale, apart from mfERG ring 1 response density and general health (p < 0.05, R2 = 0.41). mfERG latency was weakly correlated with general vision in the better eye in rings 2 and 4 (p < 0.05, R2 < 0.2).

CONCLUSION
Functional assessment in mild/moderate AMD is at best, weakly correlated with patient-reported VR-QoL. Despite the growing awareness of the importance of VR-QoL outcomes in improving patient outcomes and satisfaction, surrogate markers of these outcomes remain elusive, and testing of VR-QoL in regular clinical settings remains difficult.

Broadhead|Geoffrey K|GK|
Hong|Thomas|T|
Grigg|John R|JR|
McCluskey|Peter|P|
Schlub|Timothy E|TE|
Spooner|Kimberly|K|
Chang|Andrew A|AA|

D003430:Cross-Sectional Studies
D006801:Humans
D008268:Macular Degeneration
D011788:Quality of Life
D011795:Surveys and Questionnaires
D014792:Visual Acuity

Quality of life
Age-related macular degeneration
Perimetry
Visual function questionnaire-25


Haptoglobin phenotype modifies serum iron levels and the effect of smoking on Parkinson disease risk.

Abstract:
INTRODUCTION
Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk.

METHODS
The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk.

RESULTS
PD cases had lower serum iron than controls (83.28 ug/100 ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity.

CONCLUSIONS
Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated.

Costa-Mallen|Paola|P|
Zabetian|Cyrus P|CP|
Agarwal|Pinky|P|
Hu|Shu-Ching|SC|
Yearout|Dora|D|
Samii|Ali|A|
Leverenz|James B|JB|
Roberts|John W|JW|
Checkoway|Harvey|H|

Haptoglobin phenotype
Serum iron
Idiopathic Parkinson disease
Serum ferritin
Tobacco smoking


Fifteen Nanometer Resolved Patterns in Selective Area Atomic Layer Deposition-Defectivity Reduction by Monolayer Design.

Abstract: Selective area atomic layer deposition (SA-ALD) offers the potential to replace a lithography step and provide a significant advantage to mitigate pattern errors and relax design rules in semiconductor fabrication. One class of materials that shows promise to enable this selective deposition process are self-assembled monolayers (SAMs). In an effort to more completely understand the ability of these materials to function as barriers for ALD processes and their failure mechanism, a series of SAM derivatives were synthesized and their structure-property relationship explored. These materials incorporate different side group functionalities and were evaluated in the deposition of a sacrificial etch mask. Monolayers with weak supramolecular interactions between components (for example, van der Waals) were found to direct a selective deposition, though they exhibit significant defectivity at and below 100 nm feature sizes. The incorporation of stronger noncovalent supramolecular interacting groups in the monolayer design, such as hydrogen bonding units or pi-pi interactions, did not produce an added benefit over the weaker interacting components. Incorporation of reactive moieties in the monolayer component that enabled the polymerization of an SAM surface, however, provided a more effective barrier, greatly reducing the number and types of defects observed in the selectively deposited ALD film. These reactive monolayers enabled the selective deposition of a film with critical dimensions as low as 15 nm. It was also found that the selectively deposited film functioned as an effective barrier for isotropic etch chemistries, allowing the selective removal of a metal without affecting the surrounding surface. This work enables selective area ALD as a technology through (1) the development of a material that dramatically reduces defectivity and (2) the demonstrated use of the selectively deposited film as an etch mask and its subsequent removal under mild conditions.

atomic layer deposition
self-assembled monolayers
lithographic materials
photopolymerization
supramolecular chemistry


Significant variation in heart valve banking practice.

Abstract: The European Blood Alliance (EBA) Tissue and Cells annual benchmarking exercise identified that in 2014, the heart valve (HV) discard rate in tissue establishments (TEs) run by EBA members was between 19 and 65%. Given this significant discard rate, a decision was taken to carry out a worldwide data-gathering exercise to assess the processing methodology in different TEs. In collaboration with the Foundation of European Tissue Banks, a questionnaire asking for the details on HV processing was sent to TEs worldwide. Nineteen questionnaires were received back from 15 European TEs and 4 non-European TEs. The data provided confirmed a significant discard rate of HVs with 43-50% of aortic valves and 20-32% of pulmonary valves being discarded in 2015. The causes of HV discard varied, with microbiology contamination, anatomical and medical reasons being the main causes. This data-gathering exercise highlighted significant variations in practice in different TEs including how donor suitability is assessed, critical timings for heart retrieval and processing, heart rinsing, HV decontamination protocols and methods of microbiological testing. To reduce the discard rates, there are several aspects of HV banking that could be validated and standardised. Here, we report the findings of this data-gathering exercise. We consider this a first step that will help lead to standardising HV banking.

Heart valves
Discard
Microbiology
Transplantation


Caregivers' Perspectives of Quality of Life of People With Young- and Late-Onset Alzheimer Disease.

Abstract:
BACKGROUND
Quality of life (QoL) is a growing area of interest in dementia research. This study aims to investigate the caregivers' perspective about the QoL of people with young-onset Alzheimer disease (YOAD) and late-onset Alzheimer disease (LOAD). We also aim to investigate factors that might be associated to caregivers' perspective in YOAD and LOAD.

METHODS
We included 110 people with Alzheimer disease (PwAD; 53 YOAD) and their primary caregivers. The PwAD completed assessments about their QoL and cognition. The caregivers provided information about the PwAD (demographics, QoL, ability to perform activities of daily living, mood, and dementia severity) and had burden of care assessed.

RESULTS
We did not find a difference in caregivers' perspectives of PwAD QoL according to the age at onset. However, the linear regression analysis indicated that caregivers' burden ( P < .01) and PwAD depressive symptoms ( P < .05) were significantly related to the caregivers' perspective of YOAD QoL. Caregivers' burden ( P < .01), years of education ( P < .05), and self-reported QoL ( P < .01) were significantly related to the caregivers' perspective of LOAD QoL.

CONCLUSIONS
The factors that drive the perceptions of caregivers of PwAD QoL may vary according to the age at onset. The study provides basic information on caregivers' perspectives of PwAD QoL to create more effective interventions according to the age at onset.

Kimura|Nathália R S|NRS|
Baptista|Maria Alice T|MAT|
Santos|Raquel L|RL|
Portugal|Maria da Gloria|MDG|
Johannenssen|Aud|A|
Barca|Maria L|ML|
Engedal|Knut|K|
Laks|Jerson|J|
Simões|José Pedro|JP|
Rodrigues|Valeska Marinho|VM|
Dourado|Marcia C N|MCN|

D011569:Psychiatric Status Rating Scales

caregivers
quality of life
Alzheimer disease
depression
young onset


A rice ABC transporter, OsABCC1, reduces arsenic accumulation in the grain.

Abstract: Arsenic (As) is a chronic poison that causes severe skin lesions and cancer. Rice (Oryza sativa L.) is a major dietary source of As; therefore, reducing As accumulation in the rice grain and thereby diminishing the amount of As that enters the food chain is of critical importance. Here, we report that a member of the Oryza sativa C-type ATP-binding cassette (ABC) transporter (OsABCC) family, OsABCC1, is involved in the detoxification and reduction of As in rice grains. We found that OsABCC1 was expressed in many organs, including the roots, leaves, nodes, peduncle, and rachis. Expression was not affected when plants were exposed to low levels of As but was up-regulated in response to high levels of As. In both the basal nodes and upper nodes, which are connected to the panicle, OsABCC1 was localized to the phloem region of vascular bundles. Furthermore, OsABCC1 was localized to the tonoplast and conferred phytochelatin-dependent As resistance in yeast. Knockout of OsABCC1 in rice resulted in decreased tolerance to As, but did not affect cadmium toxicity. At the reproductive growth stage, the As content was higher in the nodes and in other tissues of wild-type rice than in those of OsABCC1 knockout mutants, but was significantly lower in the grain. Taken together, our results indicate that OsABCC1 limits As transport to the grains by sequestering As in the vacuoles of the phloem companion cells of the nodes in rice.

Song|Won-Yong|WY|
Yamaki|Tomohiro|T|
Yamaji|Naoki|N|
Ko|Donghwi|D|
Jung|Ki-Hong|KH|
Fujii-Kashino|Miho|M|
An|Gynheung|G|
Martinoia|Enrico|E|
Lee|Youngsook|Y|
Ma|Jian Feng|JF|

D018506:Gene Expression Regulation, Plant

rice
ABC transporter
arsenic
node
vacuolar sequestration


Uncertainty of Liver Cirrhosis Diagnosis and Use of Elastography.

Abstract: A case of severe jaundice in a patient with a long history of alcohol abuse led to a questionable diagnosis of liver cirrhosis. To determine its diagnostic utility in the setting of liver disease, elastography was utilized on our patient to confirm the clinically suspected diagnosis of cirrhosis. A 59-year-old male presented to our emergency department (ED) with two days of progressive jaundice and right upper quadrant (RUQ) pain. The patient admitted to drinking > 500 mL of vodka daily for the last seven years, with his last drink on the morning of admission. Physical exam revealed a man in mild acute distress with severe jaundice and an abdomen diffusely tender to palpation. Two spider angiomas were present on the torso along with caput medusae and mild asterixis. Labs revealed aspartate aminotransferase (AST) 408, alanine aminotransferase (ALT) 69, prothrombin time (PT) 16.3, partial thromboplastin time (PTT) 36, total bilirubin 22.6, and direct bilirubin 19.9 mg/dL. While admitted, total bilirubin rose as high as 31.5 mg/dL. Examination showed a Model for End-Stage Liver Disease (MELD) score of 22 and a Maddrey score of 37. Ultrasound revealed moderate hepatosplenomegaly with no signs of pancreatitis. Based on the patient's history of alcohol abuse paired with physical exam findings and elevated laboratory markers, we were able to diagnose with a high level of suspicion that this patient was suffering from chronic alcoholic liver disease, exacerbated by an acute episode of alcoholic hepatitis, which led to hepatic encephalopathy. Based on these findings, a diagnosis of liver cirrhosis was suspected; however, this diagnosis required further confirmation. We utilized ultrasound elastography to measure the velocity of shear wave transmission in the liver of our patient. A literature review was conducted on the use of elastography for the diagnosis of liver disease, and a significant correlation between the velocity of shear wave transmission and hepatic histological findings was identified. Elastography revealed a mean velocity of shear wave transmission of 1.77 m/s in our patient. This finding is consistent with a Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) score of F = 4, indicating significant fibrosis and confirming the suspected diagnosis of alcohol-induced liver cirrhosis. As a non-invasive and inexpensive diagnostic tool, elastography demonstrates significant potential for clinical utility in patients with liver disease. Clinicians may benefit from the use of elastography in diagnosis, while patients may receive both therapeutic and prognostic benefits secondary to its use. In similar cases with clinical uncertainty, elastography can reliably identify the presence of fibrous tissue in the liver without tissue biopsy, thus aiding in clinical diagnoses and enabling the use of optimal therapeutic regimens for future patients.

liver cirrhosis
cirrhosis diagnosis
elastography
jaundice
alcoholic cirrhosis
maddrey's discriminant function
meld score
severe alcoholic hepatitis


Convergence palsy secondary to amoxicillin.

Abstract:
CASE REPORT
We present the case of an 11-year-old boy with acute diplopia in near vision secondary to transient convergence palsy, possibly in relation to amoxicillin.

DISCUSSION
Convergence palsy is an uncommon eye disorder. The causes are reviewed, and amoxicilin is identified as presumptive etiologic agent. This is the first case reported.

Pérez-Roca|F|F|
Alfaro Juárez|A|A|
Sánchez Merino|C|C|
Navarro Mingorance|A|A|

Convergence palsy
Amoxicillin
Diplopia
Amoxicilina
Convergence disorders
Diplopía
Faringitis
Parálisis de la convergencia
Pharyngitis
Trastornos de la convergencia


The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity.

Abstract: The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1 mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1 mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6 mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation.

Kim|Yeha|Y|
Lim|Soyeon|S|
Ha|Taejeong|T|
Song|You-Hyang|YH|
Sohn|Young-In|YI|
Park|Dae-Jin|DJ|
Paik|Sun-Sook|SS|
Kim-Kaneyama|Joo-Ri|JR|
Song|Mi-Ryoung|MR|
Leung|Amanda|A|
Levine|Edward M|EM|
Kim|In-Beom|IB|
Goo|Yong Sook|YS|
Lee|Seung-Hee|SH|0000-0002-9486-5771
Kang|Kyung Hwa|KH|
Kim|Jin Woo|JW|0000-0003-0767-1918

D000221:Adaptation, Ocular
D000818:Animals
D003598:Cytoskeletal Proteins
D004268:DNA-Binding Proteins
D004742:Enhancer Elements, Genetic
D005786:Gene Expression Regulation
D060588:LIM Domain Proteins
D060850:LIM-Homeodomain Proteins
D051379:Mice
D018345:Mice, Knockout
D000071841:PAX6 Transcription Factor
D012160:Retina
D014157:Transcription Factors

visual adaptation
Pax6
mouse
retina
LIM domain protein
cell fate determination
chromosomes
genes
neuroscience


The HIV-1 integrase mutant R263A/K264A is 2-fold defective for TRN-SR2 binding and viral nuclear import.

Abstract: Transportin-SR2 (Tnpo3, TRN-SR2), a human karyopherin encoded by the TNPO3 gene, has been identified as a cellular cofactor of HIV-1 replication, specifically interacting with HIV-1 integrase (IN). Whether this interaction mediates the nuclear import of HIV remains controversial. We previously characterized the TRN-SR2 binding interface in IN and introduced mutations at these positions to corroborate the biological relevance of the interaction. The pleiotropic nature of IN mutations complicated the interpretation. Indeed, all previously tested IN interaction mutants also affected RT. Here we report on a virus with a pair of IN mutations, IN(R263A/K264A), that significantly reduce interaction with TRN-SR2. The virus retains wild-type reverse transcription activity but displays a block in nuclear import and integration, as measured by quantitative PCR. The defect in integration of this mutant resulted in a smaller increase in the number of two-long terminal repeat circles than for virus specifically blocked at integration by raltegravir or catalytic site mutations (IN(D64N/D116N/E152Q)). Finally, using an eGFP-IN-labeled HIV fluorescence-based import assay, the defect in nuclear import was corroborated. These data altogether underscore the importance of the HIV-IN TRN-SR2 protein-protein interaction for HIV nuclear import and validate the IN/TRN-SR2 interaction interface as a promising target for future antiviral therapy.

De Houwer|Stéphanie|S|
Demeulemeester|Jonas|J|
Thys|Wannes|W|
Rocha|Susana|S|
Dirix|Lieve|L|
Gijsbers|Rik|R|
Christ|Frauke|F|
Debyser|Zeger|Z|

D021581:Active Transport, Cell Nucleus
D001665:Binding Sites
D001667:Binding, Competitive
D015153:Blotting, Western
D002467:Cell Nucleus
D019427:HIV Integrase
D015497:HIV-1
D006367:HeLa Cells
D006801:Humans
D008958:Models, Molecular
D050505:Mutant Proteins
D009154:Mutation
D011485:Protein Binding
D017434:Protein Structure, Tertiary
D014779:Virus Replication
D028961:beta Karyopherins

TRN-SR2
Nuclear Import
TNPO3
HIV Integrase
HIV-1 Protease
Human Immunodeficiency Virus (HIV)
Nuclear Transport
Transportin-3
Viral Replication


Lack of a significant pharmacokinetic interaction between maraviroc and tacrolimus in allogeneic HSCT recipients.

Abstract:
OBJECTIVES
Emerging data suggest that the combination of tacrolimus and the CCR5 antagonist maraviroc, both cytochrome P450-3A4 substrates, may be effective in preventing graft-versus-host disease in patients undergoing allogeneic HSCT. This study evaluated whether a pharmacokinetic interaction exists between these agents.

METHODS
The study included 36 allogeneic HSCT recipients who received maraviroc + tacrolimus and 43 recipients of tacrolimus alone. We used a difference-in-differences analysis to examine the change in the concentration/dose ratios of tacrolimus after the discontinuation of maraviroc. In addition, we analysed the concentrations and dose requirements of tacrolimus in the two groups.

RESULTS
There was no significant difference in tacrolimus concentration/dose ratios in patients receiving maraviroc + tacrolimus compared with tacrolimus alone. Upon discontinuation of maraviroc, the change in concentration/dose ratio was small and not significant relative to the control group, and the effect estimate was further attenuated after adjustment for confounders [-0.35 (ng/mL)/(mg/day); P = 0.46]. In addition, the change in mean tacrolimus dose after discontinuation of maraviroc was similar between the groups (0.12 mg/day; P = 0.56), as was the change in mean tacrolimus concentration (0.02 ng/mL; P = 0.97).

CONCLUSIONS
Our findings do not support a significant inhibitory effect of maraviroc on the metabolism of tacrolimus. These data demonstrate that this drug combination is safe and imply that the protective effect of maraviroc against graft-versus-host disease was not mediated through an increase in tacrolimus concentrations. These findings are important for the design of clinical trials that evaluate maraviroc in combination with cytochrome P450-3A4 substrates.

Ganetsky|Alex|A|
Miano|Todd A|TA|
Hughes|Mitchell E|ME|
Vonderheide|Robert H|RH|
Porter|David L|DL|
Reshef|Ran|R|

D018380:Hematopoietic Stem Cell Transplantation

chemokine receptors
immunosuppression
pharmacology
transplantation


Serological biomarkers for monitoring response to treatment of pulmonary and extrapulmonary tuberculosis in children and adolescents.

Abstract: Key measures to halt the spread of tuberculosis (TB) include early diagnosis, effective treatment, and monitoring disease management. We sought to evaluate the use of serum immunoglobulin levels against antigens present in cell envelope of Mycobacterium tuberculosis to monitor TB treatment response in children and adolescents with pulmonary (PTB) or extrapulmonary TB (EPTB). Blood samples were collected prior to and one, two, and six months following treatment initiation. Serum immunoglobulin levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein were measured by ELISA. Serum from 53 TB patients and 12 healthy participants were analyzed. After six months of successful treatment, there was a significant decrease (p < 0.0001) in IgM levels against cardiolipin, sulfatide, mycolic acid and Mce1A protein and IgG levels against Mce1A protein when compared to baseline immunoglobulin levels. There was no significant variation in antibody levels during follow-up between participants with PTB and EPTB, confirmed and unconfirmed TB diagnosis, and HIV infection status. Antibody levels in control participants without TB did not decrease during follow-up. These results suggest that immunoglobulin responses to mycobacterial cell wall products may be a useful tool to monitor treatment response in children and adolescents with PTB or EPTB.

Dos Santos|Danielle C M|DCM|
Lovero|Kathryn L|KL|
Schmidt|Christiane M|CM|
Barros|Ana Cláudia M W|ACMW|
Quintanilha|Ana Paula|AP|
Barbosa|Ana Paula|AP|
Pone|Marcos V S|MVS|
Pone|Sheila M|SM|
Araujo|Julienne Martins|JM|
de Paula Martins|Camila|C|
Cosme|Estela Magalhães|EM|
Dourado de Oliveira|Thais Raquelly|TR|
Miceli|Ana Lúcia|AL|
Vieira|Maria Luíza|ML|
Queiroz|Adriano|A|
Coca Velarde|Luis Guillermo|LG|
Kritski|Afranio|A|
de Fátima Pombo March|Maria|M|
Maria de Azevedo Sias|Selma|S|
SantÀAnna|Clemax C|CC|
Riley|Lee W|LW|
Araújo Cardoso|Claudete A|CA|

Biomarkers Monitoring Treatment Tuberculosis Pediatric


Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities.

Abstract: The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NM on ILCs and other components of the serosal immune system are scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NM may lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NM on the serosal immune system.

FALC
MS
SALC
innate lymphocytes
pericardium
peritoneum
pleura
serosa


A bacterial genotoxin causes virus reactivation and genomic instability in Epstein-Barr virus infected epithelial cells pointing to a role of co-infection in viral oncogenesis.

Abstract: We have addressed the role of bacterial co-infection in viral oncogenesis using as model Epstein-Barr virus (EBV), a human herpesvirus that causes lymphoid malignancies and epithelial cancers. Infection of EBV carrying epithelial cells with the common oral pathogenic Gram-negative bacterium Aggregatibacter actinomycetemcomitans (Aa) triggered reactivation of the productive virus cycle. Using isogenic Aa strains that differ in the production of the cytolethal distending toxin (CDT) and purified catalytically active or inactive toxin, we found that the CDT acts via induction of DNA double strand breaks and activation of the Ataxia Telangectasia Mutated (ATM) kinase. Exposure of EBV-negative epithelial cells to the virus in the presence of sub-lethal doses of CDT was accompanied by the accumulation of latently infected cells exhibiting multiple signs of genomic instability. These findings illustrate a scenario where co-infection with certain bacterial species may favor the establishment of a microenvironment conducive to the EBV-induced malignant transformation of epithelial cells.

Frisan|Teresa|T|0000-0002-1209-0942
Nagy|Noemi|N|
Chioureas|Dimitrios|D|
Terol|Marie|M|
Grasso|Francesca|F|
Masucci|Maria G|MG|0000-0002-5541-2809

virus reactivation
Epstein-Barr virus
cytolethal distending toxin
DNA damage
Gram-negative bacteria


Reduced esophageal heating in high-power short-duration atrial fibrillation ablation in the contact force catheter era.

Abstract: Atrial fibrillation (AF) ablation is alternative treatment to medical therapy. Most feared complication is atrioesophageal fistula METHODS: Observational, retrospective analysis of consecutive 355 patients undergoing first AF ablation. Low-power long-duration (LPLD) group contained 158 patients, with 121 (76.58%) having paroxysmal AF who underwent ablation with power 20/30W (anterior and posterior left atrial wall), 17 mL/min flow, and a contact force of 10-30 g for 30 s. High-power short-duration group (HPSD) contained 197 patients, with 113 (57.36%) having paroxysmal AF who underwent ablation at 45/50W of power with a contact force of 8-15 g/10-20 g and a 35 mL/min flow rate for 6-8 s on the anterior and the posterior left atrial wall, respectively. Both groups had pulmonary veins isolated and atrial flutter was ablated when needed. For patients not in sinus rhythm, cardioversion was performed before ablation RESULTS: There were no complications. LPLD group: Left atrial time 118.74 min, total 145.32 min, radiofrequency time 4317.99s, X-ray 13.42 min, and elevation of luminal esophageal temperature (LET) in 132 (84.53%) patients. HPSD group: Left atrial time 72.16 min, total 93.76 min, radiofrequency time 1511.29s, X-ray 7.6 min, and LET elevation in only 75 (38.07%) patients. A markedly higher rate of first-pass isolation was observed in HPSD compared to LPLD, 77.16% versus 13.29%, respectively. Recurrence occurred in 64 (40.50%) and 32 (16.24%) in 28.45 and 22.35 months in LPLD and HPSD patients, respectively. In LPLD, 10 patients were submitted to endoscopy, and one (10%) had mild erythema and in HPSD, 13 performed the endoscopy, with two (15.38%) patients showing mild erythema CONCLUSION: HPSD technique compared to the LPLD technique showed significant reduced radiofrequency and fluoroscopy times, higher rate of first-pass isolation, lower recurrence rate, and esophageal temperature elevation and may also have a protective effect avoiding incidental esophageal injury due to these findings.

esophageal temperature and high-power short-duration


Key findings to expedite the diagnosis of hyper-IgE syndromes in infants and young children.

Abstract:
BACKGROUND
Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8.

METHODS
Here, we assess the clinical and immunologic phenotype of DOCK8- and STAT3-HIES patients including the cell activation, proliferation, and cytokine release after stimulation.

RESULTS
Existing HIES scoring systems are helpful to identify HIES patients. However, those scores may fail in infants and young children due to the age-related lack of clinical symptoms. Furthermore, our long-term observations showed a striking variation of laboratory results over time in the individual patient. Reduced memory B-cell counts in concert with low specific antibody production are the most consistent findings likely contributing to the high susceptibility to bacterial and fungal infection. In DOCK8-HIES, T-cell lymphopenia and low IFN-gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT3-HIES, DOCK8-HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers (HLA-DR, CD69, CD86, and CD154), and significantly increased inflammatory cytokines (IL1-beta, IL4, IL6, and IFN-gamma).

CONCLUSION
Differentiating HIES from other diseases such as atopic dermatitis early in life is essential for patients because treatment modalities differ. To expedite the diagnosis process, we propose here a diagnostic workflow.

Hagl|Beate|B|
Heinz|Valerie|V|
Schlesinger|Anne|A|
Spielberger|Benedikt D|BD|
Sawalle-Belohradsky|Julie|J|
Senn-Rauh|Monika|M|
Magg|Thomas|T|
Boos|Annette C|AC|
Hönig|Manfred|M|
Schwarz|Klaus|K|
Dückers|Gregor|G|
von Bernuth|Horst|H|
Pache|Christoph|C|
Karitnig-Weiss|Cäcilia|C|
Belohradsky|Bernd H|BH|
Frank|Josef|J|
Niehues|Tim|T|
Wahn|Volker|V|
Albert|Michael H|MH|
Wollenberg|Andreas|A|
Jansson|Annette F|AF|
Renner|Ellen D|ED|

D020662:Guanine Nucleotide Exchange Factors

signal transducer and activator of transcription 3


Fluctuating Dental Arch Asymmetry in Different Malocclusion Groups.

Abstract:
Objective
To compare the degree of dental arch fluctuating asymmetry (FA) among patients with Class I, II, and III malocclusions.

Subjects and methods
The sample comprised randomly selected plaster casts of 131 patients: 39 Class I (19 males and 20 females), 57 Class II (23 males and 34 females), and 35 Class III (20 males and 15 females). Dental models were scanned and digitized using ATOS II SO. The measurements of the teeth and dental arches were taken using the ATOS viewer version 6.A.2 software. Six arch widths and five arch depths were measured. The FA was assessed as a composite index of total weighted asymmetry (TWA). The analysis of variance was used to determine whether there were any statistically significant differences between the groups.

Results
Composite TWA measures of fluctuating asymmetry for dental arch variables were the highest in Class III, and lowest in Class I malocclusion. Males displayed a higher degree of asymmetry than females. The asymmetry degree was higher in the mandibular dental arches than in the maxillary dental arches in all malocclusion groups.

Conclusion
The TWA values were low but they differed significantly between the groups of malocclusion. Class III malocclusion displayed higher FA values than Class I and Class II malocclusion. Higher FA of dental arches in Angle's Class III can be considered an indicator of increased developmental instability in this malocclusion due to high levels of genetic and environmental stress during the period of early development.

Dental Arch
Malocclusion
Facial Asymmetry


Comparison of Hepatic Transporter Tissue Expression in Rodents and Interspecies Hepatic OCT1 Activity.

Abstract: Hepatic clearance may be uptake rate limited by organic anion transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1). While comparison of OATP activity has been investigated across species, little has been reported for OCT1. Additionally, while data on interspecies transporter expression in the liver exist, quantitative comparison of these transporters in multiple tissues is lacking. In the current research, the pharmacokinetics of OCT1 substrates (sumatriptan and metformin) were assessed in Oct knockout rats for comparison with previous Oct1/2-/- mice data and OCT1 pharmacogenetics in humans. Effect of OCT1 inhibitors verapamil and erlotinib on OCT1 substrate liver partitioning was also evaluated in rats. Expression of 18 transporters, including Oatps and Octs, in 9 tissues from mice and rats was quantitated using nanoLC/MS-MS, along with uptake transporters in hepatocytes from 5 species. Interspecies differences in OCT1 activity were further evaluated via uptake of OCT1 substrates in hepatocytes with corresponding in vivo liver partitioning in rodents and monkey. In Oct1-/- rats, sumatriptan hepatic clearance and liver partitioning decreased; however, metformin pharmacokinetics were unaffected. OCT1 inhibitor coadministration decreased sumatriptan liver partitioning. In rodents, Oatp expression was highest in the liver, although comparable expression of Oatps in other tissues was determined. Expression of Octs was highest in the kidney, with liver Oct1 expression comparably lower than Oatps. Liver partitioning of OCT1 substrates was lower in rodents than in monkey, in agreement with the highest OCT1 expression and uptake of OCT1 substrates in monkey hepatocytes. Species-dependent OCT1 activity requires consideration when translating preclinical data to the clinic.

Morse|Bridget L|BL|
Fallon|John K|JK|
Kolur|Anil|A|
Hogan|Andrew T|AT|
Smith|Philip C|PC|
Hillgren|Kathleen M|KM|

organic anion transporting polypeptide
organic cation transporter
pharmacokinetics
Liver partitioning
liver transporters
targeted proteomics


Patient misconceptions concerning lumbar spondylosis diagnosis and treatment.

Abstract: OBJECT Patient outcome measures are becoming increasingly important in the evaluation of health care quality and physician performance. Of the many novel measures currently being explored, patient satisfaction and other subjective measures of patient experience are among the most heavily weighted. However, these subjective measures are strongly influenced by a number of factors, including patient demographics, level of understanding of the disorder and its treatment, and patient expectations. In the present study, patients referred to a neurosurgery clinic for degenerative spinal disorders were surveyed to determine their understanding of lumbar spondylosis diagnosis and treatment. METHODS A multiple-choice, 6-question survey was distributed to all patients referred to a general neurosurgical spine clinic at a tertiary care center over a period of 11 months as a quality improvement initiative to assist the provider with individualized patient counseling. The survey consisted of questions designed to assess patient understanding of the role of radiological imaging in the diagnosis and treatment of low-back and leg pain, and patient perception of the indications for surgical compared with conservative management. Demographic data were also collected. RESULTS A total of 121 surveys were included in the analysis. More than 50% of the patients indicated that they would undergo spine surgery based on abnormalities found on MRI, even without symptoms; more than 40% of patients indicated the same for plain radiographs. Similarly, a large proportion of patients (33%) believed that back surgery was more effective than physical therapy in the treatment of back pain without leg pain. Nearly one-fifth of the survey group (17%) also believed that back injections were riskier than back surgery. There were no significant differences in survey responses among patients with a previous history of spine surgery compared with those without previous spine surgery. CONCLUSIONS These results show that a surprisingly high percentage of patients have misconceptions regarding the diagnosis and treatment of lumbar spondylosis, and that these misconceptions persist in patients with a history of spine surgery. Specifically, patients overemphasize the value of radiological studies and have mixed perceptions of the relative risk and effectiveness of surgical intervention compared with more conservative management. These misconceptions have the potential to alter patient expectations and decrease satisfaction, which could negatively impact patient outcomes and subjective valuations of physician performance. While these results are preliminary, they highlight a need for improved communication and patient education during surgical consultation for lumbar spondylosis.

Franz|Eric W|EW|
Bentley|J Nicole|JN|
Yee|Patricia P S|PP|
Chang|Kate W C|KW|
Kendall-Thomas|Jennifer|J|
Park|Paul|P|
Yang|Lynda J S|LJ|

D010342:Patient Acceptance of Health Care

misconceptions
lumbar spondylosis
patient satisfaction
patient expectations
back pain


The effect of intraoperative autofluorescence monitoring on unintentional parathyroid gland excision rates and postoperative PTH concentrations-a single-blind randomized-controlled trial.

Abstract:
PURPOSE
Intraoperative imaging of parathyroid glands (PGs) has been developed in order to reduce the risk of unintentional parathyroidectomy during total thyroidectomy. This novel modality is based on their intrinsic characteristic of autofluorescence (AF) after near-infrared light exposure. The aim of this study was to assess the effect of this method on the risk of unintentional PG excision (total or partial) during total thyroidectomy.

METHODS
This was a single-blind, randomized-controlled trial including adult patients who underwent scheduled total thyroidectomy between December 2019 and March 2020. These patients were randomly allocated to two groups: one in which near-infrared autofluorescence imaging (NIRAF) was applied (NIR group) and one without NIRAF (NONIR group). Hormonal and biochemical assessment was performed pre- and 24-h postoperatively. AF findings and the number of PGs autotransplanted were recorded.

RESULTS
One-hundred and eighty patients were eligible. Unintentional (total or partial) PG excision rates during total thyroidectomy in the NONIR (n = 90) and NIR (n = 90) groups were 28.9% [95% confidence interval (CI) 19.8-39.4%] and 14.4% (95% CI 7.7-22.1%), respectively (p = 0.02). Furthermore, NIR reduced the risk of parathyroid tissue presence in the specimen sent for pathology (relative risk 0.51, 95% CI 0.28-0.92; p = 0.02). However, the number of PGs identified by NIR could not predict the risk of postoperative hypoparthyroidism.

CONCLUSIONS
NIRAF imaging during total thyroidectomy led to a significant reduction in PG excision rates. However, this modality did not result in the reduction of postoperative hypoparathyroidism or hypocalcemia risk.

Autofluorescence
Parathyroid glands
Unintentional parathyroidectomy
Total thyroidectomy


Relationship of molecular weight distribution profile of unreduced gluten protein extracts with quality characteristics of bread.

Abstract: A statistical correlation was established among the molecular weight distribution patterns of unreduced gluten proteins and physicochemical, rheological and bread-making quality characteristics of wheat varieties. Size exclusion chromatography fractionated the gluten proteins apparently into five peaks. Peak I signified glutenins (30-130kDa), peak II as gliadins (20-55kDa), peak III as very low molecular weight monomeric gliadins (10-28kDa), peak IV and V, collectively, as albumins and globulins (<10kDa). Peaks I and II had appreciable effects on dough development time (r=0.830(∗∗) and r=-0.930(∗∗)) and dough stability (r=0.901(∗∗) and r=-0.979(∗∗)). Peak I was associated with R/E ratio (r=0.745(∗∗)), gluten index (r=0.959(∗∗)), and gliadin/glutenin ratio (r=-0.952(∗∗)), while peak II influenced inversely as expected. Peak I exhibited positive statistical significance with bread loaf volume (r=0.848(∗∗)); however, peak II had negative (r=-0.818(∗∗)) impact. Bread firmness increased with increment in peak II (r=0.625(∗∗)), and decreased with accretion in peak I (r=-0.623(∗∗)).

Chaudhary|Nisha|N|
Dangi|Priya|P|
Khatkar|B S|BS|

Molecular weight distribution
Size exclusion chromatography
Glutenins
Gliadins
Bread quality
Dough rheology


A Comprehensive Lifestyle Randomized Clinical Trial: Design and Initial Patient Experience.

Abstract:
BACKGROUND
Although epidemiological research demonstrates that there is an association between lifestyle factors and risk of breast cancer recurrence, progression of disease, and mortality, no comprehensive lifestyle change clinical trials have been conducted to determine if changing multiple risk factors leads to changes in biobehavioral processes and clinical outcomes in women with breast cancer. This article describes the design, feasibility, adherence to the intervention and data collection, and patient experience of a comprehensive lifestyle change clinical trial (CompLife).

METHODS
CompLife is a randomized, controlled trial of a multiple-behavior intervention focusing on diet, exercise, and mind-body practice along with behavioral counseling to support change. The initial exposure to the intervention takes place during the 4 to 6 weeks of radiotherapy (XRT) for women with stage III breast cancer and then across the subsequent 12 months. The intervention group will have 42 hours of in-person lifestyle counseling during XRT (7-10 hours a week) followed by up to 30 hours of counseling via video connection for the subsequent 12 months (weekly sessions for 6 months and then monthly for 6 months). The primary outcome is disease-free survival. Multiple secondary outcomes are being evaluated, including: (1) biological pathways; (2) overall survival; (3) patient-reported outcomes; (4) dietary patterns/fitness levels, anthropometrics, and body composition; and (5) economic outcomes. Qualitative data of the patient experience in the trial is collected from exit interviews, concluding remarks, direct email correspondences, and web postings from patients.

RESULTS
Fifty-five patients have been recruited and randomized to the trial to date. Accrual of eligible patients is high (72%) and dropout rates extremely low (5%). Attendance to the in-person sessions is high (95% attending greater than 80% of sessions) as well as to the 30 hours of video counseling (88% attending more than 70% of sessions). Adherence to components of the behavior change intervention is high and compliance with the intensive amount of data collection is exceptional. Qualitative data collected from the participants reveals testimonials supporting the importance of the comprehensive nature of intervention, especially the mind-body/mindfulness component and social support, and meaningful lifestyle transformations.

CONCLUSION
Conducting a comprehensive, multicomponent, lifestyle change clinical trial for women with breast was feasible and collection of biobehavioral outcomes successful. Adherence to behavior change was high and patient experience was overwhelmingly positive.

Arun|Banu|B|
Austin|Taylor|T|
Babiera|Gildy V|GV|
Basen-Engquist|Karen|K|
Carmack|Cindy L|CL|
Chaoul|Alejandro|A|
Cohen|Lorenzo|L|
Connelly|Lisa|L|
Haddad|Robin|R|
Harrison|Carol|C|
Li|Yisheng|Y|
Mallaiah|Smitha|S|
Nagarathna|Raghuram|R|
Parker|Patricia A|PA|
Perkins|George H|GH|
Reuben|James M|JM|
Shih|Ya-Chen Tina|YT|
Spelman|Amy|A|
Sood|Anil|A|
Yang|Peiying|P|
Yeung|Sai-Ching J|SJ|

comprehensive lifestyle patient experience breast cancer integrative


Genome-Wide Analysis of NF-Y Genes in Potato and Functional Identification of StNF-YC9 in Drought Tolerance.

Abstract: The nuclear factor Y (NF-Y) family is comprised of transcription factors that have been implicated in multiple plant biological processes. However, little is known about this family in potato. In the present study, a total of 41 StNF-Y genes were identified in the potato genome. In addition, the phylogenetic, gene structure, motif, and chromosomal location of this family were analyzed. The tissue expression profiles based on RNA-seq data showed that 27 StNF-Y genes had tissue-specific expression, while the remaining 14 had low expression in all tissues. Publicly available transcriptomics data from various abiotic stresses revealed several stress-responsive StNF-Y genes, which were further verified via quantitative real-time polymerase chain reaction experiments. Furthermore, the StNF-YC9 gene was highly induced by dehydration and drought treatments. StNF-YC9 protein was mainly localized in the nucleus and cytoplasmic membrane. Overexpressing StNF-YC9 potato lines (OxStNF-YC9) had significantly increased in root length and exhibited stronger stomatal closure in potato treated by polyethylene-glycol and abscisic acid. In addition, OxStNF-YC9 lines had higher photosynthetic rates and decreased water loss under short-term drought stress compared to wild-type plants. During long-term drought stress, OxStNF-YC9 lines had higher proline levels, lower malondialdehyde content, and increased activity of several antioxidant enzymes, including superoxide dismutase, catalase, and peroxidase. This study increased our understanding of the StNF-Y gene and suggested that StNF-YC9 played an important role in drought tolerance by increased the photosynthesis rate, antioxidant enzyme activity, and proline accumulation coupled to lowered malondialdehyde accumulation in potato.

Li|Shigui|S| Zhang|Ning|N| Zhu|Xi|X| Ma|Rui|R| Liu|Shengyan|S| Wang|Xiao|X| Yang|Jiangwei|J| Si|Huaijun|H|

potato
drought tolerance
abiotic stresses
root length
NF-Y transcription factor
bioinformatics
stomata closure


Molecular Mechanisms and Tumor Biological Aspects of 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells.

Abstract: 5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116RF10. HCT116RF10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116RF10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116RF10 cells. Interestingly, HCT116RF10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.

D015972:Gene Expression Regulation, Neoplastic

5-Fluorouracil
colorectal cancer cells
thymidylate synthase
drug resistance
exome sequencing


Joint statistics matching for camera model identification of recompressed images.

Abstract: Source camera identification has been well studied in laboratory environment where the training and test samples are all original images without recompression. However, image compression is quite common in the real world, when the training and test images are double JPEG compressed with different quantization tables, the identification accuracy of existing methods decreases dramati- cally. To address this challenge, we propose a novel iterative algorithm namely joint first and second order statistics matching (JSM) to learn a feature projection that projects the training and test fea- tures into a low dimensional subspace to reduce the shift caused by image recompression. Inspired by transfer learning, JSM aims to learn a new feature representation from original feature space by simultaneously matching the first and second order statistics between training and test features in a principled dimensionality reduction procedure. After the feature projection, the divergence between training and test features caused by recompression is reduced while the discriminative properties are preserved. Extensive experiments on public Dresden Image Database verify that JSM significantly outperforms several state-of-the-art methods on camera model identification of recompressed images.

Wang|Bo|B|
Li|Ya Bin|YB|
Sui|Xue|X|
Li|Ming|M|
Guo|Yan Qing|YQ|

camera model identification
recompressed images
double JPEG compression
transfer learning
image forensics


Understanding the sheet size-antibacterial activity relationship of graphene oxide and the nano-bio interaction-based physical mechanisms.

Abstract: The antibiotics-independent antimicrobial activity of graphene oxide (GO) is of great importance since antibiotic therapy is facing great challenges from drug resistance. However, the relations of GO size with its antimicrobial activity and how the size regulates the antibacterial mechanisms are still unknown. Herein, we fabricated four GO suspensions with different sizes and demonstrated the parabolic relationship between GO size and its antibacterial activity against the Gram-positive cariogenic bacterium Streptococcus mutans. More interestingly, we found out how GO size regulated the nano-bio interaction-based physical antibacterial mechanisms. Increasing the size reduced the cutting effect but enhanced the cell entrapment effect, and vice versa. In conclusion, GO size affects its edge density and lateral dimension, further regulates its physical antibacterial mechanisms in different orientations and ultimately determines its activity. These findings provide a deep understanding of GO antibacterial property and may guide the design and development of GO for clinical use.

Yu|Chen-Hao|CH| Chen|Ge-Yun|GY| Xia|Meng-Ying|MY| Xie|Yu|Y| Chi|Ya-Qi|YQ| He|Zhi-Yao|ZY| Zhang|Chao-Liang|CL| Zhang|Ting|T| Chen|Qian-Ming|QM| Peng|Qiang|Q|

D000900:Anti-Bacterial Agents
D006108:Graphite
D008826:Microbial Sensitivity Tests
D053758:Nanoparticles
D010316:Particle Size
D013295:Streptococcus mutans
D013499:Surface Properties

Graphene
Antimicrobial
Bacteria
Dental caries
Infection
Nanomaterials


Sorption behaviors of antimicrobial and antiparasitic veterinary drugs on subtropical soils.

Abstract: Brazil is one of the world's largest producers of animal protein, requiring the large-scale use of veterinary drugs. The administration of antimicrobials and antiparasitics is a common practice. However, there is a lack of information on how these drugs impact the environment. Antimicrobials are capable of altering the soil microbial population and are responsible for the development of multidrug-resistant microbial strains. Therefore, it is important to evaluate the fate and transport of these compounds in the environment, and one parameter used for this purpose is the soil-water partition coefficient. In this work, an assessment was made of the soil sorption behaviors of 18 drugs from seven different families, including antimicrobials (sulfonamides, fluoroquinolones, amphenicols, and macrolides) and antiparasitic drugs (milbemycin, avermectins, and benzimidazoles). Seven subtropical soils of different textural classes were tested. The Freundlich sorption coefficients, expressed as μg1-1/n (cm3)1/n g-1, were in the following ranges: 0.45 to 19 (sulfonamides), 72 to 2410 (fluoroquinolones), 9 to 58 (thiabendazole), 0.03 to 0.48 (florfenicol), 105 to 424 (moxidectin), 14 to 184 (avermectins), and 1.5 to 74 (macrolides). The results showed that the drugs belonging to the same family, with chemical structures in common, presented similar behaviors regarding sorption and desorption, for the different soils tested and are generally in agreement with soils from temperate regions. The data set obtained in this work give an overview of the fate of the veterinary drugs in Brazilian subtropical soils with different textures and composition and can be very helpful for exposure risk assessments.

Rath|Susanne|S|
Fostier|Anne Hélène|AH|
Pereira|Leandro Alves|LA|
Dioniso|Andreza Camilotti|AC|
de Oliveira Ferreira|Fabrício|F|
Doretto|Keity Margareth|KM|
Maniero Peruchi|Livia|L|
Viera|Alessandra|A|
de Oliveira Neto|Odilon França|OF|
Dal Bosco|Sandra Maria|SM|
Martínez-Mejía|Mónica J|MJ|

Veterinary drugs
Sorption coefficients
Brazilian subtropical soils
Freundlich isotherms
Sorption kinetics


Management of the essential data element in the differential diagnosis of oral medicine: An effective step in promoting oral health.

Abstract:
BACKGROUND
Oral soft tissue diseases include a broad spectrum, and the wide array of patient data elements need to be processed in their diagnosis. One of the biggest and most basic challenges is the analysis of this huge amount of complex patient data in an increasing number of complicated clinical decisions. This study seeks to identify the necessary steps for collecting and management of these data elements through establishing a consensus-based framework.

METHODS
This research was conducted as a descriptive, cross-sectional study from April 2016 to January 2017, which has been performed in several steps: literature review, developing the initial draft (v. 0), submitting the draft to experts, validating by an expert panel, applying expert opinions and creating version v.i, performing Delphi rounds, and creating the final framework.

RESULTS
The administrative data category with 17 and the historical data category with 23 data elements were utilized in recording data elements in the diagnosis of all of the different oral diseases. In the paraclinical indicator and clinical indicator categories, the necessary data elements were considered with respect to the 6 main axes of oral soft tissue diseases, according to Burket's Oral Medicine: ulcerative, vesicular, and bullous lesions; red and white lesions of the oral mucosa; pigmented lesions of the oral mucosa; benign lesions of the oral cavity and the jaws; oral and oropharyngeal cancer; and salivary gland diseases.

CONCLUSIONS
The study achieved a consensus-based framework for the essential data element in the differential diagnosis of oral medicine using a comprehensive search with rich keywords in databases and reference texts, providing an environment for discussion and exchange of ideas among experts and the careful use of the Delphi decision technique.

Ehtesham|Hamideh|H| Safdari|Reza|R| Mansourian|Arash|A| Tahmasebian|Shahram|S| Mohammadzadeh|Niloofar|N| Pourshahidi|Sara|S|

oral medicine
Clinical data management
dental informatics
differential diagnoses


Fungal elimination of toluene vapor in one- and two-liquid phase biotrickling filters: Effects of inlet concentration, operating temperature, and peroxidase enzyme activity.

Abstract: In this study, performance of biotrickling filters (BTFs) inoculated with fungus Phanerochaete chrysosporium at 30 °C and 40 °C in the absence and presence of silicone oil (10% v/v) was investigated. Removal of toluene was carried out at empty bed residence time (EBRT) of 1 min and at inlet concentrations of 0.5-4.4 g m-3 and 0.5-24.7 g m-3 for one-liquid phase (OLP-BTF) and two-liquid phase BTF (TLP-BTF), respectively. In general, at 40 °C, removal efficiencies (REs) > 80% were obtained in OLP-BTF for the inlet toluene concentrations < 2.5 g m-3, and REs > 70% were obtained for concentrations < 18 g m-3 in TLP-BTF. Based on the balanced equation for biodegradation, fungal respiration produced more CO2 in OLP-BTF (1.38 mol CO2/mole toluene) in comparison to TLP-BTF (0.67 mol CO2/mole toluene). In other words, the presence of oil enhanced microbial growth due to the increase of hydrophobic substrate bioavailability. The activity of extracellular ligninolytic manganese peroxidase (MnP) enzyme produced by the fungal culture was detected in the range of 27.6-71.6 U L-1 (μmol min-1 L-1) at 40 °C in TLP-BTF, while no enzymatic activity was detected in OLP-BTF.

Yousefinejad|Ali|A|
Zamir|Seyed Morteza|SM|
Nosrati|Mohsen|M|

Enzymatic activity
Biofilm
CO(2) production rate
Ligninolytic enzyme
Mass transfer limitation
T-test


Heat shock protein 72 may improve hypotension by increasing cardiac mechanical efficiency and arterial elastance in heatstroke rats.

Abstract:
OBJECTIVE
We attempted to test the hypothesis that preinduction of heat shock protein (HSP) 72 in the heart would improve left ventricular performance in rat heatstroke.

METHODS
Cardiac expression of HSP 72 was quantitatively evaluated by western blot analysis in rats 0h, 12h, or 72h after mild heat preconditioning (MHP; 43°C for 30min). They were subjected to severe heat stress (SHS; 43°C for 70min) to induce heatstroke. A 1.2F catheter-tip pressure transducer was inserted into the left ventricle of these group rats under general anesthesia to record hemodynamic in the closed chest with a pressure-volume loop module data recording and analysis system.

RESULTS
At the time point of heatstroke onset, compared with normothermic controls, group rats with 12h post-MHP had significantly increased cardiac HSP 72, decreased hyperthermia, decreased hypotension, decreased bradycardia, increased end-systolic pressure, increased end-diastolic pressure, increased stroke volume, decreased end-systolic volume, decreased end-diastolic pressure, increased cardiac output, increased ejection fraction, increased stroke work, increased arterial elastance, and decreased time constant of fall in ventricular pressure by Glantz-methods. With the loss of cardiac HSP 72 expression observed at 72h in post-MHP group rats, an insignificant protection against left ventricular performance was observed.

CONCLUSION
Preinduction of cardiac HSP 72 may improve hypotension in heatstroke rats by increasing both cardiac mechanical efficiency and arterial elastance.

Hsu|Shu-Fen|SF| Chao|Chien-Ming|CM| Chang|Ching-Ping|CP| Lin|Mao-Tsun|MT| Cheng|Bor-Chih|BC|

D000818:Animals
D001794:Blood Pressure
D050884:HSP72 Heat-Shock Proteins
D006339:Heart Rate
D018883:Heat Stroke
D007022:Hypotension
D008297:Male
D011897:Random Allocation
D051381:Rats
D017207:Rats, Sprague-Dawley
D013318:Stroke Volume
D016277:Ventricular Function, Left

Heat shock protein 72
Hypotension
Arterial elastance
Cardiac contractility


Bacterial biopolymer (polyhydroxyalkanoate) production from low-cost sustainable sources.

Abstract: Twenty-six different bacterial strains were isolated from samples taken from different locations Dammam, Saudi Arabia, for screening of their polyhydroxyalkanoate (PHA) production capability. The initial screening was conducted by staining with Sudan Black B and Nile Red, followed by examination under fluorescence and electron microscopes to characterize PHA granule formation. The PHA-producing bacterial isolates were identified using 16S rRNA gene analyses; the most potent bacterial strain was identified as Pseudomonas sp. strain-P(16). The PHA production capability of this strain in the presence of different low-cost carbon sources, such as rice bran, dates, and soy molasses, was analyzed. PHA production in the presence of rice bran, dates, and soy molasses was 90.9%, 82.6%, and 91.6%, respectively.

low-cost carbon source
dates
PHA yield
fluorescence microscopy


Local anaesthesia versus spinal anaesthesia in inguinal hernia repair: A systematic review and meta-analysis.

Abstract:
BACKGROUND
Inguinal hernias are a significant cause of morbidity. The purpose of this systematic review and meta-analysis is to determine the totality of evidence regarding the effectiveness of local anaesthesia when compared to spinal anaesthesia in individuals undergoing open inguinal hernia repair.

METHODS
A systematic literature search was conducted. Inclusion criteria were randomised controlled trials (RCTs) comparing spinal and local anaesthesia on clinical and self-reported outcomes, in patients undergoing open inguinal hernia repairs. The methodological quality was assessed using the Cochrane risk of bias tool. The mode of analysis used was the difference in outcomes between the groups post-surgery and at follow-up time points. Statistical heterogeneity was assessed using the I2 statistic.

RESULTS
Ten original RCTs were included, with a total of 1379 patients. There was no significant difference in operative time between the groups [Random Effects Model, MD -0.70 min (95% CI, -5.80 to 4.40 min), p = 0.79, I2 = 84%]. Patients in the local anaesthetic group experienced significantly less pain than those in the spinal group [Fixed Effects Model, SMD -0.63 (95% CI, -0.81 to -0.46), p < 0.01, I2 = 49%], lower rates of urinary retention [FEM, RR 0.03 (95% CI 0.01-0.08), p < 0.01, I2 = 0%], decreased rates of anaesthetic failure [FEM, OR 0.17 (95% CI 0.06-0.45), p < 0.01, I2 = 0%], and increased satisfaction with the anaesthetic [FEM, OR 3.40 (95% CI 2.09-5.52), p < 0.01, I2 = 0%]. The methodological quality of studies was variable.

CONCLUSION
Our findings support the use of local anaesthetic in adult patients undergoing open repair for a primary inguinal hernia.

Prakash|Deepali|D| Heskin|Leonie|L| Doherty|Sally|S| Galvin|Rose|R|

D000772:Anesthesia, Local
D000775:Anesthesia, Spinal
D006552:Hernia, Inguinal
D006801:Humans

Local
Anaesthesia
Spinal
Inguinal
Hernia
Systematic review
Meta-analysis


Performance Assessment of Pharmacotherapy: Results from a Content Validity Survey of the Psychopharmacotherapy-Structured Clinical Observation (P-SCO) Tool.

Abstract:
OBJECTIVE
The Psychopharmacotherapy-Structured Clinical Observation (P-SCO) tool is designed to assess performance of a medication management visit and to enhance feedback. Prior research indicated that the P-SCO was feasible to implement in a resident clinic and generated behaviorally specific, high-quality feedback. This research also highlighted problems with some of the instrument's items. This study seeks to improve the items.

METHODS
The authors initially revised the P-SCO items based on the problems identified by a prior study. Next, these items were iteratively modified by experts in clinical pharmacotherapy and educational assessment. Forty-five items emerged. Finally, faculty attending an annual department education retreat rated each item on its relevance (4-point scale) and provided comments on how the item might be revised. For final inclusion, an item must have met a quantitative threshold (i.e., content validity index equal to or greater than 0.8 and the lower end of the asymmetric confidence interval equal to or greater than 3.0) and received comments that were supportive.

RESULTS
Forty-one of the 45 items had strong quantitative support. However, the comments endorsed lumping a number of items in order to decrease overlap between items and to shorten the instrument. This process resulted in the further elimination of 15 items.

CONCLUSIONS
The revised 26-item P-SCO builds upon prior evidence of feasibility and utility and now possesses additional evidence of content validity. The use of the tool should enhance feedback and improve the capacity of educational programs to assess performance.

Young|John Q|JQ|
Irby|David M|DM|
Kusz|Martin|M|
O'Sullivan|Patricia S|PS|

Performance assessment
Pharmacotherapy
Validity


The Rhodamine Isothiocyanate Analogue as a Quorum Sensing Inhibitor Has the Potential to Control Microbially-Induced Biofouling.

Abstract: Quorum sensing inhibitors (QSIs) have been proven to be an innovative approach to interfering with biofilm formation, since this process is regulated by QS signals. However, most studies have focused on single-species biofilm formation, whereas studies of the effects of signal interference on the development of multispecies biofilm, especially in the natural environment, are still lacking. Here we develop and evaluate the anti-biofilm capability of a new QSI (rhodamine isothiocyanate analogue, RIA) in natural seawater. During the experiment, biofilm characteristics, microbial communities/functions and network interactions were monitored at 36, 80, and 180 h, respectively. The results showed that the biomass and 3D structure of the biofilm were significantly different in the presence of the QSI. The expression of genes involved in extracellular polysaccharide synthesis was also downregulated in the QSI-treated group. Dramatic differences in microbial composition, β-diversity and functions between the RIA-treated group and the control group were also observed, especially in the early stage of biofilm development. Furthermore, co-occurrence model analysis showed that RIA reduced the complexity of the microbial network. This study demonstrates that rhodamine isothiocyanate analogue is an efficient QS inhibitor and has potential applications in controlling biofouling caused by multispecies biofilm, especially in the early stage of biofouling formation.

Song|Yu|Y| Zhang|Shengjie|S| Zeng|Yanhua|Y| Zhu|Jianming|J| Du|Xiaopeng|X| Cai|Zhonghua|Z| Zhou|Jin|J|0000-0003-0372-2554

rhodamine isothiocyanate analogue
quorum sensing inhibitor
biofouling
anti-biofilm
multiple-species


The impact of a global health elective on CanMEDS competencies and future practice.

Abstract:
BACKGROUND
There is evidence that participating in global health electives generates positive educational outcomes and personal benefits for medical trainees. The objective of this study was to examine the effect and impact that a global health elective has on CanMEDS competencies and anticipated future practice.

RESULTS
The medical expert, collaborator, leader, scholar, and professional CanMEDS competencies were self-perceived to be strongly impacted through this elective. A total of 94% of participants indicated it increased their strengths as a medical expert and leader, 82% indicated a major impact on the scholar competency, 88% of participants reported a strong impact as a professional, and 76% of participants indicated that it strongly impacted them as a collaborator. The majority of participants continue to have involvement in global health, and 88% of respondents found this elective to be influential on their current practice and beliefs.

CONCLUSIONS
These results suggest that individuals who participated in this global health elective perceived value in their experience. These findings support our hypothesis that participation in this global health elective would generate self-perceived positive impacts. Global health electives may provide an opportunity for physicians to expand on their CanMEDS competencies and become more proficient in caring for diverse patient populations.

Lanys|Ashley|A|0000-0001-6773-4357
Krikler|Gena|G|
Spitzer|Rachel F|RF|

D000328:Adult
D003479:Curriculum
D014943:Global Health
D006801:Humans
D010819:Physician's Role
D011361:Professional Competence
D060728:Reproductive Health
D013337:Students, Medical
D011795:Surveys and Questionnaires

Global health
CanMEDS competencies
Reproductive health


A Novel Association of the Suppressor of Cytokine Signaling 1 (SOCS1) Gene Polymorphisms in Ischemic Stroke Patients.

Abstract: Ischemic stroke is a common neurological disease and a leading cause of permanent disability in many countries. Recent studies provide evidence on the role of the suppressor of the cytokine signaling 1 (SOCS1) gene in the development and progression of atherosclerotic lesions. However, few studies have assessed the association between single nucleotide polymorphisms (SNPs) on SOCS1 gene and ischemic stroke. Therefore, the present study aimed to investigate the role of SOCS1 polymorphism in ischemic stroke risk in a northern Chinese Han population. We examined 475 patients with ischemic stroke and 486 normal controls. Three SNPs (rs243327, rs243330, and rs33932899) of SOCS1 gene were determined for TaqMan genotyping assays. We also classified these case samples in depth by complications with hypertension or diabetes and by ischemic stroke subtypes. When adjusting models by multiple factor analysis by logistic regression, then calculated 10,000 permutations were performed for each model to correct the multiple test. Under additive model, the rs243327 was associated with ischemic stroke with hypertension (p = 0.047). Under heterozygous model, the rs33932899 and rs243330 were significantly associated with ischemic stroke subtypes by atherosclerosis (p = 0.038, p = 0.048, respectively). In summary, our data demonstrated for the first time that the polymorphisms of the SOCS1 gene are associated with the risk of ischemic stroke in a northern Chinese Han population, suggesting that SOCS1 gene polymorphisms may play an important role in the pathogenesis of ischemic stroke.

D020022:Genetic Predisposition to Disease

D000071222:Suppressor of Cytokine Signaling 1 Protein

SOCS1
Ischemic stroke
SNPs
Association studies
Genetics


Quantitative Proteomic Analysis of Cellular Resistance to the Nanoparticle Abraxane.

Abstract: Abraxane, an FDA-approved albumin-bound nanoparticle (NP) form of paclitaxel (PTX) to treat breast cancer and nonsmall cell lung cancer (NSCLC), has been demonstrated to be more effective than the original Taxol, the single molecule form. We have established a cell line from NSCLC A549 cells to be resistant to Abraxane. To further understand the molecular mechanisms involved in the NP drug resistance, global protein expression profiles of Abraxane sensitive (A549) and resistant cells (A549/Abr), along with the treatment of Abraxane, have been obtained by a quantitative proteomic approach. The most significantly differentially expressed proteins are associated with lipid metabolism, cell cycle, cytoskeleton, apoptosis pathways and processes, suggesting several mechanisms are working synergistically in A549 Abraxane-resistant cells. Overexpression of proteins in the lipid metabolism processes, such as E3 ubiquitin-protein ligase RNF139 (RNF139) and Hydroxymethylglutaryl-CoA synthase (HMGCS1), have not been reported previously in the study of paclitaxel resistance, suggesting possibly different mechanism between nanoparticle and single molecular drug resistance. In particular, RNF139 is one of the most up-regulated proteins in A549 Abraxane-resistant cell line, but remains no change when the resistant cells were further treated with Abraxane and down-regulated in the sensitive cells after 4 h treatment of Abraxane. This study shows the use of a proteomic strategy to understand the unique response of drug resistant cells to a nanoparticle therapeutic.

Zhao|Minzhi|M| Li|Haiyun|H| Bu|Xiangli|X| Lei|Chunni|C| Fang|Qiaojun|Q| Hu|Zhiyuan|Z|

quantitative proteomics
E3 ubiquitin-protein ligase RNF139
Abraxane resistance
nanoparticle drug
synergistic mechanisms


Isolation of Cell-Free DNA from Maternal Plasma.

Abstract: Noninvasive prenatal genetic tests analyzing the cell-free fetal DNA in the circulation of expectant mothers are now performed routinely in clinical diagnostic laboratories. Leveraging the power of next generation sequencing (NGS), these tests can detect variation in chromosomal copy number or microdeletions early in gestation. All methods begin with blood collection followed by transport to the diagnostic lab, plasma separation, and purification of ccfDNA from the plasma to prepare it for molecular analysis. Preservation of ccfDNA in blood samples and highly efficient purification from plasma are paramount since the quality and quantity of target nucleic acids determine the sensitivity and therefore success of these assays. Maximizing quality and quantity and minimizing variation in extraction yield pose significant challenges for diagnostic labs, many of which use manual isolation methods for plasma volumes greater than 5 mL. One way to reduce variability is to automate the extraction processes and, to the extent possible, minimize hand-on operations. This chapter details two procedures for isolating ccfDNA from 10 mL plasma by manual and automated means using the QIAamp Circulating Nucleic Acid Kit and the QIAsymphony Circulating DNA Kit. The ccfDNA recovered is suitable for downstream processing in noninvasive prenatal tests for aneuploidy detection.

D000782:Aneuploidy
D000073888:Cell-Free Nucleic Acids
D005820:Genetic Testing
D006801:Humans
D000073890:Liquid Biopsy
D020641:Polymorphism, Single Nucleotide
D011296:Prenatal Diagnosis
D011933:Reagent Kits, Diagnostic

Fetal
Automation
QIAamp
QIAsymphony
Noninvasive prenatal testing
Blood sample stabilization
Circulating DNA extraction
Circulating cell-free DNA
SNP-based aneuploidy detection


A patient-specific EMG-driven neuromuscular model for the potential use of human-inspired gait rehabilitation robots.

Abstract: A patient-specific electromyography (EMG)-driven neuromuscular model (PENm) is developed for the potential use of human-inspired gait rehabilitation robots. The PENm is modified based on the current EMG-driven models by decreasing the calculation time and ensuring good prediction accuracy. To ensure the calculation efficiency, the PENm is simplified into two EMG channels around one joint with minimal physiological parameters. In addition, a dynamic computation model is developed to achieve real-time calculation. To ensure the calculation accuracy, patient-specific muscle kinematics information, such as the musculotendon lengths and the muscle moment arms during the entire gait cycle, are employed based on the patient-specific musculoskeletal model. Moreover, an improved force-length-velocity relationship is implemented to generate accurate muscle forces. Gait analysis data including kinematics, ground reaction forces, and raw EMG signals from six adolescents at three different speeds were used to evaluate the PENm. The simulation results show that the PENm has the potential to predict accurate joint moment in real-time. The design of advanced human-robot interaction control strategies and human-inspired gait rehabilitation robots can benefit from the application of the human internal state provided by the PENm.

Gait rehabilitation
Musculoskeletal model
Hill-type muscle
Robot control
Sensitivity analysis


Two new species in Iris series Chinenses (Iridaceae) from south-central China.

Abstract: Iris dabashanensis C.A.Wilson, sp. nov. and I. probstii C.A.Wilson, sp. nov. from China are described and illustrated. Both species occur on grassy slopes in mountainous regions of south-central China. The former is known from the Daba Mountains in rocky, calcareous soils associated with shrubs or mixed conifer and hardwood forests, while the latter is known from a region of karst terrain beside rice fields or under pine woods in Guizhou Province. Molecular data resolves both species in series Chinenses in a subclade that also includes I. odaesanensis, while morphologically they are similar to I. henryi. These newly described species are two of four members of series Chinenses that occur in south-central China.

Daba Mountains
karst terrain
Guizhou Province
phylogeny


Fruit and Vegetable Intake Patterns and Their Associations with Sociodemographic Characteristics, Anthropometric Status and Nutrient Intake Profiles among Malaysian Children Aged 1-6 Years.

Abstract: This study aimed to assess fruit and vegetable intake patterns and their associations with sociodemographic characteristics, anthropometric status and nutrient intake profiles among Malaysian children aged 1-6 years. Using the Malaysian dataset of South East Asian Nutrition Surveys (SEANUTS Malaysia), a total of 1307 children aged 1-6 years with complete datasets were included in this analysis. Dietary intake was assessed using age-specific, validated food frequency questionnaires. On average, Malaysian children consumed 0.91 and 1.07 servings of fruits and vegetables per day, respectively. Less than one-fifth of the children achieved the daily recommended servings of fruits (11.7%) and vegetables (15.8%). Fruit intake was associated with age, parental educational level and geographical region, and vegetable intake was associated with ethnicity and geographical region. There was little evidence of an association between fruit and vegetable intake and children's anthropometric status, but an adequate intake of fruits and vegetables contributed significantly and differently to children's micronutrient intake. Future nutrition interventions should focus on addressing the sociodemographic determinants and be tailored to the needs of the low consumers to more effectively promote and encourage the adequate intake of fruit and vegetables among young children.

Chong|Kar Hau|KH|
Lee|Shoo Thien|ST|
Ng|Swee Ai|SA|
Khouw|Ilse|I|
Poh|Bee Koon|BK|

vegetable intake
anthropometric status
nutrient intake
fruit intake
sociodemographic determinants
young children