ACN9 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.

Abstract: A previous genome-wide linkage study of alcohol dependence (AD) in the Pittsburgh-based multiplex family study found suggestive evidence for linkage on Chromosome 7q, a region in which the ACN9 gene is located. Using the same two generation Pittsburgh family data in which linkage was found, data for a third generation was added. The expanded sample included 133 pedigrees with 995 individuals. Finer mapping was undertaken using six SNPs extending from rs1917939 to rs13475 with minor allele frequency (MAF) ≥0.15 and pair-wise linkage disequilibrium (LD) of r(2) <0.8 using the HapMap CEU population. Binary affection status, visual, and auditory P300 data were tested for family-based association. Family-based analyses found all six SNPs associated with affected status. Three SNPs are located upstream of the gene, two SNPs are within intron 1 and one is in Exon 4. FBAT P-values for the six SNPs ranged between 0.05 and 0.0005. Haplotype analysis revealed one four-SNP block formed by rs10499934, rs7794886, rs12056091, and rs13475 with an overall significant association at P = 0.0008. Analysis of visual P300 amplitude data, a known endophenotype of alcohol dependence risk, revealed a significant association for SNPs within intron 1 and exon 4 under a dominant model of transmission. Family-based association analysis shows the ACN9 gene significantly associated with alcohol dependence and P300 amplitude variation. The potential importance of the ACN9 gene for AD risk may be related to its role in gluconeogenesis which may be involved in the regulation of alcohol metabolism.

Hill|Shirley Y|SY|
Jones|Bobby L|BL|
Zezza|Nicholas|N|
Stiffler|Scott|S|

D020022:Genetic Predisposition to Disease

ACN9
alcohol dependence
family-based association
glucose metabolism


Computerized versus manual versions of the Wisconsin Card Sorting Test: Implications with typically developing and ADHD children.

Abstract: The aims of Study 1 (S1) were (a) to compare the task performance of 361 typically developing (TD) children aged 7 to 12 years, according to the mode of Wisconsin Card Sorting Test (WCST) administration (manual vs. computerized) and b) to examine the contributions of executive functions (EFs) (i.e., working memory [WM], shifting and inhibition) to each WCST version. The objectives of Study 2 (S2) were (a) to study the comparability of the results obtained from the manual version to the results from the computer version in 43 children with Attention Deficit/Hyperactivity Disorder (ADHD) and (b) to compare task performance on both versions between children with ADHD and TD children. The effect of age was only significant for the manual WCST. Regression analyses revealed that WM and shifting contributed to manual WCST performance, whereas WM and inhibition contributed to the performance on the computer version. We observed differences depending on the WCST mode of administration, as better scores for the manual version were recorded for both TD children and children with ADHD, despite similar performance on tasks involving other EFs. Additionally, children with ADHD performed worse than TD children on both versions. Our findings suggest that verbal face-to-face interactions would play a significant role in supporting children's abilities to solve novel situations characterized by uncertainty.

Arán Filippetti|Vanessa|V|
Krumm|Gabriela L|GL|
Raimondi|Waldina|W|

D001289:Attention Deficit Disorder with Hyperactivity

ADHD
executive functions
manual WCST
child neuropsychology
computerized WCST


The choice of stimulation strategy affects the ability to detect pure tone inter-aural time differences in children with early bilateral cochlear implantation.

Abstract:
OBJECTIVES
To investigate if the interaural time difference (ITD) ability is dependent of stimulation strategy. To examine the correlation between ITD, interaural level differences (ILD) and the ability to localize different sounds.

METHODS
Thirty subjects aged 8-13 who were implanted bilaterally before 3 years of age were tested. Twenty of the subjects used processors programmed with fine structure (FS) strategy on both sides. ITD and ILD just noticeable difference (JND) of a 250 Hz pure tone was measured using their clinical processors. Furthermore, their ability to localize sound in the horizontal plane was measured using eye tracking.

RESULTS
Ten of the 20 subjects with FS obtained an ITD threshold compared to none in the group without FS (0/10). ILD JND was correlated to localization ability of the broadband (BB) sound. Mean absolute error of the localization of a low-frequency (LF) sound was larger than that of a BB sound.

CONCLUSIONS
The ability to detect ITD was present only when the cochlear implant stimulation had FS. The LF sound was more difficult to localize than the BB sound and ITD ability of FS strategies did not affect the localization ability of either sound. A low ILD seems necessary to improve the localization ability.

children
Bilateral cochlear implant
interaural time difference
ITD
localization
fine structure
CI


Simple signals indicate which period of the annual cycle drives declines in seasonal populations.

Abstract: For declining wild populations, a critical aspect of effective conservation is understanding when and where the causes of decline occur. The primary drivers of decline in migratory and seasonal populations can often be attributed to a specific period of the year. However, generic, broadly applicable indicators of these season-specific drivers of population decline remain elusive. We used a multi-generation experiment to investigate whether habitat loss in either the breeding or non-breeding period generated distinct signatures of population decline. When breeding habitat was reduced, population size remained relatively stable for several generations, before declining precipitously. When non-breeding habitat was reduced, between-season variation in population counts increased relative to control populations, and non-breeding population size declined steadily. Changes in seasonal vital rates and other indicators were predicted by the season in which habitat loss treatment occurred. Per capita reproductive output increased when non-breeding habitat was reduced and decreased with breeding habitat reduction, whereas per capita non-breeding survival showed the opposite trends. Our results reveal how simple signals inherent in counts and demographics of declining populations can indicate which period of the annual cycle is driving declines.

Annual cycle
seasonality
conservation
habitat loss
breeding
non-breeding
population dynamics


Measurement of 13 C turnover into glutamate and glutamine pools in brain tumor patients.

Abstract: Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. 13 C NMR-based isotopomer analysis has been used to measure turnover of 13 C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-13 C]acetate further revealed the presence of 13 C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due to metabolism of [1,2-13 C]acetate by peripheral organs. In the tumor cells, [4-13 C] and [3,4-13 C]glutamate and glutamine isotopomers were generated from blood-borne 13 C-labeled glucose and lactate which were formed due to [1,2-13 C[acetate metabolism of peripheral tissues. [4,5-13 C] and [3,4,5-13 C]glutamate and glutamine isotopomers were produced from [1,2-13 C]acetyl-CoA that was derived from direct oxidation of [1,2-13 C] acetate in the tumor. Major portion of C4 13 C fractional enrichment of glutamate (93.3 ± 0.02%) and glutamine (90.9 ± 0.03%) were derived from [1,2-13 C]acetate-derived acetyl-CoA.

Pichumani|Kumar|K|
Mashimo|Tomoyuki|T|
Vemireddy|Vamsidhara|V|
Ijare|Omkar B|OB|
Mickey|Bruce E|BE|
Malloy|Craig R|CR|
Marin-Valencia|Isaac|I|
Baskin|David S|DS|
Bachoo|Robert M|RM|
Maher|Elizabeth A|EA|

13C isotopomer
[1,2-13C]acetate
acetyl-CoA
glutamate and glutamine synthesis
peripheral metabolism


Genetically determined lean mass and dietary response.

Abstract: Weight loss attenuates many obesity-related co-morbidities, but is difficult to sustain with dietary change. Dietary adherence, not macronutrient composition, is a better predictor of weight loss. Weight loss-induced endocrine changes promote food intake and increase energy efficiency, contributing to the difficulty with dietary adherence and weight regain. Macronutrient preference is partly genetically determined, suggesting that personalized dietary interventions might be more successful. In this issue, Li et al. report that a genetic risk score comprising the cumulative weighted effects of variants previously associated with increased lean mass is associated with increased satiety and weight loss 6 months after initiating a low- but not a high-fat diet. The effects were attenuated by 2 years. These findings suggest that genetic variants may influence response to specific diet. Further studies are necessary to assess whether genetically determined lean mass is causally associated with dietary response. Significant progress has recently been made in identifying additional genetic determinants of lean mass, which will enable such investigations and potentially inform future nutritional studies.

lean mass
weight loss
genetic risk score


Involvement of extracellular signal-regulated kinase (ERK) in the short and long-lasting antidepressant-like activity of NMDA receptor antagonists (zinc and Ro 25-6981) in the forced swim test in rats.

Abstract: Short and long acting NMDA receptor (NMDAR) antagonists exert their antidepressant-like effects by activating signaling pathways involved in the synthesis of synaptic proteins and formation of new synaptic connections in the prefrontal cortex (PFC) of rats. The blockade of the ERK pathway abolishes ketamine and Ro 25-6981 antidepressant potency. However, the role of ERK in the antidepressant-like activity of short acting NMDAR antagonists is still unclear. More puzzling is the fact that the precise role of ERK in the short and long lasting effects of long-acting NMDAR antagonists is unknown. In this study, we show that zinc, (Zn) a short-acting NMDAR antagonist evokes only transient ERK activation, which is observed 7 min after its administration in the PFC of rats. In contrast to Zn, the long acting NMDAR antagonist Ro 25-6981 produces persistent ERK activation lasting up to 24 h. Pretreatment with the MAPK/ERK inhibitor (U0126) totally abolished Zn and Ro 25-6981 antidepressant-like activities in the forced swim test in rats. However, when U0126 is administered 15 min after Zn or Ro 25-6981 both compounds maintain their short-lasting antidepressant-like activity. On the other hand, posttreatment with U0126 significantly attenuated the long lasting antidepressant-like activity of Ro 25-6981. These results indicate that the activation of ERK is crucial for the short- and long lasting antidepressant-like activity observed in the FST in rats.

Pochwat|Bartłomiej|B| Rafało-Ulińska|Anna|A| Domin|Helena|H| Misztak|Paulina|P| Nowak|Gabriel|G| Szewczyk|Bernadeta|B|

D048049:Extracellular Signal-Regulated MAP Kinases


Microsatellite development and flow cytometry in the African tree genus Afzelia (Fabaceae, Caesalpinioideae) reveal a polyploid complex.

Abstract:
UNLABELLED

PREMISE OF THE STUDY
Microsatellites were developed in the vulnerable African rainforest tree Afzelia bipindensis to investigate gene flow patterns. •

METHODS AND RESULTS
Using 454 GS-FLX technique, 16 primer sets were identified and optimized, leading to 11 polymorphic and readable markers displaying each six to 25 alleles in a population. Up to four alleles per individual were found in each of the loci, without evidence of fixed heterozygosity, suggesting an autotetraploid genome. Cross-amplification succeeded for all loci in the African rainforest species A. pachyloba and A. bella, which appeared tetraploid, and for most loci in the African woodland species A. africana and A. quanzensis, which appeared diploid, but failed in the Asian species A. xylocarpa. Flow cytometry confirmed the suspected differences in ploidy. •

CONCLUSIONS
African Afzelia species are diploid or tetraploid, a situation rarely documented in tropical trees. These newly developed microsatellites will help in the study of their mating system and gene flow patterns.

Donkpegan|Armel S L|AS|
Doucet|Jean-Louis|JL|
Dainou|Kasso|K|
Hardy|Olivier J|OJ|

microsatellites
Afzelia
Fabaceae
Caesalpinioideae
next-generation sequencing
polyploidy
tropical timber tree


Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector.

Abstract: Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer.

Ambattu|Lizebona August|LA|
Rekha|M R|MR|

Gene delivery
Pullulan
Ascorbic acid
p53
Polyethylene imine


Activation delay-induced mechanical dyssynchrony in single-ventricle heart disease.

Abstract: We present the case of an infant with a single functional ventricle who developed ventricular dysfunction and heart failure due to an electrical activation delay and dyssynchrony. Earlier recognition of this potentially reversible aetiology may have changed her poor outcome.

dyssynchrony
heart failure
Single ventricle
bundle branch block
pattern analysis
speckle tracking strain


Impact of the introduction of EUCAST's concept of "area of technical uncertainty".

Abstract: On the first of January 2019, the European Committee on Antimicrobial Susceptibility Testing, EUCAST, introduced the concept of "area of technical uncertainty" (ATU). The aim was to report on the incidence of ATU test results in a selection of common bacterial species and the subsequent impact on antimicrobial resistance categorization and workload. A retrospective analysis of clinical samples collected from February 2019 until November 2019 was performed. Susceptibility to amoxicillin-clavulanic acid and piperacillin-tazobactam in Enterobacterales (Escherichia spp., Klebsiella spp., Proteus spp.), piperacillin-tazobactam in Pseudomonas aeruginosa, and amoxicillin-clavulanic acid and cefuroxime in Haemophilus influenzae was studied. Disk diffusion antibiotic susceptibility testing was read and interpreted by ADAGIO 93400 automated system (Bio-Rad, France). In case of an inhibition zone in the ATU, strains were retested using gradient minimal inhibitory concentration method (Etest, BioMérieux, France). Overall, 14,164 isolate-antibiotic combinations were tested in 7922 isolates, resulting in 1204 (8.5%) disk zone diameters in the ATU region. Retesting of ATUs with Etest resulted in a category change from S to R for amoxicillin-clavulanic acid in 63/498 (12.7%) of Escherichia spp., 2/58 (3.4%) of Klebsiella spp., 2/37 (5.4%) of Proteus spp., and 6/125 (4.8%) of Haemophilus influenzae. For piperacillin-tazobactam, a category change from S to R was found in 33/92 (35.9%) of Pseudomonas aeruginosa. We conclude that ATU testing has a substantial impact on the correct interpretation of antimicrobial resistance, at the expense of turn-around time and with the cost of additional workload.

Van Honacker|Eveline|E|
Vandendriessche|S|S|
Coorevits|L|L|
Verhasselt|B|B|
Boelens|J|J|

Antimicrobial resistance
Disk diffusion
ATU zone
Breakpoints


Effect of Offset Implant Placement on the Stress Distribution Around a Dental Implant: A Three-Dimensional Finite Element Analysis.

Abstract: There are some anatomical restrictions in which implants are not possible to be inserted in their conventional configuration. Offset placement of implants in relation to the prosthetic unit could be a treatment solution. The aim of this study was to evaluate the effect of the offset placement of implant-supported prosthesis on the stress distribution around a dental implant using 3D finite element analysis. 3D finite element models of implant placement in the position of a mandibular molar with 4 configurations (0, 0.5, 1, 1.5 mm offset) were created in order to investigate resultant stress/strain distribution. A vertical load of 100 N was applied on the center of the crown of the models. The least stress in peri-implant tissue was found in in-line configuration (0 mm offset). Stress concentration in the peri-implant tissue increased by increasing the amount of offset placement. Maximum stress concentration in all models was detected at the neck of the implant. It can be concluded that the offset placement of a single dental implant does not offer biomechanical advantages regarding reducing stress concentration over the in-line implant configuration. It is suggested that the amount of offset should be as minimum as possible.

Siadat|Hakimeh|H|
Hashemzadeh|Shervin|S|
Geramy|Allahyar|A|
Bassir|Seyed Hossein|SH|
Alikhasi|Marzieh|M|

stress distribution
dental implants
finite element analysis
biomechanics
bone stress
occlusal load


Formulation, Characterization, and Pharmacokinetic Studies of 6-Gingerol-Loaded Nanostructured Lipid Carriers.

Abstract: In this study, an optimized nanostructured lipid carriers (NLCs) were developed and investigated for improving the solubility and oral availability of 6-Gingerol (6G), an active and abundant component of ginger with limited applications due to its poor water solubility plus oral biological availability. The NLCs consisted of a solid lipid (glyceryl monostearate), another liquid lipid (decanoyl/octanoyl-glycerides) and mixed surfactants (Tween 80 and Poloxamer 188), and was prepared by high pressure homogenization method. The optimal 6G-NLC formulation was evaluated through physical properties such as appearance, mean particle size, zeta potential, encapsulation efficiency, and in vitro drug release, alongside techniques viz., transmission electron microscopy (TEM), differential scanning calorimetry (DSC), as well as powder X-ray diffraction (XRD). Pharmacokinetics were also evaluated in rats. The 6G-NLCs prepared with optimal formulation exhibited a homogenous spherical shape with mean particle size and zeta potential of 63.59 ± 5.54 nm and - 12.18 ± 1.06 mV. Encapsulation efficiency and drug loading were 76.71 ± 1.11 and 1.17 ± 0.35%, respectively. In vitro release profile of 6G from NLCs was sustained and fitted with Weibull equation. After oral administration of the 6G-NLCs, drug concentrations in serum, MRT, and AUC0-t were significantly higher as compared with the free 6G suspension. All these results indicated that the developed NLC formulation could be effective and promising drug carriers to improve the water solubility of 6G while sustaining the drug release as well as prolonging in vivo acting time of the drug coupled with oral bioavailability enhancement.

Wei|Qiuyu|Q| Yang|Qiuxuan|Q| Wang|Qilong|Q| Sun|Congyong|C| Zhu|Yuan|Y| Niu|Ya|Y| Yu|Jiangnan|J| Xu|Ximing|X|

nanostructured lipid carriers
6-Gingerol
bioavailability
sustained release


Estimation of causal effects of binary treatments in unconfounded studies with one continuous covariate.

Abstract: The estimation of causal effects in nonrandomized studies should comprise two distinct phases: design, with no outcome data available; and analysis of the outcome data according to a specified protocol. Here, we review and compare point and interval estimates of common statistical procedures for estimating causal effects (i.e. matching, subclassification, weighting, and model-based adjustment) with a scalar continuous covariate and a scalar continuous outcome. We show, using an extensive simulation, that some highly advocated methods have poor operating characteristics. In many conditions, matching for the point estimate combined with within-group matching for sampling variance estimation, with or without covariance adjustment, appears to be the most efficient valid method of those evaluated. These results provide new conclusions and advice regarding the merits of currently used procedures.

D018849:Controlled Clinical Trials as Topic

matching
Causal inference
Rubin causal model
regression adjustment
spline


Ipsilateral free semitendinosus graft with interference screw fixation for surgical management of insertional acute Achilles tendon tears.

Abstract:
INTRODUCTION
Very distal tears of the Achilles tendon are uncommon, and poor quality tendinous tissue of the calcaneal stump can compromise healing. Little has been published about the characteristics and surgical management of such injuries. We present a surgical technique, developed by the senior author, to restore continuity of the gastrosoleus-Achilles tendon-calcaneus complex using a free ipsilateral semitendinosus graft, and clinical outcomes of a case series of 28 consecutive patients. Our hypothesis was that this is a safe technique, and patients can return to pre-injury occupation and athletic activities.

PATIENTS AND METHODS
A total of 28 patients (mean age 46 years) underwent minimally invasive reconstruction using a free ipsilateral semitendinosus graft for acute insertional rupture of tendo Achillis. The procedure required two small incisions along the course of the Achilles tendon, and one posteromedial incision at level of the ipsilateral knee to harvest the semitendinosus tendon. Patients were assessed at minimum 2 years (range, 2-2.5 years) following the index procedure.

RESULTS
The median Achilles tendon Rupture Score (ATRS) at the latest follow-up was 88. Two patients developed a superficial wound infection. All patients returned to their preinjury occupation, whilst 22 out of 28 patients (79%), returned to their preinjury level of physical activity at a mean of 6.7 months after surgery, reporting good or excellent overall satisfaction in 88.5% of cases.

CONCLUSION
This minimally invasive technique was safe, and allowed most of patients to return to preinjury daily and sport activities within 9 months from surgery.

Maffulli|Nicola|N|
D'Addona|Alessio|A|
Gougoulias|Nikolaos|N|
Oliva|Francesco|F|
Maffulli|Gayle D|GD|

D019060:Minimally Invasive Surgical Procedures

Semitendinosus graft
Achilles tendon
Minimally invasive
Acute rupture
Insertional avulsion


Genetic correlations between first parity and accumulated second to last parity reproduction traits as selection aids to improve sow lifetime productivity.

Abstract:
OBJECTIVE
The objective of this research was to estimate genetic correlations between number of piglets born alive in the first parity (NBA1), litter birth weight in the first parity (LTBW1), number of piglets weaned in the first parity (NPW1), litter weaning weight in the first parity (LTWW1), number of piglets born alive from second to last parity (NBA2+), litter birth weight from second to last parity (LTBW2+), number of piglets weaned from second to last parity (NPW2+) and litter weaning weight from second to last parity (LTWW2+), and to identify the percentages of animals (the top 10%, 25%, and 50%) for first parity and sums of second and later parity traits.

METHODS
The 9,830 records consisted of 2,124 Landrace (L), 724 Yorkshire (Y), 2,650 LY, and 4,332 YL that had their first farrowing between July 1989 and December 2013. The 8-trait animal model included the fixed effects of first farrowing year-season, additive genetic group, heterosis of the sow and the litter, age at first farrowing, and days to weaning (NPW1, LTWW1, NPW2+, and LTWW2+). Random effects were animal and residual.

RESULTS
Heritability estimates ranged from 0.08±0.02 (NBA1 and NPW1) to 0.29±0.02 (NPW2+). Genetic correlations between reproduction traits in the first parity and from second to last parity ranged from 0.17±0.08 (LTBW1 and LTBW2+) to 0.67±0.06 (LTWW1 and LTWW2+). Phenotypic correlations between reproduction traits in the first parity and from second to last parity were close to zero. Rank correlations between LTWW1 and LTWW2+ estimated breeding value tended to be higher than for other pairs of traits across all replacement percentages.

CONCLUSION
These rank correlations indicated that selecting boars and sows using genetic predictions for first parity reproduction traits would help improve reproduction traits in the second and later parities as well as lifetime productivity in this swine population.

Noppibool|Udomsak|U|
Elzo|Mauricio A|MA|
Koonawootrittriron|Skorn|S|
Suwanasopee|Thanathip|T|

Reproduction Traits
Breeding
Swine
Genetic Parameters
Subsequent Reproductive Performance


Asenapine maleate in situ forming biodegradable implant: an approach to enhance bioavailability.

Abstract: Biodegradable injectable in-situ forming implants (ISFI) correspond to an alternative parenteral depot system to microspheres and surgical implants. Objective of present work was to formulate and evaluate long acting implant of asenapine maleate (ASM) using PLGA which would release drug uniformly for 21 days. PLGA 50:50 with different drug: polymer ratios were tried. N-methyl-2-pyrrolidone and dimethyl sulphoxide were used as organic solvents. The influence of various parameters viz. polymer concentration, solvent ratio, viscosity and morphology on formation of implant was investigated. In-vitro dissolution studies indicated that drug: polymer ratio of 1:2 and N-methyl-2-pyrrolidone (0.3ml) gave desired release profile, total cumulative drug released being 97.66% at the end of 21 days. Mathematical models point towards erosion mechanism with zero order kinetics. Ex-vivo studies confirmed the formation of implant in extensor digitorum muscle with desired drug release profile. In-vivo study was performed in Sprague- Dawley rats. Compared to marketed sublingual formulation area under curve of ASM implant was found to increase 2.215 fold. The Cmax was found to be 11ng/ml. Thus long acting ISFI of ASM was successfully formulated showing improved therapeutic results for the treatment of schizophrenia and bipolar disorders which could be a potentialsubstitute to marketed sublingual tablets.

Avachat|Amelia M|AM|
Kapure|Sayali S|SS|

D006576:Heterocyclic Compounds, 4 or More Rings

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

Asenapine maleate
Bioavailability
In-situ forming implant
PLGA
Schizophrenia


Genetic deletion of Urocortin 3 does not prevent functional maturation of beta cells.

Abstract: There is great interest in generating functionally mature beta cells from stem cells, as loss of functional beta cell mass contributes to the pathophysiology of diabetes. Identifying markers of beta cell maturity is therefore very helpful for distinguishing stem cells that have been successfully differentiated into fully mature beta cells from stem cells that did not. Urocortin 3 (UCN3) is a peptide hormone whose expression is associated with the acquisition of functional maturity in beta cells. The onset of its expression occurs after other beta cell maturity markers are already expressed and its loss marks the beginning of beta cell dedifferentiation. Its expression pattern is therefore tightly correlated with beta cell maturity. While this makes UCN3 an excellent marker of beta cell maturity, it is not established whether UCN3 is required for beta cell maturation. Here, we compared gene expression and function of beta cells from Ucn3-null mice relative to WT mice to determine whether beta cells are functionally mature in the absence of UCN3. Our results show that genetic deletion of Ucn3 does not cause a loss of beta cell maturity or an increase in beta cell dedifferentiation. Furthermore, virgin beta cells, first identified as insulin-expressing, UCN3-negative beta cells, can still be detected at the islet periphery in Ucn3-null mice. Beta cells from Ucn3-null mice also exhibit normal calcium response when exposed to high glucose. Collectively, these observations indicate that UCN3 is an excellent mature beta cell marker that is nevertheless not necessary for beta cell maturation.

Huang|Jessica L|JL|
Lee|Sharon|S|
Hoek|Pelle|P|
van der Meulen|Talitha|T|
Van|Richard|R|
Huising|Mark O|MO|


Lipidomic Analysis: From Archaea to Mammals.

Abstract: Lipids are among the most important organic compounds found in all living cells, from primitive archaebacteria to flowering plants or mammalian cells. They form part of cell walls and constitute cell storage material. Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production (third-generation biofuels produced by microorganisms, e.g. algae) and human diseases such as adrenoleukodystrophy, Zellweger syndrome, or Refsum disease. Current lipidomic analysis requires fast and accurate processing of samples and especially their characterization. Because the number of possible lipids and, more specifically, molecular species of lipids is of the order of hundreds to thousands, it is necessary to process huge amounts of data in a short time. There are two basic approaches to lipidomic analysis: shotgun and liquid chromatography-mass spectometry. Both methods have their pros and cons. This review deals with lipidomics not according to the type of ionization or the lipid classes analyzed but according to the types of samples (organisms) under study. Thus, it is divided into lipidomic analysis of archaebacteria, bacteria, yeast, fungi, algae, plants, and animals.

Řezanka|Tomáš|T| Kolouchová|Irena|I| Gharwalová|Lucia|L| Palyzová|Andrea|A| Sigler|Karel|K|

D002851:Chromatography, High Pressure Liquid

Lipidomics
Archaea
Flower plants
Algae
Bacteria
Yeast
Animals
Mycobacteria


iNOS Associates With Poor Survival in Melanoma: A Role for Nitric Oxide in the PI3K-AKT Pathway Stimulation and PTEN S-Nitrosylation.

Abstract: We previously showed that inducible nitric oxide synthase (iNOS) protein expression in melanoma tumor cells is associated with poor patient prognosis. Here, we analyzed the association between iNOS and the oncogenic PI3K-AKT pathway. TCGA data show that iNOS and phospho-Akt Ser473 expression were associated significantly only in the subset of tumors with genetically intact PTEN. Employing a stage III melanoma TMA, we showed that iNOS protein presence is significantly associated with shorter survival only in tumors with PTEN protein expression. These findings led to our hypothesis that the iNOS product, nitric oxide (NO), suppresses the function of PTEN and stimulates PI3K-Akt activation. Melanoma cells in response to NO exposure in vitro exhibited enhanced AKT kinase activity and substrate phosphorylation, as well as attenuated PTEN phosphatase activity. Biochemical analysis showed that NO exposure resulted in a post-translationally modified S-Nitrosylation (SNO) PTEN, which was also found in cells expressing iNOS. Our findings provide evidence that NO-rich cancers may exhibit AKT activation due to post-translational inactivation of PTEN. This unique activation of oncogenic pathway under nitrosative stress may contribute to the pathogenesis of iNOS in melanoma. Significance: Our study shows that iNOS expression is associated with increased PI3K-AKT signaling and worse clinical outcomes in melanoma patients with wt (intact) PTEN. Mutated PTEN is already inactivated. We also demonstrate that NO activates the PI3K-AKT pathway by suppressing PTEN suppressor function concurrent with the formation of PTEN-SNO. This discovery provides insight into the consequences of inflammatory NO produced in human melanoma and microenvironmental cells. It suggests that NO-driven modification provides a marker of PTEN inactivation, and represents a plausible mechanism of tumor suppressor inactivation in iNOS expressing subset of cancers.

Ding|Zhen|Z|
Ogata|Dai|D|
Roszik|Jason|J|
Qin|Yong|Y|
Kim|Sun-Hee|SH|
Tetzlaff|Michael T|MT|
Lazar|Alexander J|AJ|
Davies|Michael A|MA|
Ekmekcioglu|Suhendan|S|
Grimm|Elizabeth A|EA|

melanoma
nitric oxide
S-nitrosylation
inducible nitric oxide synthase
AKT activation
PI3K-AKT axis
phosphatase and tensin homolog


The effect of reminiscence therapy on the adaptation of elderly women to old age: A randomized clinical trial.

Abstract:
BACKGROUND AND AIM
The changes and limitations that occur in the aging process effect people's adaptation to old age. This study aimed to assess the effect of reminiscence therapy on the adaptation levels of non-institutionalized elderly women to old age.

METHODS
We used a randomized controlled trial design. We conducted the study with 50 elderly women, including 27 women in the intervention group and 23 women in the control group. Study data were recollected by using an introductory information form, Mini-Mental State Examination (MMSE) and Assessment Scale of Adaptation Difficulty for the Elderly (ASADE). Reminiscence therapy was applied to the participants in the intervention group through individual sessions for 8 weeks by making house visits once a week.

RESULTS
At the end of reminiscence therapy made through weekly house visits, we compared the mean ASADE and MMSE scores of intervention and control groups and found that there was a statistically significant difference between the mean ASADE and MMSE scores of the participants in the intervention group (p < 0.05).

CONCLUSIONS
This study found that reminiscence therapy increased the elderly women's adaptation to old age and cognitive level.


Clinical Effectiveness of 6.5-mm-Long Implants to Support Two-Implant Fixed Prostheses in Premolar-Molar Region: The Influence of Immediate Loading and the Length of Splinting Implant.

Abstract:
PURPOSE
The purpose of this retrospective clinical study was to assess the influence of immediate loading and lengths of splinted implants on the clinical effectiveness of 6.5-mm-long implants supporting two-implant fixed prostheses in the premolar-molar regions.

MATERIALS AND METHODS
A clinical database was reviewed in a private dental center to select those patients who had 6.5-mm-long implants placed to support two-implant fixed partial prostheses in the premolar-molar regions of the maxilla and the mandible. All implants were immediately loaded. The study groups were defined according to the lengths of the implants. Two groups were identified: the short-short splinted group, when both implants had 6.5 mm lengths, and the short-long splinted group, when one implant was longer than 6.5 mm. A total of 48 dental implants were placed in 16 patients to support 24 two-implant fixed prostheses. The mean follow-up time was 14 ± 5 months. The short-short splinted group included 8 patients with 16 implants; the short-long splinted group included 16 patients with 32 implants. The main variable was implant survival, and secondary outcomes were marginal bone stability and prosthesis survival.

RESULTS
The statistical analyses indicated an absence of significant differences between the two groups in terms of implant and prosthesis survival (100% for both groups and both variables); however, distal bone loss around the splinted implants was significantly higher in the short-long splinted group. Bone loss was 0.37 ± 0.55 mm in the short-short splinted group and 0.94 ± 0.66 mm in the short-long splinted group.

CONCLUSIONS
Immediate loading of short (6.5-mm-long) implants in the premolar-molar regions did not jeopardize their survival. Two-implant supported prostheses had the same clinical effectiveness, whether extra-short implants were splinted to another extra-short implant or to a longer one.

D057893:Immediate Dental Implant Loading

immediate loading
implant survival
Dental prosthesis
marginal bone loss
short dental implants


A Six-Year Study on the Changes in Airborne Pollen Counts and Skin Positivity Rates in Korea: 2008-2013.

Abstract:
PURPOSE
The occurrence of pollen allergy is subject to exposure to pollen, which shows regional and temporal variations. We evaluated the changes in pollen counts and skin positivity rates for 6 years, and explored the correlation between their annual rates of change.

MATERIALS AND METHODS
We assessed the number of pollen grains collected in Seoul, and retrospectively reviewed the results of 4442 skin-prick tests conducted at the Severance Hospital Allergy-Asthma Clinic from January 1, 2008 to December 31, 2013.

RESULTS
For 6 years, the mean monthly total pollen count showed two peaks, one in May and the other in September. Pollen count for grasses also showed the same trend. The pollen counts for trees, grasses, and weeds changed annually, but the changes were not significant. The annual skin positivity rates in response to pollen from grasses and weeds increased significantly over the 6 years. Among trees, the skin positivity rates in response to pollen from walnut, popular, elm, and alder significantly increased over the 6 years. Further, there was a significant correlation between the annual rate of change in pollen count and the rate of change in skin positivity rate for oak and hop Japanese.

CONCLUSION
The pollen counts and skin positivity rates should be monitored, as they have changed annually. Oak and hop Japanese, which showed a significant correlation with the annual rate of change in pollen count and the rate of change in skin positivity rate over the 6 years may be considered the major allergens in Korea.

Park|Hye Jung|HJ|
Lee|Jae-Hyun|JH|
Park|Kyung Hee|KH|
Kim|Kyu Rang|KR|
Han|Mae Ja|MJ|
Choe|Hosoeng|H|
Oh|Jae-Won|JW|
Hong|Chein-Soo|CS|

change
pollen
skin positivity rate
Allergy
correlation
Seoul


Genomic imbalances in craniofacial microsomia.

Abstract: The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation-dependent probe amplification (MLPA) for all individuals. The CMA was performed only for individuals with additional major features. MLPA revealed pathogenic CNVs at the 22q11 region in 3/54 (5.6%) individuals. CMA revealed pathogenic CNVs in 4/17 (23.5%) individuals, including the three CNVs at the 22q11 region also detected by MLPA, and CNVs classified as variants of unknown significance (VOUS) in 4/17 (23.5%) individuals. Pathogenic alterations were found at the 2p12, 5p15, 13q13, and 22q11 regions. VOUS were found at 3q29, 5q22.2, 5q22.1, and 9p22 regions. All individuals with pathogenic alterations presented additional major features, including congenital heart disease (CHD). The literature review revealed pathogenic CNVs in 17/193 (8.8%) individuals and most of them also presented additional major features, such as CHD, renal anomalies, or developmental delay. In conclusion, CNVs should be investigated in patients with CFM and additional major features.

D056915:DNA Copy Number Variations
D023281:Genomics
D006053:Goldenhar Syndrome
D006330:Heart Defects, Congenital
D006801:Humans
D046228:Microarray Analysis


Clinical and Serological Characterization of the α-Gal Syndrome-Importance of Atopy for Symptom Severity in a European Cohort.

Abstract:
BACKGROUND
The galactose-α1,3-galactose (α-Gal) syndrome (AGS) is a novel form of food allergy. Patients experience delayed severe allergic reactions after mammalian meat consumption due to IgE antibodies directed against the carbohydrate α-Gal present in mammalian meat. The onset of the disease is associated with tick bites.

OBJECTIVE
To characterize a cohort of patients with AGS from Sweden on a clinical and serological level, and identify risk factors for disease severity.

METHODS
A total of 128 patients with symptoms after mammalian meat intake and IgE to α-Gal were included. Medical examination and diagnosis were made by an allergologist and questionnaires were filled in regarding onset of symptoms, tick exposure, and airborne allergies. Serum IgE reactivity against multiple food and airborne allergens, as well as protein extract from the tick Ixodes ricinus, was measured using ImmunoCAP.

RESULTS
The majority of patients were middle aged, with equal gender distribution. Nearly all reported symptoms more than 2 hours after meat consumption. Urticaria (90%) and gastrointestinal symptoms (74%) were most common. Almost half of the patients suffered from anaphylaxis, and α-Gal IgE levels were significantly higher among these patients compared with those without anaphylaxis. Nearly all patients had been tick bitten and 75% had IgE against I. ricinus. More than half of the patients with AGS were atopic, and atopy increased the risk of anaphylaxis with pulmonary manifestations. Only 2 patients belonged to blood group B/AB.

CONCLUSION
AGS is an upcoming food allergy where patients report severe symptoms and tick bites. Atopy was found to affect the manifestation of the disease in Swedish patients.

Kiewiet|M B Gea|MBG|
Apostolovic|Danijela|D|
Starkhammar|Maria|M|
Grundström|Jeanette|J|
Hamsten|Carl|C|
van Hage|Marianne|M|

Atopy
Food allergy
Airborne allergy
Anaphylaxis
Galactose-alpha-1,3-galactose
Red meat allergy
α-Gal syndrome


Rapid Progression to Complete Paraplegia After Electroacupuncture in a Patient With Spinal Dural Arteriovenous Fistula: A Case Report.

Abstract: Spinal dural arteriovenous fistula (SDAVF) usually has an insidious clinical course, but 5-15% of the cases have acute exacerbations. In some cases, there is an abrupt progression to paraplegia following an epidural injection or anesthesia. Electroacupuncture is a form of acupuncture that applies a small electrical current to needles inserted at specific points in the body. It is widely used for its analgesic effect on back pain. In this study, we report a rare case of SDAVF in which the symptoms of a patient worsened rapidly to complete paraplegia within a few hours after applying electroacupuncture to his back. A 49-year-old man had rapid progression to complete paraplegia within a few hours of electroacupuncture on his back. MRI showed SDAVF and worsening of cord signal change. An emergency operation was performed to ligate the SDAVF. The patient was able to walk 1 month post-operatively. Most of the neurological deficits had disappeared by 1 year post-operatively, with normalization of MRI. Our case emphasizes that SDAVF patients should be careful when exposed to any circumstances that might affect the circulation around the dural arteriovenous fistula, such as electroacupuncture. Patients should also be warned in advance about the possibility of rapid exacerbation of neurological symptoms. Regardless of the severity of the neurological symptoms, immediate treatment is essential for recovery and a better outcome.

Park|Ki-Hoon|KH| Jeon|Chang-Hoon|CH| Chung|Nam-Su|NS| Lee|Han-Dong|HD|

paraplegia
electroacupuncture
spinal dural arteriovenous fistula
neurologic deficits
spinal vascular malformation


Prenatal caffeine exprosure increases adult female offspring rat's susceptibility to osteoarthritis via low-functional programming of cartilage IGF-1 with histone acetylation.

Abstract: Our previous in vivo studies showed that prenatal caffeine exposure (PCE) could restrain the development of chondrogenesis, which may delay fetal articular cartilage development and increase susceptibility to osteoarthritis in adults. So, the goal of the current study is to clarify theincreasing susceptibility to adult osteoarthritis in caffeine-exposed female offspring and its'mechanism. Pregnant rats were treated with 120 mg/kg·d caffeine or equal volumes of saline from gestational day (GD) 9 to 20. knee joints were collected from GD20 female fetuses and 18-week old female offspring which was treated with strenuous running for 6 weeks (55 min/day at 20 m/min) load to induce osteoarthritis. Knee joints from GD20 fetuses and adult offspring were collected for histochemistry and immunohistochemistry. Next, chondrocytes were isolated from 1-day-old newborn rats and in vitro studies were conducted where the cells in primary culture were exposed to 1, 10, and 100 μM caffeine and 250, 500, and 1,250 nM corticosterone. Insulin-like growth factor 1 (IGF-1) signal pathway genes' expression levels in fetal chondrocytes were studied, and IGF-1 histone acetylation was detected in vitro. Immunohistochemical results showed low expression levels of IGF-1 signaling genes (IGF-1, IRS-1, AKT, and COL2A1) both in fetal and adult cartilage with PCE. For adult offspring, histological results and Mankin score revealed increased cartilage destruction and accelerated osteoarthritis progression in PCE group with strenuous running exercise. Analysis in vitro revealed that caffeine and corticosterone impeded the expression of IGF-1 signaling pathway aggrecan and COL2A1 genes, but only corticosterone decreased H3K9 and H3K27 acetylation in the IGF-1 promoter region. In concluson, PCE low functional programmed cartilage IGF-1 by histone acetylation modification via overexposure to corticosterone and delayed articular cartilage development from fetus to adults. Then, the delayed cartilage development increased susceptibility to osteoarthritis in offsprings.

Tan|Yang|Y| Lu|Kaihang|K| Li|Jing|J| Ni|Qubo|Q| Zhao|Zhe|Z| Magdalou|Jacques|J| Chen|Liaobin|L| Wang|Hui|H|

D000697:Central Nervous System Stimulants

D011297:Prenatal Exposure Delayed Effects

caffeine
osteoarthritis
insulin-like growth factor 1
glucocorticoid
intrauterine programming


Monitoring Inflammasome Priming and Activation in Response to Candida albicans.

Abstract: Candida albicans is a common mucosal colonizer, as well as a cause of lethal invasive fungal infections. The major predisposing factor for invasive fungal disease is a compromised immune system. One component of the host immune response to fungal infection is the activation of the inflammasome, a multimeric protein complex that is critical for regulating host pro-inflammatory responses. Here, we describe methods for investigating the interactions between C. albicans and host macrophages, with a focus on the inflammasome. C. albicans isolates differ in the degree to which they activate the inflammasome due to differences in internalization, morphogenic switching, and inflammasome priming. Therefore, we include protocols for identifying these factors. This simple in vitro model can be used to elucidate the contributions of specific C. albicans strains or mutants to different aspects of interactions with macrophages. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Measuring inflammasome priming in response to Candida albicans Basic Protocol 2: Measuring inflammasome activation in response to Candida albicans Support Protocol: Controlling for phagocytosis.

Santana|Darian J|DJ|
Anderson|Faith M|FM|
O'Meara|Teresa R|TR|

inflammasome priming
inflammasomes
Candida albicans
macrophages
pyroptosis


The Theoretical Basis of In Utero Hematopoietic Stem Cell Transplantation and Its Use in the Treatment of Blood Disorders.

Abstract: Since its conception, prenatal therapy has been successful in correction of mainly anatomical defects, although the range of application has been limited. Research into minimally invasive fetal surgery techniques and prenatal molecular diagnostics has facilitated the development of in utero stem cell transplantation (IUT)-a method of delivering healthy stem cells to the early gestation fetus with the hope of engraftment, proliferation, and migration to the appropriate hematopoietic compartment. An area of application that shows promise is the treatment of hematopoietic disorders like hemoglobinopathies. The therapeutic rationale of IUT with hematopoietic stem cells (HSCs) is based on the proposed advantages the fetal environment offers based on its unique physiology. These advantages include the immature immune system facilitating the development of donor-specific tolerance, the natural migration of endogenous hematopoietic cells providing space for homing and engraftment of donor cells, and the fetal environment providing HSCs with the same opportunity to survive and proliferate regardless of their origin (donor or host). Maternal immune tolerance to the fetus and placenta also implies that the maternal environment could be accepting of donor cells. In theory, the fetus is a perfect recipient for stem cell transplant. Clinically, however, IUT is yet to see widespread success calling into question these assumptions of fetal physiology. This review aims to discuss and evaluate research surrounding these key assumptions and the clinical success of IUT in the treatment of thalassemia.

in utero hematopoietic stem cell transplantation


Early psychotherapeutic empathy, alliance, and client outcome: Preliminary evidence of indirect effects.

Abstract: The association between psychotherapeutic empathy and client outcome is well established, yet the mechanisms underlying this association remain poorly understood. We hypothesized that early experiences of empathy influence outcome through the working alliance. To test this hypothesis, we used archival data collected from 56 clients (mean [M] age = 19.5 years, 83.9% female, 76.8% White) who reported mild, moderate, or severe depressive symptoms at screening and pretreatment assessments and then received five sessions of evidence-based psychotherapy. Therapists (M age = 26.0 years, 50% female, 100% White) were six students in a clinical psychology PhD program. Results of bootstrap analyses were consistent with the idea that early experiences of empathy strengthen the alliance (specifically the goals and tasks facets), which in turn facilitates improvements in depressive symptoms and psychological well-being. While preliminary, these results implicate a specific pathway of change in the treatment of depression.

McClintock|Andrew S|AS|
Anderson|Timothy|T|0000-0001-7224-2728
Patterson|Candace L|CL|
Wing|Edgar H|EH|

mechanism
alliance, empathy, indirect effect


Extracellular Microvesicles as New Industrial Therapeutic Frontiers.

Abstract: Microvesicles (MVs) are subcellular physiological vehicles present in all body fluids that mediate the transfer of intercellular information within biological systems and contribute to healthy conditions. MVs have lipid bilayer membranes decorated with multiple ligands that can interact with receptors on target cells, rendering them as promising candidates for targeted delivery. The biotechnology and cell therapy industries are developing MV-based preparations that use this subcellular therapeutic machinery (in a naïve or modified state) for regenerative medicine, as substitutes for intact cell therapy, and as intelligent targeted drug delivery carriers. However, significant production challenges must be overcome before MVs scale-up development, clinical translation, and routine therapeutic application can be realized. The unique expertise developed in the biotechnology industry should facilitate market access to MV-based therapeutics. In this review, the roles of biotechnology and cell therapy industries to manufacture MVs as inherent therapeutic agents or drug delivery systems are summarized. The manufacturing, development, characterization, and regulatory challenges for successful translation are discussed.

Agrahari|Vivek|V|
Agrahari|Vibhuti|V|
Burnouf|Pierre-Alain|PA|
Chew|Chee Ho|CH|
Burnouf|Thierry|T|

D001709:Biotechnology
D000067128:Extracellular Vesicles
D006801:Humans
D058990:Molecular Targeted Therapy
D044968:Regenerative Medicine
D013678:Technology, Pharmaceutical

microvesicles
therapies
clinical translation
delivery systems
assessment
clinical use
extracellular vesicles
functions
isolation
purification
tissue regeneration


Continuous subcutaneous insulin infusion: Special needs for children.

Abstract: Continuous subcutaneous insulin infusion (CSII) is a very common therapy for children with type 1 diabetes. Due to physiological differences they have other requirements for their insulin pump than adults. The main difference is the need for very low basal rates. Even though most available insulin pumps reach a high accuracy at usual basal rates, accuracy decreases for lower rates. In addition, the lowest delivered amount at 1 time is limiting the fine tuning of the basal rate as well as the option for temporary basal rates. Alarms in case of occlusions depend on accumulation of a certain amount of insulin in the catheter, and therefore the time until such an alarm is triggered is much longer with lower basal rates. Accordingly, the risk for hyperglycemia developing into diabetic ketoacidosis increases. The availability of bolus advisors facilitates the calculation of meal and correction boluses for children and their parents. However, there are some differences between the calculators, and the settings that the calculation is based on are very important. Better connectivity, for example with a system for continuous glucose monitoring, might help to further increase safety in the use of CSII in children. When selecting an insulin pump for a child, the features and characteristics of available pumps should be properly compared to ensure an effective and safe therapy.

D017195:Adolescent Nutritional Physiological Phenomena

D002664:Child Nutritional Physiological Phenomena

continuous subcutaneous insulin infusion


Selective predation on acorn weevils by seed-caching Siberian chipmunk Tamias sibiricus in a tripartite interaction.

Abstract: Although food-hoarding animals benefit plant seeds by generating predation pressure on granivorous insects, we lack experimental evidence of whether the tripartite interactions maintain a mutualistic relationship between the third trophic level and primary producers. Relying on the behavior of shelling, Siberian chipmunks (Tamias sibiricus) selectively consumed weevil larvae infested in acorns of Mongolian oak (Quercus mongolica) but chose the non-infested acorns to scatter-hoard. Shelling not only reduced volatile emission from acorns but also decreased cache loss to pilferers, weevil larvae and fungi, allowing T. sibiricus to gain more rewards from their caches. Moreover, shelling by T. sibiricus enhanced acorn germination and seedling establishment of Q. mongolica, possibly due to the diminishment of the negative effects of weevil infestation on acorn viability. Here, we show that both food-hoarding animal T. sibiricus and oak Q. mongolica can be conditionally benefited from selective predation on weevil larvae inside acorns. Our results highlight the need to integrate the mutualisms between the third and first trophic level into the tripartite interaction model. We suggest that more efforts should be made in the tripartite interactions of food-hoarding animals, seeds and granivorous insects.

Yang|Yueqin|Y| Wang|Zhenyu|Z| Yan|Chuan|C| Zhang|Yihao|Y| Zhang|Dongyuan|D| Yi|Xianfeng|X|

Tripartite interaction
Cache loss
Weevil infestation
Acorn selection
Hoarding animal
Seedling recruitment


Molecular epidemiology of Staphylococcus aureus nasal colonization among patients and their parents /guardian in an Iranian referral hospital.

Abstract:
INTRODUCTION
Carriage of Staphylococcus aureus in the nose appears to play a key role in the epidemiology and pathogenesis of infection. It is important to investigate the genetic relatedness of S. aureus and MRSA clones in different geographic regions. The aim of this study was to assess the nasal carriage rate of S. aureus, including MRSA strains in both hospitalized children and general adult population (parents/guardian). In addition, antibiotic susceptibility pattern and molecular diversity of S. aureus in both population was evaluated in an Iranian referral pediatrics Hospital.

MATERIAL AND METHODS
All samples were obtained through nasal screening of patients and general adult population at admission and discharge day. The prevalence, resistance, and molecular diversity of all S. aureus isolates were examined.

RESULTS
In the current study, nasal carriage of S. aureus and Staphylococcus non aureus was identified in 384 (26%) and 1004 (68%) of the study population. The prevalence of MRSA nasal carriage in children and adults was 6.6% (29 out of 438) and 2.8% (29 out of 1046), respectively. Among S. aureus strains isolated obtained from patients and general adult population at admission day, high sensitivity to most of the antibiotics such as vancomycin (100%), rifampin (95%), linezolid (94%), quinupristin/dalfopristin (94%), minocycline (94%), chloramphenicol (89%), gentamycin (87%), amikacin (87%), clindamycin (86%) and moxifloxacin (83%) was seen. The most resistance antibiotics were penicillin (96-98%) and methicillin (44-47%). The susceptibility patterns of nasal S. aureus strains isolated at discharge day was not statistically different from S. aureus isolates obtained at admission day. Admission S. aureus isolated strains of 77 patients (64%) were similar to the isolated S. aureus strains of discharge, while S. aureus isolated strains of 43 patients (36%) was not similar to the strain of discharge (had similarity of less than 70%).

CONCLUSION
High prevalence of nasal carriage of S. aureus and MRSA indicates the urgent need to improve strategies for management of S. aureus infections. Our findings are useful for understanding of S. aureus nasal colonization dynamics within the patients and general population. Surveillance for S. aureus in community settings can provide data on circulating strains and might help developing control measures for reducing of infection spread in hospitals.

Pourakbari|Babak|B|
Khodabandeh|Mahmoud|M|
Mahmoudi|Shima|S|
Sabouni|Farah|F|
Aziz-Ahari|Alireza|A|
Bahador|Abbas|A|
Keshavarz Valian|Sepideh|S|
Hosseinpour Sadeghi|Reihaneh|R|
Mamishi|Setareh|S|

D024901:Drug Resistance, Multiple, Bacterial

Staphylococcus aureus
Antibiotic susceptibility patterns
Genotyping


Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma.

Abstract:
BACKGROUND
In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.

OBJECTIVE
We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.

METHODS
Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses.

RESULTS
Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested.

CONCLUSION
Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.

McCauley|Kathryn|K|
Durack|Juliana|J|
Valladares|Ricardo|R|
Fadrosh|Douglas W|DW|
Lin|Din L|DL|
Calatroni|Agustin|A|
LeBeau|Petra K|PK|
Tran|Hoang T|HT|
Fujimura|Kei E|KE|
LaMere|Brandon|B|
Merana|Geil|G|
Lynch|Kole|K|
Cohen|Robyn T|RT|
Pongracic|Jacqueline|J|
Khurana Hershey|Gurjit K|GK|
Kercsmar|Carolyn M|CM|
Gill|Michelle|M|
Liu|Andrew H|AH|
Kim|Haejin|H|
Kattan|Meyer|M|
Teach|Stephen J|SJ|
Togias|Alkis|A|
Boushey|Homer A|HA|
Gern|James E|JE|
Jackson|Daniel J|DJ|
Lynch|Susan V|SV|
|||

airway
Microbiota
exacerbation
asthma
16S rRNA
rhinovirus
Moraxella species
Staphylococcus species


Changes in Ca2+ Signaling and Nitric Oxide Output by Human Umbilical Vein Endothelium in Diabetic and Gestational Diabetic Pregnancies.

Abstract: Diabetes (DM) complicates 3%-10% of pregnancies, resulting in significant maternal and neonatal morbidity and mortality. DM pregnancies are also associated with vascular dysfunction, including blunted nitric oxide (NO) output, but it remains unclear why. Herein we examine changes in endothelial NO production and its relationship to Ca(2+) signaling in endothelial cells of intact umbilical veins from control versus gestational diabetic (GDM) or preexisting diabetic subjects. We have previously reported that endothelial cells of intact vessels show sustained Ca(2+) bursting in response to ATP, and these bursts drive prolonged NO production. Herein we show that in both GDM and DM pregnancies, the incidence of Ca(2+) bursts remains similar, but there is a reduction in overall sustained phase Ca(2+) mobilization and a reduction in NO output. Further studies show damage has occurred at the level of NOS3 protein itself. Since exposure to DM serum is known to impair normal human umbilical vein endothelial cell (HUVEC) function, we further studied the ability of HUVEC to signal through Ca(2+) after they were isolated from DM and GDM subjects and maintained in culture for several days. These HUVEC showed differences in the rate of Ca(2+) bursting, with DM > GDM = control HUVEC. Both GDM- and DM-derived HUVEC showed smaller Ca(2+) bursts that were less capable of NOS3 activation compared to control HUVEC. We conclude that HUVEC from DM and GDM subjects are reprogrammed such that the Ca(2+) bursting peak shape and duration are permanently impaired. This may explain why ROS therapy alone is not effective in DM and GDM subjects.

Anaya|Heather A|HA|
Yi|Fu-Xian|FX|
Boeldt|Derek S|DS|
Krupp|Jennifer|J|
Grummer|Mary A|MA|
Shah|Dinesh M|DM|
Bird|Ian M|IM|

D061307:Human Umbilical Vein Endothelial Cells

nitric oxide
endothelium
diabetes
pregnancy
calcium


Effects of combined and classic training on different isometric rate of force development parameters of leg extensors in female volleyball players: Discriminative analysis approach.

Abstract:
BACKGROUND
The aim of this study is to verify the effects of the combined and classic training of different isometric rates of force development (RFD) parameters of legs.

MATERIALS AND METHODS
THREE GROUPS OF FEMALE ATHLETES WAS TESTED: Experimental group (N = 12), classically trained group (N = 11), and control group (N = 20) of athletes. The isometric "standing leg extension" and "Rise on Toes" tests were conducted to evaluate the maximal force, time necessary time to reach it and the RFD analyzed at 100 ms, 180 ms, 250 ms from the onset, and 50-100% of its maximal result.

RESULTS
The maximal RFD of legs and calves are dominant explosive parameters. Special training enhanced the RFD of calves of GROUPSPEC at 100 ms (P = 0.05), at 180 ms (P = 0.039), at 250 ms (P = 0.039), at 50% of the Fmax (P = 0.031) and the Fmax (P = 0.05). Domination of GROUPSPEC toward GROUPCLASS and GROUPCONTROL is in case of legs at 100 ms (P = 0.04); at 180 ms (P = 0.04); at 250 ms (P = 0.00); at 50% of the Fmax (P = 0.01) and at the Fmax (P = 0.00); in case of calves at 100 ms (P = 0.07); 180 ms (P = 0.001); at 250 ms (P = 0.00); at 50% of the Fmax (P = 0.00) and at Fmax (P = 0.000).

CONCLUSION
Dominant explosive factors are maximal RFD of leg extensors and calves, and legs at 250ms. Specific training enhanced explosiveness of calves of GROUPSPEC general and partial domination of GROUPSPEC by 87% over GROUPCLASS, and 35% over GROUPCONTROL.

Branislav|Rajić|R|
Milivoj|Dopsaj|D|
Abella|Carlos Pablos|CP|
Deval|Vicente Caratalla|VC|
Siniša|Karišik|K|

isometric rate of force development
leg extensors
volleyball
Calf muscles
plyometric training


From fragments to identity: reminiscence, life review and well-being of holocaust survivors. An integrative review.

Abstract: Objectives: Survivors of the Holocaust have reached an age during which it is common for them to look back on their lives. Previous research has shown that reminiscence can take on either adaptive ('self-positive') or detrimental ('self-negative') forms, which in turn are differently linked to psychological well-being. Thus, the question of "why" and "how" Holocaust survivors recall their autobiographical memories may hold important information about the underlying coping processes at play. This review aims to give insight into the current state of research on these questions.Method: A systematic literature search was conducted, looking for articles reporting quantitative and qualitative research on reminiscence and narrative styles, life review and well-being of Holocaust survivors. A methodological quality assessment was undertaken.Results: 23 articles met the criteria for inclusion. These articles focused either on reminiscence functions or on content and structure of life narratives. Such autobiographical reports were shaped by the experience of Holocaust. However, actual well-being was particularly determined by positive life events. Studies found evidence for resilience and ongoing effort to integrate the past into a coherent review. The link between reminiscence and health remains stable even after massive trauma. Contextual influences (such as culture) and age are discussed as possible covariates.Conclusions: The results show that Holocaust survivors are able to use reminiscence in a functional way, though they are increasingly more vulnerable as they reach very old age. The link between past suffering and present well-being gets stronger with age. Other stressful life experiences after the Holocaust must be considered as exacerbating factors. This review also presents the implications for therapy and open research questions are discussed.

reminiscence
life review
well-being
Holocaust survivor
narrative


Applicability of the Disruptions in Surgery Index in the Cardiovascular Management Scenarios - A Marker for Developing Functionally Efficient Teams.

Abstract:
INTRODUCTION
To support the development of practices and guidelines that might help to reduce adverse events related to human factors, we aimed to study the response and perception by members of a cardiovascular surgery team of various error-driven or adverse features that might arise in the operating room (OR).

METHODS
A previously validated Disruptions in Surgery Index (DiSI) questionnaire was completed by individuals working together in a cardiovascular surgical unit. Results were submitted to reliability analysis by calculating the Cronbach's alpha coefficient. Non-parametric Kruskal-Wallis test and Dunn's post-test were performed to estimate differences in perceptions of adverse events or outcomes between the groups (surgeons, nurses, anesthesiologists, and technicians). P<0.05 was considered statistically significant.

RESULTS
Cronbach's alpha reliability coefficients showed consistency within the recommended range for all disruption types assessed in DiSI: an individual's skill (0.85), OR environment (0.88), communication (0.81), situational awareness (0.92), patient-related disruption (0.89), team cohesion (0.83), and organizational disruption (0.83). Nurses (27.4%) demonstrated significantly higher perception of disruptions than surgeons (25.4%), anesthetists (23.3%), and technicians (23.0%) (P=0.005). Study participants were more observant of their colleagues' disruptive behaviors than their own (P=0.0001).

CONCLUSION
Our results revealed that there is a tendency among participants to hold a positive self-perception position. DiSI appears to be a reliable and useful tool to assess surgical disruptions in cardiovascular OR teams, identifying negative features that might imperil teamwork and safety in the OR. And human factors training interventions are available to develop team skills and improve safety and efficiency in the cardiovascular OR.

Nina|Vinicius|V|0000-0003-3852-0602
Mendes|Augusto Gonçalves|AG|
Sevdalis|Nick|N|
Marath|Aubyn|A|
Mejia|Omar Vilca|OV|
Brandão|Carlos Manuel A|CMA|
Monteiro|Rosangela|R|
Mendes|Vinícius Giuliano|VG|
Jatene|Fabio B|FB|

Perception
Cardiovascular Surgery
Surgeons
Communication
Patient Safety
Problem Behavior
Self-Concept


CGRP 4218T/C polymorphism correlated with postoperative analgesic effect of fentanyl.

Abstract:
PURPOSE
Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population.

METHODS
98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method.

RESULTS
The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (P<0.05). Meanwhile, the fentanyl consumption of the C/C group was much higher than the T/T group (P<0.05) at the 12th hour and the 24th hour. Besides, the fentanyl consumption of the C/C group was more than the T/C group (P<0.05) at the 24th hour. The differences in NRS scores, Ramsey scores, and postoperative adverse reactions between each group at all time points were not statistically significant.

CONCLUSIONS
CGRP 4218T/C polymorphism may be associated with the postoperative fentanyl consumption for analgesia.

Yi|Yusheng|Y| Zhao|Mingqiang|M| Xu|Fenghe|F| Liu|Chuansheng|C| Yin|Yanwei|Y| Yu|Junmin|J|

D020022:Genetic Predisposition to Disease

D012150:Polymorphism, Restriction Fragment Length


Depletion of tylosin residues in feathers, muscle and liver from broiler chickens after completion of antimicrobial therapy.

Abstract: Tylosin is one of the most commonly used antimicrobial drugs from the macrolide family and in broiler chickens it is used specially for the treatment of infectious pathologies. The poultry industry produces several by-products, among which feathers account for up to 7% of a chicken's live weight, thus they amount to a substantial mass across the whole industry. Feathers have been repurposed as an animal feed ingredient by making them feather meal. Therefore, the presence of high concentrations of residues from antimicrobial drugs in feathers might pose a risk to global public health, due to re-entry of these residues into the food chain. This work aimed to characterise the depletion behaviour of tylosin in feather samples, while considering its depletion in muscle and liver tissue samples as a reference point. To achieve this goal, we have implemented and validated an analytical methodology suitable for detecting and quantifying tylosin in these matrices. Sixty broiler chickens, raised under controlled conditions, received an oral dose of 32 mg kg-1 of tylosin for 5 days. Tylosin was quantified in muscle, liver and feathers by liquid chromatography coupled with a photodiode array detector (HPLC-DAD). High concentrations of tylosin were detected in feather samples over the whole experimental period after completing both the therapy and the recommended withdrawal time (WDT). On the other hand, tylosin concentrations in muscle and liver tissue samples fell below the limit of detection of this method on the first sampling day. Our results indicate that the WDT for feather samples is 27 days, hence using feather meal for the formulation of animal diets or for other agricultural purposes could contaminate with antimicrobial residues either other livestock species or the environment. In consequence, we recommend monitoring this matrix when birds have been treated with tylosin, within the context of poultry farming.

Cornejo|Javiera|J|
Pokrant|Ekaterina|E|
Carvallo|Carolina|C|
Maddaleno|Aldo|A|
San Martín|Betty|B|

depletion
Tylosin
feathers
muscle
liver
antibiotic residues


HomBlocks: A multiple-alignment construction pipeline for organelle phylogenomics based on locally collinear block searching.

Abstract:
Organelle phylogenomic analysis requires precisely constructed multi-gene alignment matrices concatenated by pre-aligned single gene datasets. For non-bioinformaticians, it can take days to weeks to manually create high-quality multi-gene alignments comprising tens or hundreds of homologous genes. Here, we describe a new and highly efficient pipeline, HomBlocks, which uses a homologous block searching method to construct multiple sequence alignment. This approach can automatically recognize locally collinear blocks among organelle genomes and excavate phylogenetically informative regions to construct multiple sequence alignment in a few hours. In addition, HomBlocks supports organelle genomes without annotation and makes adjustment to different taxon datasets, thereby enabling the inclusion of as many common genes as possible. Topology comparison of trees built by conventional multi-gene and HomBlocks alignments implemented in different taxon categories shows that the same efficiency can be achieved by HomBlocks as when using the traditional method. The availability of Homblocks makes organelle phylogenetic analyses more accessible to non-bioinformaticians, thereby promising to lead to a better understanding of phylogenic relationships at an organelle genome level.

AVAILABILITY AND IMPLEMENTATION
HomBlocks is implemented in Perl and is supported by Unix-like operative systems, including Linux and macOS. The Perl source code is freely available for download from https://github.com/fenghen360/HomBlocks.git, and documentation and tutorials are available at https://github.com/fenghen360/HomBlocks.

CONTACT
yxmao@ouc.edu.cn or fenghen360@126.com.

Bi|Guiqi|G| Mao|Yunxiang|Y| Xing|Qikun|Q| Cao|Min|M|

Organelle phylogenomics
Locally collinear blocks
Efficient pipeline
Alignment construction


Risk-based postprandial hypoglycemia forecasting using supervised learning.

Abstract:
BACKGROUND
Predicting insulin-induced postprandial hypoglycemic events is critical for the safety of type 1 diabetes patients because an early warning of hypoglycemia facilitates correction of the insulin bolus before its administration. The postprandial hypoglycemic event counts can be lowered by reducing the size of the bolus based on a reliable prediction but at the cost of increasing the average blood glucose.

METHODS
We developed a method for predicting postprandial hypoglycemia using machine learning techniques personalized to each patient. The proposed system enables on-line therapeutic decision making for patients using a sensor augmented pump therapy. Two risk-based approaches were developed for a window of 240 min after the meal/bolus, and they were tested based on real retrospective data from 10 patients using 70 mg/dL and 54 mg/dL as thresholds according to the consensus for Level 1 and Level 2 hypoglycemia, respectively. Due to the small size of the patient cohort, we trained personalized models for each patient.

RESULTS
The median specificity and sensitivity were 79% and 71% for Level 1 hypoglycemia, respectively, and 81% and 77% for Level 2.

CONCLUSIONS
The results demonstrated that it is feasible to anticipate hypoglycemic events with a reasonable false-positive rate. The accuracy of the results and the trade-off between performance metrics allow its use in decision support systems for patients who wear insulin pumps.

Oviedo|Silvia|S| Contreras|Ivan|I| Quirós|Carmen|C| Giménez|Marga|M| Conget|Ignacio|I| Vehi|Josep|J|

Postprandial hypoglycemia
Type 1 diabetes
Blood glucose
Machine learning
Bolus calculation
Hypoglycemia prediction


Nonlinear Ultrasound Crack Detection with Multi-Frequency Excitation-A Comparison.

Abstract: Nonlinear ultrasound crack detection methods are used as modern, non-destructive testing tools for inspecting early damages in various materials. Nonlinear ultrasonic wave modulation, where typically two or more frequencies are excited, was demonstrated to be a robust method for failure indicators when using measured harmonics and modulated response frequencies. The aim of this study is to address the capability of multi-frequency wave excitation, where more than two excitation frequencies are used, for better damage identification when compared to single and double excitation frequencies without the calculation of dispersion curves. The excitation frequencies were chosen in such a way that harmonic and modulated response frequencies meet at a specific frequency to amplify signal energy. A new concept of nonlinearity parameter grouping with multi-frequency excitation was developed as an early failure parameter. An analytical solution of the one-dimensional wave equation was derived with four fundamental frequencies, and a total of 64 individual and 30 group nonlinearity parameters. Experimental validation of the approach was conducted on metal plates with different types of cracks and on turbine blades where cracks originated under service conditions. The results showed that the use of multi-frequency excitation offers advantages in detecting cracks.

nonlinear ultrasound
crack detection
modulation
gas turbines


(Too) Anxious to help? Social support provider anxiety and cardiovascular function.

Abstract: Provider factors, such as anxiety, may be important in understanding effects of received social support (SS), which are less consistently positive than those of perceived SS. Due to the dyadic nature of support, anxiety on the part of the provider was predicted to influence the effectiveness of received SS. This laboratory study examined effects of SS provider anxiety within unacquainted dyads on cardiovascular reactivity during acute stress. 148 participants were assigned to support roles, and each dyad was randomized to low or high provider anxiety. Results include that SS provider anxiety resulted in greater blood pressure reactivity and less recovery toward baseline diastolic blood pressure within the dyad. Overall, it appears provider anxiety contributes to less effective SS for recipients and that health costs may accompany providing and receiving support under nonoptimal conditions.

Kent de Grey|Robert G|RG|
Uchino|Bert N|BN|
Smith|Timothy W|TW|
Baucom|Brian R W|BRW|

Social support
Anxiety
Cardiovascular reactivity
Health
Interpersonal relationships


Toxic leukoencephalopathy-When a Boxer's fracture requires an MRI and LP.

Abstract: This case report describes a young patient presenting to the ED with altered mental status several days after being diagnosed with a Boxer's fracture and ultimately discovered to have toxic leukoencephalopathy. We review the clinical features in his presentation leading to his diagnosis, as well as MRI imaging findings frequently found in his condition.

Leukoencephalopathy
Confusion
MRI of the brain


A Machine Learning Based Clustering Protocol for Determining Hearing Aid Initial Configurations from Pure-Tone Audiograms.

Abstract: Of the nearly 35 million people in the USA who are hearing impaired, only an estimated 25% use hearing aids (HA). A good number of HAs are prescribed but not used partially because of the time to convergence for best operation between the audiologist and user. To improve HA retention, it is suggested that a machine learning (ML) protocol could be established which improves initial HA configurations given a user's pure-tone audiogram. This study examines a ML clustering method to predict the best initial HA fitting from a corpus of over 90,000 audiogram-fitting pairs collected from hearing centers throughout the USA. We first examine the final HA comfort targets to determine a limited number of preset configurations using several multi-dimensional clustering methods (Birch, Ward, and k-means). The goal is to reduce the amount of adjustments between the centroid, selected as a fitting configuration to represent the cluster, and the final HA configurations. This may be used to reduce the adjustment cycles for HAs or as preset starting configurations for personal sound amplification products (PSAPs). Using various classification methods, audiograms are mapped to a limited number of potential preset configurations. Finally, the average adjustment between the preset fitting targets and the final fitting targets is examined.

Belitz|Chelzy|C|
Ali|Hussnain|H|
Hansen|John H L|JHL|

clustering
Hearing Aids
audiogram
classification
audiometry


Electron Density-Change in Semiconductor by Ion-Adsorption at Solid-Liquid Interface.

Abstract: The change in electrical properties of electrodes by adsorption or desorption at interfaces is a well-known phenomenon required for signal production in electrically transduced sensing technologies. Furthermore, in terms of electrolyte-insulator-semiconductor (EIS) structure, several studies of energy conversion techniques focused on ion-adsorption at the solid-liquid interface have suggested that the electric signal is generated by ionovoltaic phenomena. However, finding substantial clues for the ion-adsorption phenomena in the EIS structure is still a difficult task because direct evidence for carrier accumulation in semiconductors by Coulomb interactions is insufficient. Here, a sophisticated Hall measurement system is demonstrated to quantitatively analyze accumulated electron density-change inside the semiconductor depending on the ion-adsorption at the solid-liquid interface. Also, an enhanced EIS-structured device is designed in an aqueous-soaked system that works with the ionovoltaic principle to monitor the ion-dynamics in liquid electrolyte media, interestingly confirming ion-concentration dependence and ion-specificity by generated peak voltages. This newly introduced peculiar method contributes to an in-depth understanding of the ionovoltaic phenomena in terms of carrier actions in the semiconductors and ionic behaviors in the aqueous-bulk phases, providing informative analysis about interfacial adsorptions that can expand the scope of ion-sensing platforms.


Cationic starch derivatives as mucoadhesive and soluble excipients in drug delivery.

Abstract: The aim of this study was to develop a novel mucoadhesive cationic polymer by introducing primary amino groups to the polymeric backbone of starch. This newly synthesized polymer should exhibit superior properties over chitosan regarding solubility, mucoadhesiveness and cytotoxicity. Increasing amounts of sodium periodate were used to cleave and oxidize vicinal diols under aldehyde formation obtaining three different degrees of modification. In a subsequent step, primary amines were introduced via reductive amination with ammonia. Degree of amination was examined with TNBS-assay and zeta potential measurements. Mucoadhesiveness was investigated by rotating cylinder, tensile studies and rheological measurements. Primary amino groups were successfully attached to the polymer, proven by zeta potential measurements and UV-spectroscopy. Depending on the amount of periodate used in the reaction, coupling rates of up to 514 µmol/g polymer were achieved. All synthesized derivatives showed 100% solubility in a pH range of 1-9. Aminated starch with the highest coupling rate of 514 µmol/g showed a 9.5-fold prolonged retention time on intestinal mucosa and a 2.7-fold higher total work of adhesion on the mucosal tissue compared to chitosan. Furthermore, cytotoxic examinations of all tested polymers showed only a low impact on cell viability after 24 h, whereby starch derivatives possessed even less cell toxic effects than chitosan. Summarizing these results, cationic starch derivatives seem to be promising excipients for mucosal drug delivery with superior properties compared to chitosan, the most examined cationic polymer.

Jelkmann|Max|M| Leichner|Christina|C| Menzel|Claudia|C| Kreb|Verena|V| Bernkop-Schnürch|Andreas|A|

Cationic starch
Starch
Mucoadhesion
Drug delivery
Polymer
Amination


The effect of intestinal permeability and endotoxemia on the prognosis of acute pancreatitis.

Abstract:
BACKGROUND/AIMS
Early intestinal mucosal damage plays an important role in severe acute pancreatitis (AP). Previous studies have shown that intestinal permeability (IP), serum endotoxin and cytokines contribute to the early intestinal barrier dysfunction in AP. This study explored the predictive capacity of IP, endotoxemia and cytokines as prognostic indicators in AP patients.

METHODS
Eighty-seven AP patients were included in the study. The patients were classified into three groups according to the Balthazar computed tomography severity index (CTSI). We compared the biochemical parameters, including IP, serum endotoxin level and cytokine level among the three groups. The associations of IP with serum endotoxin, cytokines, CTSI, and other widely used biochemical parameters and scoring systems were also examined.

RESULTS
IP, serum endotoxin, interleukin (IL-6) and tumor necrosis factor (TNF)-α had a positive correlation with the CTSI of AP. Endotoxin, IL-6, TNF-α, CTSI, the Ranson/APACHE II score, the duration of hospital stay, complications and death significantly affect IP in the AP patients.

CONCLUSIONS
We believe that IP with subsidiary measurements of serum endotoxin, IL-6 and TNF-α may be reliable markers for predicting the prognosis of AP. Further studies that can restore and preserve gut barrier function in AP patients are warranted.

Koh|Young Yool|YY|
Jeon|Woo Kyu|WK|
Cho|Yong Kyun|YK|
Kim|Hong Joo|HJ|
Chung|Won Gil|WG|
Chon|Chang Uk|CU|
Oh|Tae Yun|TY|
Shin|Jun Ho|JH|


Towards a comprehensive view of 8-oxo-7,8-dihydro-2'-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability.

Abstract: 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a major product of DNA oxidation, is a pre-mutagenic lesion which is prone to mispair, if left unrepaired, with 2'-deoxyadenosine during DNA replication. While unrepaired or incompletely repaired 8-oxodG has classically been associated with genome instability and cancer, it has recently been reported to have a role in the epigenetic regulation of gene expression. Despite the growing collection of genome-wide 8-oxodG mapping studies that have been used to provide new insight on the functional nature of 8-oxodG within the genome, a comprehensive view that brings together the epigenetic and the mutagenic nature of the 8-oxodG is still lacking. To help address this gap, this review aims to provide (i) a description of the state-of-the-art knowledge on both the mutagenic and epigenetic roles of 8-oxodG; (ii) putative molecular models through which the 8-oxodG can cause genome instability; (iii) a possible molecular model on how 8-oxodG, acting as an epigenetic signal, could cause the translocations and deletions which are associated with cancer.

Gorini|Francesca|F|
Scala|Giovanni|G|
Cooke|Marcus S|MS|
Majello|Barbara|B|
Amente|Stefano|S|

Genome instability
8-oxodG
Cancer
Base excision repair
Double-strand break
Single-Strand break
TOP1-DPC


Identifying Treatment Modalities for a Multidisciplinary and Blended Care Intervention for Patients With Moderate Medically Unexplained Physical Symptoms: Qualitative Study Among Professionals.

Abstract:
BACKGROUND
Medically unexplained physical symptoms (MUPS) are a substantial health problem in primary care with a high burden for patients, general practitioners, and the health care system. Most studies focus on chronic MUPS patients. Little research is conducted in patients with moderate MUPS, and an effective primary care intervention for prevention of chronic MUPS is lacking.

OBJECTIVE
The objective of our study was to identify treatment modalities based on expert opinions for the development of a multidisciplinary and blended intervention for patients with moderate MUPS to prevent chronicity.

METHODS
Two focus groups with 8 and 6 experts (general practitioners, physical therapists, psychologists, and mental health nurses) were carried out. The focus groups were structured using the nominal group technique.

RESULTS
A total of 70 ideas were generated from two nominal group meetings, and 37 of these got votes, were included in the rank order, and were sorted into 8 separate themes. According to the participants, the most important treatment modalities for a multidisciplinary and blended intervention in patients with moderate MUPS were (1) coaching to a healthier lifestyle, (2) education regarding psychosocial factors, (3) therapeutic neuroscience education, (4) multidisciplinary intake, (5) multidisciplinary cooperation and coordination, (6) relaxation or body awareness exercises, (7) clear communication by professionals to the patient, and (8) graded activity. Five independent researchers checked the ideas and linked them to themes to confirm the content analysis and check the validity of the themes.

CONCLUSIONS
From professional expert perspectives, 8 themes should be included in a multidisciplinary and blended intervention to prevent chronicity. These themes provide a first step in developing an intervention for patients with moderate MUPS. Future research should focus on further development steps in which patients with moderate MUPS should be involved to determine if the intervention matches their needs.

medically unexplained physical symptoms
qualitative study
primary care
nominal group technique
intervention development


Heat shock protein 70 as a supplementary receptor facilitates enterovirus 71 infections in vitro.

Abstract: As one of the major causative agents of hand, foot and mouth disease (HFMD), enterovirus 71 (EV71) is a small, non-enveloped positive stranded RNA virus. Children suffering EV71 infection may cause severe symptoms including neurological complications, pulmonary edema and aseptic meningitis. EV71 is a neurotropic virus and it can cause the damage of nervous cells, cytokine storm and toxic substance. Identifying the factors that mediate viral binding or entry to host cells is important to uncover the mechanisms which viruses utilize to cause diseases in human body. Heat shock protein 70 (HSP70) is induced during virus infection and facilitates proper protein folding during viral propagation. The role that HSP70 plays during EV71 infection is still unclear. In this study, siRNA interference technique and transgenic technique were used to investigate the interaction between HSP70 and EV71 virus. The result demonstrated that the cell surface HSP70 is not essential for EV71 infection but helps the initial binding of virus to host cells and that multiple receptors are involved during EV71 infection. In addition, HSP70 was upregulated in human neuroblastoma cells (SK-N-SH) infected with EV71.

Xu|Tiantian|T| Lin|Zhengfang|Z| Wang|Changbing|C| Li|Yinghua|Y| Xia|Yu|Y| Zhao|Mingqi|M| Hua|Liang|L| Chen|Yi|Y| Guo|Min|M| Zhu|Bing|B|

D002460:Cell Line
D029821:Enterovirus A, Human
D004769:Enterovirus Infections
D055785:Gene Knockdown Techniques
D018840:HSP70 Heat-Shock Proteins
D054884:Host-Pathogen Interactions
D006801:Humans
D009447:Neuroblastoma
D009474:Neurons
D034741:RNA, Small Interfering
D015854:Up-Regulation
D053585:Virus Attachment
D053586:Virus Internalization
D014779:Virus Replication

Heat shock protein 70
Enterovirus 71
Hand
Foot and mouth disease
Nerve cells


Co-processing of nateglinide with meglumine for enhanced dissolution rate: in vitro and in vivo evaluation.

Abstract:
OBJECTIVE
The aim of this work was to investigate dry co-grinding of nateglinide with meglumine for enhanced dissolution rate of nateglinide. The study was extended to investigate the effect of this dissolution enhancement on the hypoglycemic effect of the drug in diabetic rats.

METHODS
Nateglinide was subjected to dry co-grinding with increasing proportions of meglumine to prepare products containing the drug with meglumine at 1:1, 1:2, and 1:3 molar ratios. These products were evaluated using combined instrumental analysis which employed Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). Drug dissolution was also monitored before and after processing with and without meglumine. The optimum ratio was used to assess the effect of dissolution enhancement on the hypoglycemic effect of nateglinide on diabetic rats. The unprocessed nateglinide was used as control.

RESULTS
Co-grinding of nateglinide resulted in changes in the FTIR spectral patterns of nateglinide and meglumine. The changes suggested the formation of amide bond between both compounds at 1:1 molar ratio. The new species was confirmed by DTA and XRD. This species exhibited fast dissolution of nateglinide after incorporation of higher proportions of meglumine. Co-grinding was essential as indicated from slower dissolution from physical mixture containing the highest proportion of meglumine. Enhanced dissolution was reflected in vivo as improved rate and extent of hypoglycemia.

CONCLUSION
Dry co-grinding of nateglinide with meglumine developed new species which liberated nateglinide rapidly and enhanced the rate and extent of hypoglycemia of nateglinide.

Bazeed|Alaa Y|AY|
Essa|Ebtessam A|EA|
Nouh|Ahmed|A|
El Maghraby|Gamal M|GM|

D017550:Spectroscopy, Fourier Transform Infrared

Nateglinide
meglumine
dissolution rate
hypoglycemic effect
salt formation


Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation.

Abstract: Mitophagy is a cellular quality control pathway in which the E3 ubiquitin ligase parkin targets damaged mitochondria for degradation by autophagosomes. We examined the role of optineurin in mitophagy, as mutations in optineurin are causative for amyotrophic lateral sclerosis (ALS) and glaucoma, diseases in which mitochondrial dysfunction has been implicated. Using live cell imaging, we demonstrate the parkin-dependent recruitment of optineurin to mitochondria damaged by depolarization or reactive oxygen species. Parkin's E3 ubiquitin ligase activity is required to ubiquitinate outer mitochondrial membrane proteins, allowing optineurin to stably associate with ubiquitinated mitochondria via its ubiquitin binding domain; in the absence of parkin, optineurin transiently localizes to damaged mitochondrial tips. Following optineurin recruitment, the omegasome protein double FYVE-containing protein 1 (DFCP1) transiently localizes to damaged mitochondria to initialize autophagosome formation and the recruitment of microtubule-associated protein light chain 3 (LC3). Optineurin then induces autophagosome formation around damaged mitochondria via its LC3 interaction region (LIR) domain. Depletion of endogenous optineurin inhibits LC3 recruitment to mitochondria and inhibits mitochondrial degradation. These defects are rescued by expression of siRNA-resistant wild-type optineurin, but not by an ALS-associated mutant in the ubiquitin binding domain (E478G), or by optineurin with a mutation in the LIR domain. Optineurin and p62/SQSTM1 are independently recruited to separate domains on damaged mitochondria, and p62 is not required for the recruitment of either optineurin or LC3 to damaged mitochondria. Thus, our study establishes an important role for optineurin as an autophagy receptor in parkin-mediated mitophagy and demonstrates that defects in a single pathway can lead to neurodegenerative diseases with distinct pathologies.

Wong|Yvette C|YC|
Holzbaur|Erika L F|EL|

D048868:Adaptor Proteins, Signal Transducing

optineurin
mitophagy
autophagosome
amyotrophic lateral sclerosis
Parkinson's disease


A study on the potential of ants to act as vectors of foodborne pathogens.

Abstract: Ants (Technomyrmex difficilis and Solenopsis geminata) are insects often found in domestic kitchens of Mauritius. Unfortunately, they harbour disease-causing organisms and can potentially transfer these pathogens to food. This study was carried out to (i) investigate the knowledge, perception and behaviors of consumers in relation to the problem of ant infestation of domestic kitchens; (ii) identify the pathogenic microorganisms carried by ants; and (iii) determine the potential for ants to transfer these pathogenic microorganisms to food. A survey based on a stratified sampling design was carried out with 100 consumers using a questionnaire. To identify the pathogenic microorganism(s) harbored by ants, bait traps were set up using sterile sugar as a non-toxic attractant. Captured ants were then subjected to microbiological analyses. Most respondents (72%) agreed that ants constitute a hygienic issue but they did not perceive ants as a serious threat to human health. However microbiological analyses of ants (n = 50) confirmed the presence of various pathogenic microorganisms as well as fecal contaminants. Ants were found to harbor yeasts and molds systematically (100%), coliforms frequently (52%), Bacillus spp. and Escherichia coli occasionally (26% and 18% respectively) and Salmonella and Listeria monocytogenes sporadically (8 and 6 % respectively). Ants were also found to transfer E. coli to food surfaces at a moderately high frequency of 70%. This study demonstrated that the majority of consumers acknowledged the problem of ant infestation as a sanitation-related problem rather than a food safety issue. Since ants have the ability to harbor and subsequently transfer pathogenic or toxigenic microorganisms, ants may act as disease vectors and contaminate food, water and food- contact surfaces of kitchens resulting in foodborne illnesses.