Hip and wrist accelerometers showed consistent associations with fitness and fatness in children aged 8-12 years.

Abstract:
AIM
Physical activity (PA) has traditionally been measured wearing accelerometers on the hip, but they are increasingly being worn on the wrist. We compared hip and wrist accelerometers with regard to their acceptability and any associations between PA and fatness and fitness.

METHODS
This cross-sectional study comprised 103 children aged 8-12 years (62% boys) who participated in the ActiveBrains trial by the University of Granada, Spain, in 2014-2016. The children wore both ActiGraph GT3X+ hip and wrist accelerometers round the clock for 7 days. The acceptability of both placements was evaluated by a questionnaire, while the children's fat mass index, waist circumference and cardiorespiratory fitness (CRF) were assessed.

RESULTS
Wearing wrist accelerometers caused less disturbance, mainly because hip accelerometers caused more issues during the night. The measurements from both placements showed that lower PA levels were associated with fatness and that higher PA levels were associated with better CRF.

CONCLUSION
Both placements showed consistent results with regard to measuring associations between PA levels and fatness and fitness. However, wearing them on the wrist caused less discomfort at night. Future studies are needed to confirm the best placement for accelerometers during PA studies.

Leppänen|Marja H|MH|0000-0001-6933-8809
Migueles|Jairo H|JH|
Cadenas-Sanchez|Cristina|C|
Henriksson|Pontus|P|
Mora-Gonzalez|Jose|J|
Henriksson|Hanna|H|
Labayen|Idoia|I|
Löf|Marie|M|
Esteban-Cornejo|Irene|I|
Ortega|Francisco B|FB|

hip accelerometers
adiposity
exercise
physical fitness
waist accelerometers


Long-term follow-up in infantile-onset SCAR18: A case report.

Abstract: Autosomal recessive spinocerebellar ataxia type 18 (SCAR18) is caused by pathogenic variants in the Glutamate Receptor, Ionotropic, Delta-2 (GRID2) gene. We describe the long-term follow-up from 1 to 31 years of an Italian patient with congenital SCAR18 who is compound heterozygous for a maternally-inherited nonsense variant and a de novo microdeletion. To date, this is the longest follow-up in congenital SCAR18.

Iodice|Alessandro|A|
Spagnoli|Carlotta|C|
Cangini|Margherita|M|
Soliani|Luca|L|
Rizzi|Susanna|S|
Salerno|Grazia Gabriella|GG|
Frattini|Daniele|D|
Pisani|Francesco|F|
Fusco|Carlo|C|


Evaluating the task effectiveness and user satisfaction with different operation modes of an assistive bathing robot in older adults.

Abstract: Bathing robots have the potential to foster the independence of older adults who require assistance with bathing. Making human-robot interaction (HRI) for older persons as easy, effective, and user-satisfying as possible is, however, a major challenge in the development of such robots. The study aimed to evaluate the effectiveness (coverage, step effectiveness) and user satisfaction (After-Scenario Questionnaire, ASQ) with three operation modes (autonomous operation, shared control, tele-manipulation) for the HRI with a bathing robot in potential users. Twenty-five older adults who require bathing assistance tested these operation modes in a water rinsing task for the upper back. Autonomous operation led to maximum effectiveness (100%), which was significantly worse in the shared control (51.6-79.4%, p ≤ 0.001) and tele-manipulation mode (43.9-64.4%, p < .001). In the user-controlled modes, effectiveness decreased with decreasing robot assistance (shared control: 51.6-79.4% vs. tele-manipulation: 43.9-64.4%, p = 0.009-0.016). User satisfaction with the autonomous operation (ASQ: 2.0 ± 1.0pt.) was higher than with the tele-manipulation mode (ASQ: 3.0 ± 1.4pt., p = 0.003) and in trend also than with the shared control mode (ASQ: 2.5 ± 1.5pt., p = 0.071). Our study suggests that for an effective and highly satisfying HRI with a bathing robot in older users, operation modes with high robot autonomy requiring a minimum of user input seem to be necessary.

baths
robotics
human-robot interaction
Activities of daily living
aged


Ginseng treatment reverses obesity and related disorders by inhibiting angiogenesis in female db/db mice.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Korean red ginseng (ginseng, Panax ginseng C.A. Meyer) has traditionally been used in the treatment of most ageing-related diseases, such as obesity, diabetes, and dyslipidemia, but the mechanism of the effects is unclear. The aim of this study was to determine the effects of ginseng on obesity in a mouse model of female obesity (obese female db/db mouse) and to investigate the mechanism of anti-obesity effects.

MATERIALS AND METHODS
After female db/db (B6.Cg-m Lepr(db)/++/J) mice were treated with 5% (w/w) ginseng for 13 weeks, variables and parameters of obesity and disorders related to obesity were examined. Blood vessel density and the expression of genes involved in angiogenesis were also measured.

RESULTS
Mice treated with ginseng for 13 weeks had less body weight and lower adipose tissue mass compared to control, untreated mice. The size of adipocytes was smaller in visceral adipose tissues of ginseng-treated mice. Obesity-related complications, such as hepatic steatosis, hypertriglyceridemia, and hyperglycemia, were markedly improved in treated mice. Blood vessel density was lower in visceral adipose tissue sections from treated mice than those from control mice. Concomitantly, mRNA levels for VEGF-A and FGF-2 were lower in both visceral adipose tissue from treated mice and treated 3T3-L1 cells compared to those from untreated controls. Protein levels for VEGF were also lower in visceral adipose tissue from treated mice. In contrast, ginseng increased mRNA expression of genes responsible for energy expenditure and fatty acid β-oxidation in visceral adipose tissue during ginseng-induced weight reduction.

CONCLUSIONS
These results suggest that ginseng may effectively treat female obesity and related disorders in part by inhibition of angiogenesis.

Lee|Hyunghee|H|
Kim|Mina|M|
Shin|Soon Shik|SS|
Yoon|Michung|M|

D042461:Vascular Endothelial Growth Factor A

Obesity
Angiogenesis
Female
Korean red ginseng
db/db Mouse
Adipose tissue growth


Venous thromboembolism and subsequent permanent work-related disability.

Abstract:
Essentials The burden of venous thromboembolism (VTE) related to permanent work-related disability is unknown. In a cohort of 66 005 individuals, the risk of work-related disability after a VTE was assessed. Unprovoked VTE was associated with 52% increased risk of work-related disability. This suggests that indirect costs due to loss of work time may add to the economic burden of VTE.

SUMMARY
Background The burden of venous thromboembolism (VTE) related to permanent work-related disability has never been assessed among a general population. Therefore, we aimed to estimate the risk of work-related disability in subjects with incident VTE compared with those without VTE in a population-based cohort. Methods From the Tromsø Study and the Nord-Trøndelag Health Study (HUNT), Norway, 66 005 individuals aged 20-65 years were enrolled in 1994-1997 and followed to 31 December 2008. Incident VTE events among the study participants were identified and validated, and information on work-related disability was obtained from the Norwegian National Insurance Administration database. Cox-regression models using age as time-scale and VTE as time-varying exposure were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for sex, body mass index, smoking, education level, marital status, history of cancer, diabetes, cardiovascular disease and self-rated general health. Results During follow-up, 384 subjects had a first VTE and 9862 participants were granted disability pension. The crude incidence rate of work-related disability after VTE was 37.5 (95% CI, 29.7-47.3) per 1000 person-years, vs. 13.5 (13.2-13.7) per 1000 person-years among those without VTE. Subjects with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE (HR, 1.52; 95% CI, 1.09-2.14) after multivariable adjustment, and the association appeared to be driven by deep vein thrombosis. Conclusion VTE was associated with subsequent work-related disability in a cohort recruited from the general working-age population. Our findings suggest that indirect costs because of loss of work time may add to the economic burden of VTE.

Braekkan|S K|SK|
Grosse|S D|SD|
Okoroh|E M|EM|
Tsai|J|J|
Cannegieter|S C|SC|
Naess|I A|IA|
Krokstad|S|S|
Hansen|J-B|JB|
Skjeldestad|F E|FE|

D000328:Adult
D000368:Aged
D015992:Body Mass Index
D002318:Cardiovascular Diseases
D015331:Cohort Studies
D006233:Disabled Persons
D005260:Female
D017048:Health Care Costs
D006801:Humans
D015994:Incidence
D008297:Male
D008875:Middle Aged
D015999:Multivariate Analysis
D009664:Norway
D016016:Proportional Hazards Models
D011446:Prospective Studies
D018570:Risk Assessment
D012307:Risk Factors
D016896:Treatment Outcome
D054556:Venous Thromboembolism
D020246:Venous Thrombosis
D055815:Young Adult

venous thromboembolism
disability
risk
deep vein thrombosis


'I will be at death's door and realize that I've wasted maybe half of my life on one body part': the experience of living with body dysmorphic disorder.

Abstract:
OBJECTIVES
The purpose of this study was to explore the experiences of patients living with body dysmorphic disorder (BDD), including their experiences with the health care system.

METHODS
Fifteen individuals with BDD were interviewed, and interpretive description was used to analyse the interviews.

RESULTS
The following six themes were identified: being absorbed in time-consuming procedures, facing tension between one's own ideal and the perceived reality, becoming the disorder, being restricted in life, attempting to reduce one's problems and striving to receive care. The overarching concept derived from the themes was feeling imprisoned - struggling to become free and to no longer feel abnormal.

CONCLUSIONS
Ideas of imprisonment and abnormality compose the entire experience of living with this disorder. Although the participants suffered greatly from their BDD, these patients encountered difficulties in accessing health care and had disappointing experiences during their encounters with the health care system. Therefore, it is important to increase awareness and knowledge of BDD among health care professionals to ensure that patients with BDD receive the appropriate care.

Brohede|Sabina|S| Wijma|Barbro|B| Wijma|Klaas|K| Blomberg|Karin|K|

Body dysmorphic disorder
interview
body image
qualitative research


Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.

Abstract:
BACKGROUND
In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR.

HYPOTHESIS/OBJECTIVES
To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge.

ANIMALS
Twenty-two mixed-breed ponies.

METHODS
Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean).

RESULTS
5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet.

CONCLUSIONS AND CLINICAL IMPORTANCE
Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies.

Burns|T A|TA|
Watts|M R|MR|
Weber|P S|PS|
McCutcheon|L J|LJ|
Geor|R J|RJ|
Belknap|J K|JK|

D060888:Real-Time Polymerase Chain Reaction

Laminitis
Insulin resistance
Energy regulation
Equine metabolic syndrome


Metal-free catalysis of persulfate activation and organic-pollutant degradation by nitrogen-doped graphene and aminated graphene.

Abstract: We evaluated three types of functionalized, graphene-based materials for activating persulfate (PS) and removing (i.e., sorption and oxidation) sulfamethoxazole (SMX) as a model emerging contaminant. Although advanced oxidative water treatment requires PS activation, activation requires energy or chemical inputs, and toxic substances are contained in many catalysts. Graphene-based materials were examined herein as an alternative to metal-based catalysts. Results show that nitrogen-doped graphene (N-GP) and aminated graphene (NH2-GP) can effectively activate PS. Overall, PS activation by graphene oxide was not observed in this study. N-GP (50 mg L(-1)) can rapidly activate PS (1 mM) to remove >99.9% SMX within 3 h, and NH2-GP (50 mg L(-1)) activated PS (1 mM) can also remove 50% SMX within 10 h. SMX sorption and total removal was greater for N-GP, which suggests oxidation was enhanced by increasing proximity to PS activation sites. Increasing pH enhanced the N-GP catalytic ability, and >99.9% SMX removal time decreased from 3 h to 1 h when pH increased from 3 to 9. However, the PS catalytic ability was inhibited at pH 9 for NH2-GP. Increases in ionic strength (100 mM NaCl or Na2SO4) and addition of radical scavengers (500 mM ethanol) both had negligible impacts on SMX removal. With bicarbonate addition (100 mM), while the catalytic ability of N-GP remained unaltered, NH2-GP catalytic ability was inhibited completely. Humic acid (250 mg L(-1)) was partially effective in inhibiting SMX removal in both N-GP and NH2-GP systems. These results have implications for elucidating oxidant catalysis mechanisms, and they quantify the ability of functionalization of graphene with hetero-atom doping to effectively catalyze PS for water treatment of organic pollutants including emerging contaminants.

Persulfate
Graphene
Aminated graphene
Sulfamethoxazole
Emerging contaminant
Nitrogen doped graphene


Socioeconomic status and nonadherence to antihypertensive drugs: a systematic review and meta-analysis.

Abstract:
BACKGROUND
Although conventional wisdom suggests that low socioeconomic status (SES) is a robust predictor of medication nonadherence, the strength of this association remains unclear.

OBJECTIVES
1) To estimate the proportion of studies that identified SES as a potential risk indicator of nonadherence, 2) to describe the type of SES measurements, and 3) to quantify the association between SES and nonadherence to antihypertensive pharmacotherapy.

METHODS
A systematic review and meta-analysis research design was used. We searched multiple electronic databases for studies in English or French examining nonadherence to antihypertensive medications measured by electronic prescription databases where explanatory factors were considered. Two authors independently assessed quality, described the SES measure(s), and recorded its association with nonadherence to antihypertensives. A random-effects model meta-analysis was performed, and heterogeneity was examined by using the I(2) statistic.

RESULTS
Fifty-six studies with 4,780,293 subjects met the inclusion criteria. Twenty-four of these studies (43%) did not report any SES measures. When it was reported (n = 32), only seven (13%) examined more than one component but none performed a multidimensional assessment. Most of the studies relied on income or income-related measures (such as prescription-drug benefits or co-payments) (27 of 32 [84%]). Meta-analysis could be quantified in 40 cohorts reported in 30 studies. Overall, the pooled adjusted risk estimate for nonadherence according to SES (high vs. low) was 0.89 (95% confidence interval 0.87-0.92; I(2) = 95%; P < 0.001). Similar patterns were observed in all subgroups examined.

CONCLUSIONS
Published studies have not found a strong association between low SES and nonadherence to antihypertensive medications. However, important limitations in the assessment of SES can be identified in virtually all studies. Future studies are required to ascertain whether a stronger association is observed when SES is determined by comprehensive measures.

Alsabbagh|M H D Wasem|MH|
Lemstra|Mark|M|
Eurich|Dean|D|
Lix|Lisa M|LM|
Wilson|Thomas W|TW|
Watson|Erin|E|
Blackburn|David F|DF|

D000959:Antihypertensive Agents
D006801:Humans
D006973:Hypertension
D007182:Income
D055118:Medication Adherence
D015233:Models, Statistical
D012107:Research Design
D012307:Risk Factors
D012923:Social Class

socioeconomic status
antihypertensive medications
drug adherence
pharmacy
population-level


Variation of phytoplankton functional groups modulated by hydraulic controls in Hongze Lake, China.

Abstract: Hongze Lake is a large, shallow, polymictic, eutrophic lake in the eastern China. Phytoplankton functional groups in this lake were investigated from March 2011 to February 2013, and a comparison was made between the eastern, western, and northern regions. The lake shows strong fluctuations in water level caused by monsoon rains and regular hydraulic controls. By application of the phytoplankton functional group approach, this study aims to investigate the spatial and temporal dynamics and analyze their influencing factors. Altogether, 18 functional groups of phytoplankton were identified, encompassing 187 species. In order to seek the best variable describing the phytoplankton functional group distribution, 14 of the groups were analyzed in detail using redundancy analysis. Due to the turbid condition of the lake, the dominant functional groups were those tolerant of low light. The predominant functional groups in the annual succession were D (Cyclotella spp. and Synedra acus), T (Planctonema lauterbornii), P (Fragilaria crotonensis), X1 (Chlorella vulgaris and Chlorella pyrenoidosa), C (Cyclotella meneghiniana and Cyclotella ocellata), and Y (Cryptomonas erosa). An opposite relationship between water level and the biomass of predominant groups was observed in the present study. Water level fluctuations, caused by monsoonal climate and artificial drawdown, were significant factors influencing phytoplankton succession in Hongze Lake, since they alter the hydrological conditions and influence light and nutrient availability. The clearly demonstrated factors, which significantly influence phytoplankton dynamics in Hongze Lake, will help government manage the large shallow lakes with frequent water level fluctuations.

Tian|Chang|C|
Pei|Haiyan|H|
Hu|Wenrong|W|
Hao|Daping|D|
Doblin|Martina A|MA|
Ren|Ying|Y|
Wei|Jielin|J|
Feng|Yawei|Y|

Hydraulic control
Water level
Redundancy analysis
Phytoplankton dynamic


Potential drug-drug interactions in infant, child, and adolescent patients in children's hospitals.

Abstract:
BACKGROUND AND OBJECTIVES
Hospitalized infants, children, and adolescents are typically exposed to numerous distinct medications during inpatient admissions, increasing their risk of potential drug-drug interactions (PDDIs). We assessed the prevalence and characteristics of PDDI exposure of pediatric patients treated in children's hospitals.

METHODS
This retrospective cohort study included patients <21 years old hospitalized in children's hospitals throughout the United States. PDDIs were identified by using the MicroMedex DRUG-REAX system. We calculated the patients exposed to PDDIs, stratified according to the seriousness of the interaction; daily and cumulative counts of PDDI exposures; and characterization of the cited potential adverse effects.

RESULTS
Of 498 956 hospitalizations in 2011, 49% were associated with ≥1 PDDI, with a "contraindicated" PDDI occurring in 5% of all hospitalizations, a "major" PDDI present in 41%, a "moderate" PDDI in 28%, and a "minor" PDDI in 11%. Opioids were involved in 25% of all PDDIs, followed by antiinfective agents (17%), neurologic agents (15%), gastrointestinal agents (13%), and cardiovascular agents (13%). One-half of all PDDI exposures were due to specific drug pairs occurring in ≤3% of patients per hospital day. The most common potential adverse drug events included additive respiratory depression (in 21% of PDDIs), bleeding risk (5%), QT interval prolongation (4%), reduced iron absorption/availability (4%), central nervous system depression (4%), hyperkalemia (3%), and altered diuretic effectiveness (3%).

CONCLUSIONS
Exposure to PDDIs is common among hospitalized children. Empirical data are needed to determine the probability and magnitude of the actual harm for each specific PDDI, particularly for less common drug pairs.

Feinstein|James|J| Dai|Dingwei|D| Zhong|Wenjun|W| Freedman|Jason|J| Feudtner|Chris|C|

D064420:Drug-Related Side Effects and Adverse Reactions

pediatrics
adverse drug event
drug–drug interaction
medication safety
pharmacoepidemiology
polypharmacy


Crystal structure of 6-(4-chloro-phen-yl)-6a-nitro-6,6a,6b,7,9,11a-hexa-hydro-spiro[chromeno[3',4':3,4]pyrrolo-[1,2-c]thia-zole-11,11'-indeno-[1,2-b]quinoxaline] chloro-form monosolvate.

Abstract: In the title compound, C33H23ClN4O3S·CHCl3, the thia-zole ring adopts an envelope conformation with the N atom as the flap, and the pyrrolidine ring adopts a half-chair conformation. The thia-zole ring mean plane makes a dihedral angle of 59.31 (1)° with the pyrrolidine ring mean plane, 71.67 (1)° with the chromene ring and 82.59 (1)° with the chloro-benzene ring. An intra-molecular C-H⋯N hydrogen bond occurs. In the crystal, a second C-H⋯N hydrogen bond links the main and solvent mol-ecules. The solvent chloroform molecule is disordered about two positions with an occupancy ratio of 0.508 (14):0.492 (14).

Sivakumar|Nithya|N|
Viswanathan|Vijayan|V|
Rao|Jonnalagadda Naga Siva|JN|
Raghunathan|Raghavachary|R|
Velmurugan|Devadasan|D|

crystal structure
C—H⋯N hydrogen bonding
thiazole


Temperature cycle amplitude alters the adult eclosion time and expression pattern of the circadian clock gene period in the onion fly.

Abstract: Soil temperature cycles are considered to play an important role in the entrainment of circadian clocks of underground insects. However, because of the low conductivity of soil, temperature cycles are gradually dampened and the phase of the temperature cycle is delayed with increasing soil depth. The onion fly, Delia antiqua, pupates at various soil depths, and its eclosion is timed by a circadian clock. This fly is able to compensate for the depth-dependent phase delay of temperature change by advancing the eclosion time with decreasing amplitude of the temperature cycle. Therefore, pupae can eclose at the appropriate time irrespective of their location at any depth. However, the mechanism that regulates eclosion time in response to temperature amplitude is still unknown. To understand whether this mechanism involves the circadian clock or further downstream physiological processes, we examined the expression patterns of period (per), a circadian clock gene, of D. antiqua under temperature cycles that were square wave cycles of 12-h warm phase (W) and 12-h cool phase (C) with the temperature difference of 8 °C (WC 29:21 °C) and 1 °C (WC 25.5:24.5 °C). The phase of oscillation in per expression was found to commence 3.5h earlier under WC 25.5:24.5 °C as compared to WC 29:21 °C. This difference was in close agreement with the eclosion time difference between the two temperature cycles, suggesting that the mechanism that responds to the temperature amplitude involves the circadian clock.

Miyazaki|Yosuke|Y|
Watari|Yasuhiko|Y|
Tanaka|Kazuhiro|K|
Goto|Shin G|SG|

D000595:Amino Acid Sequence
D000818:Animals
D001483:Base Sequence
D057906:Circadian Clocks
D004175:Diptera
D015870:Gene Expression
D019476:Insect Proteins
D008675:Metamorphosis, Biological
D008969:Molecular Sequence Data
D056950:Period Circadian Proteins
D012269:Ribosomal Proteins
D017422:Sequence Analysis, DNA
D013696:Temperature

Temperature cycle
Circadian clock gene
period
Onion fly
Delia antiqua
Eclosion rhythm


CXCL1-LCN2 paracrine axis promotes progression of prostate cancer via the Src activation and epithelial-mesenchymal transition.

Abstract:
BACKGROUND
Mechanisms driving the progression of castration-resistant prostate cancer are believed to relate substantially to the tumor microenvironment. However, the cross-talks between tumor epithelial cell, stromal cells, and immune cells are yet to be fully elucidated. The present study aims to determine the role of chemokine and neutrophil derived cytokine paracrine axis in mediating the interaction between tumor cells, stromal myofibroblasts, and neutrophils in the tumor microenvironment of prostate cancer.

METHODS
To identify myofibroblasts and neutrophil derived specific proteins affecting progression of prostate cancer, bioinformatics analyses were firstly performed in independent human prostate cancer gene expression data sets from the GEO data bank. Expression of stromal myofibroblasts secretory chemokine CXCL1 and neutrophil derived cytokine LCN2 was evaluated in prostate tissues via immunohistochemistry assay. We further investigated the effect of CXCL1 and LCN2 on prostate cancer using in vivo and in vitro models, and explored the underlying signal transduction pathways.

RESULTS
A CXCL1-LCN2 paracrine network was confirmed in prostate cancer tissue samples, which was correlated with the biochemical recurrence of prostate cancer. Of note, CXCL1-LCN2 axis activates Src signaling, triggers the epithelial-mesenchymal transition (EMT), consequently promotes the migration of prostate cancer cells, leading to enhanced tumor metastasis.

CONCLUSIONS
Our findings may provide enhanced insight into the interactions of carcinoma-stromal cells and immune cells linked to prostate cancer progression, wherein CXCL1-LCN2 axis is a key contributor to prostate cancer cells migration. These data indicate tumor microenvironment and Src signaling pathway may be potential therapeutic targets of prostate cancer treatment.

Lu|Yongning|Y| Dong|Baijun|B| Xu|Fan|F| Xu|Yunze|Y| Pan|Jiahua|J| Song|Jiajia|J| Zhang|Jin|J| Huang|Yiran|Y| Xue|Wei|W|

Tumor microenvironment
Chemokine
Cytokine
Tumor metastasis
Tumor cell migration


Novel methods to determine complement activation in human serum induced by the complex of Dezamizumab and serum amyloid P.

Abstract: Lack of simple and robust methods to determine complement activation in human serum induced by antigen-antibody complexes is a major hurdle for monitoring therapeutic antibody drug quality and stability. Dezamizumab is a humanized IgG1 monoclonal antibody that binds to serum amyloid P component (SAP) for potential treatment of systemic amyloidosis. The mechanism of action of Dezamizumab includes the binding of SAP, complement activation through classical pathway, and phagocytosis; however, the steps in this process cannot be easily monitored. We developed two novel methods to determine Dezamizumab-SAP complex-induced complement activation. Complement component 3 (C3) depletion was detected by homogeneous time-resolved fluorescence (HTRF), and C3a desArg fragment, formed after the cleavage of C3 to yield C3a followed by removal of its C-terminal arginine residue, was determined using Meso Scale Discovery (MSD) technology. We found that the presence of both Dezamizumab and SAP was required for complement activation via both methods. The optimal molar ratio of Dezamizumab:SAP was 6:1 in order to obtain maximal complement activation. The relative potency from both methods showed a good correlation to Dezamizumab-SAP-dependent complement component 1q (C1q) binding activity in Dezamizumab thermal-stressed samples. Both SAP and C1q binding, as determined by surface plasmon resonance and the two complement activation potency methods described here, reflect the mechanism of action of Dezamizumab. We conclude that these methods can be used to monitor Dezamizumab quality for drug release and stability testing, and the novel potency methods reported here can be potentially used to evaluate complement activity induced by other antigen-antibody complexes.

Ma|Jianhong|J|
Liu|Qi|Q|
White|John R|JR|

D000911:Antibodies, Monoclonal
D003167:Complement Activation
D003165:Complement System Proteins
D006801:Humans
D007074:Immunoglobulin G
D000683:Serum Amyloid P-Component
D020349:Surface Plasmon Resonance

Dezamizumab
SAP
C3
HTRF
C3a desArg
MSD
classical complement pathway
complement method


The Expression of Proteins Related to Serotonin Pathway in Pulmonary Arteries of Dogs Affected With Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease.

Abstract: Background: Pulmonary hypertension (PH) can cause medial thickening, a hallmark of pulmonary arterial remodeling. The serotonin (5HT) pathway has been suggested as a factor associated with PH by inducing pulmonary arterial smooth muscle cells (SMCs) proliferation, a major cause of medial thickening. This study aims to demonstrate the expression of molecules in the 5HT pathway in the pulmonary artery of dogs affected with PH secondary to degenerative mitral valve disease (DMVD) compared to DMVD and healthy control dogs. Materials and Methods: The study included lung samples from the carcasses of 19 older small-breed dogs (Control n = 5, DMVD n = 7, DMVD+PH n = 7). Lung tissue sections were performed Hematoxylin and Eosin staining for measuring the percentage of medial thickness and immunohistochemistry for evaluating the expression of proteins in the 5HT pathway including serotonin transporter (SERT), serotonin 2A receptor (5HT2A), tryptophan hydroxylase 1 (TPH1), extracellular regulated kinase 1/2 (ERK1/2), and phosphorylated ERK1/2 (pERK1/2). Results: Medial thickening of the pulmonary arteries was found in the DMVD and DMVD+PH groups compared to the control. The medial thickening of the DMVD+PH group was increased significantly compared to that in the DMVD group. Intracytoplasmic expression of proteins related to the 5HT pathway was mainly presented in the medial layer of the pulmonary arteries. The control group showed a low expression of proteins related to the 5HT pathway. An intensive expression of SERT, 5HT2A, TPH1, and ERK1/2 protein was seen in the DMVD and DMVD+PH groups. Interestingly, pERK1/2 was strongly represented only in the DMVD+PH group. Conclusions: Overexpression of proteins related to the 5HT pathway including SERT, 5HT2A, TPH1, ERK1/2, and pERK1/2 was associated with medial remodeling in dogs affected with secondary to DMVD.

Sakarin|Siriwan|S|
Surachetpong|Sirilak Disatian|SD|
Rungsipipat|Anudep|A|

serotonin
pulmonary artery
pulmonary hypertension
degenerative mitral valve disease
smooth muscle cells
hyperplasia


Phytochemical and anti-inflammatory properties of Senegalese propolis and isolated compounds.

Abstract: Propolis is a chemically complex resinous product collected from various plant sources by honeybees that has been used historically a traditional folk medicine in many parts of the world. The main constituents of propolis are beeswax and plant resins. We recently obtained Senegalese propolis, which, to our knowledge, has not been previously reported. The purpose of this study was to analyze the composition of Senegalese propolis and evaluate its anti-inflammatory activity. Ten known phenolic compounds with phenanthrene or stilbene skeletons were isolated. Nitric oxide (NO) production assay revealed that Senegalese propolis suppresses lipopolysaccharide (LPS)-stimulated production of NO in J774.1 cells in a dose-dependent manner. The anti-inflammatory potency of Senegalese propolis was higher than that of other previously reported propolis. Furthermore, the eight compounds isolated from Senegalese propolis showed high anti-inflammatory activity by inhibiting the LPS-induced expression of inducible NO synthase (iNOS). These results suggest that Senegalese propolis and its components have potential applications as anti-inflammatory agents.

Inui|Saori|S| Hosoya|Takahiro|T| Yoshizumi|Kazuma|K| Sato|Hajime|H| Kumazawa|Shigenori|S|

Senegalese propolis
Anti-inflammatory activity
Phenanthrene
Stilbene
Inducible nitric oxide synthase


The Effect of Computed Tomography-Guided 125I Radioactive Particle Implantation in Treating Cancer and Its Pain.

Abstract:
BACKGROUND AND AIM
Pain is a prevalent and serious problem in patients with cancer. This study aimed to investigate the clinical value of the implantation of radioactive particle 125I in treating cancer and its pain.

MATERIALS AND METHODS
From February 2014 to February 2015, 38 patients with malignant tumor received computed tomography (CT)-guided 125I radioactive particle implantation to treat cancer pain in this hospital. Before surgery, the lesions were calculated by brachytherapy treatment planning system (TPS) to get the local number of particles that are required for implantation. For a period after implantation, TPS was used again to assess the effect of treatment. The 38 patients received 6-month follow-up, and the CT scan was used to evaluate the local tumor. The visual analogue scale (VAS) was used to assess the pain.

RESULTS
The curative effect was evaluated at postoperative 2, 4, and 6 months, and the curative effect was 34.2%, 73.68%, and 89.47%, respectively. The preoperative VAS score of the 38 patients was 5.48 ± 2.50 (13 cases of mild pain, 19 cases of moderate pain, and 6 cases of severe pain), and their pain was improved in different degrees after operation.

CONCLUSIONS
CT-guided 125I radioactive particle implantation is a safe and effective treatment for cancer and its pain.

Lu|Wei|W| Du|Peng|P| Yang|Chao|C| Jiang|Fuqiang|F| Xie|Peng|P| Yang|Jian|J| Zhang|Zhe|Z| Ma|Junpeng|J|

125I radioactive particle
cancer pain
brachytherapy
implantation treatment


Exercise Training-Related Changes in Cortical Gray Matter Diffusivity and Cognitive Function in Mild Cognitive Impairment and Healthy Older Adults.

Abstract: Individuals with Mild Cognitive Impairment (MCI) are at an elevated risk of dementia and exhibit deficits in cognition and cortical gray matter (GM) volume, thickness, and microstructure. Meanwhile, exercise training appears to preserve brain function and macrostructure may help delay or prevent the onset of dementia in individuals with MCI. Yet, our understanding of the neurophysiological effects of exercise training in individuals with MCI remains limited. Recent work suggests that the measures of gray matter microstructure using diffusion imaging may be sensitive to early cognitive and neurophysiological changes in the aging brain. Therefore, this study is aimed to determine the effects of exercise training in cognition and cortical gray matter microstructure in individuals with MCI vs. cognitively healthy older adults. Fifteen MCI participants and 17 cognitively intact controls (HC) volunteered for a 12-week supervised walking intervention. Following the intervention, MCI and HC saw improvements in cardiorespiratory fitness, performance on Trial 1 of the Rey Auditory Verbal Learning Test (RAVLT), a measure of verbal memory, and the Controlled Oral Word Association Test (COWAT), a measure of verbal fluency. After controlling for age, a voxel-wise analysis of cortical gray matter diffusivity showed individuals with MCI exhibited greater increases in mean diffusivity (MD) in the left insular cortex than HC. This increase in MD was positively associated with improvements in COWAT performance. Additionally, after controlling for age, the voxel-wise analysis indicated a main effect of Time with both groups experiencing an increase in left insular and left and right cerebellar MD. Increases in left insular diffusivity were similarly found to be positively associated with improvements in COWAT performance in both groups, while increases in cerebellar MD were related to gains in episodic memory performance. These findings suggest that exercise training may be related to improvements in neural circuits that govern verbal fluency performance in older adults through the microstructural remodeling of cortical gray matter. Furthermore, changes in left insular cortex microstructure may be particularly relevant to improvements in verbal fluency among individuals diagnosed with MCI.

Callow|Daniel D|DD|
Won|Junyeon|J|
Pena|Gabriel S|GS|
Jordan|Leslie S|LS|
Arnold-Nedimala|Naomi A|NA|
Kommula|Yash|Y|
Nielson|Kristy A|KA|
Smith|J Carson|JC|

MCI
exercise training
diffusion imaging
verbal fluency
episodic memory
physical activity


Novel therapeutic modalities and drug delivery in pancreatic cancer - an ongoing search for improved efficacy.

Abstract: Pancreatic cancer is an incredibly challenging disease due to its high rates of resistance to traditional chemotherapy and radiotherapy. There has been little improvement in the prognosis of pancreatic cancer cases in the past decades, highlighting the crucial need for more effective therapeutic approaches. Erlotinib, an EGFR inhibitor, and gemcitabine, a nucleoside analog, are currently used in combination for chemotherapy treatment, but new developments in drug delivery systems using liposomes and nanoparticles may be promising new modalities for management of the disease. In addition to standard chemotherapeutic drugs, these delivery systems can be utilized to deliver therapeutic agents such as siRNA, oncolytic viruses, small molecule inhibitors, antibodies, and suicide genes. Further work is required to elucidate how ligands and antibodies could be used to enhance the targeted delivery of drugs, thus increasing specificity, improving stability, and reducing the effect of the drugs on healthy tissue. Despite significant preclinical data, there are currently very few clinical trials involving pancreatic cancer targeted drug delivery. This article summarizes current developments in targeted pancreatic cancer drug delivery, focusing on delivery systems, targets, and therapeutic agents.

pancreatic cancer
erlotinib
EGFR
gemcitabine
liposomes
nanoparticles
siRNA
oncolytic viruses
suicide genes
FOLFIRINOX
KRAS
MUC1
Rb
VEGFR
carbon nanotubes
mesothelin
monoclonal antibodies
p16
p21
p53
shRNA

P P P P P P P P P U U U U U U U M U U U U


Global Trends and Forecast of the Burden of Adverse Effects of Medical Treatment: Epidemiological Analysis Based on the Global Burden of Disease Study.

Abstract: Aim To quantify and update the years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALY) due to the adverse effects of medical treatment (AEMT) between 1990 and 2017. Subject and methods We analyzed the latest dataset from the Global Burden of Disease (GBD) 2017 study. We described the burden of AEMT based on the number of DALY. We additionally evaluated the global age and sex-specific DALY and compared the age-standardized rates of DALY across the World Health Organization (WHO) regions from 1990 to 2017. Results Worldwide, the total DALYs due to AEMT were 84.93 [95% uncertainty interval (UI), 62.52 to 102.21] in 1990 and 62.79 (52.09 to 75.45) in 2017 per 100,000 population. The global percentage of change in DALY showed a negative trend of -26.06 % (-41.52 to -10.59) across all WHO regions between 1990 and 2017. The YLD has increased during the period from 1997 to 2017 by 29.47% (17.87 to 41.06). In 2017, men were affected more than women with a DALY of 66.78 in comparison to 58.91 DALY in women. DALY rates per 100,000 were highest across all the WHO regions in the first years of life. The predicted DALY rates were 59.92 (57.52 to 62.32) in the year 2020, 50.36 (32.03 to 68.70) in 2030, and 40.8 (-1.33 to 82.93) in 2040. Conclusion Using the GBD 2017 study data, we found a decrease in the DALY rate due to AEMT between 1990 and 2017 with a varying range of DALY between different WHO regions. DALY also differed by age and sex. The forecasting analyses showed a decrease in DALY due to AEMTs with a significant drop in the European region when compared to the African and American regions. However, the increasing trend for YLD signifies an increasing burden of people living with poor health due to AEMT. Our study proposes to identify disability due to AEMT as a significant public health crisis and calls for policymakers to create a robust revised policy.

Debaib Mohammed Saeed Al Darei|Shaikha|S|

global burden
yll
disability
yld
daly
adverse events
complication of treatment
health care system
health policy
patient safety


Combined Metabolic Targeting With Metformin and the NSAIDs Diflunisal and Diclofenac Induces Apoptosis in Acute Myeloid Leukemia Cells.

Abstract: The accelerated metabolism of tumor cells, inevitable for maintaining high proliferation rates, is an emerging target for tumor therapy. Increased glucose and lipid metabolism as well as mitochondrial activity have been shown in solid tumors but also in leukemic cells. As tumor cells are able to escape the blockade of one metabolic pathway by a compensatory increase in other pathways, treatment strategies simultaneously targeting metabolism at different sites are currently developed. However, the number of clinically applicable anti-metabolic drugs is still limited. Here, we analyzed the impact of the anti-diabetic drug metformin alone or in combination with two non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and diflunisal on acute myeloid leukemia (AML) cell lines and primary patient blasts. Diclofenac but not diflunisal reduced lactate secretion in different AML cell lines (THP-1, U937, and KG-1) and both drugs increased respiration at low concentrations. Despite these metabolic effects, both NSAIDs showed a limited effect on tumor cell proliferation and viability up to a concentration of 0.2 mM. In higher concentrations of 0.4-0.8 mM diflunisal alone exerted a clear effect on proliferation of AML cell lines and blocked respiration. Single treatment with the anti-diabetic drug metformin blocked mitochondrial respiration, but proliferation and viability were not affected. However, combining all three drugs exerted a strong cytostatic and cytotoxic effect on THP-1 cells. Comparable to the results obtained with THP-1 cells, the combination of all three drugs significantly reduced proliferation of primary leukemic blasts and induced apoptosis. Furthermore, NSAIDs supported the effect of low dose chemotherapy with cytarabine and reduced proliferation of primary AML blasts. Taken together we show that low concentrations of metformin and the two NSAIDs diclofenac and diflunisal exert a synergistic inhibitory effect on AML proliferation and induce apoptosis most likely by blocking tumor cell metabolism. Our results underline the feasibility of applying anti-metabolic drugs for AML therapy.

Renner|Kathrin|K|
Seilbeck|Anton|A|
Kauer|Nathalie|N|
Ugele|Ines|I|
Siska|Peter J|PJ|
Brummer|Christina|C|
Bruss|Christina|C|
Decking|Sonja-Maria|SM|
Fante|Matthias|M|
Schmidt|Astrid|A|
Hammon|Kathrin|K|
Singer|Katrin|K|
Klobuch|Sebastian|S|
Thomas|Simone|S|
Gottfried|Eva|E|
Peter|Katrin|K|
Kreutz|Marina|M|

metabolism
metformin
diflunisal
diclofenac
apoptosis
acute myeloid leukemia
AML


Preparation and Characterization of Nanosuspension of Aprepitant by H96 Process.

Abstract:
PURPOSE
Nanosuspension in drug delivery is known to improve solubility, dissolution and eventually bioavailability of the drugs. The purpose of the study was to compare particle size of nanosuspensions prepared by the first generation approach and H96 approach and to evaluate the effectiveness of H96 approach.

METHODS
The nanosuspension of aprepitant was prepared by HPH and H96 approach. The prepared nanosuspensions were characterized for their particle size and zeta potential. The optimized nanosuspension was further evaluated for DSC, FT-IR, solubility and dissolution.

RESULTS
The optimized nanosuspension (NCLH5) prepared using combination of tween 80 and poloxamer 188 as stabilizer, showed particle size of 35.82 nm and improved solubility and dissolution profile over pure drug. NCLH5 was chosen optimized formulation and further evaluated for other parameters after lyophilization. Lyophilization resulted in increase in particle size. The solubility and dissolution studies showed favorable increase in the performance. The FT-IR and DSC analysis showed change in the crystallinity after nanosizing.

CONCLUSION
The observations indicated that lyophilization prior to high pressure homogenization resulted in efficient particle size reduction yielding smaller particles than first generation preparation technique. H96 is a good and easy alternative to achieve efficient particle size reduction of drug in lesser time and increase its solubility and dissolution.

Kalvakuntla|Sunethra|S|
Deshpande|Mangesh|M|
Attari|Zenab|Z|
Kunnatur B|Koteshwara|K|

Nanosuspension
Particle size
Lyophilization
High pressure homogenization
Second generation approach


Ellipse method for measuring Liaw's anteversion of the acetabular component after total hip arthroplasty.

Abstract:
BACKGROUND
Several cup anteversion measurements for post-operative total hip arthroplasty (THA) surgery have been described. We developed the standardized Liaw's trigonometric method to eliminate the influence of patient position, which is the most accurate method for cup anteversion measurement. We then developed an ellipse method using the Elliversion software and reported an interobserver error reduction in 2013. In this study, we attempted to apply this ellipse method in the clinic and compared its accuracy with the standard trigonometric version.

METHODS
In the present study, we attempted to incorporate the ellipse method with Liaw's standardized anteversion in the simulated cup position. We measured standardized Liaw's anteversion for 434 radiographs in the clinic using the ellipse method. Repeated standard deviation (RSD) was calculated for accuracy evaluation. Furthermore, paired t-test was used for comparison with the interobserver and intraobserver errors.

RESULTS
We found that the standardized Liaw's anteversion measured using the ellipse method showed lower RSD than the radiographic version. RSD was 0.795 in the standardized Liaw's anteversion with ellipse method group. The p-values of the paired t-test were all higher than 0.05 when measuring the interobserver and intraobserver errors. It indicated that the ellipse method was a precise and simple tool for cup anteversion measurement.

CONCLUSION
We believe that this ellipse measurement can assist surgeons while placing the acetabulum cup into the precise position and enable early diagnosis of acetabulum loosening.

Yeh|Kuei-Lin|KL| Wu|Tai-Yin|TY| Ma|Hsuan-Hsiao|HH| Hou|Sheng-Mou|SM| Liaw|Chen-Kun|CK|

Ellipse method
Total hip arthroplasty
Anteversion measurement
Liaw’s anteversion


Late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of dementia: a case report.

Abstract:
BACKGROUND
Although adult attention-deficit/hyperactivity disorder has recently gained increased attention, few reports on attention-deficit/hyperactivity disorder in the pre-elderly or elderly have been published. Here, we present the case of a patient with attention-deficit/hyperactivity disorder who gradually developed dementia-like symptoms as she aged, which initially made her condition difficult to distinguish from early onset Alzheimer's disease. This report illustrates that some types of attention-deficit/hyperactivity disorder may be misdiagnosed as dementia.

CASE PRESENTATION
The patient was a 58-year-old woman. Although she presented with a tendency for inattentiveness and forgetfulness since childhood, she did not have a history of psychiatric disorders prior to consultation. Around the age of 52 years, her inattentiveness and forgetfulness gradually progressed, and at 57 years of age, she became inattentive and forgetful that it interfered with her work and daily life. For example, she forgot meetings with important clients and transferred money to the wrong bank account; these failures resulted in poor management of her company. At home, she experienced increasing difficulties with remembering prior commitments with her family and misplacing items, which her family members noticed. With the encouragement of her family and employees, who worried that she was suffering from dementia, she visited our memory clinic, whereby she was suspected of having early onset Alzheimer's disease. However, neuropsychological tests and brain imaging evaluations did not reveal any significant abnormalities. After dismissing various possible diagnoses, including dementia, other organic diseases, mood disorders, and delirium, we diagnosed her with attention-deficit/hyperactivity disorder. Treatment with 18 mg of methylphenidate was initiated, and significant improvements in her symptoms were observed within a few days; for example, she stopped losing her things, was able to concentrate for long durations, and could complete more tasks than she could before treatment. Since initiating treatment, she has returned to work and has been able to perform her daily activities without difficulty.

CONCLUSIONS
This case supports that some patients with late-onset attention-deficit/hyperactivity disorder may gradually develop dementia-like symptoms during the pre-elderly and elderly stages of life. Therefore, clinicians should consider late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of some types of dementias.

D001289:Attention Deficit Disorder with Hyperactivity


Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo.

Abstract: Cannabis sativa produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells. Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Cytotoxic activity was determined using the XTT assay on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients (SPBL). Annexin V assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle. RNA sequencing and quantitative PCR were used to determine gene expression. Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-78 cell lines were identified in crude extract fractions designated S4 and S5, and their synergistic mixture was specified. This mixture induced cell cycle arrest and cell apoptosis; a relatively selective apoptosis was also recorded on the malignant CD4+CD26- SPBL cells. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5. The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture. We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies.

Mazuz|Moran|M|
Tiroler|Amir|A|
Moyal|Lilach|L|
Hodak|Emmilia|E|
Nadarajan|Stalin|S|
Vinayaka|Ajjampura C|AC|
Gorovitz-Haris|Batia|B|
Lubin|Ido|I|
Drori|Avi|A|
Drori|Guy|G|
Cauwenberghe|Owen Van|OV|
Faigenboim|Adi|A|
Namdar|Dvora|D|
Amitay-Laish|Iris|I|
Koltai|Hinanit|H|

cannabinoids
cannabis
cutaneous T-cell lymphoma
peripheral blood lymphocytes
CTCL cell lines


A Giant Left Intraventricular Thrombus Associated With Apical Hypertrophic Cardiomyopathy Mimics Cancer.

Abstract: Hypertrophic cardiomyopathy (HCM) is a common disease that can be acquired due to chronic hypertension or via autosomal dominant inheritance. Several patterns of HCM have been described, of which a rare variant is apical hypertrophic cardiomyopathy (AHCM). Atrial thrombus is a well-recognized complication of HCM especially in the setting of atrial fibrillation (AF). However, left ventricular thrombus (LVT) formation is not nearly as prevalent as atrial thrombus. Here is a case of a 57-year-old Hispanic female with AHCM who presented with significant unintentional weight loss and unexplained anemia and was subsequently found to have a large left intraventricular mass suspicious for a tumor vs. ventricular thrombus. The diagnosis was complicated due to the large size of the mass and presenting symptoms suspicious of malignancy.

Raza|Nadia|N|
Burnette|Shane|S|
Joolhar|Fowrooz S|FS|
Ghandforoush|Aslan|A|
Win|Theingi Tiffany|TT|

apical hypertrophy cardiomyopathy
giant lv thrombus
hypertrophy cardiomyopathy
left ventricle (lv) thrombus
lv thrombus


Graphene quantum dots enhanced ToF-SIMS for single-cell imaging.

Abstract: Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has shown promising applications in single-cell analysis owing to its high spatial resolution molecular imaging capability. One of the main drawbacks hindering progress in this field is the relatively low ionization efficiency for biological systems. The complex chemical micro-environment in single cells typically causes severe matrix effects, leading to significant signal suppression of biomolecules. In this work, we investigated the signal enhancement effect of graphene quantum dots (GE QDs) in ToF-SIMS analysis. A × 160 magnification of ToF-SIMS signal for amiodarone casted on glass slide was observed by adding amino-functionalized GE QDs (amino-GE QDs), which was significantly higher than adding previously reported signal enhancement materials and hydroxyl group-functionalized GE QDs (hydroxyl-GE QDs). A possible mechanism for GE QD-induced signal enhancement was proposed. Further, effects of amino-GE QDs and hydroxyl-GE QDs on amiodarone-treated breast cancer cells were compared. A significant signal improvement for lipids and amiodarone was achieved using both types of GE QDs, especially for amino-GE QDs. In addition, ToF-SIMS chemical mapping of single cells with better quality was obtained after signal enhancement. Our strategy for effective ToF-SIMS signal enhancement holds great potential for further investigation of drug metabolism pathways and the interactions between the cell and micro-environment.

D018629:Spectrometry, Mass, Secondary Ion


Area asymmetry of heart rate variability signal.

Abstract:
BACKGROUND
Heart rate fluctuates beat-by-beat asymmetrically which is known as heart rate asymmetry (HRA). It is challenging to assess HRA robustly based on short-term heartbeat interval series.

METHOD
An area index (AI) was developed that combines the distance and phase angle information of points in the Poincaré plot. To test its performance, the AI was used to classify subjects with: (i) arrhythmia, and (ii) congestive heart failure, from the corresponding healthy controls. For comparison, the existing Porta's index (PI), Guzik's index (GI), and slope index (SI) were calculated. To test the effect of data length, we performed the analyses separately using long-term heartbeat interval series (derived from >3.6-h ECG) and short-term segments (with length of 500 intervals). A second short-term analysis was further carried out on series extracted from 5-min ECG.

RESULTS
For long-term data, SI showed acceptable performance for both tasks, i.e., for task i p < 0.001, Cohen's d = 0.93, AUC (area under the receiver-operating characteristic curve) = 0.86; for task ii p < 0.001, d = 0.88, AUC = 0.75. AI performed well for task ii (p < 0.001, d = 1.0, AUC = 0.78); for task i, though the difference was statistically significant (p < 0.001, AUC = 0.76), the effect size was small (d = 0.11). PI and GI failed in both tasks (p > 0.05, d < 0.4, AUC < 0.7 for all). However, for short-term segments, AI indicated better distinguishability for both tasks, i.e., for task i, p < 0.001, d = 0.71, AUC = 0.71; for task ii, p < 0.001, d = 0.93, AUC = 0.74. The rest three measures all failed with small effect sizes and AUC values (d < 0.5, AUC < 0.7 for all) although the difference in SI for task i was statistically significant (p < 0.001). Besides, AI displayed smaller variations across different short-term segments, indicating more robust performance. Results from the second short-term analysis were in keeping with those findings.

CONCLUSION
The proposed AI indicated better performance especially for short-term heartbeat interval data, suggesting potential in the ambulatory application of cardiovascular monitoring.

Yan|Chang|C| Li|Peng|P| Ji|Lizhen|L| Yao|Lianke|L| Karmakar|Chandan|C| Liu|Changchun|C|

Area asymmetry
Heart rate asymmetry (HRA)
Poincaré plot
Heart rate variability (HRV)
Phase asymmetry


Improved genome sequence of the phytopathogenic fungus Rhizoctonia solani AG1-IB 7/3/14 as established by deep mate-pair sequencing on the MiSeq (Illumina) system.

Abstract: The phytopathogenic fungus Rhizoctonia solani AG1-IB of the phylum Basidiomycota affects various economically important crops comprising bean, rice, soybean, figs, cabbage and lettuce. The R. solani isolate 7/3/14 of the anastomosis group AG1-IB was deeply resequenced on the Illumina MiSeq system applying the mate-pair mode to improve its genome sequence. Assembly of obtained sequence reads significantly reduced the amount of scaffolds and improved the genome sequence of the isolate compared to the previous sequencing approach. The genome sequence of the AG1-IB isolate 7/3/14 now provides an up-graded basis to analyze genome features predicted to play a role in pathogenesis and for the development of strategies to antagonize the pathogenic impact of this fungus.

Wibberg|Daniel|D| Rupp|Oliver|O| Jelonek|Lukas|L| Kröber|Magdalena|M| Verwaaijen|Bart|B| Blom|Jochen|J| Winkler|Anika|A| Goesmann|Alexander|A| Grosch|Rita|R| Pühler|Alfred|A| Schlüter|Andreas|A|

Rhizoctonia solani AG1-IB
AUGUSTUS
Plant pathogenic fungus
Ultrafast sequencing


Endovascular Treatment of Small Ruptured Intracranial Aneurysms (<5 mm) : Long-term Clinical and Angiographic Outcomes and Related Predictors.

Abstract:
PURPOSE
To investigate the long-term clinical and angiographic outcomes and their related predictors in endovascular treatment (EVT) of small (<5 mm) ruptured intracranial aneurysms (SRA).

METHODS
The study retrospectively reviewed patients with SRAs who underwent EVT between September 2011 and December 2016 in two Chinese stroke centers. Medical charts and telephone call follow-up were used to identify the overall unfavorable clinical outcomes (OUCO, modified Rankin score ≤2) and any recanalization or retreatment. The independent predictors of OUCO and recanalization were studied using univariate and multivariate analyses. Multivariate Cox proportional hazards models were used to identify the predictors of retreatment.

RESULTS
In this study 272 SRAs were included with a median follow-up period of 5.0 years (interquartile range 3.5-6.5 years) and 231 patients with over 1171 aneurysm-years were contacted. Among these, OUCO, recanalization, and retreatment occurred in 20 (7.4%), 24 (12.8%), and 11 (7.1%) patients, respectively. Aneurysms accompanied by parent vessel stenosis (AAPVS), high Hunt-Hess grade, high Fisher grade, and intraoperative thrombogenesis in the parent artery (ITPA) were the independent predictors of OUCO. A wide neck was found to be a predictor of recanalization. The 11 retreatments included 1 case of surgical clipping, 6 cases of coiling, and 4 cases of stent-assisted coiling. A wide neck and AAPVS were the related predictors.

CONCLUSION
The present study demonstrated relatively favorable clinical and angiographic outcomes in EVT of SRAs in long-term follow-up of up to 5 years. THE AAPVS, as a morphological indicator of the parent artery for both OUCO and retreatment, needs further validation.

Peng|Fei|F| Feng|Xin|X| Tong|Xin|X| Zhang|Baorui|B| Wang|Luyao|L| Guo|Erkang|E| Qi|Peng|P| Lu|Jun|J| Wu|Zhongxue|Z| Wang|Daming|D| Liu|Aihua|A|

D017542:Aneurysm, Ruptured
D002533:Cerebral Angiography
D004621:Embolization, Therapeutic
D057510:Endovascular Procedures
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D002532:Intracranial Aneurysm
D008875:Middle Aged
D012189:Retrospective Studies
D015607:Stents
D016896:Treatment Outcome

Treatment
Intracranial aneurysms
Retreatment
Angiography
Risk factors


Early childhood caries among 3- to 5-year-old children in Hong Kong.

Abstract:
OBJECTIVE
The aim of this study was to describe the prevalence of dental caries among 3- to 5-year-old children in Hong Kong and to investigate the factors associated with their dental caries status.

METHODS
Seven kindergartens in Hong Kong were selected using stratified random sampling. The 3- to 5-year-old kindergarten children were invited to join the study. The participants' parents were asked to complete a questionnaire regarding their children's demographic and socio-economic backgrounds, their dental habits and their own dental knowledge. Dental caries experience was measured using the decayed, missing and filled primary teeth (dmft) index. The visible plaque index was adopted for recording oral hygiene. The relationships between caries experience and children's demographic backgrounds, dental habits, oral hygiene and parental dental knowledge were studied using a zero-inflated negative binomial (ZINB) regression analysis.

RESULTS
Among the 1,204 participating preschool children, the overall prevalence of dental caries (dmft > 0) was 46%. The mean dmft score was 2.1 ± 3.4. The prevalences of dental caries among the 3-, 4- and 5-year-old children were 38%, 43% and 55%, respectively. ZINB regression analysis revealed that the study children who were boys, came from families with lower incomes, had dental visit experiences, had higher plaque scores and had parents with lower levels of dental knowledge, had higher dmft scores (P < 0.05).

CONCLUSIONS
Dental caries is prevalent among preschool children in Hong Kong. The caries experiences of the study children are associated with gender, family income, parental dental knowledge, dental visit experience and oral hygiene.

children
Dental caries
dental public health
epidemiology
oral health


Detection of Acetaminophen-Protein Adducts in Decedents with Suspected Opioid-Acetaminophen Combination Product Overdose.

Abstract: Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid-acetaminophen overdose. Samples were assayed for protein-derived acetaminophen-protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen. Protein-derived APAP-CYS was detected in 17 of 22 decedents and was measurable in blood that was not degraded or hemolyzed. Heart blood concentrations ranged from 11 ng/mL (0.1 μM) to 7817 ng/mL (28.9 μM). Protein-derived acetaminophen-protein adducts were detectable in liver tissue for 20 of 22 decedents. Liver histology was also performed for all decedents, and no evidence of centrilobular hepatic necrosis was observed.

Thomas|Karen C|KC|
Wilkins|Diana G|DG|
Curry|Steven C|SC|
Grey|Todd C|TC|
Andrenyak|David M|DM|
McGill|Lawrence D|LD|
Rollins|Douglas E|DE|

D056486:Chemical and Drug Induced Liver Injury

acetaminophen-protein adducts
acetaminophen
protein-derived APAP-CYS
clinical laboratory techniques
forensic science
postmortem redistribution


Evaluating the effectiveness of ultraviolet-C lamps for reducing keyboard contamination in the intensive care unit: A longitudinal analysis.

Abstract:
BACKGROUND
Ultraviolet (UV) spectrum light for decontamination of patient care areas is an effective way to reduce transmission of infectious pathogens. Our purpose was to investigate the efficacy of an automated UV-C device to eliminate bioburden on hospital computer keyboards.

METHODS
The study took place at an academic hospital in Chicago, Illinois. Baseline cultures were obtained from keyboards in intensive care units. Automated UV-C lamps were installed over keyboards and mice of those computers. The lamps were tested at varying cycle lengths to determine shortest effective cycles. Delay after use and prior to cycle initiation was varied to minimize cycle interruptions. Finally, 218 postinstallation samples were analyzed.

RESULTS
Of 203 baseline samples, 193 (95.1%) were positive for bacteria, with a median of 120 colony forming units (CFU) per keyboard. There were numerous bacteria linked to health care-associated infections (HAIs), including Staphylococcus, Streptococcus, Enterococcus, Pseudomonas, Pasteurella, Klebsiella, Acinetobacter, and Enterobacter. Of the 193 keyboards, 25 (12.3%) had gram-negative species. Of 218 postinstallation samples, 205 (94%) were sterile. Of the 13 that showed bacterial growth, 6 produced a single CFU. Comparison of pre- and post-UV decontamination median CFU values (120 and 0, respectively) revealed a >99% reduction in bacteria.

CONCLUSIONS
The UV lamp effectively decontaminates keyboards with minimal interruption and low UV exposure. Further studies are required to determine reduction of HAI transmission with use of these devices.

Gostine|Andrew|A| Gostine|David|D| Donohue|Cristina|C| Carlstrom|Luke|L|

bioburden
Disinfection
MRSA
UV light
UVC
VRE
hospital equipment
hospital-acquired infections


Transient Monocular Visual Loss: When Is It an Emergency?

Abstract:
BACKGROUND
Patients who experienced transient monocular vision loss (TMVL) commonly present to the emergency department for evaluation. Although multiple etiologies can cause TMVL, it is most important to identify patients with retinal ischemia and those with vasculitis (giant cell arteritis) as the cause of TMVL. Patients with transient retinal ischemia have the same risk of cardiovascular events and death as patients who experienced transient brain ischemia. Patients with giant cell arteritis are at imminent risk of visual loss.

CASE REPORT
A 65-year-old man noticed three separate episodes of sudden onset of blurry vision in one eye. Ophthalmologic examination was normal but, as his symptoms were compatible with transient retinal ischemic attack, urgent investigations were initiated. He had normal inflammatory markers but computed tomography angiogram of the brain and neck demonstrated a large plaque in the ipsilateral internal carotid artery. Double anti-platelet therapy was started and stenting of the involved carotid artery was performed. The patient was symptom-free at the last follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients with retinal ischemia as the etiology of TMVL are at high risk of cardiovascular events and death. Their risk of cerebrovascular accidents is highest within 48 h from the episode of TMVL, thus they should have an urgent ophthalmologic examination and, if it is unrevealing, inflammatory markers should be checked and an urgent stroke prevention protocol should be initiated. Appropriate management with medical or surgical interventions significantly reduces morbidity and mortality in these patients.

transient monocular visual loss
retinal TIA
transient visual loss


Ovarian aromatase loss-of-function mutant medaka undergo ovary degeneration and partial female-to-male sex reversal after puberty.

Abstract: Although estrogens have been generally considered to play a critical role in ovarian differentiation in non-mammalian vertebrates, the specific functions of estrogens during ovarian differentiation remain unclear. We isolated two mutants with premature stops in the ovarian aromatase (cyp19a1) gene from an N-ethyl-N-nitrosourea-based gene-driven mutagenesis library of the medaka, Oryzias latipes. In XX mutants, gonads first differentiated into normal ovaries containing many ovarian follicles that failed to accumulate yolk. Subsequently, ovarian tissues underwent extensive degeneration, followed by the appearance of testicular tissues on the dorsal side of ovaries. In the newly formed testicular tissue, strong expression of gsdf was detected in sox9a2-positive somatic cells surrounding germline stem cells suggesting that gsdf plays an important role in testicular differentiation during estrogen-depleted female-to-male sex reversal. We conclude that endogenous estrogens synthesized after fertilization are not essential for early ovarian differentiation but are critical for the maintenance of adult ovaries.

Nakamoto|Masatoshi|M| Shibata|Yasushi|Y| Ohno|Kaoru|K| Usami|Takeshi|T| Kamei|Yasuhiro|Y| Taniguchi|Yoshihito|Y| Todo|Takeshi|T| Sakamoto|Takashi|T| Young|Graham|G| Swanson|Penny|P| Naruse|Kiyoshi|K| Nagahama|Yoshitaka|Y|

Aromatase
Estrogens
Ovarian differentiation
cyp19a1
Sex plasticity
Teleost fish


Interference from HONO in the measurement of ambient air NO2 via photolytic conversion and quantification of NO.

Abstract: The reference method to quantify mixing ratios of the criteria air pollutant nitrogen dioxide (NO2) is NO-O3 chemiluminescence (CL), in which mixing ratios of nitric oxide (NO) are measured by sampling ambient air directly, and mixing ratios of NOx (= sum of NO and NO2) are measured by converting NO2 to NO using, for example, heated molybdenum catalyst or, more selectively, photolytic conversion (P-CL). In this work, the nitrous acid (HONO) interference in the measurement of NO2 by P-CL was investigated. Results with two photolytic NO2 converters are presented. The first used radiation centered at 395 nm, a wavelength region commonly utilized in P-CL. The second used light at 415 nm, where the overlap with the HONO absorption spectrum and hence its photolysis rate are less. Mixing ratios of NO2, NOx and HONO entering and exiting the converters were quantified by Thermal Dissociation Cavity Ring-down Spectroscopy (TD-CRDS). Both converters exhibited high NO2 conversion efficiency (CFNO2; > 90%) and partial conversion of HONO. Plots of CF against flow rate were consistent with photolysis frequencies of 4.2 s-1 and 2.9 s-1 for NO2 and 0.25 s-1 and 0.10 s-1 for HONO at 395 nm and 415 nm, respectively. CFHONO was larger than predicted from the overlap of the emission and HONO absorption spectra. The results imply that measurements of NO2 by P-CL marginally but systematically overestimate true NO2 concentrations, and that this interference should be considered in environments with high HONO:NO2 ratios such as the marine boundary layer or in biomass burning plumes.

Gingerysty|Nicholas J|NJ|
Odame-Ankrah|Charles A|CA|
Jordan|Nick|N|
Osthoff|Hans D|HD|

D000393:Air Pollutants
D009569:Nitric Oxide
D009585:Nitrogen Dioxide
D009608:Nitrous Acid
D010782:Photolysis

HONO interference
Photolytic conversion of NO(2)


Comparison of the Predictive Capacity of the Erotophobia-Erotophilia and the Attitudes Toward Sexual Behaviors in the Sexual Experience of Young Adults.

Abstract: The prediction of sexual behaviors in emerging adult population is important because the number of sexually active individuals is high, and many young adults engage in sexually risky behaviors. Attitudes are an effective way to predict behaviors. The attitude-behavior relation is stronger when both attitude and behavior are measured at equivalent levels of specificity. The aim of this study was to provide empirical support of the Attitudes toward Sexual Behaviors Scale (ASBS) predictive capacity for the sexual experience (number of different sexual behaviors performed) as well as to compare it with the Sexual Opinion Survey (SOS; erotophobia-erotophilia dimension) predictive capacity. Participants were 632 heterosexual young adults (57.8% were women) of Spanish nationality aged 18 to 30 years, selected by incidental and snowball sampling. Sociodemographic questions, the ASBS, the SOS, and a checklist about sexual experience were administered online. When the age and sex variables were controlled, the ASBS predictive capacity for the sexual experience was found to be greater than the SOS predictive capacity in both young men and women. These results might be explained by the higher correspondence in the sexual experience measure (specific sexual behaviors) with the ASBS than with the SOS.

D007722:Health Knowledge, Attitudes, Practice

attitudes toward sexual behaviors
sexual behaviors
young adults
Sexual attitudes
erotophobia–erotophilia


Differences in salaries of physician assistants in the USA by race, ethnicity and sex.

Abstract: Objectives Data from the Academy of American Physician Assistants have suggested there are no differences in salaries by race and ethnic group. Our objective was to compare salaries of physician assistants for different racial and ethnic groups and sexes using another data source. Methods Data from the American Community Surveys (2010-2012) to examine pay differentials of physician assistants. Ordinary least squares regression analysis to compare the salaries of males and females, and those of racial and ethnic groups. Results The majority of physician assistants in recent decades have been women. Their salaries are substantially below those of their male counterparts. The number from racial and ethnic minorities remains low. American Community Surveys data show salaries to be lower than that reported by the American Academy of Physician Assistants. The salaries of Black and Hispanic physician assistants lag significantly behind the salaries of those who are White. Conclusions American Community Surveys data suggest that previously published Academy of American Physician Assistants survey data may have been biased with a low percentage of physician assistants from racial and ethnic minorities which suggests that the Academy of American Physician Assistants need to focus on recruiting greater numbers of minorities.

physician assistant
gender disparities
health services research
income disparities
racial disparities


Abnormality in Wnt signaling is causatively associated with oxidative stress-induced intestinal tumorigenesis in MUTYH-null mice.

Abstract: MUTYH is a DNA glycosylase that excises adenine paired with 8-oxoguanine to prevent mutagenesis in mammals. Biallelic germline mutations of MUTYH have been found in patients predisposed to a recessive form of familial adenomatous polyposis (MAP: MUTYH-associated polyposis). We previously reported that Mutyh-deficient mice showed a high susceptibility to spontaneous and oxidative stress-induced intestinal adenoma/carcinoma. Here, we performed mutation analysis of the tumor-associated genes including Apc, Ctnnb1, Kras and Trp53 in the intestinal tumors of Mutyh-deficient mice. In the 62 tumors, we identified 25 mutations in Apc of 18 tumors and 36 mutations in Ctnnb1 of 36 tumors. Altogether, 54 out of the 62 tumors (87.1%) had a mutation in either Apc or Ctnnb1; no tumor displayed mutations simultaneously in the both genes. Similar to MAP, 60 out of 61 mutations (98.3%) were identified as G:C to T:A transversions of which 85% occurred at either AGAA or TGAA sequences. Immunohistochemical analyses revealed the accumulation of β-catenin in the nuclei of tumors. No mutation was found in either Kras or Trp53 in the tumors. These results indicate that the uncontrolled activation of Wnt signaling pathway is causatively associated with oxidative stress-induced intestinal tumorigenesis in the Mutyh-deficient mice.

Isoda|Takuro|T| Nakatsu|Yoshimichi|Y| Yamauchi|Kazumi|K| Piao|Jingshu|J| Yao|Takashi|T| Honda|Hiroshi|H| Nakabeppu|Yusaku|Y| Tsuzuki|Teruhisa|T|

D025601:Adenomatous Polyposis Coli Protein

D020022:Genetic Predisposition to Disease

mutagenesis
MAP
Wnt signaling pathway
DNA repair
oxidative DNA damage


Population dynamics of a natural red deer population over 200 years detected via substantial changes of genetic variation.

Abstract: Most large mammals have constantly been exposed to anthropogenic influence over decades or even centuries. Because of their long generation times and lack of sampling material, inferences of past population genetic dynamics, including anthropogenic impacts, have only relied on the analysis of the structure of extant populations. Here, we investigate for the first time the change in the genetic constitution of a natural red deer population over two centuries, using up to 200-year-old antlers (30 generations) stored in trophy collections. To the best of our knowledge, this is the oldest DNA source ever used for microsatellite population genetic analyses. We demonstrate that government policy and hunting laws may have strong impacts on populations that can lead to unexpectedly rapid changes in the genetic constitution of a large mammal population. A high ancestral individual polymorphism seen in an outbreeding population (1813-1861) was strongly reduced in descendants (1923-1940) during the mid-19th and early 20th century by genetic bottlenecks. Today (2011), individual polymorphism and variance among individuals is increasing in a constant-sized (managed) population. Differentiation was high among periods (F ST > ***); consequently, assignment tests assigned individuals to their own period with >85% probability. In contrast to the high variance observed at nuclear microsatellite loci, mtDNA (D-loop) was monomorphic through time, suggesting that male immigration dominates the genetic evolution in this population.

Hoffmann|Gunther Sebastian|GS|
Johannesen|Jes|J|
Griebeler|Eva Maria|EM|

microsatellites
mtDNA
Cervidae
Cervus elaphus
natural history collections


Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

Abstract: Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

Nazel Khosroshahi|Behzad|B|
Jafari|Mohammad|M|
Vazini|Hossein|H|
Ahmadi|Alireza|A|
Shams|Keivan|K|
Kholoujini|Mahdi|M|

Cold autoimmune hemolytic anemia
High-grade
Rituximab
Chemotherapy
non-Hodgkin's lymphoma


Is early breast milk fortification more effective in preterm infants?: a clinical trial.

Abstract:
OBJECTIVE
Breast feeding alone does not provide adequate nutrition for growth in preterm infants; therefore, fortifiers are added when over 70-80 cc/kg/day of breast milk is tolerated. As there are few studies comparing early and late breast milk fortification, the following study was conducted.

STUDY DESIGN
This double-blind clinical trial was performed on 80 preterm infants (gestational age of 28-34 weeks, birth weight <2 kg). The newborns were randomly divided into two groups to receive either early or late fortification. The primary and secondary outcomes were the difference in growth indices and complications (including feeding intolerance, necrotizing enterocolitis (NEC), and septicemia) between the two groups, respectively.

RESULTS
Both groups showed increases in growth indices; however, there was no statistically significant difference in increments of growth indices and complications between the two groups.

CONCLUSION
Our findings suggest that early fortification from the first feeding in neonates with exclusive breast feeding did not improve growth in the first 4 weeks in preterm neonates in comparison with late fortification; so early fortification may not be cost effective.

Alizadeh Taheri|Peymaneh|P|
Sajjadian|Negar|N|
Asgharyan Fargi|Marzieh|M|
Shariat|Mamak|M|

late fortification
Early fortification
human milk
preterm newborns


Tree species affects the concentration of total mercury (Hg) in forest soils: Evidence from a forest soil inventory in Poland.

Abstract: This study was performed to test the hypothesis that tree species significantly affects mercury (Hg) sequestration in forest soils. We analyzed the effect of seven dominant tree species (Scots pine, black alder, Norway spruce, silver birch, deciduous oak, silver fir, and European beech on the concentrations and pools of Hg in a range of forest soils in Poland. We set up 277 sample plots representing dominant tree species in Poland. Soil samples were taken and analyzed for total Hg content, soil texture, and soil C and nitrogen (N) content. Concentrations of total Hg in forest soil (organic and mineral horizons) varied by several orders of magnitude as a result of natural variations in organic matter, sand content, and altitude. Spatial analysis revealed that maximum concentrations (mg kg-1) and stocks (mg m-2) of Hg were related to mountain stands at higher elevations with loamy soils and greater accumulation of soil organic matter. The stocks of Hg in the investigated soil profiles increased in the order of: pine (12 mg m-2) ≈ birch (15 mg m-2) < oak (21 mg m-2) ≈ alder (24 mg m-2) < beech (45 mg m-2) ≈ spruce (50 mg m-2) < fir (66 mg m-2). Simple analysis of variance suggested an important effect of dominant tree species on Hg concentrations and stocks in entire soil profiles, but multiple regression analysis showed that dominant tree species had a significant effect on accumulation of Hg in soil, but only in the organic horizon; in mineral soil the Hg was content was related to C content, soil texture and altitude. The organic horizon had greater accumulation of Hg under coniferous tree species (Scots pine, silver fir and Norway spruce) and European beech when compared with deciduous oak, black alder, and silver birch.

Gruba|Piotr|P| Socha|Jarosław|J| Pietrzykowski|Marcin|M| Pasichnyk|Daryna|D|

Mercury
Forest soil
Poland
Organic matter
Sand fraction


Endocytosis, Cytotoxicity, and Translocation of Shiga Toxin-2 Are Stimulated by Infection of Human Intestinal (HCT-8) Monolayers With an Hypervirulent E. coli O157:H7 Lacking stx2 Gene.

Abstract: Shiga toxin-producing Escherichia coli (STEC) strains are responsible for multiple clinical syndromes, including hemolytic uremic syndrome (HUS). E. coli O157:H7 is the most prevalent serotype associated with HUS and produces a variety of virulence factors being Stx2 the responsible of the most HUS severe cases. After intestinal colonization by STEC, Stx2 is released into the intestinal lumen, translocated to the circulatory system and then binds to its receptor, globotriaosylceramide (Gb3), in target cells. Thus, Stx2 passage through the colonic epithelial barrier is a key step in order to produce disease, being its mechanisms still poorly understood. We have previously reported that STEC interaction with the human colonic mucosa enhanced Stx2 production. In the present work, we have demonstrated that infection with O157:H7Δstx2, a mutant unable to produce Stx2, enhanced either Stx2 cytotoxicity on an intestinal cell line (HCT-8), or translocation across HCT-8 monolayers. Moreover, we found that translocation was enhanced by both paracellular and transcellular pathways. Using specific endocytosis inhibitors, we have further demonstrated that the main mechanisms implicated on Stx2 endocytosis and translocation, either when O157:H7Δstx2 was present or not, were Gb3-dependent, but dynamin-independent. On the other hand, dynamin dependent endocytosis and macropinocytosis became more relevant only when O157:H7Δstx2 infection was present. Overall, this study highlights the effects of STEC infection on the intestinal epithelial cell host and the mechanisms underlying Stx2 endocytosis, cytotoxic activity and translocation, in the aim of finding new tools toward a therapeutic approach.

Garimano|Nicolás|N|
Amaral|María Marta|MM|
Ibarra|Cristina|C|

D002460:Cell Line
D002470:Cell Survival
D002478:Cells, Cultured
D004705:Endocytosis
D004927:Escherichia coli Infections
D019453:Escherichia coli O157
D054884:Host-Pathogen Interactions
D006801:Humans
D007413:Intestinal Mucosa
D010873:Pinocytosis
D021381:Protein Transport
D022641:Shiga Toxin 2
D015398:Signal Transduction
D037521:Virulence Factors

endocytosis
cytotoxicity
translocation
HCT-8
O157
STEC
shiga toxin
transcytosis


How Successful is Switching from Bevacizumab or Ranibizumab to Aflibercept in Age-Related Macular Degeneration? A Systematic Overview.

Abstract: Emerging anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have revolutionised medical retina practice and the management and eventual outcome of nAMD. Recent research has focused on evaluating and comparing the efficacy of the two most widely employed anti-VEGF agents, bevacizumab and ranibizumab; however, a subgroup of patients with nAMD demonstrates a suboptimal response to standard therapy. We have therefore conducted a review of pertinent studies published until August 2018 which have documented the clinical efficacy when switching to a different anti-VEGF. Evidence on baseline disease characteristics, injection frequency and disease outcome has been obtained for patients treated with ranibizumab 0.5 mg and/or bevacizumab 1.25 mg and were switched to aflibercept 2 mg. Our review identified 45 studies investigating switching to aflibercept. Our review showed a clear anatomical benefit after the switch in terms of central retinal thickness and pigment epithelium detachment characteristics, whereas the functional outcomes were variable. Remarkable heterogeneity was documented among the relevant studies with regard to several factors including the baseline characteristics of the cohorts, the non-response definition and previous treatment protocols. Larger prospective trials with appropriate control arms are therefore required to elucidate the potential benefit when switching between anti-VEGF agents in refractory nAMD.

Empeslidis|Theodoros|T|
Storey|Matthew|M|
Giannopoulos|Theodoros|T|
Konidaris|Vassileios|V|
Tranos|Paris G|PG|
Panagiotou|Evangelia S|ES|
Voudouragkaki|Irini C|IC|
Konstas|Anastasios G|AG|

D040262:Receptors, Vascular Endothelial Growth Factor

Bevacizumab
Ranibizumab
Aflibercept
Macular degeneration
Anti-VEGF


Ten year survivorship after cemented and uncemented medial Uniglide® unicompartmental knee arthroplasties.

Abstract:
BACKGROUND
Results of knee replacement registries have shown that unicompartmental knee arthroplasty (UKA) has a significantly higher revision and failure rate than current state-of-the-art TKA. The aim of this prospective study is to evaluate the long-term outcomes and to calculate the 10 year survival of knees with medial osteoarthritis treated with Uniglide® UKA.

METHODS
Two hundred thirty-four patients were assessed by an independent clinical observer using the American Knee Society Clinical Rating System, a validated outcome measure. Kaplan-Meier analysis was used to calculate the 10 year survival rates using revision surgery for any cause as the end point.

RESULTS
There were no revisions due to progression of lateral osteoarthritis or polyethylene failure. There were one traumatic and three non-traumatic bearing dislocations and two revisions due to aseptic loosening of the tibial component. One joint was revised for traumatic ligament rupture, one for synovitis from bearing impingement, one due to femoral component mal-positioning and one for infection. A total of 10 cases were revised due to failures for any cause in the 61 patients withdrawn because they had died, thus giving a cumulative survival rate at 10 years of 95.57%. The knee (function) score showed an increase from 33.4 (54.7) pre-operatively to 94 (83.4) points post-operatively. The average range of motion increased from 107 to 122° (p<0.01).

CONCLUSION
Based on our findings we believe that the Uniglide® unicompartmental knee prosthesis offers a safe and effective solution for the treatment of medial compartment osteoarthritis.

Schlueter-Brust|Klaus|K| Kugland|Karoline|K| Stein|Gregor|G| Henckel|Johann|J| Christ|Hildegard|H| Eysel|Peer|P| Bontemps|Gustav|G|

Cemented
Uncemented
UKA
Survival
Mobile bearing


Validation of an Algorithm for Semi-automated Estimation of Voice Relative Fundamental Frequency.

Abstract:
OBJECTIVES
Relative fundamental frequency (RFF) has shown promise as an acoustic measure of voice, but the subjective and time-consuming nature of its manual estimation has made clinical translation infeasible. Here, a faster, more objective algorithm for RFF estimation is evaluated in a large and diverse sample of individuals with and without voice disorders.

METHODS
Acoustic recordings were collected from 154 individuals with voice disorders and 36 age- and sex-matched controls with typical voices. These recordings were split into training and 2 testing sets. Using an algorithm tuned to the training set, semi-automated RFF estimates in the testing sets were compared to manual RFF estimates derived from 3 trained technicians.

RESULTS
The semi-automated RFF estimations were highly correlated ( r = 0.82-0.91) with the manual RFF estimates.

CONCLUSIONS
Fast and more objective estimation of RFF makes large-scale RFF analysis feasible. This algorithm allows for future work to optimize RFF measures and expand their potential for clinical voice assessment.

Lien|Yu-An S|YS|
Heller Murray|Elizabeth S|ES|
Calabrese|Carolyn R|CR|
Michener|Carolyn M|CM|
Van Stan|Jarrad H|JH|
Mehta|Daryush D|DD|
Hillman|Robert E|RE|
Noordzij|J Pieter|JP|
Stepp|Cara E|CE|


Enzyme technology in food preservation: A promising and sustainable strategy for biocontrol of post-harvest fungal pathogens.

Abstract: Population aging has reinforced the need for production of foods with high nutritional value, especially fresh fruits and vegetables. In general, due to their perishable nature, these foods are prone to spoilage by post-harvest microorganisms. For this reason, I aim to discuss in this article the alternative use of enzymes as biocontrol agents against fungal infections in post-harvest fruits and vegetables. This article therefore proposes a sustainable alternative with demonstrated success to improve the preservation of food in its fresh form and facilitating its storage, mainly in domestic space. Food spoilage caused by microorganisms has adverse economic effects. Pathogens such as Monilinia spp., Botrytis cinerea, and Penicillium expansum are important fungi that cause post-harvest spoilage of fruits.Thus, the application of enzymes in food chemistry offers a promising approach to improve the shelf life of foods without altering the organoleptical characteristics and nutritional content.

Food spoilage
Chitinase
Microbial enzyme
Mold
Proteolytic enzymes


Socioeconomic determinants of use of reproductive health services in Ghana.

Abstract:
BACKGROUND
The study examines trends in the consumption of reproductive health services (use of modern contraceptives, health facility deliveries, assisted deliveries, first trimester antenatal visit and 4+ antenatal visits) and their determinants using four rounds of Ghana Demographic and Health Surveys (1993, 1998, 2003 and 2008) data.

METHODS
The study uses cross-sectional and pooled probit and negative bionomial regressions models to estimate the determinants of use of the above listed reproductive health services for the period from 1993 to 2008.

RESULTS
Summary statistics suggest that the above-listed reproductive health services have consistently improved from 1993 to 2008. However, use of traditional methods of contraception increased in urban centers between 2003 and 2008, although the reverse was the case in rural areas. Regression results suggest that place of residence, access to and availability of health services, religion, and birth order are significant correlates of use of reproductive health services. Additionally, the study suggests that the number of living children has the largest effect on use of modern contraception. The effect of a partner's education on use of modern contraception is higher than that of the woman, and a much stronger correlation exists between household wealth and use of reproductive health inputs than expected.

CONCLUSION
The study associates the increasing use of traditional contraceptives in urban centers and the much stronger effect of household wealth with urban poverty and the increasing indirect cost of health services, and argues for interventions to improve quality of service in public facilities and reduce inequities in the distribution of health facilities. Finally, the study advocates for family planning-related interventions that involve and target partners given the importance of partner education in the use of modern contraception.

Socioeconomic
Determinants
Reproductive Health


Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer's disease.

Abstract: Alzheimer's disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over-activation of N-methyl-D-aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN-08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice (for a 6-month preventative course) and in the 8-month-old triple-transgenic (3×Tg-AD) mice (for a 4-month therapeutic course). In vitro, MN-08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate-induced neuronal loss. In addition, MN-08 had favorable pharmacokinetics, blood-brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD.

Wu|Liangmiao|L|
Zhou|Xinhua|X|
Cao|Yiwan|Y|
Mak|Shing Hung|SH|
Zha|Ling|L|
Li|Ning|N|
Su|Zhiyang|Z|
Han|Yifan|Y|
Wang|Yuqiang|Y|
Man Hoi|Maggie Pui|MP|
Sun|Yewei|Y|
Zhang|Gaoxiao|G|
Zhang|Zaijun|Z|0000-0002-0690-1673
Yang|Xifei|X|0000-0002-9000-7016

memantine nitrate
N-methyl-D-aspartate (NMDA) receptors
cognitive deficits
Alzheimer’s disease
nitric oxide


The diverse nematicidal properties and biocontrol efficacy of Bacillus thuringiensis Cry6A against the root-knot nematode Meloidogyne hapla.

Abstract: Cry6A toxin from Bacillus thuringiensis is a representative nematicidal crystal protein with a variety of nematicidal properties to free-living nematode Caenorhabditis elegans. Cry6A shares very low homology and different structure with Cry5B, another representative nematicidal crystal protein, and probably acts in a distinct pathway. All these strongly indicate that Cry6A toxin is likely a potent candidate for nematicide. The present study dealt with global investigation to determine the detrimental impacts of Cry6Aa2 toxin on Meloidogyne hapla, a root-knot nematode, and evaluated its biocontrol efficacy in pot experiment. Obtained results indicated that Cry6Aa2 toxin exhibits obvious toxicity to second-stage juvenile of M. hapla, and significantly inhibits egg hatch, motility, and penetration to host plant. Pot experiment suggested that soil drenching with spore-crystal mixture of Cry6Aa2 can clearly lighten the disease of root-knot nematode, including reduction of galling index and egg masses on host plant root, decreasing final population of nematode in soil. Moreover, application of Cry6Aa2 can obviously promote plant growth. These results demonstrated that Cry6Aa2 toxin is a promising nematicidal agent, and possesses great potential in plant-parasitic nematode management and construction of transgenic crop with constant resistance to nematode.

Yu|Ziquan|Z| Xiong|Jing|J| Zhou|Qiaoni|Q| Luo|Haiyan|H| Hu|Shengbiao|S| Xia|Liqiu|L| Sun|Ming|M| Li|Lin|L| Yu|Ziniu|Z|

Nematicidal properties
Biocontrol efficacy
Bacillus thuringiensis
Cry6A
Meloidogyne hapla


High attainment of optimal nutritional and growth status observed among Greek pediatric cystic fibrosis patients: results from the GreeCF study.

Abstract:
BACKGROUND
Pediatric cystic fibrosis (CF) patients suffer high rates of undernutrition, subject to several parameters. We aimed to assess growth and nutritional status of Greek children and adolescents with CF.

METHODS
Eighty-four patients (35 boys) formed the sample. Anthropometrics and FEV1 were measured, growth and weight status were assessed. Body mass index (BMI), arm circumference (MUAC), fat (MUAFA) and muscle (MUAMA) were calculated.

RESULTS
In the total sample, 6.0% of the patients were underweight, 4.8% stunted, 8.3% wasted and 17.9% in nutritional failure, whereas 59.5% attained the ideal BMI for CF. FEV1 positively associated with BMI (B=0.03, p≤0.003), weight (B=0.03, p≤0.003) and MUAMA z-scores (B=0.04, p≤0.005). Meconium ileus negatively associated with FEV1 (B=-14.17, p≤0.003) and stature (B=-0.65, p≤0.043). Pancreatic insufficiency negatively influenced MUAC and MUAFA z-scores (p≤0.05 for both).

CONCLUSIONS
The examined CF patients appear to be thriving. Unlike published research, the participants' sex, gene mutation and acquisition of pathogens did not affect growth.

growth
cystic fibrosis
underweight
nutritional failure
lung function