Metabolic engineering of Ralstonia eutropha for the biosynthesis of 2-hydroxyacid-containing polyhydroxyalkanoates.

Abstract: Polyhydroxyalkanoates (PHAs) are bio-based and biodegradable polyesters synthesized by numerous microorganisms. PHAs containing 2-hydroxyacids as monomer units have attracted much attention, but their production has not been efficient. Here, we metabolically engineered Ralstonia eutropha strains for the in vivo synthesis of PHAs containing 2-hydroxyacids as monomers. This was accomplished by replacing the R. eutropha phaC gene in the chromosome with either the R. eutropha phaC S506G A510K gene, which contains two point mutations, or the Pseudomonas sp. MBEL 6-19 phaC1437 gene. In addition, the R. eutropha phaAB genes in the chromosome were replaced with the Clostridium propionicum pct540 gene. All of the engineered R. eutropha strains produced PHAs containing 2-hydroxyacid monomers, including lactate and 2-hydroxybutyrate (2HB), along with 3-hydroxybutyrate (3HB) and/or 3-hydroxyvalerate (3HV), when they were cultured in nitrogen-free medium containing 5 g/L lactate or 4 g/L 2HB and 20 g/L glucose as carbon sources. Expression of the Escherichia coli ldhA gene in engineered R. eutropha strains allowed production of poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] from glucose as the sole carbon source. This is the first report on the production of 2-hydroxyacid-containing PHAs by metabolically engineered R. eutropha.

Park|Si Jae|SJ|
Jang|Young-Ah|YA|
Lee|Hyuk|H|
Park|A-Reum|AR|
Yang|Jung Eun|JE|
Shin|Jihoon|J|
Oh|Young Hoon|YH|
Song|Bong Keun|BK|
Jegal|Jonggeon|J|
Lee|Seung Hwan|SH|
Lee|Sang Yup|SY|


The COVID-19 Pandemic Did Not Affect Target Weight Loss 1 Year Post Bariatric Surgery.

Abstract:
BACKGROUND
Bariatric surgery is one of the most effective treatments for patients with severe and complex obesity. Lifestyle modifications in diet and exercise habits have long been important adjunct to the long-term success after bariatric surgery. The effect of the COVID-19 pandemic on the postoperative bariatric patient is not well understood. We sought to evaluate the impact the COVID-19 pandemic on postoperative weight loss at 1 year in a bariatric cohort.

METHODS
All patients who underwent bariatric surgery from January 1, 2020, to March 12, 2020, were included. Patients who underwent bariatric surgery during the same period of the two preceding years (2018 and 2019) were included as control groups. Primary end point was %EBMIL at 1 year. A telephone survey was administered to all patients from 2020 to assess for their perception on the effects of the COVID-19 pandemic on weight loss.

RESULTS
A total of 596 patients were included: 181 from 2020, 199 from 2019, and 216 from 2018. The response rate was 97% and 53.4% of patients reported that the lockdown affected their ability to lose weight. The %EBMIL at 1 year was 64.1%, 63.7%, and 68.1% for 2020, 2019, and 2018, respectively. There was no difference in weight loss at 1 year (p = 0.77) despite a decrease in exercise activity in those who had surgery just before the pandemic.

CONCLUSION
There was no difference in target weight loss at 1 year in a cohort who underwent bariatric surgery before the pandemic.

Pereira|Xavier|X|
Romero-Velez|Gustavo|G|
Skendelas|John P|JP|
Rodriguez-Quintero|Jorge Humberto|JH|
Grosser|Rachel|R|
Lima|Diego L|DL|
Moran-Atkin|Erin|E|
Choi|Jenny|J|
Camacho|Diego|D|

COVID-19
Bariatric surgery
Gastric bypass
Laparoscopic
Roux-en-Y gastric bypass
Sleeve gastrectomy


Familial characteristics of street children in tehran, iran.

Abstract:
OBJECTIVE
The phenomenon of street children is one of the most important concerns facing global community. Identifying risk factors in such children could lead to crucial investigations to find their essential needs by intervention programs. The present study examined the family profile of street children in Tehran, Iran.

METHODS
The sample consisted of 576 street children who were evaluated by 15 examiners. Using multi-stage sampling, twenty-seven different areas of Tehran were divided into 5 clusters and the children were selected randomly from each cluster. The two questionnaires applied included a demographic questionnaire and a questionnaire about high-risk behaviors such as substance use, alcohol consumption, cigarette smoking, etc.

RESULTS
There was a statistical significant association between the length of work time and two variables: sex and economic status of family (p < 0.05). Incarceration history of street children who had lost both their parents and their parents had been divorced was significantly higher than others (p < 0.05).

CONCLUSION
The street children's lifestyle is a risk factor for affecting them to variety types of socio-mental problems. Statistical significant association between parental divorces or the loss of both parents with a history of conviction mentions the important role of parents in transmitting moral and social values to children.

Ahmad Khaniha|Ahmad Reza|AR|
Hakim Shooshtari|Mitra|M|
Mohammadian|Mehrdad|M|
Bidaki|Reza|R|
Pourrashidi Boshrabadi|Ahmad|A|

Street Children
Tehran
Iran
amilial Characteristics


Head-down tilt bed rest with or without artificial gravity is not associated with motor unit remodeling.

Abstract:
PURPOSE
The objective of this study was to assess whether artificial gravity attenuates any long-duration head-down 60 bed rest (HDBR)-induced alterations in motor unit (MU) properties.

METHODS
Twenty-four healthy participants (16 men; 8 women; 26-54 years) underwent 60-day HDBR with (n = 16) or without (n = 8) 30 min artificial gravity daily induced by whole-body centrifugation. Compound muscle action potential (CMAP), MU number (MUNIX) and MU size (MUSIX) were estimated using the method of Motor Unit Number Index in the Abductor digiti minimi and tibialis anterior muscles 5 days before (BDC-5), and during day 4 (HDT4) and 59 (HDT59) of HDBR.

RESULTS
The CMAP, MUNIX, and MUSIX at baseline did not change significantly in either muscle, irrespective of the intervention (p > 0.05). Across groups, there were no significant differences in any variable during HDBR, compared to BDC-5.

CONCLUSION
Sixty days of HDBR with or without artificial gravity does not induce alterations in motor unit number and size in the ADM or TA muscles in healthy individuals.

Bed rest
Motor unit
MUNIX
Microgravity
Muscle strength
Neuromuscular
Spaceflight


Testing the Integrated Motivational-Volitional Model of Suicidal Behavior in Chinese Adolescents.

Abstract: The integrated motivational-volitional model of suicidal behavior (IMV; O'Connor & Kirtley, 2018) integrates some key factors of suicidal behavior (e.g., defeat and entrapment) to explain the development of suicidal ideation and suicidal attempts. This study aimed to empirically test this model in a sample of Chinese adolescents. A number of 1,239 Chinese adolescents (679 girls; Mage = 14.07, SD = 1.54) completed self-report questionnaires. Results showed that defeat was associated with entrapment, which, in turn, was related to suicidal ideation and suicidal attempts. In addition, the relationship between entrapment and suicidal ideation was significant at high levels of thwarted belongingness and perceived burdensomeness, and low levels of resilience. These findings support the application of the IMV model in Chinese adolescents, and might help mental health organizations and educational agencies formulate effective suicidal prevention programs geared toward Chinese adolescents.

Li|Xiaoan|X| Ren|Yaxuan|Y| Zhang|Xu|X| Zhou|Jiazhi|J| Su|Binyuan|B| Liu|Sihan|S| Cai|Huisi|H| Liu|Jiaqi|J| You|Jianing|J|

the integrated motivational-volitional model


Comparison of Experimental and Modeled EMI Shielding Properties of Periodic Porous xGNP/PLA Composites.

Abstract: Microwave absorbing materials, particularly ones that can achieve high electromagnetic interference (EMI) absorption while minimizing weight and thickness are in high demand for many applications. Herein we present an approach that relies on the introduction of periodically placed air-filled pores into polymer composites in order to reduce material requirements and maximize microwave absorption. In this study, graphene nano platelet (xGNP)/poly-lactic acid (PLA) composites with different aspect ratio fillers were characterized and their complex electromagnetic properties were extracted. Using these materials, we fabricated non-perfect electrical conductor (PEC) backed, porous composites and explored the effect of filler aspect ratio and pore geometry on EMI shielding properties. Furthermore, we developed and experimentally verified a computational model that allows for rigorous, high-throughput optimization of absorbers with periodic porous geometries. Finally, we extend the modeling approach to explore the effect of pore addition on PEC-backed composites. Our composite structures demonstrated decreased fractions of reflected power and increased fractions of absorbed power over the majority of the X Band due to the addition of periodically arranged cylindrical pores. Furthermore, we showed that for xGNP/PLA composite material, reflection loss can be increased by as much as 13 dB through the addition of spherical pores. The ability to adjust shielding properties through the fabrication of polymer composites with periodically arranged pores opens new strategies for the modeling and development of new microwave absorption materials.

EMI shielding
reflection loss
COMSOL
compression molding
computational design
graphene nanoplatelets
poly-lactic acid
scattering parameters


Metacognitive domain specificity in feeling-of-knowing but not retrospective confidence.

Abstract: Previous research has converged on the idea that metacognitive evaluations of memory dissociate between semantic and episodic memory tasks, even if the type of metacognitive judgement is held constant. This often observed difference has been the basis of much theoretical reasoning about the types of cues available when making metacognitive judgements of memory and how metacognition is altered in memory pathologies. Here, we sought to revisit the difference between episodic and semantic feeling-of-knowing (FOK) judgements in the light of recent research which has supported a domain general account of metacognition. One hundred participants performed classical episodic and semantic memory tasks with FOK judgements and confidence judgements. Using the meta-d' framework, we applied a hierarchical Bayesian model to estimate metacognitive sensitivity and cross-task covariance. Results revealed a significant correlation in metacognitive efficiency (meta-d'/d') between the episodic memory task and the semantic memory task for confidence judgements; however, no evidence was found for a cross-task correlation for FOK judgements. This supports the view that FOK judgements are based on different cues in semantic and episodic memory, whereas confidence judgements are domain general.

Mazancieux|Audrey|A|0000-0003-1764-3582
Dinze|Claire|C|
Souchay|Céline|C|
Moulin|Chris J A|CJA|

metacognition
feeling-of-knowing
confidence
episodic memory
semantic memory


Incidence of childhood injuries and modifiable household risk factors in rural Ghana: a multistage, cluster-randomised, population-based, household survey.

Abstract:
OBJECTIVE
We aimed to describe the incidence of childhood household injuries and prevalence of modifiable household risk factors in rural Ghana to inform prevention initiatives.

SETTING
357 randomly selected households in rural Ghana.

PARTICIPANTS
Caregivers of children aged <5 years.

PRIMARY AND SECONDARY OUTCOME MEASURES
Childhood injuries that occurred within 6 months and 200 metres of the home that resulted in missed school/work, hospitalisation and/or death. Sampling weights were applied, injuries were described and multilevel regression was used to identify risk factors.

RESULTS
Caregivers from 357 households had a mean age of 35 years (SD 12.8) and often supervised ≥2 children (51%). Households typically used biomass fuels (84%) on a cookstove outside the home (79%). Cookstoves were commonly <1 metre of the ground (95%). Weighted incidence of childhood injury was 542 per 1000 child-years. Falls (37%), lacerations (24%), burns (12%) and violence (12%) were common mechanisms. There were differences in mechanism across age groups (p<0.01), but no gender differences (p=0.25). Presence of older children in the home (OR 0.15, 95% CI 0.09 to 0.24; adjusted OR (aOR) 0.26, 95% CI 0.13 to 0.54) and cooking outside the home (OR 0.28, 95% CI 0.19 to 0.42; aOR 0.25, 95% CI 0.13 to 0.49) were protective against injury, but other common modifiable risk factors (eg, stove height, fuel type, secured cabinets) were not.

CONCLUSIONS
Childhood injuries occurred frequently in rural Ghana. Several common modifiable household risk factors were not associated with an increase in household injuries. Presence of older children was a protective factor, suggesting that efforts to improve supervision of younger children might be effective prevention strategies.

accident & emergency medicine
epidemiology
non-accidental injury
preventive medicine


Detection of emerging antibiotic resistance in bacteria isolated from subclinical mastitis in cattle in West Bengal.

Abstract:
AIM
The aim of this work was to detect antibiotic resistance in Gram-negative bacteria isolated from subclinical mastitis in cattle in West Bengal.

MATERIALS AND METHODS
The milk samples were collected from the cattle suffering with subclinical mastitis in West Bengal. The milk samples were inoculated into the nutrient broth and incubated at 37°C. On the next day, the growth was transferred into nutrient agar and MacConkey agar. All the pure cultures obtained from nutrient agar slant were subjected to Gram-staining and standard biochemical tests. All the bacterial isolates were tested in vitro for their sensitivity to different antibiotics commonly used in veterinary practices. All Gram-negative isolates including positive control were subjected to polymerase chain reaction (PCR) for detection of blaCTX-M, blaTEM, blaSHV, blaVIM, tetA, tetB, tetC, and tetM genes considered for extended-spectrum β-lactamase (ESBL), metallo-β-lactamase, and tetracycline resistance.

RESULTS
In total, 50 Gram-negative organisms (Escherichia coli, Proteus, Pseudomonas, Klebsiella, and Enterobacter) were isolated from milk samples of subclinical mastitis infected cattle. Among these Gram-negative isolates, 48% (24/50) were found either ESBL producing or tetracycline resistant. Out of total 50 Gram-negative isolates, blaCTX-M was detected in 18 (36%) isolates, and 6 (12%) harbored blaTEM genes in PCR. None of the isolates carried blaSHV genes. Further, in this study, 5 (10%) isolates harbored tet(A) gene, and 8 (16%) isolates carried tet(B) gene. No tet(C) gene was detected from the isolates.

CONCLUSION
This study showed emerging trend of antibiotic-resistant Gram-negative bacteria associated with subclinical mastitis in cattle in West Bengal, India.

Das|Arnab|A|
Guha|Chanchal|C|
Biswas|Ujjwal|U|
Jana|Partha Sarathi|PS|
Chatterjee|Amaresh|A|
Samanta|Indranil|I|

antibiotic resistance
cattle
Escherichia coli
India
sub-clinical mastitis


Pediatric contrast-enhanced ultrasound: optimization of techniques and dosing.

Abstract: When performing contrast-enhanced ultrasound (CEUS), ultrasound (US) scanner settings, examination technique, and contrast agent dose and administration must be optimized to ensure that high-quality, diagnostic and reproducible images are acquired for qualitative and quantitative interpretations. When carrying out CEUS in children, examination settings should be tailored to their body size and specific indications, similar to B-mode US. This review article details the basic background knowledge that is needed to perform CEUS optimally in children, including considerations related to US scanner settings and US contrast agent dose selection and administration techniques.

Contrast-enhanced ultrasound
Ultrasound
Technique
Dose
Children
Ultrasound contrast agent


Application of a real-time fluorescence resonance energy transfer polymerase chain reaction assay with melting curve analysis for the detection of Paragonimus heterotremus eggs in the feces of experimentally infected cats.

Abstract: Paragonimus heterotremus is a medically important lung fluke that causes human and animal paragonimiasis in Southeast Asia, including Thailand. In the current study, a real-time fluorescence resonance energy transfer polymerase chain reaction (real-time FRET PCR) with melting curve analysis was developed and evaluated to detect P. heterotremus eggs in the feces of experimentally infected cats. The detection limit of this method for the P. heterotremus DNA sequence was 3 × 10(2) copies of the positive control plasmid and 10(-3) ng of P. heterotremus genomic DNA. The assay system could detect 10 eggs of P. heterotremus per gram of cat feces. No fluorescence signal was observed when DNA purified from 16 other organisms or genomic DNA from cats and human beings were tested. Real-time FRET PCR yielded positive results for all fecal samples from 17 P. heterotremus-infected cats and showed a negative relationship (r = -0.852, P < 0.001) between the number of parasite eggs in feces and the number of PCR cycles. The assay could detect genomic DNA from P. heterotremus, P. westermani, P. macrorchis, P. siamensis, P. harinasutai, and P. bangkokensis and can differentiate P. heterotremus from the other 5 species. The 6 Paragonimus species examined were divided into 4 groups by melting peak analysis. This assay can be useful for the detection of, and epidemiological studies on, P. heterotremus infection in endemic areas.

Tantrawatpan|Chairat|C|
Intapan|Pewpan M|PM|
Thanchomnang|Tongjit|T|
Sanpool|Oranuch|O|
Janwan|Penchom|P|
Lulitanond|Viraphong|V|
Anamnart|Witthaya|W|
Maleewong|Wanchai|W|

D031541:Fluorescence Resonance Energy Transfer

D060888:Real-Time Polymerase Chain Reaction


Outcomes of 200 digital flexor tendon repairs using updated protocols and 30 repairs using an old protocol: experience over 7 years.

Abstract: We reviewed outcomes of 230 flexor tendon repairs in 27 thumbs and 203 fingers in Zone 1 and 2 over 7 years. In 2013, we used a 2-strand modified Kessler method followed by passive motion exercise in repairing flexor digitorum profundus tendon injuries in Zone 2 in 30 fingers; 24 fingers were followed, five (26%) had repair ruptures. Between 2014 and 2017, we used a 4- or 6-strand method to repair 111 flexor digitorum profundus tendons in Zone 2, followed by true early active motion. Two had repair ruptures. Among 101 fingers followed over 6 months, two fingers had tenolysis and 87 (87%) good or excellent outcomes. In 2018 to 2019, we used a 6-strand method to repair 42 flexor digitorum profundus tendons in Zone 2 with out-of-splint early active motion. None had repair ruptures or tenolysis. From 2014 to 2019, 27 flexor pollicis longus tendons were repaired in Zone 1 or 2, and 20 fingers had end-to-end flexor digitorum profundus repairs in Zone 1; none had repair ruptures or tenolysis. We conclude that a strong repair and true active motion are necessary for best outcomes of flexor tendon repairs in the thumb and fingers, and out-of-splint true active motion is safe.

Pan|Zhang Jun|ZJ|
Pan|Lei|L|
Xu|Yun Fei|YF|
Ma|Tao|T|
Yao|Lei Hui|LH|

outcomes
Flexor tendons
early active flexion
out of splint motion
pulley venting
repair methods


A new species catfish, Amphilius pagei (Siluriformes: Amphiliidae) from Angola.

Abstract: Amphilius pagei, a new species of amphiliid catfish is described from the Cuanza River basin in Angola. It is distinguished from all other species of Amphilius by the combination of presence (vs. absence) of an epidermal fold at the base of the caudal fin, 6+7 (i,5,6,i) principal caudal-fin rays (vs. 7+8 or 8+9), a variably mottled body coloration that includes dark saddles (vs. body coloration not mottled with dark saddles), head and body heavily spotted (vs. head and body not heavily spotted), epidermal fold smooth (vs. crenelations present on epidermal fold), branchiostegal rays usually eight or nine, and total gill rakers usually 12-16. It is most similar to A. lentiginosus which has a crenelated epidermal fold and fewer branchiostegal rays.


Continuous integration in urban social-ecological systems science needs to allow for spacing co-existence : This article belongs to Ambio's 50th Anniversary Collection. Theme: Urbanization.

Abstract: Urbanization brings benefits and burdens to both humans and nature. Cities are key systems for integrated social-ecological research and the interdisciplinary journal of Ambio has published ground-breaking contributions in this field. This reflection piece identifies and discusses integration of the human and natural spheres in urban social-ecological research using the following foundational papers as important milestones: Folke et al. (1997), Ernstson et al. (2010) and Andersson et al. (2014). These papers each take unique approaches that aim to uncover core properties-processes, structures, and actors-of urban systems and set them into mutual relationship. This piece will end with a forward-looking vision for the coming 50 years of urban sustainability and resilience study in Ambio.

D000846:Anniversaries and Special Events

Integration
Social-ecological systems
Urban systems


Biliary stent migration to hepatic duct-case report of a late complication.

Abstract: Endoscopic retrieval of proximally migrated biliary plastic stents may be technically challenging and sometimes unsuccessful. Here we report the case of a 59-year-old woman with a migrated biliary stent in the right hepatic duct, which was diagnosed after the patient presented with cholangitis. The patient presented with constant abdominal pain in the right upper quadrant lasting for two days, along with nausea and bilious vomiting. The stent was retrieved by a polypectomy snare after failure of biliary basket and forceps. We performed a novel procedure for extraction of a migrated plastic stent, by using a polypectomy snare.

Mohammad Alizadeh|Amir Houshang|AH|
Donboli|Kianoush|K|
Khodakarami|Mehran|M|
Baghbani|Salar|S|
Zali|Mohammad Reza|MR|

biliary stent
migration
hepatic duct
polypectomy snare


Engagement in Favorite Activity and Implications for Cognition, Mental Health, and Function in Persons Living With and Without Dementia.

Abstract: Little is known about the impact of engagement in personally meaningful activities for older adults. Thus, this study examines the impact of engagement in one's favorite activity on cognitive, emotional, functional, and health-related outcomes in older adults with and without cognitive impairment. Data were obtained from 1,397 persons living with dementia (PLWD) and 4,719 cognitively healthy persons (CHP) who participated in wave 2 of the National Health and Aging Trends Study (NHATS). Sociodemographic characteristics were examined by cognitive status. A multivariate analysis of variance indicated that, for PLWD, engagement in favorite activity was associated with greater functional independence and decreased depression. For CHP, engagement in favorite activity was associated with greater functional independence, decreased depression and anxiety, and better performance on memory measures. Findings suggest that engagement in valued activities that are considered personally meaningful may have significant and distinct benefits for persons with and without dementia.

mental health
dementia
National Health and Aging Trends Study
memory
successful aging


Maturity offset affects standing postural control in youth male soccer players.

Abstract: Quantifying the response of postural control in developmental athletes makes it possible to understand critical coordination and learning phases and to improve technical-physical interventions. However, the influence of maturation on postural control amongst young soccer players has neither been tested using quantitative methods, nor over a wide age range. In this study, we examined stabilometric parameters of 238 young male soccer players from 9 to 17 years old relative to maturity offset. Two 30-s tests (eyes open and eyes closed) were recorded on a baropodometric platform at 50 Hz. Participants were split into six groups according to their maturity offset, expressed as years from individual's peak height velocity. Dependent variables were: Sway Area, Center-of-Pressure velocity, standard deviation of the antero-posterior and medio-lateral Center-of-Pressure trajectory, Romberg Quotient. Sway Area was significantly higher in players with maturity offset <-1.5 than in groups with maturity offset > 0.5 years (p < 0.001, large effect). Center-of-Pressure velocity markedly dropped in players with maturity offset >-0.5 years (p < 0.001, very large effect). Antero-posterior standard deviation was higher before than after peak height velocity (p < 0.05, large effect) and significantly higher with closed eyes at some points. Medio-lateral standard deviation was higher in the youngest group of players (maturity offset <-2.5 years, large effect) than in those with maturity offset >-0.5 years. In sum, stabilometric parameters improved with age until zero maturity offset was achieved. Thereafter, variables describing postural control in developing soccer players were almost stable. No evidence of a changing role of vision in postural sway control during maturation was observed.

Zago|Matteo|M|
Moorhead|Alex Patten|AP|
Bertozzi|Filippo|F|
Sforza|Chiarella|C|
Tarabini|Marco|M|
Galli|Manuela|M|

Peak height velocity
Balance
Stability
Team sports


Depression in Parents of Children Diagnosed with Autism Spectrum Disorder: A Claims-Based Analysis.

Abstract: Previous studies showing that Autism Spectrum Disorder (ASD) in children can have secondary effects on the child's parents are limited by small sample sizes and parent self-report. We examined the odds of depression in parents of children with ASD compared to parents of children without ASD using a large national claims database. Mothers (OR 2.95, 95% CI 2.81-3.09) and fathers (OR 2.41, 95% CI 2.25-2.58) of children with ASD were more likely to have a diagnosis of depression than parents of children without ASD. Odds of depression also increased when there was more than one child with ASD in the family and with child age. Study results reinforce the benefits of support and education for parents of children with ASD.

Depression
Parents
Autism spectrum disorder
Claims data
Regression analysis
Services research


The data on the quality of services, satisfaction, psychological commitment and oral advertising in clinical centers in Kermanshah.

Abstract: These data were acquired to investigate the relationship between quality of services with satisfaction, psychological commitment and oral advertising among patients in selected clinical centers of Kermanshah University of Medical Sciences. A total of 420 patients referring to the health centers were agreed to participate, and 201 patients were selected finally using a simple random sampling. Data were collected by multiple questionnaires, including quality of service, satisfaction, psychological commitment and oral promotion. In order to check the reliability of questionnaires, Chronbach׳s alpha coefficients were calculated using 50 patients. Structural Equation Modeling was used to determine the relationship between quality of services with satisfaction, psychological commitment and oral advertising.

Safari|Yahya|Y|
Mohammadi Cheshmeh-Kaboodi|Asma|A|
Yousefi|Bahram|B|

Quality of service
Satisfaction
Oral promotion
Attraction
Therapeutic centers


The effect of caffeic acid phenethyl ester and thymoquinone on otitis media with effusion in rats.

Abstract:
OBJECTIVE
In this study, we aimed to investigate the effect of CAPE and thymoquinone in experimental rat otitis media with effusion (OME) model.

METHODS
Intraoral approach of eustachian tube orifice cauterization were administered to 36 of 40 rats participating the study. After application of exclusion criterias, 22 rats with appropriate conditions were determined. Totally 26 rats (44 otitis model ears and 8 normal ears) were randomly divided into 5 groups. While group I was consisted of healthy rats, the other groups were consisted of rats with otitis model. Group I (saline + control group; n = 8 normal ears) and group II (saline + otitis model; n = 10 otitis model ears) received intraperitoneally saline solution. CAPE was given intraperitoneally to group III (CAPE + otitis model; n = 12 otitis model ears) at a concentration of 10 mg/kg for treatment of otitis media. Group IV (thymoquinone + otitis model; n = 12 otitis model ears) was treated orally with 10 mg/kg of thymoquinone. Group V (methylprednisolone + otitis model; n = 10 otitis model ears) was treated intraperitoneally with 1 mg/kg of methylprednisolone. Tympanic bulla samples were excised after 10th day of treatment and examined under light microscopy.

RESULTS
Submucosal neutrophil leukocyte count of group I was significantly lower than other groups (II, IV, V) (respectively p < 0,0001, p < 0,001, p < 0,0001, Tukey test), while it was not significantly different from group III (p = 0,056, Tukey test). Submucosal neutrophil leukocyte count of group III was significantly lower than group II and group V (p = 0.029 ve p = 0.03, Tukey test). There was no significant difference between group IV and group V (p = 0,28, Tukey test).

CONCLUSION
Based on these findings, it could be suggested that CAPE, anti inflammatory properties proven in the literature, plays an important role in OME treatment.

Gülmez|Mehmet İhsan|Mİ|
Okuyucu|Şemsettin|Ş|
Dokuyucu|Recep|R|
Gökçe|Hasan|H|

D000818:Animals
D000893:Anti-Inflammatory Agents
D016227:Benzoquinones
D002109:Caffeic Acids
D004195:Disease Models, Animal
D005064:Eustachian Tube
D007274:Injections, Intraperitoneal
D008297:Male
D010034:Otitis Media with Effusion
D010626:Phenylethyl Alcohol
D051381:Rats
D017208:Rats, Wistar
D013701:Temporal Bone

Thymoquinone
Otitis media with effusion
Caffeic acid phenyl ester
Inflammation


Spleen associated immune-response mediates brain-heart interaction after intracerebral hemorrhage.

Abstract:
BACKGROUND AND PURPOSE
Intracerebral hemorrhage (ICH) patients frequently encounter cardiovascular complications which may contribute to increased mortality and poor long term outcome. ICH induces systemic oxidative stress and activates peripheral immune responses which are involved in the pathological cascade leading to cardiac dysfunction and heart failure after ICH. We have previously reported that ICH induces progressive cardiac dysfunction in mice without primary cardiac diseases. In this study, we have investigated the role of immune response in mediating cardiac dysfunction post ICH in mice.

METHODS
Adult male C57BL/6 J mice were randomly assigned to the following groups (n = 8/group): 1) sham control; 2) ICH; 3) splenectomy with ICH (ICH + Spx); 4) splenectomy alone (Spx). Echocardiography was performed at 7 and 28 days after ICH. A battery of neurological and cognitive tests were performed. Flow cytometry, western blot and immunostaining were used to test mechanisms of ICH induced cardiac dysfunction.

RESULTS
Compared to sham control mice, Spx alone does not induce acute (7 day) or chronic (28 day) cardiac dysfunction. ICH induces significant neurological and cognitive deficits, as well as acute and chronic cardiac dysfunction compared to sham control mice. Mice subjected to ICH + Spx exhibit significantly improved neurological and cognitive function compared to ICH mice. Mice with ICH + Spx also exhibit significantly improved acute and chronic cardiac function compared to ICH mice indicated by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), decreased cardiac fibrosis, decreased cardiomyocyte hypertrophy, decreased cardiac infiltration of immune cells and decreased expression of inflammatory factor and oxidative stress in the heart.

CONCLUSIONS
Our study demonstrates that splenectomy attenuates ICH-induced neurological and cognitive impairment as well as ICH-induced cardiac dysfunction in mice. Inflammatory cell infiltration into heart and immune responses mediated by the spleen may contribute to ICH-induce acute and chronic cardiac dysfunction and pathological cardiac remodeling.

Li|Wei|W| Li|Linlin|L| Li|Wenkui|W| Chopp|Michael|M| Venkat|Poornima|P| Zacharek|Alex|A| Chen|Zhili|Z| Landschoot-Ward|Julie|J| Chen|Jieli|J|

Intracerebral hemorrhage
Oxidative stress
Cardiac dysfunction
Splenectomy
Brain-heart axis
Neurological recovery


Exploring the potential of rapid evaporative ionization mass spectrometry (Intelligent Knife) for point-of-care testing in aortic surgery.

Abstract:
OBJECTIVES
Many intraoperative decisions regarding the extent of thoracic aortic surgery are subjective and are based on the appearance of the aorta, perceived surgical risks and likelihood of early recurrent disease. Our objective in this work was to carry out a cross-sectional study to demonstrate that rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical aerosol is able to empirically discriminate ex vivo aneurysmal human thoracic aorta from normal aorta, thus providing supportive evidence for the development of the technique as a point-of-care test guiding intraoperative surgical decision-making.

METHODS
Human aortic tissue was obtained from patients undergoing surgery for thoracic aortic aneurysms (n = 44). Normal aorta was obtained from a mixture of post-mortem and punch biopsies from patients undergoing coronary surgery (n = 13). Monopolar electrocautery was applied to samples and surgical aerosol aspirated and analysed by REIMS to produce mass spectral data.

RESULTS
Models generated from REIMS data can discriminate aneurysmal from normal aorta with accuracy and precision of 88.7% and 85.1%, respectively. In addition, further analysis investigating aneurysmal tissue from patients with bicuspid and tricuspid aortic valves was discriminated from normal tissue and each other with accuracies and precision of 93.5% and 91.4% for control, 83.8% and 76.7% for bicuspid aortic valve and 89.3% and 86.0% for tricuspid aortic valve, respectively.

CONCLUSIONS
Analysis of electrosurgical aerosol from ex vivo aortic tissue using REIMS allowed us to discriminate aneurysmal from normal aorta, supporting its development as a point-of-care test (Intelligent Knife) for guiding surgical intraoperative decision-making.

D001011:Aorta
D001021:Aortic Valve
D003430:Cross-Sectional Studies
D006801:Humans
D013058:Mass Spectrometry
D000067716:Point-of-Care Testing

Rapid evaporative ionization mass spectrometry


MiR-200b suppresses TNF-α-induced AMTN production in human gingival epithelial cells.

Abstract: Amelotin (AMTN) is an enamel protein that is localized in junctional epithelium (JE) of gingiva and suggested to be involved in the attachment between JE and tooth enamel. MicroRNA is a small non-coding RNA that regulates gene expression at post-transcriptional level by binding to the 3'-untranslated region (3'-UTR) of target mRNAs. In this study, we have analyzed the effects of miR-200b on the expression of AMTN in human gingival epithelial (Ca9-22) cells. Total RNAs and proteins were extracted from Ca9-22 cells transfected with miR-200b expression plasmid or miR-200b inhibitor and stimulated by TNF-α (10 ng/ml, 12 h). AMTN and inhibitor of kappa-B kinase beta (IKKβ) mRNA and protein levels were measured by qPCR and Western blot. Human AMTN 3'-UTR that contains putative miR-200b target sites were cloned downstream of -353AMTN luciferase (LUC) plasmid. Ca9-22 cells were transfected with -353AMTN 3'-UTR LUC constructs and miR-200b expression plasmid, and LUC activities were measured with or without stimulation by TNF-α. TNF-α-induced AMTN mRNA levels were partially inhibited by miR-200b overexpression and enhanced by miR-200b inhibitor. TNF-α-induced IKKβ mRNA and protein levels were almost completely inhibited by miR-200b. Transcriptional activities of -353AMTN 3'-UTR LUC constructs were induced by TNF-α and partially inhibited by miR-200b. IKKβ inhibitor IMD0354 and NF-κB inhibitor triptolide decreased TNF-α-induced LUC activities. Furthermore, both inhibitors reduced AMTN mRNA levels in the presence or absence of TNF-α. These results suggest that miR-200b suppresses AMTN expression by targeting to AMTN and IKKβ mRNAs in the human gingival epithelial cells.

miR-200b
Gingival epithelial cells
Amelotin
Junctional epithelium
TNF-α
Gene promoter
Inflammation


Circular RNA UBAP2 contributes to tumor growth and metastasis of cervical cancer via modulating miR-361-3p/SOX4 axis.

Abstract:
Background
Increasing researches have reported that circular RNA UBAP2 (circUBAP2) may be a potential prognosis biomarker and participate in the development of several cancers; however, the role of circUBAP2 in cervical cancer (CC) remains largely unclear.

Methods
We applied qRT-PCR and Western blot to examine expression levels of circUBAP2, miR-361-3p, SOX4, Bax, Bcl-2, Cleaved caspase 3, N-cadherin, Vimentin and E-cadherin. Cell proliferation, apoptosis, invasion and migration were analyzed by MTT assay, Flow cytometry, and Transwell assay, respectively. The interaction between miR-361-3p and circUBAP2 or SOX4 was confirmed by luciferase reporter assay and pull-down assay. Murine xenograft model was established by injecting SiHa cells which stably transfected sh-circUBAP2.

Results
CircUBAP2 was up-regulated in CC tissues and cell lines and high circUBAP2 expression predicated poor outcome. Knockdown of circUBAP2 suppressed cell proliferation, migration, invasion and EMT, while induced apoptosis in CC in vitro, and inhibited tumor growth and metastasis in vivo. MiR-361-3p directly bound to circUBAP2 or SOX4, and circUBAP2 could regulate SOX4 expression by sponging miR-361-3p in CC cells. Furthermore, rescue assay results demonstrated that the inhibitory effects of circUBAP2 knockdown on cell growth and metastasis were partially reversed by miR-361-3p down-regulation or SOX4 up-regulation in CC.

Conclusion
CircUBAP2 represents a prognostic marker and contributes to tumor growth and metastasis via modulating miR-361-3p/SOX4 axis in CC, which indicates a potential therapeutic target for CC treatment.

Meng|Lingli|L| Jia|Xiupeng|X| Yu|Wenying|W| Wang|Chunnian|C| Chen|Jie|J| Liu|Fenglei|F|0000-0003-0726-0211


LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma.

Abstract: LGR5 is a marker of normal and cancer stem cells in various tissues where it functions as a receptor for R-spondins and increases canonical Wnt signalling amplitude. Here we report that LGR5 is also highly expressed in a subset of high grade neuroblastomas. Neuroblastoma is a clinically heterogenous paediatric cancer comprising a high proportion of poor prognosis cases (~40%) which are frequently lethal. Unlike many cancers, Wnt pathway mutations are not apparent in neuroblastoma, although previous microarray analyses have implicated deregulated Wnt signalling in high-risk neuroblastoma. We demonstrate that LGR5 facilitates high Wnt signalling in neuroblastoma cell lines treated with Wnt3a and R-spondins, with SK-N-BE(2)-C, SK-N-NAS and SH-SY5Y cell-lines all displaying strong Wnt induction. These lines represent MYCN-amplified, NRAS and ALK mutant neuroblastoma subtypes respectively. Wnt3a/R-Spondin treatment also promoted nuclear translocation of β-catenin, increased proliferation and activation of Wnt target genes. Strikingly, short-interfering RNA mediated knockdown of LGR5 induces dramatic Wnt-independent apoptosis in all three cell-lines, accompanied by greatly diminished phosphorylation of mitogen/extracellular signal-regulated kinases (MEK1/2) and extracellular signal-regulated kinases (ERK1/2), and an increase of BimEL, an apoptosis facilitator downstream of ERK. Akt signalling is also decreased by a Rictor dependent, PDK1-independent mechanism. LGR5 expression is cell cycle regulated and LGR5 depletion triggers G1 cell-cycle arrest, increased p27 and decreased phosphorylated retinoblastoma protein. Our study therefore characterises new cancer-associated pathways regulated by LGR5, and suggest that targeting of LGR5 may be of therapeutic benefit for neuroblastomas with diverse etiologies, as well as other cancers expressing high LGR5.

Vieira|Gabriella Cunha|GC|
Chockalingam|S|S|
Melegh|Zsombor|Z|
Greenhough|Alexander|A|
Malik|Sally|S|
Szemes|Marianna|M|
Park|Ji Hyun|JH|
Kaidi|Abderrahmane|A|
Zhou|Li|L|
Catchpoole|Daniel|D|
Morgan|Rhys|R|
Bates|David O|DO|
Gabb|Peter David|PD|
Malik|Karim|K|

D048049:Extracellular Signal-Regulated MAP Kinases

D015972:Gene Expression Regulation, Neoplastic

D020929:Mitogen-Activated Protein Kinase Kinases

D020133:Reverse Transcriptase Polymerase Chain Reaction

LGR5
MEK/ERK
Wnt/β-catenin
neuroblastoma
cell survival


Hysteroscopy in patients with repeated implantation failure improves the outcome of assisted reproductive technology in fresh and frozen cycles.

Abstract:
AIM
Repeated implantation failure (RIF) is still a problem for many patients and their physicians. Some interventions have been practiced to overcome the problem; one is uterine cavity assessment before assisted reproductive technology (ART) cycles. This study aimed to evaluate the effect of hysteroscopy in women experiencing recurrent implantation failure with apparently normal uterine cavity before assisted reproductive techniques.

MATERIAL AND METHODS
This was a cohort study with historical controls conducted in a university hospital. A total of 353 women with RIF undergoing ART with normal hysterosalpingography and transvaginal ultrasound were evaluated. The intervention group underwent hysteroscopy with a rigid, 30°, 4-mm hysteroscope in the menstrual cycle just before ART; in the control group hysteroscopy was not performed. Basal characteristics, stimulation parameters and pregnancy rates were compared between the two groups.

RESULTS
Chemical pregnancy occurred in 58.5% of women in the hysteroscopy group versus 34.1% of control women (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.7-4.2; P < 0.001). Clinical pregnancy occurred in 50.7% and 30.3% of women in the hysteroscopy and control groups, respectively (OR: 2.4; 95%CI: 1.5-3.7; P < 0.001). Delivery rate was 35.5% in hysteroscopy women and 21.1% in control women (OR: 1.9; 95%CI: 1.2-3.1; P = 0.008). The results of hysteroscopy were normal in 103 women (72.5%), and they revealed inflammation in 22 (15.5%), polyp in 16 (11.3%) and Asherman syndrome in one patient (0.7%).

CONCLUSIONS
Hysteroscopy in the menstrual cycle before ovarian stimulation in fresh cycles and before endometrial preparation in frozen thawed cycles in women experiencing recurrent implantation failure with apparently normal uterine cavity significantly increases the pregnancy rates in fresh and frozen cycles, respectively.

Hosseini|Marzieh Agha|MA|
Ebrahimi|Nasim|N|
Mahdavi|Atossa|A|
Aleyasin|Ashraf|A|
Safdarian|Leili|L|
Fallahi|Parvin|P|
Esfahani|Fatemeh|F|

hysteroscopy
implantation failure
assisted reproductive technology
fresh
pregnancy


Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome.

Abstract: CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26- cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.

chronic myeloid leukemia
immunoliposome
CD26
leukemia stem cell
liposome
nanomedicine
targeted therapy


Concomitant administration of GonaCon™ and rabies vaccine in female dogs (Canis familiaris) in Mexico.

Abstract: Mexico serves as a global model for advances in rabies prevention and control in dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16 million doses of parenteral rabies vaccine has resulted in significant reductions in canine rabies during the past 20 years. One collateral parameter of rabies programs is dog population management. Enhanced public awareness is critical to reinforce responsible pet ownership. Surgical spaying and neutering remain important to prevent reproduction, but are impractical for achieving dog population management goals. GonaCon™, an anti-gonadotropin releasing hormone (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation, 2008. The MMH led this international collaborative study on an improved formulation of GonaCon™ in captive dogs with local representatives in Hidalgo, Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control), Group B (7 GonaCon™), and Group C (7 GonaCon™ and rabies vaccine). Vaccines were delivered IM. Animals were placed under observation and evaluated during the 61-day trial. Clinically, all dogs behaved normally. No limping or prostration was observed, in spite of minor muscle atrophy post-mortem in the left hind leg of dogs that received GonaCon™. Two dogs that began the study pregnant give birth to healthy pups. Dogs that received a GonaCon™ injection had macro and microscopic lesions consistent with prior findings, but the adverse injection effects were less frequent and lower in intensity. Both vaccines were immunogenic based on significant increases in rabies virus neutralizing antibodies and anti-GnRH antibodies in treatment Groups B and C. Simultaneous administration of GonaCon™ and rabies vaccine in Group C did not affect immunogenicity. Progesterone was suppressed significantly in comparison to controls. Future studies that monitor fertility through multiple breeding cycles represent a research need to determine the value of integrating this vaccine into dog rabies management.

Vargas-Pino|Fernando|F|
Gutiérrez-Cedillo|Verónica|V|
Canales-Vargas|Erick J|EJ|
Gress-Ortega|Luis R|LR|
Miller|Lowell A|LA|
Rupprecht|Charles E|CE|
Bender|Scott C|SC|
García-Reyna|Patricia|P|
Ocampo-López|Juan|J|
Slate|Dennis|D|

GonaCon™ Rabies Dog Canine GnRH Immunocontraception


Cervical nerve roots and the dural sheath: a histological study using human fetuses near term.

Abstract: We have previously reported that the thoracolumbar posterior nerve root shows a tortuous epidural course, based on studies of human fetuses near term. For comparison with the cervical nerve, examinations were conducted using frontal, sagittal and horizontal sections of cervical vertebrae from 22 fetuses at 30-38 weeks of gestation. The cervical nerve root showed a short, straight and lateral course near the zygapophysial joint. Multiple rather than single bundles of the cervical posterior root seemed to account for the majority of sensory nerve fibers innervating the upper extremity. Fasciculation of rootlets was evident near the thoracolumbar spinal cord, whereas it was seen in the dural pocket at the nerve exit from the dural sac although both sites were subdural. As in the thoracolumbar region, the nerve sheath was continuous with the dura mater and independently surrounded each of the anterior and posterior roots. Radicular arteries were few in the cervical region. In 2 of the 22 fetuses (31 weeks and 33 weeks), there was a segmental, unilateral abnormality of nerve rootlet fasciculation where the dorsal root ganglion was located lateral or peripheral to the intervertebral region. Long nerve roots running inferiorly are a necessary adaptation to the delayed and marked growth of the thoracolumbar vertebral column. In children, the cervical nerve roots are likely to be affected by movement or dislocation of the vertebrae. The segmental abnormality of the cervical nerve root may be linked to rare variations in the brachial plexus.


Effect of senescence on some apoptosis and oxidative stress markers in infertile normozospermic and oligospermic men: A cross-sectional study.

Abstract:
Background
Male senescence may affect testicular function, sperm indices and generation of high levels of oxidants and apoptosis.

Objective
This study evaluates the effect of male age on the expression of some apoptosis and oxidative stress markers in seminal fluid of males investigated for infertility in a tertiary health institution in Nigeria.

Materials and Methods
In this cross-sectional study, 122 men aged 20-60 yr who were investigated for infertility and were stratified according to age into four groups. Seminal plasma caspase 3, cytochrome C, and total antioxidant capacity (TAC) were assayed by ELISA technique, while manual semen analysis was performed according to WHO standard.

Results
Seminal caspase 3, and cytochrome C activity increased while TAC and sperm indices decreased with increasing age. Cytochrome C (r=0.288; p=0.002) and caspase 3 (r=0.250; p=0.05) correlated significantly with age in normospermia while cytochrome C (r=0.314; p=0.02), caspase 3 (r=0.268; p=0.05), TAC (r=-0.342; p=0.01) and morphology percentage (r=-0.414; p=0.002) correlated with age in oligospermic infertile males.

Conclusion
The measured apoptotic markers increased with increasing age while TAC and sperm indices decreased with increasing age of subjects evaluated. Although the levels of measured apoptosis and oxidative stress markers correlated with age in normozospermia, the effect on sperm indices was severe among oligospermia compare to normozospermia. Therefore, these markers may be assayed in aged men attending fertility clinics.

Emokpae|Mathias Abiodun|MA|
Chima|Happy Ngozi|HN|

Apoptosis
Caspase 3
Cytochrome C
Male infertility


Epigenetic mechanisms of dietary restriction induced aging in Drosophila.

Abstract: Aging is a long-standing problem that people are always interested in. Thus, it is critical to understand the underlying molecular mechanisms in aging and explore the most efficient method to extend life expectancy. To achieve this goal, a wide range of systems including cells, rodent models, budding yeast, worms and flies have been employed for decades. In recent years, the effect of dietary restriction (DR) on lifespan is in the prime focus. Although we have confirmed that reduced insulin and/or insulin-like growth factor (IGF) and the target of rapamycin (TOR) signaling can increase Drosophila lifespan; the precise molecular mechanisms and nutritional response landscape of diet-mediated aging is ambiguous. Epigenetic events have been considered as the major contributors to lifespan extension with response to DR. The role of DNA methylation in aging is well acknowledged in mammals and rodents where it has been shown to impact aging by regulating the transcription, though the mechanism of regulation is not limited to only transcription. In Drosophila, the contribution of methylation during DR in aging is definitely less explored. In this review, we will update the advances in mechanisms of DR, with a particular focus on methylation as an upcoming target for aging studies and discuss Drosophila as a powerful model to understand mechanisms of aging with response to diet.

Lian|Ting|T| Gaur|Uma|U| Yang|Deying|D| Li|Diyan|D| Li|Ying|Y| Yang|Mingyao|M|

D000824:Animal Nutritional Physiological Phenomena

Aging
Drosophila
Methylation
Signaling pathways


Does multitasking mediate the relationships between episodic memory, attention, executive functions and apathetic manifestations in traumatic brain injury?

Abstract: Apathy is frequently described in patients with traumatic brain injury (TBI); its negative consequences particularly affect functional independence. Among apathetic manifestations, lack of initiative and lack of interest have mainly been associated with cognitive impairments. However, few studies have been conducted to precisely identify the underlying cognitive processes. Our aims were (1) to determine the best predictor of apathy from among several cognitive processes, including episodic memory and attention/executive mechanisms and multitasking, and (2) to examine to what extent multitasking could mediate the relationships between specific cognitive processes and lack of initiative/interest. Seventy participants (34 patients with TBI matched with 36 control participants) were given a questionnaire to assess anxio-depressive symptoms, four tasks to assess specific cognitive processes, and one task to assess real-life multitasking. Participants' relatives completed an apathy questionnaire. Multitasking, as assessed by the number of goals not achieved, was the only significant predictor of apathetic manifestations. In addition, the mediation analyses revealed that multitasking performance mediated the relationships between verbal episodic memory and lack of initiative/interest, whereas executive and attentional functions were only indirectly related to lack of initiative/interest due to their significant impacts on multitasking. These results shed new light on the aetiology of apathetic manifestations in patients with TBI, indicating how specific cognitive deficits are expressed in real-life multitasking, and consequently, how they may lead to the development and/or maintenance of apathetic manifestations.

Arnould|Annabelle|A|
Rochat|Lucien|L|
Dromer|Emilie|E|
Azouvi|Philippe|P|
Van der Linden|Martial|M|

multitasking
episodic memory
executive functions
traumatic brain injury
apathy
initiative
interest


The EGFRvIII transcriptome in glioblastoma, a meta-omics analysis.

Abstract:
BACKGROUND
EGFR is among the genes most frequently altered in glioblastoma, with exons 2-7 deletions (EGFRvIII) being amongst its most common genomic mutations. There are conflicting reports about its prognostic role and it remains unclear whether and how it differs in signalling compared with wildtype EGFR.

METHODS
To better understand the oncogenic role of EGFRvIII, we leveraged four large datasets into one large glioblastoma transcriptome dataset (n=741) alongside 81 whole-genome samples from two datasets.

RESULTS
The EGFRvIII/EGFR expression ratios differ strongly between tumours and ranges from 1% to 95%. Interestingly, the slope of relative EGFRvIII expression is near-linear, which argues against a more positive selection pressure than EGFR wildtype. An absence of selection pressure is also suggested by the similar survival between EGFRvIII positive and negative glioblastoma patients. EGFRvIII levels are inversely correlated with pan-EGFR (all wildtype and mutant variants) expression, which indicates that EGFRvIII has a higher potency in downstream pathway activation. EGFRvIII-positive glioblastomas have a lower CDK4 or MDM2 amplification incidence than EGFRvIII-negative (p=0.007), which may point towards crosstalk between these pathways. EGFRvIII-expressing tumours have an upregulation of 'classical' subtype genes compared to those with EGFR-amplification only (p=3.873e-6). Genomic breakpoints of the EGFRvIII deletions have a preference towards the 3' end of the large intron-1. These preferred breakpoints preserve a cryptic exon resulting in a novel EGFRvIII variant and preserve an intronic enhancer.

CONCLUSIONS
These data provide deeper insights into the complex EGFRvIII biology and provide new insights for targeting EGFRvIII mutated tumours.

Hoogstrate|Youri|Y|0000-0003-2166-0676
Ghisai|Santoesha A|SA|
de Wit|Maurice|M|
de Heer|Iris|I|
Draaisma|Kaspar|K|
van Riet|Job|J|
van de Werken|Harmen J G|HJG|
Bours|Vincent|V|
Buter|Jan|J|
Vanden Bempt|Isabelle|I|
Eoli|Marica|M|
Franceschi|Enrico|E|
Frenel|Jean-Sebastien|JS|
Gorlia|Thierry|T|
Hanse|Monique C|MC|
Hoeben|Ann|A|
Kerkhof|Melissa|M|
Kros|Johan M|JM|
Leenstra|Sieger|S|
Lombardi|Giuseppe|G|
Lukacova|Slávka|S|
Robe|Pierre A|PA|
Sepulveda|Juan M|JM|
Taal|Walter|W|0000-0002-5530-7259
Taphoorn|Martin|M|
Vernhout|René M|RM|
Walenkamp|Annemiek M E|AME|
Watts|Colin|C|
Weller|Michael|M|0000-0002-1748-174X
de Vos|Filip Y F|FYF|
Jenster|Guido W|GW|
van den Bent|Martin|M|
French|Pim J|PJ|

EGFRvIII glioblastoma EGFR Breakpoints RNA-seq


Assessment of fatigue in patients with a permanent cardiac pacemaker: prevalence and associated factors.

Abstract:
Introduction
Fatigue is a debilitating symptom of subjective nature which lacks effective therapy. The aim of the study was to assess levels of fatigue and the associated factors among patients with permanent cardiac pacemaker (PCM).

Material and methods
This was a cross-sectional study carried out in Athens. The study sample consisted of 250 patients with a PCM.

Results
Data indicated moderate to low levels of fatigue. Furthermore, women (median: 24, p = 0.001), those with primary school education (median: 21, p = 0.001), those who were "a little-not at all" informed about PCM (median: 31, p = 0.001), those who had someone to help them in daily activities (median: 23, p = 0.001), those who did not believe that PCM solved their cardiac problem (median: 36, p = 0.001), and those who did not believe that their quality of life was improved (median: 35, p = 0.001) had high levels of fatigue. Moreover, high levels of fatigue were felt by those who characterized themselves as anxious and those who reported to be very anxious about their heart rate and the proper function of PCM (medians: 21.5, 25 and 25 respectively). Additionally, more fatigue was felt by participants who did not smoke after implantation and did not exercise at all (medians: 20 and 24 respectively). Finally, older patients felt more fatigue (rho = 0.248) while the later the implantation device was inserted the more fatigue the patients felt (rho = 0.274).

Conclusions
The present results will help clinicians to acquire an in-depth knowledge of factors associated with fatigue after implantation.

Polikandrioti|Maria|M| Tzirogiannis|Konstantinos|K| Zyga|Sofia|S| Gerogianni|Georgia|G| Stefanidou|Spyridoula|S| Tsami|Athanasia|A| Panoutsopoulos|Georgios|G|


A Case Report of Angioedema and Anaphylactic Shock Induced by Ingestion of Polyethylene Glycol.

Abstract:
Introduction
We report one of few documented cases of a severe anaphylactic reaction with angioedema to polyethylene glycol (PEG).

Case Report
The patient presented 30 minutes after onset of his symptoms and quickly developed hypoxia and hypotension refractory to intramuscular epinephrine, intravenous fluids, methylprednisolone, and supplemental oxygen via non-rebreather mask. He ultimately required intubation, an epinephrine infusion, and admission to the medical intensive care unit.

Discussion
This case depicts a clinical reaction to PEG, a medication rarely implicated in severe anaphylaxis or angioedema.

Conclusion
The allergenic potential of PEG-containing products should be raised, and providers should have a heightened awareness of these potential side effects.

angioedema
Polyethylene glycol
PEG
allergic


Off label use of lithium in the treatment of Huntington's disease: A case series.

Abstract: Huntington's disease is characterized by choreic movements, psychiatric disorders, striatal atrophy with selective small neuronal loss, and autosomal dominant inheritance. The genetic abnormality is CAG expansion in Huntingtin gene. Newer therapeutic strategies are evolving to treat this progressive disorder. The neuroprotective agents are one such group of drugs being tried. Lithium has been used to treat Huntington's disease in the past due to its neuroprotective effects. Though the precise mechanism of action is not clear, Lithium can directly or indirectly modulate proteins involved in neuronal survival/differentiation which may account for its neuroprotective effects. We report three patients with Huntington's disease in whom Lithium prevented the progression of chorea and also helped stabilize mood.

Danivas|Vijay|V|
Moily|Nagaraj S|NS|
Thimmaiah|Rohini|R|
Muralidharan|Kesavan|K|
Purushotham|Meera|M|
Muthane|Uday|U|
Jain|Sanjeev|S|

lithium
Huntington's disease
neuroprotection


Capping with multivalent surfactants for zeolite nanocrystal synthesis.

Abstract: Multiammonium surfactants exhibited a remarkable capping effect for zeolite synthesis in the forms of nanoparticles, nanorods, and nanosponges in cases where common monovalent surfactants failed. A nanorod-shaped mordenite zeolite synthesized in this manner showed significantly enhanced catalytic lifetimes in acid-catalyzed cumene synthesis reactions.

Jo|Changbum|C|
Jung|Jinhwan|J|
Shin|Hye Sun|HS|
Kim|Jaeheon|J|
Ryoo|Ryong|R|

multivalent surfactants
zeolites
nanoparticles
capping agents


An effective thermal therapy against cancer using an E-jet 3D-printing method to prepare implantable magnetocaloric mats.

Abstract: Magnetic hyperthermia has been rapidly developed as a potential cancer treatment in recent years. Artificially induced hyperthermia close to a tumor can raise the temperature to 45°C causing tumor cell death. Herein, we introduce a novel method for rapid preparation of anti-cancer magnetocaloric PCL/Fe3 O4 mats capable of high-performance hyperthermia using E-jet 3D printing technology. Our 3D printed mats not only maintained the heating efficiency of traditional techniques for magnetic hyperthermia but also prolonged the effective therapy in vivo. When Fe3 O4 nanoparticles (NPs) were used in mats at a concentration of 6 mmol/L, 0.07 g PCL/Fe3 O4 mats were able to increase the temperature peripherally to 45°C under an alternating magnetic field (AMF) within 45 min. Moreover, the reproducibility experiment indicated that the maximum temperature was achieved following repeated heating and cooling cycles. Cell toxicity tests showed a high cell death rate during one treatment cycle. In vivo experiments indicated clear signs of tumor growth inhibitory and prolonged survival time of tumor-bearing mice after 4 weeks of treatment. The present magnetic mats may be a potential candidate for a novel heat-generating substrate for localized hyperthermia cancer therapy. Furthermore, the main advantage of such implantable magnetic mats is the local and precise delivery of Fe3 O4 NPs, ideal for the hyperthermia treatment of easily accessible tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1827-1841, 2018.

Yang|Yikun|Y| Tong|Chunyi|C| Zhong|Juchang|J| Huang|Ruiying|R| Tan|Weihong|W| Tan|Zhikai|Z|

D023041:Xenograft Model Antitumor Assays

thermal therapy
anti-cancer
E-jet 3D printing
magnetic nanoparticles mats
precise drug delivery


The Delivery Challenge in Neurodegenerative Disorders: The Nanoparticles Role in Alzheimer's Disease Therapeutics and Diagnostics.

Abstract: Alzheimer's disease (AD) is one of the main causes of disability and dependency among elderly people. AD is a neurodegenerative disorder characterized by a progressive and irreversible cognitive impairment, whose etiology is unclear because of the complex molecular mechanisms involved in its pathophysiology. A global view of the AD pathophysiology is described in order to understand the need for an effective treatment and why nanoparticles (NPs) could be an important weapon against neurodegenerative diseases by solving the general problem of poor delivery into the central nervous system (CNS) for many drugs. Drug delivery into the CNS is one of the most challenging objectives in pharmaceutical design, due to the limited access to the CNS imposed by the blood-brain barrier (BBB). The purpose of this review is to present a comprehensive overview of the use of NPs as delivery systems for therapeutic and diagnostic purposes in models of AD.

nanoparticles
blood-brain barrier
Alzheimer’s disease
animal models


Local sequence of protein β-strands influences twist and bend angles.

Abstract: β-Sheet twisting is thought to be mainly determined by interstrand hydrogen bonds with little contribution from side chains, but some proteins have large, flat β-sheets, suggesting that side chains influence β-structures. We therefore investigated the relationship between amino acid composition and twists or bends of β-strands. We calculated and statistically analyzed the twist and bend angles of short frames of β-strands in known protein structures. The most frequent twist angles were strongly negatively correlated with the proportion of hydrophilic amino acid residues. The majority of hydrophilic residues (except serine and threonine) were found in the edge regions of β-strands, suggesting that the side chains of these residues likely do not affect β-strand structure. In contrast, the majority of serine, threonine, and asparagine side-chains in β-strands made contacts with a nitrogen atom of the main chain, suggesting that these residues suppress β-strand twisting.

Fujiwara|Kazuo|K| Ebisawa|Shinichi|S| Watanabe|Yuka|Y| Toda|Hiromi|H| Ikeguchi|Masamichi|M|

D057927:Hydrophobic and Hydrophilic Interactions

interstrand hydrogen bond
effect of side chain to the β-sheet
large flat β-sheet
protein design
statistical analysis


Effect of heat stress on superoxide anion production in native and crossbred cattle under in vitro whole blood culture model.

Abstract: Impact of global warming on the dairy industry has gained attention due to huge economic losses through low production and fertility caused by heat stress. Exposure to hyperthermia provokes a series of complex responses in mammals which are been related to morphological and physiological alterations including the production of reactive oxygen species (ROS). A quantitative spectrophotometric based nitroblue tetrazolium (NBT) reduction assay was used to estimate the superoxide anion (•O2-) level in heat stressed (at 42 °C) whole blood cultures of native and crossbred bulls (Sahiwal and Frieswal), in vitro. The breed effect in the kinetics of •O2- production at different time periods of continual heat stress was analyzed by repeated measures ANOVA. Comparison between different time periods in reference to 37 °C was analyzed by paired t-test. The •O2- level was significantly different (p < 0.05) between cells at 37 °C and 42 °C at different periods of incubation. Kinetics study showed increment of •O2- production on the acute phase of stress followed by a reduction in both Sahiwal and Frieswal breeds. In Sahiwal breed, the inflated superoxide level continued abated till 4 h and raised again at 6 h, while in Frieswal •O2- level reverted to raise sooner with in 2 h of incubation itself. Contrarily, kinetic of •O2- level in plasma showed a significant reduction (p < 0.001) at 30 min of 42 °C incubation followed by increment of •O2- level. Further, the breed variation was significant (p < 0.05) and a significant high reduction of •O2- level was observed in Sahiwal breed. Our finding indicates that, a better and longer •O2- production homeostasis and higher plasma scavenging ability of native breed may be one of the reasons for the higher thermal tolerance of these breeds in tropical climate.

Verma|Nitika|N|
Alyethodi|Rafeeque R|RR|
Kathuria|Ashima|A|
Alex|Rani|R|
Hussain|Shaziya|S|
Singh|Umesh|U|
Tyagi|S|S|
Sirohi|Ajveer Singh|AS|
Kumar|Sushil|S|
Deb|Rajib|R|
Sengar|Gyanendra S|GS|
Raja|T V|TV|
Prakash|B|B|

Heat stress
In vitro whole blood culture
Sahiwal
Frieswal
Spectrophotometric NBT assay


Ectopic Expression of Aeluropus littoralis Plasma Membrane Protein Gene AlTMP1 Confers Abiotic Stress Tolerance in Transgenic Tobacco by Improving Water Status and Cation Homeostasis.

Abstract: We report here the isolation and functional analysis of AlTMP1 gene encoding a member of the PMP3 protein family. In Aeluropus littoralis, AlTMP1 is highly induced by abscisic acid (ABA), cold, salt, and osmotic stresses. Transgenic tobacco expressing AlTMP1 exhibited enhanced tolerance to salt, osmotic, H₂O₂, heat and freezing stresses at the seedling stage. Under greenhouse conditions, the transgenic plants showed a higher level of tolerance to drought than to salinity. Noteworthy, AlTMP1 plants yielded two- and five-fold more seeds than non-transgenic plants (NT) under salt and drought stresses, respectively. The leaves of AlTMP1 plants accumulated lower Na⁺ but higher K⁺ and Ca2+ than those of NT plants. Tolerance to osmotic and salt stresses was associated with higher membrane stability, low electrolyte leakage, and improved water status. Finally, accumulation of AlTMP1 in tobacco altered the regulation of some stress-related genes in either a positive (NHX1, CAT1, APX1, and DREB1A) or negative (HKT1 and KT1) manner that could be related to the observed tolerance. These results suggest that AlTMP1 confers stress tolerance in tobacco through maintenance of ion homeostasis, increased membrane integrity, and water status. The observed tolerance may be due to a direct or indirect effect of AlTMP1 on the expression of stress-related genes which could stimulate an adaptive potential not present in NT plants.

Ben Romdhane|Walid|W|
Ben-Saad|Rania|R|
Meynard|Donaldo|D|
Verdeil|Jean-Luc|JL|
Azaza|Jalel|J|
Zouari|Nabil|N|
Fki|Lotfi|L|
Guiderdoni|Emmanuel|E|
Al-Doss|Abdullah|A|
Hassairi|Afif|A|

Aeluropus littoralis
plasma membrane protein
AlTMP1
transgenic tobacco
drought and salt tolerance


Mushroom poisoning: a retrospective study concerning 11-years of admissions in a Swiss Emergency Department.

Abstract: Wild mushroom intoxication is an unusual cause of toxic ingestion in Europe. A great diversity of clinical symptoms may arise depending on the variety of wild mushrooms ingested. These initial symptoms are often non-specific, with frequent gastrointestinal symptoms, and have no direct correlation with the outcome. Therefore, management of mushroom poisoning and risk evaluation are a challenge for emergency clinicians. We retrospectively reviewed all cases of mushroom poisoning identified in the ED database spanning 11 years. Demographic and clinical data, time from consumption to symptoms, type of mushrooms, the number of patients presenting at the same time, treatment(s) provided, length of stay, discharge diagnosis, in-hospital mortality, and serious complications were evaluated. We identify 87 cases of mushroom poisoning. The most common symptoms are nausea and vomiting (71 cases, 82%), followed by diarrhea (68%), syncope (10%), abdominal pain (8%), and hallucinations (7%). Sixty-four patients (74%) exhibited early symptoms (appearance <6 h after ingestion) and 23 (26%) late symptoms (appearance >6 h after ingestion). Eleven patients (13%) required hospitalization over 24 h. Patients with late symptoms tended to have longer in-hospital lengths of stay. Only one patient had Amanita phalloides intoxication, with a favorable outcome. Thirty-eight patients (44%) were involved in cluster presentations. Mushroom poisoning is an unusual but potentially severe form of intoxication. Patients presenting with late-appearing symptoms (>6 h) are associated with a higher risk of A. phalloides intoxication, and therefore require specific investigation and management.

Schmutz|Maxime|M| Carron|Pierre-Nicolas|PN| Yersin|Bertrand|B| Trueb|Lionel|L|0000-0002-2803-2448

Mushroom poisoning
Amanita
Emergency medicine


Online marketing practices of regenerative medicine clinics in US-Mexico border region: a web surveillance study.

Abstract:
INTRODUCTION
The potential of regenerative medicine to improve human health has led to the rapid expansion of stem cell clinics throughout the world with varying levels of regulation and oversight. This has led to a market ripe for stem cell tourism, with Tijuana, Mexico, as a major destination. In this study, we characterize the online marketing, intervention details, pricing of services, and assess potential safety risks through web surveillance of regenerative medicine clinics marketing services in Tijuana.

METHODS
We conducted structured online search queries from March to April 2019 using 296 search terms in English and Spanish on two search engines (Google and Bing) to identify websites engaged in direct-to-consumer advertising of regenerative medicine services. We performed content analysis to characterize three categories of interest: online presence, tokens of scientific legitimacy, and intervention details.

RESULTS
Our structured online searches resulted in 110 unique websites located in Tijuana corresponding to 76 confirmed locations. These clinics' online presence consisted of direct-to-consumer advertising mainly through a dedicated website (94.5%) or Facebook page (65.5%). The vast majority of these websites (99.1%) did not mention any affiliation to an academic institutions or other overt tokens of scientific legitimacy. Most clinics claimed autologous tissue was the source of treatments (67.3%) and generally did not specify route of administration. Additionally, of the Tijuana clinics identified, 13 claimed licensing, though only 1 matched with available licensing information.

CONCLUSIONS
Regenerative medicine clinics in Tijuana have a significant online presence using direct-to-consumer advertising to attract stem-cell tourism clientele in a bustling border region between Mexico and the USA. This study adds to existing literature evidencing the unregulated nature of online stem cell offerings and provides further evidence of the need for regulatory harmonization, particularly to address stem cell services being offered online across borders.

Chavez|Javier|J|
Shah|Neal A|NA|
Ruoss|Severin|S|
Cuomo|Raphael E|RE|
Ward|Samuel R|SR|
Mackey|Tim K|TK|0000-0002-2191-7833

Online marketing
Regenerative medicine
Mexico
Regulatory science
Stem cell therapy


Interactions between seed-dispersing ant species affect plant community composition in field mesocosms.

Abstract: In generalized mutualisms, species vary in the quality of services they provide to their partners directly via traits that affect partner fitness and indirectly via traits that influence interactions among mutualist species that play similar functional roles. Myrmecochory, or seed dispersal by ants, is a generalized mutualism with ant species varying in the quality of dispersal services they provide to their plant partners. Variation in ant species identity can directly impact seed dispersal patterns and plant community composition; however, we know less about how interactions among seed-dispersing ant species indirectly influence plant partners. The invasive ant Myrmica rubra, is a high-quality seed-disperser in its native range that interacts with myrmecochores (ant-dispersed plants) and the high-quality seed disperser Aphaenogaster sp. in its invaded range. We use this system to examine how interactions between two functionally similar mutualist ant species influence the recruitment and community composition of ant-dispersed plants. We performed a field mesocosm experiment and a laboratory behavioural experiment to compare discovery and dominance behaviours between ant species, and seed dispersal and seedling recruitment of four myrmecochore species among intraspecific interaction treatments of each ant species and an interspecific interaction treatment. We found that M. rubra was better at discovering and dispersing seeds, but Aphaenogaster sp. was dominantly aggressive over M. rubra. Interspecific interactions dampened seed dispersal relative to dispersal by the better disperser. Despite this dampening, we found no effect of interspecific interactions on seedling recruitment. However, community composition of seedlings in the interspecific interaction treatment was more similar to composition in the aggressively dominant ant (Aphaenogaster sp.) treatment than in the better discoverer ant M. rubra treatment. We show that interspecific interactions between mutualist species in the same functional guild affect the outcome of mutualistic interactions with partner species. Despite the native ant dispersing fewer seeds, its dominance over the subordinate (invasive) ant has the potential to allow for some level of biotic resistance against the effects of M. rubra on plant communities when these species coexist.

mutualism
myrmecochory
seed dispersal
Myrmica rubra
Aphaenogaster
invasive species
multispecies mutualism


Yaws: towards the WHO eradication target.

Abstract: In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey.

Yaws
Eradication
Azithromycin
Neglected Tropical Diseases
Treponema pallidum
World Health Organization


Environmental fate, toxicity and risk management strategies of nanoplastics in the environment: Current status and future perspectives.

Abstract: Tiny plastic particles considered as emerging contaminants have attracted considerable interest in the last few years. Mechanical abrasion, photochemical oxidation and biological degradation of larger plastic debris result in the formation of microplastics (MPs, 1 μm to 5 mm) and nanoplastics (NPs, 1 nm to 1000 nm). Compared with MPs, the environmental fate, ecosystem toxicity and potential risks associated with NPs have so far been less explored. This review provides a state-of-the-art overview of current research on NPs with focus on currently less-investigated fields, such as the environmental fate in agroecosystems, migration in porous media, weathering, and toxic effects on plants. The co-transport of NPs with organic contaminants and heavy metals threaten human health and ecosystems. Furthermore, NPs may serve as a novel habitat for microbial colonization, and may act as carriers for pathogens (i.e., bacteria and viruses). An integrated framework is proposed to better understand the interrelationships between NPs, ecosystems and the human society. In order to fully understand the sources and sinks of NPs, more studies should focus on the total environment, including freshwater, ocean, groundwater, soil and air, and more attempts should be made to explore the aging and aggregation of NPs in environmentally relevant conditions. Considering the fact that naturally-weathered plastic debris may have distinct physicochemical characteristics, future studies should explore the environmental behavior of naturally-aged NPs rather than synthetic polystyrene nanobeads.

Wang|Liuwei|L|
Wu|Wei-Min|WM|
Bolan|Nanthi S|NS|
Tsang|Daniel C W|DCW|
Li|Yang|Y|
Qin|Muhan|M|
Hou|Deyi|D|

Risk management
Contaminant migration
Environmental remediation
Plastic pollution
Terrestrial ecosystem
Virus


Tunable Hydrophilic or Amphiphilic Coatings: A "Reactive Layer Stack" Approach.

Abstract: Thin films with tunable properties are very interesting for potential applications as functional coatings with, for example, anti-icing or improved easy-to-clean properties. A novel "reactive layer stack" approach was developed to create covalently grafted mono- and multilayers of poly(glycidyl methacrylate)/poly(tert-butyl acrylate) diblock copolymers. Because these copolymers contain poly(glycidyl methacrylate) blocks they behave as self-cross-linking materials after creation of acrylic acid functionalities by splitting off the tert-butyl units. The ellipsometrically determined coating thickness of the resulting hydrophilic multilayers depended linearly on the number of applied layers. Amphiphilic films with tunable wettability were prepared using triblock terpolymers with an additional poly(methyl methacrylate) block. The mechanism of the formation of the (multi)layers was investigated in detail by studying the acidolysis of the surface-linked tert-butyl acrylate blocks by infrared reflection absorbance spectroscopy, accompanied by surface analysis using atomic force microscopy and contact angle measurements. In the case of the amphiphilic and switchable terpolymer layers this reaction was very sensitive to the used acidic reagent.

Frenzel|Ralf|R| Höhne|Susanne|S| Hanzelmann|Christian|C| Schmidt|Thomas|T| Winkler|René|R| Drechsler|Astrid|A| Bittrich|Eva|E| Eichhorn|Klaus-Jochen|KJ| Uhlmann|Petra|P|

multilayers
triblock terpolymers
IRRAS
anchor block
glycidyl methacrylate
self-cross-linking polymer layers


Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long-Standing Model.

Abstract: The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L-DOPA and dopamine agonists. Nevertheless, with the introduction of toxin-induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.

Leão|Anderson H F F|AH|
Sarmento-Silva|Aldair J|AJ|
Santos|José R|JR|
Ribeiro|Alessandra M|AM|
Silva|Regina H|RH|

reserpine
Parkinson's disease
rodent
dopamine
animal model


Clinically Diagnosing Pertussis-associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report.

Abstract:
BACKGROUND
The decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation. The current guideline focuses on making the clinical diagnosis of pertussis-associated cough in adults and children.

METHODS
The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on findings from a systematic review that was recently published on the topic; final grading was reached by consensus according to Delphi methodology. The systematic review was carried out to answer the Key Clinical Question: In patients presenting with cough, how can we most accurately diagnose from clinical features alone those who have pertussis-associated cough as opposed to other causes of cough?

RESULTS
In adults, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 4 clinical features: paroxysmal cough, post-tussive vomiting, inspiratory whooping, and absence of fever. Both paroxysmal cough and absence of fever had high sensitivity (93.2% [95% CI, 83.2-97.4] and 81.8% [95% CI, 72.2-88.7], respectively) and low specificity (20.6% [95% CI, 14.7-28.1] and 18.8% [95% CI, 8.1-37.9]). Inspiratory whooping and posttussive vomiting had a low sensitivity (32.5% [95% CI, 24.5-41.6] and 29.8% [95% CI, 18.0-45.2]) but high specificity (77.7% [95% CI, 73.1-81.7] and 79.5% [95% CI, 69.4-86.9]). In children, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 1 clinical feature in children (0-18 years): posttussive vomiting. Posttussive vomiting in children was only moderately sensitive (60.0% [95% CI, 40.3-77.0]) and specific (66.0% [95% CI, 52.5-77.3]).

CONCLUSIONS
In adults with acute (< 3 weeks) or subacute (3-8 weeks) cough, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children with acute (< 4 weeks) cough, posttussive vomiting is suggestive of pertussis but is much less helpful as a clinical diagnostic test. Guideline suggestions are made based upon these findings and conclusions.

Moore|Abigail|A|
Harnden|Anthony|A|
Grant|Cameron C|CC|
Patel|Sheena|S|
Irwin|Richard S|RS|
|||

cough
guidelines
evidence-based medicine
infectious disease


Cystic artery pseudoaneurysm due to carcinoma of the gallbladder.

Abstract: A 52-year-old man, with known case of hypertension and stroke, presented to us with an upper gastrointestinal bleed and abdominal pain. Ultrasonography of the abdomen showed haematoma within the gallbladder (GB), and Doppler ultrasound was suggestive of an aneurysm arising from the cystic artery (CA). CT of the abdomen showed a well-enhancing thick-walled GB suggestive of malignancy. It also showed the presence of a double CA along with an aneurysm of one of the cystic arteries, haematoma within the GB and haemoperitoneum. Digital subtraction angiography confirmed the presence of double CA and CA pseudoaneurysm. The CA was selective catheterised and embolised with N-butyl cyanoacrylate glue. The patient underwent extended radical cholecystectomy later and was reported to have adenocarcinoma of the GB.

gastrointestinal surgery
hepatic cancer
surgery
vascular surgery


Understanding and improving the quality and reproducibility of Jupyter notebooks.

Abstract: Jupyter Notebooks have been widely adopted by many different communities, both in science and industry. They support the creation of literate programming documents that combine code, text, and execution results with visualizations and other rich media. The self-documenting aspects and the ability to reproduce results have been touted as significant benefits of notebooks. At the same time, there has been growing criticism that the way in which notebooks are being used leads to unexpected behavior, encourages poor coding practices, and makes it hard to reproduce its results. To better understand good and bad practices used in the development of real notebooks, in prior work we studied 1.4 million notebooks from GitHub. We presented a detailed analysis of their characteristics that impact reproducibility, proposed best practices that can improve the reproducibility, and discussed open challenges that require further research and development. In this paper, we extended the analysis in four different ways to validate the hypothesis uncovered in our original study. First, we separated a group of popular notebooks to check whether notebooks that get more attention have more quality and reproducibility capabilities. Second, we sampled notebooks from the full dataset for an in-depth qualitative analysis of what constitutes the dataset and which features they have. Third, we conducted a more detailed analysis by isolating library dependencies and testing different execution orders. We report how these factors impact the reproducibility rates. Finally, we mined association rules from the notebooks. We discuss patterns we discovered, which provide additional insights into notebook reproducibility. Based on our findings and best practices we proposed, we designed Julynter, a Jupyter Lab extension that identifies potential issues in notebooks and suggests modifications that improve their reproducibility. We evaluate Julynter with a remote user experiment with the goal of assessing Julynter recommendations and usability.

Quality
Reproducibility
Jupyter notebook
GitHub
Lint


Development of depression in patients with oral cavity cancer: a systematic review.

Abstract:
BACKGROUND
The incidence of oral cancer is approximately 300,000 patients annually. A cancer diagnosis and treatment affect both physical and mental issues.

OBJECTIVES
The aim of this systematic review was to examine the development of depression in patients who have been treated for oral squamous cell carcinoma (OSCC).

MATERIAL AND METHODS
PubMed and EMBASE were systematically searched for studies addressing depression among patients treated for OSCC and published within the past ten years.

RESULTS
We identified three studies comprising 528 patients (range: 75-349), primarily men (66-83%), treated for OSCC from Europe and India. Tumour stage, treatment modality, and scales used to evaluate depressive symptoms varied in the studies. The European studies showed that 28% of the patients experienced depressive symptoms on the Hospital Anxiety and Depression Scale (HADS) and a mean of 8.0 on depression in the Brief Symptom Inventory (BSI). The Indian study showed a significant increase (p Value < .001) from moderate to severe depressive symptoms on the Depression, Anxiety, and Stress Scale-21 (DASS-21).Conclusion and Significance: This systematic review showed that OSCC patients are at risk of developing depressive symptoms after treatment, though severity of symptoms varied. This knowledge could preferably be implemented in future follow-up regimes.

depression
oral cavity cancer
Systematic review
oral squamous cell carcinoma
OSCC
depressive symptoms
after treatment


Identification of lncRNAs Responsive to Infection by Plasmodiophora brassicae in Clubroot-Susceptible and -Resistant Brassica napus Lines Carrying Resistance Introgressed from Rutabaga.

Abstract: Clubroot disease, caused by Plasmodiophora brassicae Woronin, is a major threat to the production of Brassica' crops. Resistance to different P. brassicae pathotypes has been reported in the A genome, chromosome A08; however, the molecular mechanism of this resistance, especially the involvement of long noncoding RNAs (lncRNAs), is not understood. We have used a strand-specific lncRNA-Seq approach to catalog lncRNAs from the roots of clubroot-susceptible and -resistant Brassica napus lines. In total, 530 differentially expressed (DE) lncRNAs were identified, including 88% of long intergenic RNAs and 11% natural antisense transcripts. Sixteen lncRNAs were identified as target mimics of the microRNAs (miRNAs) and eight were identified as the precursors of miRNAs. KEGG pathway analysis of the DE lncRNAs showed that the cis-regulated target genes mostly belong to the phenylpropanoid biosynthetic pathway (15%) and plant-pathogen interactions (15%) while the transregulated target genes mostly belong to carbon (18%) and amino acid biosynthesis pathway (19%). In all, 24 DE lncRNAs were identified from chromosome A08, which is known to harbor a quantitative trait locus conferring resistance to different P. brassicae pathotypes; however, eight of these lncRNAs showed expression only in the resistant plants. These results could form the basis for future studies aimed at delineating the roles of lncRNAs in plant-microbe interactions.

D029688:Brassica napus
D060467:Disease Resistance
D056909:Plasmodiophorida
D062085:RNA, Long Noncoding

Plasmodiophora brassicae
clubroot
genomics
RNA-seq
canola
long non-coding RNAs
metabolomics
plant responses to pathogens
primary metabolism
proteomics


Transcriptomes of Saussurea (Asteraceae) Provide Insights into High-Altitude Adaptation.

Abstract: Understanding how species adapt to extreme environments is an extension of the main goals of evolutionary biology. While alpine plants are an ideal system for investigating the genetic basis of high-altitude adaptation, genomic resources in these species are still limited. In the present study, we generated reference-level transcriptomic data of five Saussurea species through high-throughput sequencing and de novo assembly. Three of them are located in the highland of the Qinghai-Tibet Plateau (QTP), and the other two are close relatives distributed in the lowland. A series of comparative and evolutionary genomics analyses were conducted to explore the genetic signatures of adaptive evolution to high-altitude environments. Estimation of divergence time using single-copy orthologs revealed that Saussurea species diversified during the Miocene, a period with extensive tectonic movement and climatic fluctuation on the QTP. We characterized gene families specific to the alpine species, including genes involved in oxidoreductase activity, pectin catabolic process, lipid transport, and polysaccharide metabolic process, which may play important roles in defense of hypoxia and freezing temperatures of the QTP. Furthermore, in a phylogenetic context with the branch model, we identified hundreds of genes with signatures of positive selection. These genes are involved in DNA repair, membrane transport, response to UV-B and hypoxia, and reproductive processes, as well as some metabolic processes associated with nutrient intake, potentially responsible for Saussurea adaptation to the harsh environments of high altitude. Overall, our study provides valuable genomic resources for alpine species and gained helpful insights into the genomic basis of plants adapting to extreme environments.

Zhang|Xu|X|0000-0001-5743-3497
Sun|Yanxia|Y|
Landis|Jacob B|JB|0000-0002-5631-5365
Shen|Jun|J|
Zhang|Huajie|H|
Kuang|Tianhui|T|
Sun|Wenguang|W|0000-0001-9707-2665
Sun|Jiao|J|
Tiamiyu|Bashir B|BB|0000-0002-2840-9209
Deng|Tao|T|
Sun|Hang|H|
Wang|Hengchang|H|

transcriptomes
Saussurea
high-altitude adaptation
extreme environments
positive selection
lineage-specific genes


Histrelin implantation in the pediatric population: A 10-year institutional experience.

Abstract:
PURPOSE
To perform the largest review of the safety and clinical management practices of histrelin implantation in children.

METHODS
A retrospective cohort study was performed including all patients (age ≤ 20) that underwent histrelin implant insertion, replacement, or removal by a single surgeon at a large pediatric tertiary care center (2008-2017). Data analyzed included patient demographics, procedure details, and complications.

RESULTS
A total of 377 patients, with a mean age of 9.3 ± 2.4 years, underwent 866 unique procedures (352 insertions, 329 replacements, and 185 removals) for a diagnosis of either central precocious puberty (343 patients, 821 cases) or gender identity disorder (34 patients, 45 cases). There were 271 (72%) female patients, 72 (19%) male patients, and 34 (9%) children in gender transition. Procedures were performed in three settings: 415 (47.9%) in the outpatient clinic, 401 (46.3%) in a sedation unit, and 50 (5.8%) in the operating room. The preferred setting shifted over time to more clinic-based procedures (9.4% vs. 62.9% in the first five vs. second five years, respectively). Complications were rare (1% of cases).

CONCLUSION
Histrelin implantation in the pediatric population is safe, with minimal morbidity. Implantation and removal in the clinic setting are appropriate for the majority of patients.

LEVEL OF EVIDENCE
Treatment study; Level IV.

Swendiman|Robert A|RA|
Vogiatzi|Maria G|MG|
Alter|Craig A|CA|
Nance|Michael L|ML|

D000554:Ambulatory Care Facilities
D002648:Child
D004343:Drug Implants
D005260:Female
D000068116:Gender Dysphoria
D005783:Gender Identity
D007987:Gonadotropin-Releasing Hormone
D006801:Humans
D008297:Male
D009873:Operating Rooms
D011629:Puberty, Precocious
D012189:Retrospective Studies

Histrelin
Implant
Precocious puberty
Gender dysphoria


Lemon sole Microstomus kitt in the northern North Sea: a multidisciplinary approach to the early life-history dynamics.

Abstract: Lemon sole Microstomus kitt is a commercially valuable flatfish species that occurs in shelf waters around the northeast Atlantic. Only the most basic life-history information is available for the North Sea. Spawning is generally assumed to occur between early May and October, with a peak between May and August. Lemon sole larvae have been found in the water column in the northern North Sea in winter during standard surveys. Larvae captured in November/December 2016 and January/February 2017 using the International Council for the Exploration of the Seas standard 2 m Midwater Ring trawls (MIK) were analysed to gain a better understanding of the pelagic early life-history stages of lemon sole, especially in relation to the timing of spawning and the dispersal of overwintering larvae. Larval age was estimated from sagittal otolith primary increment counts. The larvae caught in November/December ranged in nominal age from 4 to 45 days post-hatching which suggests that spawning continues into late October and November. Most, but not all, of the larvae caught in January/February were post metamorphosis, and the difference in age between the two sampling dates was consistent with the elapsed time between samplings. The estimated hatching dates confirm that lemon sole spawning extends into late autumn in the northern North Sea, with overwintering larvae in all developmental stages. Drift modelling of eggs and larvae released at historically documented spawning grounds in the northern North Sea suggests that these grounds are also the source for all of the larvae sampled during the 2016-2017 surveys.

North Sea
flatfish
overwintering
hatching date
larval dispersal
otolith microstructure


The use of spect/ct in the evaluation of heterotopic ossification in para/tetraplegics.

Abstract:
OBJECTIVE
To evaluate the stage of maturation and the metabolism of neurogenic heterotopic ossification by using SPECT/CT.

METHODS
A total of 12 medical records of patients with spinal cord injury, all of them classified according to the ASIA protocol (disability scale from the American Spinal Injury Association) in complete lesion (A) and partial lesions (B, C and D) and registered at the Laboratory of Biomechanics and Rehabilitation of the Locomotor System, were submitted to SPECT/CT evaluation.

RESULTS
Sixteen hips with heterotopic ossification observed in X-ray were studied and only two (12.5%) had high osteoblastic activity. Five hips showed medium activity, three (18.75%) low activity and six (37.5%) did not present any activity detected by SPECT/CT.

CONCLUSION
SPECT/CT helps to determinate which patients have a greater risk of relapse after surgical resection, proving to be a useful imaging study in preoperative evaluation that can be used to determinate the postoperative prognosis of these patients. Level of Evidence III, Investigating a Diagnostic Test.

Lima|Maurício Coelho|MC|
Passarelli|Marcus Ceregati|MC|
Dario|Virgílio|V|
Lebani|Bruno Rodrigues|BR|
Monteiro|Paulo Henrique Silva|PH|
Ramos|Celso Darío|CD|