Analysis of α-particle-induced chromosomal aberrations by chemically-induced PCC. Elaboration of dose-effect curves.

Abstract: In a similar way to high-dose exposures to low-LET radiations, cells show difficulties reaching mitosis after high-LET radiation exposure. For this reason, techniques have been proposed that are able to analyze chromosome aberrations in interphase by prematurely condensing the chromosomes (PCC-techniques). Few dose-effect curves for high-LET radiation types have been reported, and none for α-particles. The aim of this study was to evaluate, by chemically-induced PCC, the chromosome aberrations induced by several doses of α-particles. Monolayers of peripheral lymphocytes were exposed to an α-source of Americium-241 with a mean energy entering the cells of 2.7 MeV. Lymphocytes were exposed to 10 doses, from 0-2.5 Gy, and then cultured for 48 h. Colcemid and Calyculin-A were added at 24 and 1 h before harvesting, respectively. During microscope analysis, chromosome rings and extra chromosome pieces were scored in G2/M-PCC and M cells, while dicentric chromosomes were only scored in M cells. As the dose increased, fewer cells were able to reach mitosis and the proportion of G2/M-PCC cells increased. Chromosome rings were hardly observed in M cells when compared to G2/M-PCC cells. Extra fragments were more frequent than rings in both G2/M-PCC and M cells, but with lower frequencies than in G2/M-PCC cells. The distribution of dicentrics and extra fragments showed a clear overdispersion; this was not so evident for rings. The dose-effect curves obtained fitted very well to a linear model. Damaged cells after α-particle irradiation show more difficulties in reaching mitosis than cells exposed to γ-rays. After α-particle irradiation the frequency of all the chromosome aberrations considered increased linearly with the dose, and α-particles clearly produced more dicentrics and extra chromosome pieces with respect to γ-rays. After α-particle exposure, the existence of extra chromosome fragments in PCC cells seems to be a good candidate for use as a biomarker for dose assessment. However, the observed frequencies of different types of chromosomal aberrations could be influenced by some methodological aspects; for this reason, and in order to avoid possible methodological bias, standardization of the technique will be desirable.

Puig|Roser|R|
Pujol|Mònica|M|
Barrios|Leonardo|L|
Caballín|María Rosa|MR|
Barquinero|Joan-Francesc|JF|

PCC
Alpha emitters
biological dosimetry
chromosome abberations


Aroma formation during cheese ripening is best resembled by Lactococcus lactis retentostat cultures.

Abstract:
BACKGROUND
Cheese ripening is a complex, time consuming and expensive process, which involves the generation of precursors from carbohydrates, proteins and fats and their subsequent conversion into a wide range of compounds responsible for the flavour and texture of the cheese. This study aims to investigate production of cheese aroma compounds outside the cheese matrix that could be applied for instance as food supplements in dairy or non-dairy products.

RESULTS
In this study, aroma formation by a dairy Lactococcus lactis was analysed as a function of the growth medium [milk, hydrolysed micellar casein isolate (MCI) and chemically defined medium (CDM)] and the cultivation conditions (batch culture, retentostat culture and a milli-cheese model system). In the retentostat cultures, the nutrient supply was severely restricted resulting in low growth rates (~ 0.001 h-1), thereby mimicking cheese ripening conditions in which nutrients are scarce and bacteria hardly grow. In total 82 volatile organic compounds were produced by the bacteria. Despite the use of a chemically defined medium, retentostat cultures had the biggest qualitative overlap in aroma production with the milli-cheese model system (36 out of 54 compounds). In the retentostat cultures, 52 known cheese compounds were produced and several important cheese aroma compounds and/or compounds with a buttery or cheese-like aroma increased in retentostat cultures compared to batch cultures and milli-cheeses, such as esters, methyl ketones, diketones and unsaturated ketones. In cultures on CDM and MCI, free fatty acids and their corresponding degradation products were underrepresented compared to what was found in the milli-cheeses. Addition of a mixture of free fatty acids to CDM and MCI could help to enhance flavour formation in these media, thereby even better resembling flavour formation in cheese.

CONCLUSIONS
This study demonstrates that retentostat cultivation is the preferred method to produce cheese flavours outside the cheese matrix by mimicking the slow growth of bacteria during cheese ripening.


Parental views of antenatal testing and termination following a diagnosis of cleft lip.

Abstract: Fetal anomaly screening at 18-21 weeks now routinely includes cleft lip. If detected, the manner in which the diagnosis is communicated can considerably influence prospective parents' decision-making in regard to further testing and termination of pregnancy (TOP). Given the known psychological impact of an antenatal diagnosis of cleft lip on prospective parents, this study aimed to explore the decision-making process from the parents' perspective, in order to evaluate how well current practice is meeting guidelines. Data from 217 parents of children born with cleft lip (with or without cleft palate) were collected using a mixed-methods online survey. Respondents reported feeling upset, offended and/or anxious following the diagnosis, due to unsatisfactory information and a perceived lack of empathy from health professionals. Some respondents had felt under pressure to make a decision quickly, with a minority having regretted undergoing amniocentesis, and/or experiencing significant distress at having come close to TOP unnecessarily. A number of suggestions are made as to how the discussion between parents and health professionals could be improved, to ensure that the information and support needs of families affected by cleft lip are fully addressed.

At The Centre For Appearance Research|The Vtct Foundation Research Team|TVFRT|

termination
Diagnosis
cleft lip
pregnancy
amniocentesis
parent perspective
sonography
ultrasound


Oxidative stress and brain morphology in individuals with depression, anxiety and healthy controls.

Abstract: Oxidative stress is a biological process, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, in favour of the ROS. This imbalance leads to oxidative damage to lipids, proteins and DNA and ultimately cell death. Studies in rodents have shown that the brain, particularly the amygdala and hippocampus, is sensitive to oxidative stress, although studies on the association between oxidative stress and brain morphology in humans are lacking. Oxidative stress has also been associated with major depressive disorder (MDD) and may be related to volumetric abnormalities in the amygdala and hippocampus in MDD and anxiety disorders. In this study we aimed to examine the association between two robust measures of oxidative damage in plasma (8-OHdG and F2-isoprostanes) and volume of the hippocampus and amygdala in a large sample of individuals with and without MDD and/or anxiety (N=297). In secondary analyses, we examine whether this association is similar in patients and controls. 8-OHdG and F2-isoprostanes plasma levels were determined using liquid chromatography tandem mass spectrometry and volume of the hippocampus and amygdala and hippocampal subfields was determined using Freesurfer. We found no association between plasma markers (or interaction with MDD and/or anxiety disorder diagnosis) and subcortical volume, suggesting that peripheral oxidative stress damage is not associated with subcortical brain volume.

van Velzen|Laura S|LS|
Wijdeveld|Madelief|M|
Black|Catherine N|CN|
van Tol|Marie-Jose|MJ|
van der Wee|Nic J A|NJA|
Veltman|Dick J|DJ|
Penninx|Brenda W J H|BWJH|
Schmaal|Lianne|L|

Oxidative stress
Brain morphology
Amygdala
Hippocampus
8-OHdG
f2-Isoprostanes


Evaluation of Anatomic Variations of Fibula Free Flap in Human Fresh Cadavers.

Abstract:
BACKGROUND
Reconstruction of the head and neck defects is still one of the most challenging surgeries for the surgeons. This study investigated on anatomic variations of fibula free flap in human fresh cadavers.

METHODS
Twenty fibula free flaps harvested from 10 fresh human corpses were enrolled. The number and type of skin perforators and their origin were recorded during the flap harvesting. After the completion of flap harvesting, the length of vascular pedicle and diameter of the artery and vein at the origin, the fibula length, the distance of the head of fibula to the site of peroneal artery bifurcation and harvesting time were also recorded.

RESULTS
The fibula free flaps were performed on 2 women and 8 men with the mean age of 35.6 years. The average number of perforators per flap was 1.7, most of which were musculocutaneous (35.29%) from soleus muscle. The mean fibula length was 33.1 (range: 31-35) cm. The mean distance of the head of fibula to the site of peroneal artery bifurcation from the tibialis posterior trunk was 5.76 (range: 4.5-6.5) cm. The mean length of the pedicle flap was 11.15 (range: 10-13) cm. The mean diameters of the peroneal artery and vein at the origin were 2.83 and 51.5 mm, respectively.

CONCLUSION
Although the fibula osteocutaneous flap is a reliable choice for maxillofacial reconstruction, flap harvesting is fairly difficult. Accordingly, surgeons must be aware of anatomical variations of the flap and have a suitable case selection to minimize the risk of surgical complications.

Gholami|Mahdi|M|
Hedjazi|Arya|A|
Kiamarz Milani|Amir|A|

Fibula
Free flap
Fresh cadaver
Skin perforators


Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy.

Abstract:
BACKGROUND
Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response.

METHODS
Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex.

RESULTS
Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1β, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups.

CONCLUSIONS
A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.

Verhage|R J J|RJ|
Boone|J|J|
Rijkers|G T|GT|
Cromheecke|G J|GJ|
Kroese|A C|AC|
Weijs|T J|TJ|
Borel Rinkes|I H M|IH|
van Hillegersberg|R|R|

D045422:Continuous Positive Airway Pressure

one-lung ventilation
cytokines
clinical trial
esophageal neoplasm
esophagectomy


The Red Queen in a potato field: integrated pest management versus chemical dependency in Colorado potato beetle control.

Abstract: Originally designed to reconcile insecticide applications with biological control, the concept of integrated pest management (IPM) developed into the systems-based judicious and coordinated use of multiple control techniques aimed at reducing pest damage to economically tolerable levels. Chemical control, with scheduled treatments, was the starting point for most management systems in the 1950s. Although chemical control is philosophically compatible with IPM practices as a whole, reduction in pesticide use has been historically one of the main goals of IPM practitioners. In the absence of IPM, excessive reliance on pesticides has led to repeated control failures due to the evolution of resistance by pest populations. This creates the need for constant replacement of failed chemicals with new compounds, known as the 'insecticide treadmill'. In evolutionary biology, a similar phenomenon is known as the Red Queen principle - continuing change is needed for a population to persevere because its competitors undergo constant evolutionary adaptation. The Colorado potato beetle, Leptinotarsa decemlineata (Say), is an insect defoliator of potatoes that is notorious for its ability to develop insecticide resistance. In the present article, a review is given of four case studies from across the United States to demonstrate the importance of using IPM for sustainable management of a highly adaptable insect pest. Excessive reliance on often indiscriminate insecticide applications and inadequate use of alternative control methods, such as crop rotation, appear to expedite evolution of insecticide resistance in its populations. Resistance to IPM would involve synchronized adaptations to multiple unfavorable factors, requiring statistically unlikely genetic changes. Therefore, integrating different techniques is likely to reduce the need for constant replacement of failed chemicals with new ones.

Alyokhin|Andrei|A|
Mota-Sanchez|David|D|
Baker|Mitchell|M|
Snyder|William E|WE|
Menasha|Sandra|S|
Whalon|Mark|M|
Dively|Galen|G|
Moarsi|Wassem F|WF|

integrated pest management
Colorado potato beetle
insecticide resistance


Neural Correlates of Moral Evaluation and Psychopathic Traits in Male Multi-Problem Young Adults.

Abstract: Multi-problem young adults (18-27 years) present with a plethora of problems, including varying degrees of psychopathic traits. The amygdala and ventromedial prefrontal cortex (vmPFC) have been implicated in moral dysfunction in psychopathy in adolescents and adults, but no studies have been performed in populations in the transitional period to adulthood. We tested in multi-problem young adults the hypothesis that psychopathic traits are related to amygdala and vmPFC activity during moral evaluation. Additionally, we explored the relation between psychopathic traits and other regions consistently implicated in moral evaluation. Our final sample consisted of 100 multi-problem young adults and 22 healthy controls. During fMRI scanning, participants judged whether pictures showed a moral violation on a 1-4 scale. Whole brain analysis revealed neural correlates of moral evaluation consistent with the literature. Region of interest analyses revealed positive associations between the affective callous-unemotional dimension of psychopathy and activation in the left vmPFC, left superior temporal gyrus, and left cingulate. Our results are consistent with altered vmPFC function during moral evaluation in psychopathy, but we did not find evidence for amygdala involvement. Our findings indicate the affective callous-unemotional trait of psychopathy may be related to widespread altered activation patterns during moral evaluation in multi-problem young adults.

Zijlmans|Josjan|J|
Marhe|Reshmi|R|
Bevaart|Floor|F|
Luijks|Marie-Jolette A|MA|
van Duin|Laura|L|
Tiemeier|Henning|H|
Popma|Arne|A|

morality
amygdala
ventromedial prefrontal cortex
psychopathy
fMRI
young adulthood


Gender differences in the impact on physical activity and lifestyle in Italy during the lockdown, due to the COVID-19 pandemic.

Abstract:
BACKGROUND AND AIMS
Italy responded to the Covid-19 pandemic early by forcing the entire population into a 2-month domestic confinement. The aim of this study was to assess gender differences in the impact of lockdown on physical activity and lifestyle habits.

METHODS AND RESULTS
A cross-sectional web-based survey was conducted in April 2020 on a general population sample residing in Italy. Participants completed validated questionnaires. Gender differences were assessed using a multivariable adjusted logistic regression model using gender as independent and exposures as dependent variables. Metabolic equivalents-hour/week was used to evaluate physical activity. A total of 2218 participants (761 men and 1457 women) agreed to participate in the study and completed the questionnaire. The survey found that women compared to men showed 1) a lower level of physical activity before the institution of lockdown, 2) a lower tendency to reduce physical activity levels during the lockdown, when gender differences in compliance with guideline recommendations for physical activity disappeared, 3) and a worsening of sleep and stool passage; men experienced an increase in alcohol consumption.

CONCLUSIONS
Women, who previously had a lower level of physical activity than men, showed a lower tendency to reduce it during lockdown, revealing greater resilience than men. However, the worsening in sleep, in stool passage, and a trend to weight increase revealed signs of psychological suffering after a protracted lockdown period.

Orlandi|Melissa|M|
Rosselli|Martina|M|
Pellegrino|Alessio|A|
Boddi|Maria|M|
Stefani|Laura|L|
Toncelli|Loira|L|
Modesti|Pietro Amedeo|PA|

Physical activity
COVID-19
Cross-sectional study
Daily living habits
Prevention strategies
SARS-CoV-2


Hill-based musculoskeletal model for a fracture reduction robot.

Abstract:
BACKGROUND
The introduction of fracture reduction robot can solve the problem of large reduction forces during fracture reduction surgeries and the need to collect multiple medical images. However, because its safety has not been certified, there are few academic achievements on this type of robot. To calculate the safety factor during its operation, a musculoskeletal model needs to be established to study the constraints of muscles on the robot. The existing academic achievements of musculoskeletal modelling are mainly for application such as rehabilitation treatment and collision in car accidents.

METHODS
A musculoskeletal model applied to the fracture reduction robot is proposed in this paper. First, by comparing the characteristics of mainstream muscle models and combining the biological characteristics of the anesthetised muscles, the Hill model was selected as the muscle model for this study. Second, based on the motion composition of six spatial degrees of freedom, five basic fractural malposition situations are proposed. Then, a 170-cm tall male musculoskeletal model was built in Opensim. Based on this model, the muscle force curves of the above malposition situations are calculated. Finally, a similar musculoskeletal model was established in Adams, and the accuracy of its muscle force data was tested. The study is approved by the ethics committee of the Rehabilitation Hospital, National Research Center for Rehabilitation Technical Aids, Beijing, China.

RESULTS
The muscle force curve of Opensim and Adams model under situations of five basic malposition are compared. Most of the correlation coefficients are in the range of 0.98-0.99. The overall correlation coefficient is greater than 0.95.

CONCLUSIONS
The simulation results prove that this model can be used for the safety assessment of the fracture reduction robots. This model will be served as an environmental constraint to study the control of fracture reduction robot.

musculoskeletal modelling
fracture reduction robot
Hill model
muscle force


Simulated rRNA/DNA Ratios Show Potential To Misclassify Active Populations as Dormant.

Abstract: The use of rRNA/DNA ratios derived from surveys of rRNA sequences in RNA and DNA extracts is an appealing but poorly validated approach to infer the activity status of environmental microbes. To improve the interpretation of rRNA/DNA ratios, we performed simulations to investigate the effects of community structure, rRNA amplification, and sampling depth on the accuracy of rRNA/DNA ratios in classifying bacterial populations as "active" or "dormant." Community structure was an insignificant factor. In contrast, the extent of rRNA amplification that occurs as cells transition from dormant to growing had a significant effect (P < 0.0001) on classification accuracy, with misclassification errors ranging from 16 to 28%, depending on the rRNA amplification model. The error rate increased to 47% when communities included a mixture of rRNA amplification models, but most of the inflated error was false negatives (i.e., active populations misclassified as dormant). Sampling depth also affected error rates (P < 0.001). Inadequate sampling depth produced various artifacts that are characteristic of rRNA/DNA ratios generated from real communities. These data show important constraints on the use of rRNA/DNA ratios to infer activity status. Whereas classification of populations as active based on rRNA/DNA ratios appears generally valid, classification of populations as dormant is potentially far less accurate.IMPORTANCE The rRNA/DNA ratio approach is appealing because it extracts an extra layer of information from high-throughput DNA sequencing data, offering a means to determine not only the seedbank of taxa present in communities but also the subset of taxa that are metabolically active. This study provides crucial insights into the use of rRNA/DNA ratios to infer the activity status of microbial taxa in complex communities. Our study shows that the approach may not be as robust as previously supposed, particularly in complex communities composed of populations employing different growth strategies, and identifies factors that inflate the erroneous classification of active populations as dormant.

D001419:Bacteria
D004269:DNA, Bacterial
D012335:RNA, Ribosomal

simulation
activity
sampling
error
RNA/DNA ratios
dormancy


Acetabular fractures in patients aged > 55 years: a systematic review of the literature.

Abstract: The increasing prevalence of osteoporosis in an ageing population has contributed to older patients becoming the fastest-growing group presenting with acetabular fractures. We performed a systematic review of the literature involving a number of databases to identify studies that included the treatment outcome of acetabular fractures in patients aged > 55 years. An initial search identified 61 studies; after exclusion by two independent reviewers, 15 studies were considered to meet the inclusion criteria. All were case series. The mean Coleman score for methodological quality assessment was 37 (25 to 49). There were 415 fractures in 414 patients. Pooled analysis revealed a mean age of 71.8 years (55 to 96) and a mean follow-up of 47.3 months (1 to 210). In seven studies the results of open reduction and internal fixation (ORIF) were presented: this was combined with simultaneous hip replacement (THR) in four, and one study had a mixture of these strategies. The results of percutaneous fixation were presented in two studies, and a single study revealed the results of non-operative treatment. With fixation of the fracture, the overall mean rate of conversion to THR was 23.1% (0% to 45.5%). The mean rate of non-fatal complications was 39.8% (0% to 64%), and the mean mortality rate was 19.1% (5% to 50%) at a mean of 64 months (95% confidence interval 59.4 to 68.6; range 12 to 143). Further data dealing with the classification of the fracture, the surgical approach used, operative time, blood loss, functional and radiological outcomes were also analysed. This study highlights that, of the many forms of treatment available for this group of patients, there is a trend to higher complication rates and the need for further surgery compared with the results of the treatment of acetabular fractures in younger patients.

Daurka|J S|JS|
Pastides|P S|PS|
Lewis|A|A|
Rickman|M|M|
Bircher|M D|MD|

D000077:Acetabulum
D000367:Age Factors
D019644:Arthroplasty, Replacement, Hip
D050723:Fractures, Bone
D006801:Humans
D008875:Middle Aged
D058866:Osteoporotic Fractures
D016896:Treatment Outcome

Acetabular Fracture Hip Percutaneous Acetabulum Elderly


Notes on the Nest Architecture and Colony Composition in Winter of the Yellow-Legged Asian Hornet, Vespa velutina Lepeletier 1836 (Hym.: Vespidae), in Its Introduced Habitat in Galicia (NW Spain).

Abstract: Fifteen years ago, at least one multimated female yellow-legged Asian hornet (Vespa velutina Lepeletier 1836) arrived in France, giving rise to a pan-European invasion, altering the environment, affecting ecosystem processes, and impacting society. During winter, V. velutina nests (n = 3) were collected in Galicia and data on internal and external aspects of the nests and the colony as a whole were collected. The whole colony population (WCPN; adult insects, larvae, and pupae in percentages) was as follows: nest A: n = 176 (49%, 3%, and 48%); nest B: n = 1979 (52%, 36%, and 12%); and nest C: n = 662 (5%, 27%, and 8%). The adult insect population (IAPN; males, workers, and gynes in percentages) was as follows: nest A: n = 87 (11%, 66%, and 23%); nest B: n = 1021 (3%, 62%, and 35%); and nest C: n = 430 (20%, 73%, and 7%). As a small number of queens is sufficient for a population to develop, it is necessary to avoid continued spread by deactivating and removing all nests, even those detected in winter. This practice can be of greatest importance in border areas where V. velutina is expanding into new territory.

Feás Sánchez|Xesús|X|
Charles|Rebecca Jane|RJ|

nest
colony
winter
Asian hornet
Vespa velutina
Galicia
invasive species


Preparation of chitin nanofiber-reinforced carboxymethyl cellulose films.

Abstract: In this study, we investigated the preparation of chitin nanofiber (CNF)-reinforced carboxymethyl cellulose (CMC) films by their electrostatic interaction. First, CMC films and self-assembled CNF dispersions with methanol were prepared by casting technique and regeneration from chitin ion gels with an ionic liquid, respectively. Then, the CMC films were immersed in the dispersions with the different CNF contents, followed by centrifugation to obtain the desired composite films. The amounts of the absorbed CNFs on the films were calculated by the weight increases after the above compatibilization procedure. The presence of CNFs on the films was also confirmed by the SEM and IR measurements. The mechanical properties of the composite films were evaluated by tensile testing, which suggested the reinforcing effect of CNFs present on the CMC films.

Carboxymethyl cellulose
Chitin nanofiber
Electrostatic interaction
Composite film
Ionic polysaccharide


Real-time, quantitative and sensitive detection of urea by whispering gallery mode lasing in liquid crystal microdroplet.

Abstract: In this study, we demonstrate a novel nematic liquid crystal (LC) 4-cyano-4'-pentylbiphenyl (5CB) microdroplet-based biosensor for real-time, quantitative and sensitive detection of urea by whispering gallery mode (WGM) lasing technology. The single stearic acid-doped 5CB microdroplet is taken as both optical resonator and sensing reactor. To the best of our knowledge, this work is the first report of urea detection with WGM lasing. The enzymatic reaction between urea and urease produces hydroxide ions. Deprotonation and self-assembly of stearic acid occur at the aqueous/LC interface with increased pH value, promoting the reorientation of LC molecules. The detectable shift of WGM lasing spectra related to the configuration transition of LC microdroplets can be used as an indicator of enzymatic reaction, and this allows detection of urea molecules by the sensor at a concentration of only 0.1 mM. The proposed sensor also demonstrated the ability to detect urea in real urine samples. Compared with conventional POM observations, monitoring and identification of lasing spectra from LC microdroplets as a versatile method allow for more quantitative and sensitive detection of analyte reactions and can be expected to replace POM imaging technology for current LC-based biosensor systems.

Duan|Rui|R| Li|Yanzeng|Y| Shi|Bojian|B| Li|Hanyang|H| Yang|Jun|J|

Whispering gallery mode lasing
Biosensor
5CB microdroplets
Urea molecules


"This Could Mean Death for My Child": Parent Perspectives on Laws Banning Gender-Affirming Care for Transgender Adolescents.

Abstract:
OBJECTIVES
Numerous U.S. state legislatures have proposed bills to ban gender-affirming medical interventions for minors. Parents and caregivers play a critical role in advocating for and supporting their transgender and gender-diverse youth (TGDY). We aimed to understand parent and caregiver perspectives about this potential legislation and perceived effects on their TGDY's mental health.

METHODS
We developed and launched a social-media based, anonymous online survey in February 2020 to assess parent and caregiver perspectives on proposed laws to ban gender-affirming medical interventions for minors. Participants were asked to respond to two open-ended questions about these laws; responses were coded to identify key themes.

RESULTS
We analyzed responses from 273 participants from 43 states. Most identified as white (86.4%) female (90.0%) mothers (93.8%), and 83.6% of their TGDY had received gender-affirming medical interventions before age 18 years. The most salient theme, which appeared in the majority of responses, described parent and caregiver fears that these laws would lead to worsening mental health and suicide for their TGDY. Additional themes included a fear that their TGDY would face increased discrimination, lose access to gender-affirming medical interventions, and lose autonomy over medical decision-making due to government overreach.

CONCLUSIONS
In this convenience sample, parents and caregivers overwhelmingly expressed fear that the proposed legislation will lead to worsening mental health and increased suicidal ideation for their TGDY. They implored lawmakers to hear their stories and to leave critical decisions about gender-affirming medical interventions to families and their medical providers.

Kidd|Kacie M|KM|
Sequeira|Gina M|GM|
Paglisotti|Taylor|T|
Katz-Wise|Sabra L|SL|
Kazmerski|Traci M|TM|
Hillier|Amy|A|
Miller|Elizabeth|E|
Dowshen|Nadia|N|

Parents
Laws
Gender-affirming care
Transgender
Youth
Mental health
Access
Suicidal ideation
Gender diverse


Mid-term results of arthroscopic subacromial decompression in patients with or without partial thickness rotator cuff tears.

Abstract:
AIM
To evaluate mid-term outcome in patients who underwent arthroscopic subacromial decompression (ASD) for shoulder impingement syndrome with intact and partially torn rotator cuffs.

MATERIALS AND METHODS
A total of 80 consecutive patients (83 shoulders) who underwent ASD for impingement syndrome between 2003 and 2006 were analyzed. Mean age was 57.1 years. Patients' self-reported Oxford Shoulder Score (OSS) for pain was collected prospectively and was used as an instrument to measure surgical outcome.

RESULTS
The mean initial and final OSS for patients with an intact rotator cuff was 26.1 and 40.3, respectively, at a mean follow up of 71.9 months (nearly 7 years). The mean initial and final OSS for patients with a partially torn articular sided tear was 22.6 and 41.9, respectively, at mean follow up of 70.7 months. Both groups showed significant sustained improvement (P < 0.0001). The mean improvement of OSS following ASD was statistically greater (P < 0.03) for partially torn rotator cuff group (19.3 points) as compared to those with normal rotator cuff (14.2 points).

CONCLUSION
Patients with dual pathology (partial rotator cuff tear and impingement) appreciated a significantly greater improvement following ASD compared to those with impingement alone. Both groups of patients had a similar final outcome at a mid-term follow up.

LEVEL OF EVIDENCE
IV, retrospective study on consecutive series of patients.

Eid|Ahmed S|AS|
Dwyer|Amitabh J|AJ|
Chambler|Andrew F W|AF|

Arthroscopic subacromial decompression
rotator cuff
surgical outcome
partial rotator cuff tear
patient reported outcome measures


Influence of pH and temperature on ziconotide stability in intrathecal analgesic admixtures in implantable pumps and syringes.

Abstract:
PURPOSE
The aim of our study was to investigate the influence of pH and temperature on the stability of ziconotide in analgesic admixtures containing morphine and ropivacaine.

METHODS
All admixtures were combined using a wide range of concentrations, in implantable pumps and syringes, using temperatures from 4°C to 37°C. Quantification was made thanks to a specific chromatographic technique. pH has also been measured throughout the study.

RESULTS
Admixtures confirm excellent stability for morphine and ropivacaine. Concerning ziconotide, an acid hydrolysis has been observed, reducing the time of use of our admixtures in a significant way, but producing non-toxic degradation products. The degradation was linear in all conditions. Inside the implantable pumps at body temperature turned out to be the best conditions for lower protein breakdown. Finally the degradation process showed a high correlation with the pH and the morphine concentration with a median loss of concentration delay due to degradation of 3.5 days [3; 5] when pH<4.5 and 13 days [13; 24] when pH ≥ 4.5.

CONCLUSION
Our admixtures showed different stability depending on the drug concentrations, pH and temperature. The great majority of mixtures in real life in our institution have stability highly compatible with our practice and with the delay between two pump refilling.

D002851:Chromatography, High Pressure Liquid

Morphine sulphate (PubChem CID: 5464280)


Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma.

Abstract: Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel hypoxia-activated prodrug, Q6, exhibits potent antiproliferative efficacy under hypoxic conditions and induces caspase-dependent apoptosis in 2 hepatocellular carcinoma (HCC) cell lines, with no obvious toxicity being detected in 2 normal liver cell lines. Treatment with Q6 markedly downregulated HIF1A [hypoxia inducible factor 1, α subunit (basic helix-loop-helix transcription factor)] expression and transcription of the downstream target gene, VEGFA (vascular endothelial growth factor A). This dual hypoxia-targeted modulation mechanism leads to high potency in suppressing tumor growth and vascularization in 2 in vivo models. Intriguingly, it is the autophagy-dependent degradation pathway that plays a crucial role in Q6-induced attenuation of HIF1A expression, rather than the proteasome-dependent pathway, which is normally regarded as the predominant mechanism underlying posttranslational regulation of HIF1A. Inhibition of autophagy, either by short interfering RNA (siRNA) or by chemical inhibitors, blocked Q6-induced HIF1A degradation. Autophagic degradation of HIF1A was further confirmed by the observation that HIF1A coimmunoprecipitated with the ubiquitin-binding adaptor protein, SQSTM1, which is degraded through autophagy. Additionally, silencing of SQSTM1 inhibited Q6-induced HIF1A degradation. These findings suggest that the novel hypoxia-targeted agent, Q6, has potential clinical value in the therapy of HCC. Furthermore, the identification of autophagy as a crucial regulator of HIF1A provides new insights into hypoxia-related treatments.

Liu|Xiao-Wen|XW| Cai|Tian-Yu|TY| Zhu|Hong|H| Cao|Ji|J| Su|Yi|Y| Hu|Yong-Zhou|YZ| He|Qiao-Jun|QJ| Yang|Bo|B|

D048868:Adaptor Proteins, Signal Transducing

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

hypoxia-activated prodrug
posttranslational regulation
autophagy
dual modulation mechanisms
targeting treatment


Superior vena cava syndrome due to mediastinal Gardner fibroma presenting as syncope.

Abstract: Superior vena cava (SVC) syndrome refers to the clinical manifestation due to an obstruction in the SVC; resulting in decreased venous return from the head, neck and upper extremities. The obstruction can occur either due to tumour invasion of the vessel wall with associated thrombus or due to vessel wall compression by the tumour mass. The patient being reported is a young male who presented with recurrent episodes of syncope and was found to have mediastinal Gardner fibroma causing SVC syndrome. Gardner fibroma is a benign soft tissue lesion; and its occurrence in the mediastinum resulting in SVC syndrome has not been reported yet.

superior vena cava syndrome
Gardner fibroma
pulmonary artery hypertension


Brachytherapy in Belgium in 2018. A national survey of the brachytherapy study group of the Belgian SocieTy for Radiotherapy and Oncology (BeSTRO).

Abstract:
PURPOSE
To explore the current practices patterns and evaluate the actual brachytherapy (BT) resources in Belgium.

MATERIAL AND METHODS
In 2019, the Brachytherapy Study Group proposed to conduct a survey on behalf of the Belgian SocieTy of Radiation Oncology (BeSTRO) in order to identify current BT practice patterns. An electronic questionnaire was sent to all primary radiotherapy centers in Belgium. This questionnaire was based on the questionnaire that was used by the Italian Association of Radiation Oncology (AIRO) in 2016, asking for: (a) General information on the Radiation Oncology Centre; (b) BT equipment and human resources; (c) BT procedures; (d) BT assessment (number of patients treated annually, treated sites, and different modalities of treatments).

RESULTS
All 24 radiation oncology centers (100% response rate) answered the questionnaire and gave also information on the performance of brachytherapy in their (eventual) satellite centers. Eighteen (18) BT afterloader units were installed and operational in 2018. Thirteen centers mentioned a prostate seed implant program, one center a prostate and eye plaque program and one center only an eye plaque program. Less than 50% of centers have the infrastructure to offer the full-range of BT in their own department. In 2018, 1486 patients received a BT-treatment, 28% of them were treated by prostate seed implant, 8% were treated by eye-(seed) BT and 64% by high dose rate (HDR)/pulsed dose rate (PDR) BT. Forty-five percent of HDR/PDR patients were treated by vaginal dome BT, 22% by intra-uterine BT, 11% by skin BT, 10% by breast BT (almost exclusively in one centre), 8% for benign pathology (keloid) and the remaining 4% were treated for prostate (as a boost or as salvage in one centre), anal, penile, lung or oesophageal cancer.

CONCLUSIONS
Belgian radiotherapy departments often perform BT only in a (highly) selected group of pathologies, resulting in a limited number of patients treated by this technique despite the sufficient availability of BT equipment. Modern indications are often not covered, hence patients do not have regular access to recognized treatment options, possibly leading to inferior oncological outcome. BeSTRO will use the results of this survey to stimulate improvements in training, awareness, education, implementation, collaboration and cooperation in the field of brachytherapy.

Salembier|Carl|C|
De Hertogh|Olivier|O|
Daisne|Jean-François|JF|
Palumbo|Samuel|S|
Van Gestel|Dirk|D|

BeSTRO (Belgian SocieTy of Radiation Oncology)


Prognostic significance of Daxx NCR (Nuclear/Cytoplasmic Ratio) in gastric cancer.

Abstract: In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer (GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples (GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort (n = 277, treatment between 2006 and 2009) and Recent cohort (n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high- and low-risk groups. Relative to the low-risk group, the high-risk patients had a shorter disease free survival (DFS) and overall survival (OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high- and low-risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high-risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery.

D015972:Gene Expression Regulation, Neoplastic

Daxx
gastric cancer
subcellular localization
survival
Chemotherapy


A simple lens-sparing technique to treat hypotonic maculopathy secondary to large cyclodialysis.

Abstract:
Purpose
Hypotonic maculopathy secondary to cyclodialysis often persists and causes irreversible visual loss despite a variety of treatments proposed. The purpose of this study is to report two cases with persistent hypotonic maculopathy due to a large cyclodialysis cleft treated with a simple, lens-sparing technique of external drainage, diathermy, and suturing under the placement of an infusion cannula.

Observations
Both patients had sustained blunt trauma to one eye, causing persisting hypotonic maculopathy. One eye was phakic. The ciliary body was totally detached with a large cyclodialysis cleft. After half-thickness scleral flaps were made and a 25-gauge infusion cannula was placed at the pars plana, external drainage was performed. Transscleral diathermy and interrupted suturing also were done.

Results
In both cases, the ciliary detachment promptly improved and the intraocular pressure normalized after transient elevation for a few days. No adverse events were observed.

Conclusions and importance
We successfully treated two cases with hypotonic maculopathy by a simple technique with an infusion cannula. This procedure is simple, immediately effective, less invasive, and applicable to all cases including phakic eyes.

Hypotonic maculopathy
Cyclodialysis
External drainage
Infusion cannula
Blunt trauma
Ciliary body detachment


Flow field-flow fractionation and multi-angle light scattering as a powerful tool for the characterization and stability evaluation of drug-loaded metal-organic framework nanoparticles.

Abstract: Asymmetric flow field-flow fractionation (AF4) coupled with UV-Vis spectroscopy, multi-angle light scattering (MALS) and refractive index (RI) detection has been applied for the characterization of MIL-100(Fe) nanoMOFs (metal-organic frameworks) loaded with nucleoside reverse transcriptase inhibitor (NRTI) drugs for the first time. Empty nanoMOFs and nanoMOFs loaded with azidothymidine derivatives with three different degrees of phosphorylation were examined: azidothymidine (AZT, native drug), azidothymidine monophosphate (AZT-MP), and azidothymidine triphosphate (AZT-TP). The particle size distribution and the stability of the nanoparticles when interacting with drugs have been determined in a time frame of 24 h. Main achievements include detection of aggregate formation in an early stage and monitoring nanoMOF morphological changes as indicators of their interaction with guest molecules. AF4-MALS proved to be a useful methodology to analyze nanoparticles engineered for drug delivery applications and gave fundamental data on their size distribution and stability. Graphical abstract .

Roda|Barbara|B| Marassi|Valentina|V| Zattoni|Andrea|A| Borghi|Francesco|F| Anand|Resmi|R| Agostoni|Valentina|V| Gref|Ruxandra|R| Reschiglian|Pierluigi|P| Monti|Sandra|S|

D019380:Anti-HIV Agents
D000963:Antimetabolites
D056831:Coordination Complexes
D054306:Dideoxynucleotides
D004337:Drug Carriers
D000067493:Dynamic Light Scattering
D031521:Fractionation, Field Flow
D000073396:Metal-Organic Frameworks
D008958:Models, Molecular
D053758:Nanoparticles
D010316:Particle Size
D012031:Refractometry
D013056:Spectrophotometry, Ultraviolet
D013942:Thymine Nucleotides
D015215:Zidovudine

Metal–organic framework nanoparticles characterization


Immediate Effects of Acapella® on Dynamic Lung Compliance in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome: A Case Series.

Abstract:
Background and Aims
One potential complication of acute respiratory distress syndrome (ARDS) is reduced dynamic compliance, saturation for peripheral oxygenation (SpO2) and increased sputum in patients that are mechanically ventilated. Airway clearance technique is the treatment given for patients on mechanically ventilator with ARDS. The purpose of the case series is to know the immediate effects of Acapella® on dynamic lung compliance (Cdyn) in subject with ARDS.

Subjects and Methods
Patients who are on ventilator for more than 48hrs were included in the study. Readings for Cdyn, SpO2 were noted at baseline, immediately post treatment, 10, 20, 30 and 60minutes. Pre and post treatment sputum volume was also noted.

Results
Five patients were included with age range of 25 to 75 years. Clinical improvement was seen immediately after treatment in Cdyn and SpO2. There was not much change in sputum volume.

Conclusion
Acapella® increased the dynamic compliance of lungs and sputum clearance in mechanically ventilated ARDS patients.

Acapella®
mechanical ventilation
acute respiratory distress syndrome
airways clearance technique


Correlation of Probe-Based Confocal Laser Endomicroscopy (pCLE) and Mucosal Integrity Testing (MIT) with Epithelial Barrier Function and Presence of Gastroesophageal Reflux Disease (GERD).

Abstract:
INTRODUCTION
Epithelial barrier function (EBF) disruption is a key mechanism underlying gastroesophageal reflux disease (GERD). Our aim was to assess whether two novel technologies, probe-based confocal laser endomicroscopy (pCLE) and mucosal integrity testing (MIT), could assess EBF.

METHODS
We prospectively enrolled patients undergoing upper endoscopy for refractory GERD or non-GERD conditions. Patients underwent esophagogastroduodenoscopy, pCLE, MIT, esophageal biopsy at 2 cm and 6 cm above the esophagogastric junction, and wireless pH testing. To assess EBF in vitro, biopsies were mounted in a mini-Ussing chamber, 1 ml of fluorescein was instilled on the mucosal side, and concentration of fluorescein on the serosal side was measured at 3 h.

RESULTS
We enrolled 54 subjects (28 GERD, 26 non-GERD based on Lyon consensus criteria). In vivo permeability assessed by pCLE did not differ significantly between GERD vs. non-GERD patients and did not correlate with in vitro permeability. Mean MIT at 2 cm was lower in GERD compared to non-GERD (1914 vs. 3727 ohms). MIT correlated inversely with in vitro permeability at 2 cm and at 6 cm. Using a predictive model that used slope and intercept of MIT at 2 cm and 6 cm, sensitivity and specificity of MIT at identifying GERD was 76% and 72%, respectively.

CONCLUSION
pCLE did not differentiate GERD vs non-GERD and did not correlate with EBF measured in vitro. MIT, on the other hand, may be more promising as it differentiated GERD vs non-GERD and correlated with EBF measured in vitro.

Gastroesophageal reflux
Barrett esophagus
Diagnostic technique, Digestive system
Electric impedance
Microscopy, Confocal


Effects of Co-Solvent Nature and Acid Concentration in the Size and Morphology of Wrinkled Mesoporous Silica Nanoparticles for Drug Delivery Applications.

Abstract: Hierarchically porous materials, such as wrinkled mesoporous silica (WMS), have gained interest in the last couple of decades, because of their wide range of applications in fields such as nanomedicine, energy, and catalysis. The mechanism of formation of these nanostructures is not fully understood, despite various groups reporting very comprehensive studies. Furthermore, achieving particle diameters of 100 nm or less has proven difficult. In this study, the effects on particle size, pore size, and particle morphology of several co-solvents were evaluated. Additionally, varying concentrations of acid during synthesis affected the particle sizes, yielding particles smaller than 100 nm. The morphology and physical properties of the nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). Homogeneous and spherical WMS, with the desired radial wrinkle morphology and particle sizes smaller than 100 nm, were obtained. The effect of the nature of the co-solvents and the concentration of acid are explained within the frame of previously reported mechanisms of formation, to further elucidate this intricate process.

D017550:Spectroscopy, Fourier Transform Infrared

co-solvent
drug delivery
wrinkled mesoporous silica (WMS)


Mutant p53 and ETS2, a Tale of Reciprocity.

Abstract: TP53 is one of the most frequently inactivated tumor suppressor genes in human cancer. However, unlike other tumor suppressor genes whose expression is lost, TP53 is usually inactivated as a result of a single nucleotide change within the coding region. Typically, these single nucleotide mutations result in a codon change that creates an amino acid substitution. Thus, unlike other tumor suppressor genes whose expression is lost due to genetic or epigenetic changes, the p53 gene primarily suffers missense mutations, and therefore, the cells retain and express a mutant form of the p53 protein (mtp53). It is now well established that mtp53 contributes to tumor development through its gain-of-function (GOF) activities. These GOF activities can arise from novel protein-protein interactions that can either disable other tumor suppressors (e.g., p63 and p73) or enable oncogenes such as ETS2, an ETS family member. In this review, I will focus on the identification of the mtp53/ETS2 complex and outline the diverse activities that this transcriptional regulatory complex controls to promote cancer.


Declining prevalence of Helicobacter pylori infection in Jordanian children, report from developing country.

Abstract:
Introduction
Helicobacter pylori (H. pylori) is a Gram-negative bacteria that is harbored in the stomach and linked to chronic gastritis, peptic ulcer disease, and gastric malignancy. Most Helicobacter infections are acquired during early infancy. This study aimed to establish the prevalence of H. pylori infection in Jordanian children using the 13C-urea breath test.

Materials and methods
We prospectively enrolled children between the ages of 4 and 17 years from April 2019 to July 2019. Enrolled children were patients with nongastrointestinal complaints at the pediatric clinics of two hospitals and at community centers caring for healthy children in Irbid, Jordan. Questionnaires obtaining data on sociodemographics, clinical symptomatology, and hygienic risk factors were completed. Recruited children underwent a urea breath test (UBT).

Results
Of 340 children who were recruited, 328 (96.5%) were included in the final analysis. The mean age (±standard deviation) was 9.56 (±3.98) years (range, 4.0-17 years), and 168 (51.2%) were males. Only 48 children (14.6%) tested positive. There were no gender differences. Living in an urban area and a family history of previous H. pylori infection were risk factors for the acquisition of infection (P = 0.007 and 0.001, respectively). Although gastrointestinal symptoms were more common in H. pylori-infected children, only hiccups and constipation were statistically significant (P = 0.035 and 0.038, respectively).

Conclusion
H. pylori infects at least 15% of Jordanian children, suggesting a significant drop in infection rates in this group. Larger-scale studies combined with clinical evaluations will be important for further understanding the reasons for the observed decrease in H. pylori infections in Jordanian children.

Altamimi|Eyad|E|
Alsharkhat|Noor|N|
AlJawarneh|Afnan|A|
Abu Hamad|Moh D Rawhi|MDR|
Assi|Anas Abu|AA|
Alawneh|Sarah|S|
Al-Ahmad|Majd|M|

Helicobacter pylori
Infection
Children
13C-urea breath test
Pediatrics
Jordan
Gastrointestinal system
Health sciences
Infectious disease
Laboratory medicine


Effect of interval-training exercise on subchondral bone in a chemically-induced osteoarthritis model.

Abstract:
OBJECTIVES
The role of subchondral bone in osteoarthritis (OA) development is well admitted. Cross-talk between subchondral bone and cartilage may be disrupted in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in bone remodeling control and could play a key role in OA progression. Our purpose of this study was to evaluate the preventive effect of interval-training exercise on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of experimental OA.

METHODS
At baseline, 48 male Wistar rats (8 weeks old) were separated into two groups: interval-training exercise or no exercise for 10 weeks. After this training period, each group was divided into two subgroups: MIA-injected knee (1 mg/100 μl saline) and saline-injected knee. Four weeks later, rats were sacrificed and carefully dissected. Evaluated parameters were: cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X-ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro-computed tomography (μCT), cortical subchondral bone lacunar osteocyte occupancy (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by epifluorescence).

RESULTS
Our results showed deleterious effects of MIA on cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented by exercise. Exercise induced increase in full osteocyte lacunae surface and osteocyte occupancy (+60%) of cortical subchondral bone independently of OA. Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever the group at sacrifice.

CONCLUSION
Our results suggest that preliminary interval-training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our interval-training did not prevent MIA-induced cartilage degeneration.

Boudenot|A|A| Presle|N|N| Uzbekov|R|R| Toumi|H|H| Pallu|S|S| Lespessailles|E|E|

D015502:Absorptiometry, Photon
D000818:Animals
D001169:Arthritis, Experimental
D015519:Bone Density
D002358:Cartilage, Articular
D004195:Disease Models, Animal
D004791:Enzyme Inhibitors
D019807:Iodoacetic Acid
D008297:Male
D010003:Osteoarthritis
D010011:Osteocytes
D010805:Physical Conditioning, Animal
D051381:Rats
D017208:Rats, Wistar
D055114:X-Ray Microtomography

Interval-training
Subchondral bone
Osteoarthritis
Knee
Bone mineral density
Microarchitecture


Toward a phenomenology of congenital illness: a case of single-ventricle heart disease.

Abstract: Phenomenology has contributed to healthcare by providing resources for understanding the lived experience of the patient and their situation. But within a burgeoning literature on the characteristic features of illness, there has not yet been an account appropriate to describe congenital illnesses: conditions which are present from birth and cause suffering or medical threat to their bearers. Congenital illness sits uncomfortably with standard accounts in phenomenology of illness, in which concepts such as loss, doubt, alienation and unhomelikeness presuppose prior health. These accounts reflect, in different ways, Maurice Merleau-Ponty's assumption that the ways of living of the ill contain allusions to fundamental, healthy functions. The originality of congenital illness complicates this assumption and demands its own original phenomenology. In this paper, I sketch my personal experience living with a single-ventricle heart condition. While some of this story may reflect my own idiosyncratic experience, I hope that much of it will resonate with the congenital illness experience. I argue that the phenomenological literature on illness, grounded in the notion of loss, does not describe the congenital illness experience. I show how a number of other patient-centred theories of health and illness which have been influential on phenomenology can and cannot elucidate congenital illness. In particular, I consider Georges Canguilhem's account of the normal and the pathological; debates in disability; and the notion of illness as biographical disruption. I show that congenital illness results in the preadmission of its patients to a paradoxical logic of medical palliation, one product of which is existential maturity.

Phenomenology
Congenital illness
Lived experience
Biographical disruption
Congenital heart disease


Carbon black vs. black carbon and other airborne materials containing elemental carbon: physical and chemical distinctions.

Abstract: Airborne particles containing elemental carbon (EC) are currently at the forefront of scientific and regulatory scrutiny, including black carbon, carbon black, and engineered carbon-based nanomaterials, e.g., carbon nanotubes, fullerenes, and graphene. Scientists and regulators sometimes group these EC-containing particles together, for example, interchangeably using the terms carbon black and black carbon despite one being a manufactured product with well-controlled properties and the other being an undesired, incomplete-combustion byproduct with diverse properties. In this critical review, we synthesize information on the contrasting properties of EC-containing particles in order to highlight significant differences that can affect hazard potential. We demonstrate why carbon black should not be considered a model particle representative of either combustion soots or engineered carbon-based nanomaterials. Overall, scientific studies need to distinguish these highly different EC-containing particles with care and precision so as to forestall unwarranted extrapolation of properties, hazard potential, and study conclusions from one material to another.

Long|Christopher M|CM|
Nascarella|Marc A|MA|
Valberg|Peter A|PA|

Carbon black
Black carbon
Elemental carbon
Nanomaterial
Soot


Plasma levels of acylated ghrelin in patients with insulinoma and expression of ghrelin and its receptor in insulinomas.

Abstract:
BACKGROUND
Insulinoma is a subtype of pancreatic neuroendocrine tumors. Many patients with insulinoma are obese due to frequent food intake. Ghrelin is associated with obesity and blood levels of insulin. It is not clear if plasma levels of ghrelin in insulinoma patients correlate with hyperinsulinemia and obesity. Expression of ghrelin and its receptor has not been well demonstrated in insulinoma.

OBJECTIVE
To study if plasma levels of ghrelin is associated with obesity and hyperinsulinemia or hyperproinsulinemia in patients with insulinoma, and to detect the expression of ghrelin and its receptor in insulinoma.

METHODS
Plasma levels of acylated ghrelin, insulin, and proinsulin were measured in 37 patients with insulinoma and 25 controls by ELISA. Expression of ghrelin and its receptor GHS-R1A was examined in 20 insulinoma and paired pancreatic specimens by immunostaining. P ≤ 0.05 was considered significant.

RESULTS
The plasma levels of acylated ghrelin in patients with insulinoma were significantly lower than that in the controls (median 15 pg/ml vs. 19 pg/ml, respectively, P = 0.016). The reduced plasma levels of acylated ghrelin in patients were significantly correlated with obesity, hyperinsulinemia, and hyperproinsulinemia (P = 0.029 and P = 0.028, respectively). Expression of ghrelin and its receptor GHS-R1A was shown in the majority of insulinoma specimens. The expression of GHS-R1A was positively correlated with ghrelin expression in insulinoma (P = 0.014).

CONCLUSIONS
Plasma levels of acylated ghrelin decreased in patients with insulinoma, probably due to the hyperinsulinemia and obesity in the patients. Expression of both ghrelin and its receptor is common in insulinoma.

Wu|Hai-Yan|HY| Li|Nai-Shi|NS| Song|Yu-Li|YL| Bai|Chun-Mei|CM| Wang|Qiang|Q| Zhao|Yu-Pei|YP| Xiao|Yu|Y| Yu|Shuang|S| Li|Ming|M| Chen|Yuan-Jia|YJ|

Growth hormone secretagogue receptor (GHS-R)


The Simpson grading: defining the optimal threshold for gross total resection in meningioma surgery.

Abstract: Classification of the extent of resection into gross and subtotal resection (GTR and STR) after meningioma surgery is derived from the Simpson grading. Although utilized to indicate adjuvant treatment or study inclusion, conflicting definitions of STR in terms of designation of Simpson grade III resections exist. Correlations of Simpson grading and dichotomized scales (Simpson grades I-II vs ≥ III and grade I-III vs ≥ IV) with postoperative recurrence/progression were compared using Cox regression models. Predictive values were further compared by time-dependent receiver operating curve (tdROC) analyses. In 939 patients (28% males, 72% females) harboring WHO grade I (88%) and II/III (12%) meningiomas, Simpson grade I, II, III, IV, and V resections were achieved in 29%, 48%, 11%, 11%, and < .5%, respectively. Recurrence/progression was observed in 112 individuals (12%) and correlated with Simpson grading (p = .003). The risk of recurrence/progression was increased after STR in both dichotomized scales but higher when subsuming Simpson grade ≥ IV than grade ≥ III resections (HR: 2.49, 95%CI 1.50-4.12; p < .001 vs HR: 1.67, 95%CI 1.12-2.50; p = .012). tdROC analyses showed moderate predictive values for the Simpson grading and significantly (p < .05) lower values for both dichotomized scales. AUC values differed less between the Simpson grading and the dichotomization into grade I-III vs ≥ IV than grade I-II vs ≥ III resections. Dichotomization of the extent of resection is associated with a loss of the prognostic value. The value for the prediction of progression/recurrence is higher when dichotomizing into Simpson grade I-III vs ≥ IV than into grade I-II vs ≥ III resections.

Simpson grading
Meningiomas
Recurrence
Progression
Microsurgery


Constructing a Biomaterial to Simulate Extracellular Drug Transport in Solid Tumors.

Abstract: Designing an in vitro model of the tumor extracellular microenvironment to screen intratumoral drugs is an active challenge. As recent clinical successes of human intratumoral therapies stimulate research on intratumoral delivery, a need for a 3D tumor model to screen intratumoral therapies arises. When injecting the drug formulation directly into the tumor, the biophysics affecting intratumoral retention must be considered; especially for biologic therapies, which may be dominated by extracellular transport mechanisms. Fibrotic regions in solid tumors are typically rich in collagen I fibers. Using shear rheology, head and neck tumors with higher collagen density show a higher stiffness. Similarly, the stiffness of the hyaluronic acid (HA) hydrogel models is increased by adding collagen fibers to model the bulk biomechanical properties of solid tumors. HA hydrogels are then used as intratumoral injection site simulators to model in vitro the retention of glatiramer acetate (GA) and polyethylene glycol (PEG) administered intratumorally. Both compounds are also injected in murine tumors and retention is studied ex vivo for comparison. Retention of GA in the hydrogels is significantly longer than PEG, analogous to the solid tumors, suggesting the utility of HA hydrogels with collagen I fibers for screening extracellular drug transport after intratumoral administration.

D023041:Xenograft Model Antitumor Assays

intratumoral therapy
hydrogels
injection site simulator
drug delivery
intratumoral drug transport


Role of ASIC1a in Aβ-induced synaptic alterations in the hippocampus.

Abstract: Acid-sensing ion channels (ASICs) are widely expressed in the mammalian central nervous system where they play a key role in synaptic transmission and in specific forms of memory. On the other hand, ASICs can be persistently active under pathological conditions contributing to neuronal damage in ischemic stroke, brain trauma, epilepsy and Parkinson's disease. However, to date no experimental evidence has linked ASICs to Alzheimer's disease (AD). Aim of the present work was to investigate, in CA1 pyramidal neurons, the possible involvement of ASIC1a in the Aβ-mediated effect on metabotropic glutamate (mGlu) receptor dependent transmission. We found that, in slices pretreated with Aβ, the pharmacological blockade of ASIC1a restored the increased intrinsic excitability following group I mGlu receptor activation. This suggests that, under certain conditions, ASIC1a might further contribute to the Aβ-related depolarizing response. We have recently demonstrated that ASIC1a is also involved long-term depression (LTD) induced either by low-frequency stimulation or by application of the group I mGlu receptor agonist DHPG. Here, we have shown that psalmotoxin-1, a selective blocker of ASIC1a, rescued the DHPG-LTD facilitation associated with genetic and non-genetic models of AD. Overall, these results suggest that a functional coupling between ASIC1a and mGlu receptors occurs and might contribute to the synaptic alterations associated with AD.

ASIC1a
Hippocampus
Alzheimer's disease
Long-term depression
Transgenic mice
β-Amyloid


TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease.

Abstract: Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV-producing macrophages with TPP1-encoding plasmid DNA (pDNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1-encoding pDNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV-TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV-TPP1 (≈70%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late-infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV-TPP1.

brain
Batten disease
EVs
drug delivery systems
lysosomal storage diseases


Multiblock metabolomics: An approach to elucidate whole-body metabolism with multiblock principal component analysis.

Abstract: Principal component analysis (PCA) is a useful tool for omics analysis to identify underlying factors and visualize relationships between biomarkers. However, this approach is limited in addressing life complexity and further improvement is required. This study aimed to develop a new approach that combines mass spectrometry-based metabolomics with multiblock PCA to elucidate the whole-body global metabolic network, thereby generating comparable metabolite maps to clarify the metabolic relationships among several organs. To evaluate the newly developed method, Zucker diabetic fatty (ZDF) rats (n = 6) were used as type 2 diabetic models and Sprague Dawley (SD) rats (n = 6) as controls. Metabolites in the heart, kidney, and liver were analyzed by capillary electrophoresis and liquid chromatography mass spectrometry, respectively, and the detected metabolites were analyzed by multiblock PCA. More than 300 metabolites were detected in the heart, kidney, and liver. When the metabolites obtained from the three organs were analyzed with multiblock PCA, the score and loading maps obtained were highly synchronized and their metabolism patterns were visually comparable. A significant finding in this study was the different expression patterns in lipid metabolism among the three organs; notably triacylglycerols with polyunsaturated fatty acids or less unsaturated fatty acids showed specific accumulation patterns depending on the organs.

Tanabe|Kazuhiro|K| Hayashi|Chihiro|C| Katahira|Tomoko|T| Sasaki|Katsuhiko|K| Igami|Ko|K|

CE/MS, capillary electrophoresis mass spectrometry

GC/MS, gas chromatography mass spectrometry

LC/MS, liquid chromatography mass spectrometry

PPAR, peroxisome proliferator-activated receptor

TCA, tricarboxylic acid. CoA, coenzyme A

UPLC, ultra-performance liquid chromatography


Backbone and side chain assignments of human cell cycle regulatory protein S-phase kinase-associated protein 1.

Abstract: Ubiquitination of proteins is required to regulate several cellular mechanisms in cells. Skp1-Cullin-1-F-box (SCF), the largest family of the RING E3 ligases, recognizes and carries out the poly-ubiquitination of many substrate proteins. SCF E3 ligase is a multi-component protein complex, and the human S-phase kinase-associated protein 1 (Skp1) is the adapter protein, which binds and presents the substrate binding protein F-box (FBP) to the rest of the E3 ligase. Several crystallographic studies have solved the partial structure of Skp1 in complex with various FBPs, but there is no structure of standalone Skp1. Understanding the conformational and structural properties of Skp1 with and without FBPs is required to understand the complete mechanism of poly-ubiquitination. Here, we report ~90 % backbone and 64 % side chain (1)H, (13)C, (15)N assignments of Skp1 protein using various double and triple resonance NMR experiments.

Kachariya|Nitin Nathubhai|NN|
Dantu|Sarath Chandra|SC|
Kumar|Ashutosh|A|

D019906:Nuclear Magnetic Resonance, Biomolecular

Ubiquitination
SCF E3 ligase
Adapter protein
F-box protein


External validation of a model to predict women most at risk of postpartum venous thromboembolism: Maternity clot risk.

Abstract:
INTRODUCTION
Venous thromboembolism (VTE) is the leading cause of direct maternal mortality in high-income countries. We previously developed a risk prediction score for postpartum venous thromboembolism (VTE) in women without a previous VTE. In this paper, we provide further external validation and assess its performance across various groups of postpartum women from England.

MATERIALS AND METHODS
Cohort study using primary and secondary care data covering England. We used data from QResearch comprising women with pregnancies ending in live birth or stillbirth recoded in Hospital Episodes Statistics between 2004 and 2015. Outcome was VTE in the 6 weeks postpartum. Our predictor variables included sociodemographic and lifestyle characteristics, pre-existing comorbidities, and pregnancy and delivery characteristics.

RESULTS
Among 535,583 women with 700,185 deliveries, 549 VTE events were recorded (absolute risk of 7.8 VTE events per 10,000 deliveries). When we compared predicted probabilities of VTE for each woman from the original model with actual VTE events, we obtained a C-statistic of 0.67 (95% CI 0.65 to 0.70). However, our model slightly over-predicted VTE risk for the higher risk women (calibration slope = 0.84; 95% CI 0.74 to 0.94). Performance was similar across groups defined by calendar time, socioeconomic status, age group and geographical area. The score performed comparably with the existing algorithm used by the UK Royal College of Obstetrician and Gynaecologists.

CONCLUSIONS
Our model enables flexibility in setting new treatment thresholds. Adopting it in clinical practice may help optimise use of low-molecular-weight heparin postpartum to maximise health gain by better targeting of high-risk groups.

Ban|Lu|L|
Abdul Sultan|Alyshah|A|
West|Joe|J|
Tata|Laila J|LJ|
Riley|Richard D|RD|
Nelson-Piercy|Catherine|C|
Grainge|Matthew J|MJ|

Venous thromboembolism
Risk prediction score
Cohort study
Childbirth
Electronic health data
Thromboprophylaxis


Gene expression changes in rat brain after short and long exposures to particulate matter in Los Angeles basin air: Comparison with human brain tumors.

Abstract: Air pollution negatively impacts pulmonary, cardiovascular, and central nervous systems. Although its influence on brain cancer is unclear, toxic pollutants can cause blood-brain barrier disruption, enabling them to reach the brain and cause alterations leading to tumor development. By gene microarray analysis validated by quantitative RT-PCR and immunostaining we examined whether rat (n=104) inhalation exposure to air pollution particulate matter (PM) resulted in brain molecular changes similar to those associated with human brain tumors. Global brain gene expression was analyzed after exposure to PM (coarse, 2.5-10μm; fine, <2.5μm; or ultrafine, <0.15μm) and purified air for different times, short (0.5, 1, and 3 months) and chronic (10 months), for 5h per day, four days per week. Expression of select gene products was also studied in human brain (n=7) and in tumors (n=83). Arc/Arg3.1 and Rac1 genes, and their protein products were selected for further examination. Arc was elevated upon two-week to three-month exposure to coarse PM and declined after 10-month exposure. Rac1 was significantly elevated upon 10-month coarse PM exposure. On human brain tumor sections, Arc was expressed in benign meningiomas and low-grade gliomas but was much lower in high-grade tumors. Conversely, Rac1 was elevated in high-grade vs. low-grade gliomas. Arc is thus associated with early brain changes and low-grade tumors, whereas Rac1 is associated with long-term PM exposure and highly aggressive tumors. In summary, exposure to air PM leads to distinct changes in rodent brain gene expression similar to those observed in human brain tumors.

Ljubimova|Julia Y|JY|
Kleinman|Michael T|MT|
Karabalin|Natalya M|NM|
Inoue|Satoshi|S|
Konda|Bindu|B|
Gangalum|Pallavi|P|
Markman|Janet L|JL|
Ljubimov|Alexander V|AV|
Black|Keith L|KL|

D020411:Oligonucleotide Array Sequence Analysis

D060888:Real-Time Polymerase Chain Reaction

Brain tumor
Gene microarray
Arc/Arg3.1
Rac1
Air pollution particles
Chronic exposure


Her2 Expression in Circulating Tumor Cells Is Associated with Poor Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer.

Abstract: HER2-dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through ligand-independent mechanisms. From 41 mCRPC patients (including 31 treated with Androgen Receptor Signaling Inhibitors [ARSI]), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a multiplexed assay for HER2 and AR-V7 mRNA expression. Then, we evaluated the impact of HER2 expression on PSA-response, Progression Free Survival (PFS) and Overall Survival (OS). HER2 expression was detected in CTCs of 26 patients (63%). Although PSA response was similar regardless of HER2 status, patients with HER2 positive CTCs had shorter PSA-PFS (median: 6.2 months versus 13.0 months, p = 0.034) and radiological-PFS (6.8 months versus 25.6 months, p = 0.022) than patients without HER2 expression. HER2 expression was also associated with a shorter OS (22.7 months versus not reached, p = 0.05). In patients treated with ARSI, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the detection of CTCs by an AdnaTest. We showed for the first time the poor prognostic value of HER2 expression in CTCs from patients with mCRPC. The therapeutic interest of targeting this actionable pathway remains to be explored.

Maillet|Denis|D| Allioli|Nathalie|N| Péron|Julien|J|0000-0002-1709-5152 Plesa|Adriana|A| Decaussin-Petrucci|Myriam|M| Tartas|Sophie|S| Sajous|Christophe|C|0000-0001-5725-0199 Ruffion|Alain|A| Crouzet|Sébastien|S|0000-0001-5812-6771 Freyer|Gilles|G| Vlaeminck-Guillem|Virginie|V|

androgen receptor signaling inhibitors (ARSI)

androgen receptor splice variant 7 (AR-V7)

metastatic castration resistant prostate cancer (mCRPC)


Internal rotation of the tibial component in total knee arthroplasty can lead to extension deficit.

Abstract:
PURPOSE
Stiffness is a common problem following total knee arthroplasty (TKA). Mal-rotated components have been claimed to be the major cause of pain and limited motion after TKA. The present study investigates whether intra-operative intentional malrotation of the tibial component would change in vivo kinematics. The hypothesis is excessive internal rotation of the tibial component would result in postoperative extension deficit.

METHODS
Thirty-one patients were enrolled in this study. After completing bony cuts and proper soft tissue balancing, the femoral and tibial trials were impacted and fixed using small pins. Lateral radiographs were used to measure and compare intraoperative full knee extension during normal and after intentional internal rotation of the tibial component. The extension deficit angles were also compared between the posterior stabilised (PS) and cruciate retaining (CR) implants.

RESULTS
For normal tibial component rotation, the median (interquartile range) extension deficit was 0° (4). The mean tibial trial intentional internal rotation was 21.2° (± 4.5). The median (interquartile range) extension deficit significantly increased to 6° (4) after tibial component internal rotation (p = 0.001). The use of PS spacers resulted in a significantly greater extension deficit after intentional internal rotation 9° (5) compared to that of the CR implant 1° (4) (p = 0.001).

CONCLUSION
Internal rotation of the tibial component in total knee arthroplasty can lead to postoperative extension deficit. This could be attributed to interference with "screw home" mechanism that requires full external rotation of the tibia on the femur. Consequently, this deficit may cause pain and knee stiffness following TKA.

LEVEL OF EVIDENCE
III.

Abdelnasser|Mohammad Kamal|MK|
Adi|Mohammad Muath|MM|
Elnaggar|Ahmed Aly|AA|
Tarabichi|Samih|S|

Internal rotation
Tibial component
Total knee arthroplasty
Extension deficit


Subscapular tumoral calcinosis in a toddler: case report.

Abstract: Tumoral calcinosis is uncommon in toddlers, and rare within the subscapular area. Although typically benign, tumoral calcinosis is often incorrectly diagnosed prior to biopsy. We present a case of subscapular tumoral calcinosis in a 16-month old girl and discuss the radiological findings on X-ray, ultrasound, computed tomography and magnetic resonance imaging, including the first description of T1-weighted post contrast imaging, which demonstrate the fibrotic components of tumoral calcinosis.

Zvaigzne|Cheryl G|CG|
Patton|David J|DJ|
Kaur|Harmeet|H|
Trevenen|Cynthia L|CL|
Kaura|Deepak|D|

Tumoral Calcinosis
Case Report
Computed Tomography
Magnetic Resonance Imaging


A Statistical Model of Fibre Distribution in a Steel Fibre Reinforced Concrete.

Abstract: The aim of the research was to create a model of steel fibre distribution in a Steel Fibre Reinforced Concrete space using statistical probability means. The model was created in order to better understand the behaviour of the composite under operating conditions. Four statistical distributions (Beta, Kumaraswamy, Three Parameter Beta and Generalised Transmuted Kumaraswamy) were examined to find the distribution that best described fibre settling phenomenon caused by manufacturing process conditions. In the next stage the chosen statistical distribution was adapted to create the model of steel fibre distribution in a Steel Fibre Reinforced Concrete space. The model took into account technological conditions such as vibrating time and properties such as consistency of the tested concrete. The model showed a good agreement with the real fibre distribution.

model
fibre
distribution
statistical probability
SFRC


Review of the existing maximum residue levels for tembotrione according to Article 12 of Regulation (EC) No 396/2005.

Abstract: According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance tembotrione. To assess the occurrence of tembotrione residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EU) No 188/2011 as well as the import tolerances and European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

|||
Brancato|Alba|A|
Brocca|Daniela|D|
Carrasco Cabrera|Luis|L|
De Lentdecker|Chloe|C|
Erdos|Zoltan|Z|
Ferreira|Lucien|L|
Greco|Luna|L|
Jarrah|Samira|S|
Kardassi|Dimitra|D|
Leuschner|Renata|R|
Lostia|Alfonso|A|
Lythgo|Christopher|C|
Medina|Paula|P|
Miron|Ileana|I|
Molnar|Tunde|T|
Pedersen|Ragnor|R|
Reich|Hermine|H|
Sacchi|Angela|A|
Santos|Miguel|M|
Stanek|Alois|A|
Sturma|Juergen|J|
Tarazona|Jose|J|
Theobald|Anne|A|
Vagenende|Benedicte|B|
Villamar-Bouza|Laura|L|

tembotrione
regulation (EC) No 396/2005
consumer risk assessment
MRL review
herbicide
triketone


Salvianolic Acid A Attenuates Endoplasmic Reticulum Stress and Protects Against Cholestasis-Induced Liver Fibrosis via the SIRT1/HSF1 Pathway.

Abstract: Background: Endoplasmic reticulum stress (ER stress) plays a critical role in the pathogenesis of liver fibrosis; thus, it can be a potential therapeutic target of fibrosis. However, the mechanism of ER stress regulation in fibrosis, particularly through sirtuin 1 (SIRT1), remains unclear. The objective of this study was to investigate the effect of SIRT1-mediated inhibition of ER stress in bile duct ligation (BDL)-induced liver fibrosis, and to explore the effect of salvianolic acid A (SalA) on BDL-induced liver fibrosis through SIRT1/heat shock factor 1 (HSF1) signaling. Materials and Methods: We explored the effects of SalA on liver fibrosis and ER stress in BDL-induced liver fibrosis in rats and the human hepatic stellate cell line LX2 cells. The LX2 cells were treated with 20 ng of platelet-derived growth factor-BB homodimer (PDGF-BB) for 24 h, and then incubated in the absence or presence of SalA (25 μM) for 24 h. Results: In vivo, SalA treatment alleviated BDL-induced liver injury and ER stress. Importantly, SalA treatment increased HSF1 expression and activity using a SIRT1-dependent mechanism. In LX2 cells, PDGF-BB induced ER stress and fibrosis were blocked by HSF1 overexpression. Furthermore, SIRT1 siRNA abrogated the SalA-mediated promotion of HSF1 deacetylation and expression, suggesting that SalA-mediated protection occurs by SIRT1 targeting HSF1 for deacetylation. Conclusion: This is the first study to identify the SIRT1/HSF1 pathway as a key therapeutic target for controlling BDL-induced liver fibrosis and to show that SalA confers protection against BDL- and PDGF-BB-induced hepatic fibrosis and ER stress through SIRT1-mediated HSF1 deacetylation.

Zhu|Jie|J| Wang|Ruiwen|R| Xu|Ting|T| Zhang|Shuai|S| Zhao|Yan|Y| Li|Zhenlu|Z| Wang|Chao|C| Zhou|Junjun|J| Gao|Dongyan|D| Hu|Yan|Y| Tian|Xiaofeng|X| Yao|Jihong|J|


Teachers' beliefs in inclusive education and the attributional responses toward students with and without specific learning difficulties.

Abstract: Teachers' beliefs in inclusive education can be influential toward the success of inclusive practices and also students' successes and failures within the classroom. Having a clear understanding and high expectations toward students with specific learning difficulties (SpLD) is important if these students are to reach their potential. This study examined 276 British primary and secondary teachers' perceptions toward inclusive education for all, and their causal attributions toward students with and without SpLD. The results show that teachers who believe that inclusive education is an effective way to teach all students, provide greater positive feedback, feel less frustrated, and hold lower expectations for future failure, in comparison to their colleagues with more negative inclusive educational beliefs. Teachers need to believe that inclusive education is an effective way to teach all students, and that they, as teachers are capable of managing this. However, they need to be provided with relevant systemic support.

inclusive education
specific learning difficulties
attribution theory


Bladder Transplantation of Amniotic Fluid Stem Cell may Ameliorate Bladder Dysfunction After Focal Cerebral Ischemia in Rat.

Abstract: The objective is to investigate whether human amniotic fluid stem cells (hAFSCs) grafting into the bladder may influence bladder functional and molecular changes in an animal stroke model. Female rats were divided into three groups: sham, middle cerebral artery occlusion (MCAO) alone, and MCAO plus 1 × 106 hAFSCs transplanting into bladder wall. Bladder function was analyzed by cystometry at days 3 and 10 after MCAO. The expressions of bladder nerve growth factor (NGF), M2-muscarinic, M3-muscarinic, and P2X1 receptors were measured by immunohistochemistry and real-time polymerase chain reaction. When compared with sham-operated group, MCAO alone rats had significant increase in residual volume and decrease in voided volume and intercontraction interval; however, these bladder dysfunctions were improved following hAFSCs transplantation. The immunoreactivities of NGF, M3, and P2X1 significantly decreased at days 3 and 10, but M2 increased at day 3 after MCAO. Following hAFSCs transplantation, the immunoreactivities of NGF and P2X1 significantly increased at day 3, and M2 increased at day 10 after MCAO. The mRNAs of NGF, M2, and M3 significantly increased at day 3, but NGF and M2 decreased at day 10 after MCAO. Following hAFSCs transplantation, there was significant decrease in M2 mRNA at day 3 and increase in P2X1 mRNA at days 3 and 10 after MCAO. Bladder dysfunction caused by MCAO can be improved by hAFSCs transplanting into bladder which may be related to the expressions of bladder NGF, and muscarinic and P2X1 receptors. Stem Cells Translational Medicine 2017;6:1227-1236.

Liang|Ching-Chung|CC|
Shaw|S W Steven|SW|
Huang|Yung-Hsin|YH|
Lin|Yi-Hao|YH|
Lee|Tsong-Hai|TH|

Bladder
Amniotic fluid stem cell
Stroke
Middle cerebral artery occlusion
Cystometry


Walking disabilities are associated with tenosynovitis at the metatarsophalangeal joints: A longitudinal MRI-study in early arthritis.

Abstract:
OBJECTIVES
The relationship between functional disability and MRI-inflammation has been studied for the hands, but has not been well established for the feet, even though walking-difficulties are common. Therefore we studied whether walking-difficulties were associated with MRI-inflammation at metatarsophalangeal(MTP)-joints in early arthritis patients, at diagnosis and during 24-months follow-up.

METHODS
532 consecutive patients presenting with early arthritis reported on presence and severity of walking-difficulties (HAQ-question 4a, scale 0-3), and underwent unilateral contrast-enhanced MRI of MTP(1-5)-joints at baseline. 107 patients had clinical and MRI-data at follow-up (4-, 12- and 24-months). MRI-inflammation (synovitis, tenosynovitis and osteitis) was scored in line with RAMRIS. At baseline the association of walking-disability with MRI-inflammation was assessed using regression. Longitudinally the association between a change in walking-disability with a change in MRI-inflammation was studied with linear mixed models.

RESULTS
At baseline, 81% patients with walking-disabilities had MRI-inflammation at MTP-joints, versus 68% without walking-disabilities (P<0.001). Total MRI-inflammation (i.e. the sum of tenosynovitis, synovitis and osteitis) was associated with severity of walking disability (β=0.023, P<0.001). Studying the MRI-features separately, tenosynovitis, synovitis and osteitis were all univariable associated with severity of walking-disability (P<0.001, P<0.001 and P=0.014 respectively). Multivariable, the association was strongest for tenosynovitis. During follow-up a decrease in MTP-inflammation was associated with a decrease in walking-disability (β=0.029, P=0.001): in multivariable analyses only tenosynovitis was independently associated (β=0.073, P=0.049).

CONCLUSION
Of the different inflamed tissues in MTP-joints, predominantly MRI-detected tenosynovitis was associated with walking-disabilities. Likewise a reduction in tenosynovitis related to a decrease in walking-disabilities. This increases our understanding of the involvement of tenosynovitis in walking-disabilities in early arthritis.

disability
tenosynovitis
arthritis
MRI
synovitis
osteitis
foot
inflammation
rheumatoid arthritis


Spatio-temporal modelling as a way to reconstruct patterns of past human activities.

Abstract: This paper examines the possibilities of creating quantified models of past human activities in both time and space. The study area lies in the southeastern Czech Republic and western Slovakia. The spatio-temporal model of behavioural categories was calculated with the help of Monte Carlo simulations and statistical testing. One of the main advantages of our approach is that it admits the probabilistic nature of input data, quantifies them and provides probabilistic results comparable with other proxies. It also presents a less biased way of how archaeological data from regions and periods with low numbers of 14C datings can be incorporated into models of past population dynamics.

Kolář|Jan|J| Macek|Martin|M| Tkáč|Peter|P| Szabó|Péter|P|

modelling
past human activities
Monte Carlo simulation
Central Europe
chronology
prehistoric population dynamics
temporal uncertainty


Predictors of Booster Engagement Following a Web-Based Brief Intervention for Alcohol Misuse Among National Guard Members: Secondary Analysis of a Randomized Controlled Trial.

Abstract:
BACKGROUND
Alcohol misuse is a major health concern among military members. Reserve component members face unique barriers as they live off base with limited access to behavioral health services. Web and app-based brief interventions are a promising means to improve access to treatment for those who misuse alcohol, with the use of booster sessions to enhance effectiveness, solidify gains, and reinforce changes. However, little is known about who will engage in booster sessions.

OBJECTIVE
This study aims to evaluate booster engagement across booster delivery modalities (Web and Peer) and identify participant-specific factors associated with booster session engagement.

METHODS
Following a brief web-based alcohol misuse intervention in National Guard members (N=739), we examined engagement in a series of three booster sessions. Using unadjusted and adjusted models, demographic and clinical characteristics that may serve as predictors of booster session engagement were examined across the 2 arms of the trial with different types of booster sessions: peer-delivered (N=245) and web-delivered (N=246).

RESULTS
Booster session completion was greater for Peer than Web Booster sessions, with 142 (58%) service members in the Peer Booster arm completing all three boosters compared with only 108 (44%) of participants in the Web Booster arm (χ23=10.3; P=.006). In a model in which the 2 groups were combined, socioeconomic factors predicted booster engagement. In separate models, the demographic and clinical predictors of booster engagement varied between the 2 delivery modalities.

CONCLUSIONS
The use of peer-delivered boosters, especially among subsets of reserve members at risk of lack of engagement, may foster greater uptake and improve treatment outcomes.

TRIAL REGISTRATION
ClinicalTrials.gov NCT02181283; https://clinicaltrials.gov/ct2/show/NCT02181283.

boosters
engagement
brief intervention
National Guard
alcohol use


Neuronal ceroid lipofuscinosis with cardiac involvement.

Abstract: Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders with clinical presentation predominantly in the childhood. The NCLs represent lysosomal storage disorders characterized by the accumulation of autofluorescent lipopigment storage material. The most common clinical features include development failure, psychomotor regression, seizures, and progressive loss of vision. We present a case of neuronal ceroid lipofuscinosis with cardiac involvement diagnosed post-mortem in a 9,5-year-old boy, whose clinical symptomatology comprised partial epilepsy, psychomotor decline and sinus bradycardia. In contrast to ventricular hypertrophy, being more frequently associated with NCLs, we discovered cardiac atrophy. Histologic examination of the heart revealed not only the lipofuscinosis affecting cardiac conducting cells and cardiomyocytes, but also basophilic degeneration of myocardium.

Iannaccone Farkašová|Silvia|S|
Vasovčák|Peter|P|
Sopková|Dorota|D|
Pisarčíková|Mária|M|
Švajdler|Marián|M|
Fröhlichová|Lucia|L|
Mistríková|Lucia|L|
Farkaš|Daniel|D|

Neuronal ceroid lipofuscinosis
Bradycardia
Basophilic degeneration of myocardium
NCL7/MFSD8


Clinical study of advanced glycation end products in egyptian diabetic obese and non-obese patients.

Abstract: Advanced glycation end products (AGEs) are complex, heterogenous molecules generated by glycation and oxidation of proteins in vivo, which are thought to markedly increase in diabetic patients. One of the recently identified AGEs is carboxy methyl lysine (CML), which is the main ligand of receptors for advanced glycation end products (RAGE). The present study aimed to assess the effect of obesity on such pathways in presence and absence of Type 2 diabetes mellitus. CML, soluble receptors for advanced glycation end products (sRAGE), HbA1C, lipid profile, liver function tests and kidney function tests were determined in 29 diabetic obese, 29 diabetic non-obese, 15 non-diabetic obese and 15 non-diabetic non-obese subjects. The study compared obese and non-obese subjects in presence and absence of type 2 diabetes. The results showed a significant increase in CML and a significant decrease in sRAGE in each of the diabetic obese group when compared with the diabetic non-obese group and the non-diabetic obese group when compared with the non-diabetic non-obese group. A significant positive correlation was found between CML and markers of obesity (body mass index and waist/hip ratio). These results suggest that obesity can increase CML independent of diabetes and support the reports that CML could be generated from both sugars and lipids. The present study suggests that treatment using glycation inhibitors like aminoguanidine or recombinant sRAGE will not only retard the diabetic complications, but may also have a prophylactic effect.

Amin|Mohamed N|MN|
Mosa|Amany A|AA|
El-Shishtawy|Mamdouh M|MM|


Association of autonomic symptoms with presynaptic striatal dopamine depletion in drug-naive Parkinson's disease: An analysis of the PPMI data.

Abstract: While the involvement of the central and peripheral autonomic networks is thought to play an integral role in the development of autonomic symptoms in Parkinson's disease (PD), there is little evidence for an association between autonomic symptoms and striatal dopaminergic depletion. We compared dopamine transporter activity in striatal subregions with various autonomic symptoms covered by the SCOPA-AUT domains including gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual symptoms in 418 untreated patients with PD. We found evidence for a dopaminergic association with only urinary symptoms. Moreover, dopaminergic denervation in the putamen but not in the caudate may underlie these symptoms.

D001342:Autonomic Nervous System Diseases

D050483:Dopamine Plasma Membrane Transport Proteins

Autonomic
Striatal
Parkinson's disease
Dopamine transporter
DAT


Is the Moon the future of infrared astronomy?

Abstract: Infrared astronomy, particularly in spectroscopy, could benefit in a decisive way from an implementation of telescopes on the Moon since the largest telescopes on Earth are practically limited to 40 m and in space to 10 m. On the Moon, a collector larger than on Earth becomes conceivable, thanks to the low gravity and the absence of wind, in having the advantages of space. Passively cooled in the bottom of a permanently shadowed crater at the northern or the southern pole, it could reach unprecedented spectral sensitivity on a large part of the infrared domain, making possible spectral analysis of the most primitive galaxies and of the terrestrial exoplanet atmospheres. A project aiming at the detection of the weak cosmic microwave background spectral distortions is also presented. Several identical 1.5 m cryo-cooled telescopes at 2.5 K to fit in a launcher, with an imaging Fourier transform spectrometer in each unit, deposited in a cold crater and pointing in the same direction in lunar survey mode, would build for this fundamental goal the equivalent of a large telescope at an extremely low temperature. Last, the feasibility of these projects is discussed. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades'.

CMB spectral distortions
Fourier spectrometer
extremely large telescopes
infrared spectroscopy