Systematic Review: The Measurement Properties of the Children's Depression Rating Scale-Revised in Adolescents With Major Depressive Disorder.

Abstract:
OBJECTIVE
To systematically appraise existing evidence of the measurement properties of the Children's Depression Rating Scale-Revised (CDRS-R) in adolescents with major depressive disorder (MDD). The CDRS-R is the most commonly used scale in adolescent depression research, yet was originally designed for use in children 6 to 12 years old.

METHOD
Seven databases were searched for studies that evaluated the measurement properties of the CDRS-R in adolescents (ages 12-18 years). Of 65 studies screened by full-text, 6 were included. Measurement properties were appraised using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. The COSMIN minimum requirements for recommending the use of an outcome measurement instrument are (1) evidence for sufficient content validity (any level of evidence), and (2) at least low-quality evidence for sufficient internal consistency.

RESULTS
Four studies assessed an English-language version of the CDRS-R; the other 2 assessed German and Korean versions, respectively. No study assessed content validity, cross-cultural validity/measurement invariance, or measurement error of the CDRS-R in adolescents with MDD. Low-quality evidence was found for sufficient construct validity (n = 4 studies) and responsiveness (n = 2 studies) assessed via comparator instruments. Very-low-quality evidence was found for sufficient interrater reliability (n = 2 studies). The results for structural validity (n = 3 studies) and internal consistency (n = 5 studies) were inconclusive.

CONCLUSION
It remains unclear whether the CDRS-R appropriately measures depressive symptom severity in adolescent MDD. Before use of the CDRS-R in adolescent MDD research can be recommended, evidence of sufficient psychometric properties in adolescents with MDD is needed.

Stallwood|Emma|E|
Monsour|Andrea|A|
Rodrigues|Craig|C|
Monga|Suneeta|S|
Terwee|Caroline|C|
Offringa|Martin|M|
Butcher|Nancy J|NJ|

D011569:Psychiatric Status Rating Scales

Children’s Depression Rating Scale−Revised


Do craniopharyngioma molecular signatures correlate with clinical characteristics?

Abstract: OBJECTIVE Exome sequencing studies have recently demonstrated that papillary craniopharyngiomas (PCPs) and adamantinomatous craniopharyngiomas (ACPs) have distinct genetic origins, each primarily driven by mutually exclusive alterations: either BRAF ( V600E), observed in 95% of PCPs, or CTNNB1, observed in 75%-96% of ACPs. How the presence of these molecular signatures, or their absence, correlates with clinical, radiographic, and outcome variables is unknown. METHODS The pathology records for patients who underwent surgery for craniopharyngiomas between May 2000 and March 2015 at Weill Cornell Medical College were reviewed. Craniopharyngiomas were identified and classified as PCP or ACP. Patients were placed into 1 of 3 groups based on their genomic mutations: BRAF mutation only, CTNNB1 mutation only, and tumors with neither of these mutations detected (not detected [ND]). Demographic, radiological, and clinical variables were collected, and their correlation with each genomic group was tested. RESULTS Histology correlated strongly with mutation group. All BRAF tumors with mutations were PCPs, and all CTNNB1 with mutations and ND tumors were ACPs. Preoperative and postoperative clinical symptoms and radiographic features did not correlate with any mutation group. There was a statistically significant relationship (p = 0.0323) between the age group (pediatric vs adult) and the mutation groups. The ND group tumors were more likely to involve the sella (p = 0.0065). CONCLUSIONS The mutation signature in craniopharyngioma is highly predictive of histology. The subgroup of tumors in which these 2 mutations are not detected is more likely to occur in children, be located in the sella, and be of ACP histology.

Omay|Sacit Bulent|SB|
Chen|Yu-Ning|YN|
Almeida|Joao Paulo|JP|
Ruiz-Treviño|Armando Saul|AS|
Boockvar|John A|JA|
Stieg|Philip E|PE|
Greenfield|Jeffrey P|JP|
Souweidane|Mark M|MM|
Kacker|Ashutosh|A|
Pisapia|David J|DJ|
Anand|Vijay K|VK|
Schwartz|Theodore H|TH|

ACP = adamantinomatous craniopharyngioma


Developmental milestones across the programmatic life cycle: implementing the CDC's Colorectal Cancer Screening Demonstration Program.

Abstract:
BACKGROUND
In 2005 through 2009, the Centers for Disease Control and Prevention (CDC) funded 5 sites to implement a colorectal cancer screening program for uninsured, low-income populations. These 5 sites composed a demonstration project intended to explore the feasibility of establishing a national colorectal cancer screening program through various service delivery models.

METHODS
A longitudinal, multiple case study was conducted to understand and document program implementation processes. Using metaphor as a qualitative analytic technique, evaluators identified stages of maturation across the programmatic life cycle.

RESULTS
Analysis rendered a working theory of program development during screening implementation. In early stages, program staff built relationships with CDC and local partners around screening readiness, faced real-world challenges putting program policies into practice, revised initial program designs, and developed new professional skills. Midterm implementation was defined by establishing program cohesiveness and expanding programmatic reach. In later stages of implementation, staff focused on sustainability and formal program closeout, which prompted reflection about personal and programmatic accomplishments.

CONCLUSIONS
Demonstration sites evolved through common developmental stages during screening implementation. Findings elucidate ways to target technical assistance to more efficiently move programs along their maturation trajectory. In practical terms, the time and cost associated with guiding a program to maturity may be potentially shortened to maximize return on investment for both organizations and clients receiving service benefits.

Glover-Kudon|Rebecca|R|
DeGroff|Amy|A|
Rohan|Elizabeth A|EA|
Preissle|Judith|J|
Boehm|Jennifer E|JE|

D002487:Centers for Disease Control and Prevention, U.S.

colorectal cancer screening
multiple case study
program implementation
program development
technical assistance
program evaluation
qualitative methods


Sexually dimorphic expression of the sex chromosome-linked genes cntfa and pdlim3a in the medaka brain.

Abstract: In vertebrates, sex differences in the brain have been attributed to differences in gonadal hormone secretion; however, recent evidence in mammals and birds shows that sex chromosome-linked genes, independent of gonadal hormones, also mediate sex differences in the brain. In this study, we searched for genes that were differentially expressed between the sexes in the brain of a teleost fish, medaka (Oryzias latipes), and identified two sex chromosome genes with male-biased expression, cntfa (encoding ciliary neurotrophic factor a) and pdlim3a (encoding PDZ and LIM domain 3 a). These genes were found to be located 3-4 Mb from and on opposite sides of the Y chromosome-specific region containing the sex-determining gene (the medaka X and Y chromosomes are genetically identical, differing only in this region). The male-biased expression of both genes was evident prior to the onset of sexual maturity. Sex-reversed XY females, as well as wild-type XY males, had more pronounced expression of these genes than XX males and XX females, indicating that the Y allele confers higher expression than the X allele for both genes. In addition, their expression was affected to some extent by sex steroid hormones, thereby possibly serving as focal points of the crosstalk between the genetic and hormonal pathways underlying brain sex differences. Given that sex chromosomes of lower vertebrates, including teleost fish, have evolved independently in different genera or species, sex chromosome genes with sexually dimorphic expression in the brain may contribute to genus- or species-specific sex differences in a variety of traits.

Maehiro|Sayaka|S| Takeuchi|Akio|A| Yamashita|Junpei|J| Hiraki|Towako|T| Kawabata|Yukika|Y| Nakasone|Kiyoshi|K| Hosono|Kohei|K| Usami|Takeshi|T| Paul-Prasanth|Bindhu|B| Nagahama|Yoshitaka|Y| Oka|Yoshitaka|Y| Okubo|Kataaki|K|

D020411:Oligonucleotide Array Sequence Analysis

D020133:Reverse Transcriptase Polymerase Chain Reaction

Medaka
Brain
Sex differences
Sex chromosome
cntf
pdlim3


Oral Microbiome in Dogs and Cats: Dysbiosis and the Utility of Antimicrobial Therapy in the Treatment of Periodontal Disease.

Abstract: Advances in gene sequence technology and data analysis have enabled the detection and taxonomic identification of microorganisms in vivo based on their unique RNA or DNA sequences. Standard culture techniques can only detect those organisms that readily grow on artificial media in vitro. Culture-independent technology has been used to provide a more accurate assessment of the richness (total number of species) and diversity (relative abundance of each species) of microorganisms present in a prescribed location. The microbiome has been defined as the genes and genomes of all microbial inhabitants within a defined environment. Microorganisms within a microbiome interact with each other as well as with the host. A microbiome is dynamic and may change over time as conditions within the defined environment become altered. In oral health, neither gingivitis nor periodontitis is present, and the host and microbiome coexist symbiotically without evoking an inflammatory response. The circumstances that cause a shift from immune tolerance to a proinflammatory response remain unknown, and a unified, all-encompassing hypothesis to explain how and why periodontal disease develops has yet to be described. The purpose of this review is to clarify the current understanding of the role played by the oral microbiome in dogs and cats, describe how the microbiome changes in periodontal disease, and offer guidance on the utility of systemic antimicrobial agents in the treatment of periodontitis in companion animals.

Periodontitis
Antibiotic therapy
Canine oral microbiome
Feline oral microbiome


Exploration of social factors associated to maternal deaths due to haemorrhage and convulsions: Analysis of 28 social autopsies in rural Bangladesh.

Abstract:
BACKGROUND
Social autopsy is an innovative approach to explore social barriers and factors associated to a death in the community. The process also sensitize the community people to avert future deaths. Social autopsy has been introduced in maternal deaths in Bangladesh first time in 2010. This study is to identify the social factors in the rural community associated to maternal deaths. It also looks at how the community responses in social autopsy intervention to prevent future maternal deaths.

METHODS
The study was conducted in the Thakurgaon district of Bangladesh in 2010. We have purposively selected 28 social autopsy cases of which maternal deaths occurred due to either haemorrhage or due to convulsions. The autopsy was conducted by the Government health and family planning first line field supervisors in rural community. Family members and neighbours of the deceased participated in each autopsy and provided their comments and responses.

RESULTS
A number of social factors including delivery conducted by the untrained birth attendant or family members, delays in understanding about maternal complications, delays in decision making to transfer the mother, lack of proper knowledge, education and traditional myth influences the maternal deaths. The community identified their own problems, shared within them and decide upon rectify themselves for future death prevention.

CONCLUSIONS
Social autopsy is a useful tools to identify social community within the community by discussing the factors that took place during a maternal death. The process supports villagers to think and change their behavioural patterns and commit towards preventing such deaths in the future.

Biswas|Animesh|A|
Halim|M A|MA|
Dalal|Koustuv|K|
Rahman|Fazlur|F|

Maternal death
Social autopsy
Bangladesh
Rural community
Death review


Mechanism of nonthermal induction of apoptosis by high-intensity focused electromagnetic procedure: Biochemical investigation in a porcine model.

Abstract:
BACKGROUND
Multiple studies have reported adipose tissue reduction after the application of the High-Intensity Focused Electromagnetic (HIFEM) field technology, yet cellular level evidence of the mechanisms has remained scarce.

OBJECTIVES
This study aims to verify or refute previous single-study histological evidence and further investigates the proposed mechanism of apoptotic induction.

METHODS
The thigh of two Large White pigs was treated with HIFEM for 30 minutes. Fat punch biopsies were collected from the application area before, immediately after, and 8 hours post-treatment. Control samples were taken from the abdomen immediately after and 8 hours post-treatment. Samples were analyzed for pro-apoptotic DNA markers (BAX, BCL-2, TXNIP, MMP9, TNF-α), the levels of free fatty acids (FFA), and the pH levels of the adipose tissue.

RESULTS
The levels of FFA in the treated adipose tissue increased on average by 127.1% immediately post-treatment and by 134.1% 8 hours post-treatment, indicating a rapid breakdown of lipids. The average recorded adipose pH changed from 7.30 ± 0.12 at baseline to 6.60 ± 0.07 immediately post-treatment (P = .001) and to 7.19 ± 0.12 8 hours post-treatment. The levels of BAX, TXNIP, MMP9, and TNF-α increased post-treatment while BCL-2 decreased. Control samples showed constant levels of pH and pro-apoptotic markers. The FFAs in the control samples were increased by 41.6%-51.4%.

CONCLUSION
The changes in the levels of the pro-apoptotic markers conformed to the previously reported elevated fat apoptosis post-HIFEM treatments. These effects were accompanied by an increase in FFA levels, and by reduced pH levels, due to the increased acidity in the adipose tissue. Further research is required to explore the potential of nonthermal induction of apoptosis.

D017667:Adipocytes
D000818:Animals
D017209:Apoptosis
D000073880:Body Contouring
D005230:Fatty Acids, Nonesterified
D006863:Hydrogen-Ion Concentration
D055909:Magnetic Field Therapy
D023421:Models, Animal
D050507:Subcutaneous Fat, Abdominal
D034421:Sus scrofa

high-intensity focused electromagnetic field technology


Smoking, obesity, and their co-occurrence in the U.S. military veterans: results from the national health and resilience in veterans study.

Abstract:
BACKGROUND
Smoking and obesity are major public health concerns, though little is known about the mental and physical health burden of co-occurring obesity and smoking.

METHODS
Using a nationally representative sample of U.S. military veterans, we examined the prevalence of mental and physical co-morbidities, physical and mental functioning, and quality of life between obese only; smoking only; and obese smokers.

RESULTS
Among current smokers, 31.7% were obese; among obese veterans, 16.4% were current smokers; and in the total sample, 5.4% were obese and current smokers. Relative to the obese-only group, obese smokers were more likely to be younger, male, non-white, non-married, unemployed and VA-served, and have lower household incomes. These also reported higher levels of perceived stress and trauma and were more likely to endorsed current suicidal ideation and lifetime suicide attempts (odds ratio [OR]=2.0), medical (2.3<=OR<=3.9) and psychiatric (1.5<=OR<=2.9) comorbidities, and lower overall health status and quality of life. Compared to the smoking-only group, obese smokers were more likely to endorse current suicidal ideation (OR=2.0) and nicotine dependence (OR=1.5), and reported poorer physical health and overall quality of life. Analyses were adjusted for sociodemographic and military characteristics.

LIMITATIONS
The cross-sectional study design precludes causal inference.

CONCLUSIONS
These findings suggest that co-occurring obesity and smoking is associated with substantial mental and physical health burden in U.S. veterans. Collectively, they underscore the importance of multicomponent interventions targeting, obesity, smoking, and co-occurring issues, such as trauma and internalizing disorders, in this population.

Stefanovics|Elina A|EA|
Potenza|Marc N|MN|
Pietrzak|Robert H|RH|


Evidence for West Nile virus spillover into the squirrel population in Atlanta, Georgia.

Abstract:
BACKGROUND
In the United States, spillover of West Nile virus (WNV) into wild mammal populations has been reported since the introduction of the virus into the New World in 1999. Eastern gray squirrels (Sciurus carolinensis) exhibit a high seroprevalence for WNV in urban settings where high virus circulation and human spillover have been reported. In Atlanta, Georgia, human cases of WNV are uncommon despite high infection rates in birds and mosquitoes. In this study, we evaluated WNV exposure of eastern gray squirrels in a WNV hot spot in Atlanta.

MATERIALS AND METHODS
Gray squirrels were live-trapped in Grant Park, Atlanta, during July-October, 2012, and a census was conducted to estimate squirrel density in the study site. Sera from trapped animals were tested for circulating virus-by-virus isolation in cell culture and for WNV-specific antibodies by enzyme-linked immunosorbent assay and plaque reduction neutralization test. Mosquitoes were collected at the same location and tested for virus isolation.

RESULTS
Among the 69 collected squirrels, 25 (36.2%) tested positive for WNV antibodies, although none were viremic. Seroprevalence was lower in juveniles (18.8%) than in adults (37.5%), but this difference was not statistically significant. Gender and squirrel density had no effect on seroprevalence. Seasonality of squirrel seroprevalence and of mosquito infection were significantly associated, both peaking in August. No difference in squirrel exposure was detected across the collection sites.

CONCLUSIONS
We report a high degree of WNV exposure in squirrels in Grant Park that was correlated with seasonality of mosquito infection. The detection of antibodies in juveniles suggests that circulation of WNV in the surveyed population is ongoing. Eastern gray squirrels may be suitable indicators for virus amplification and for risk of human spillover on a local scale in urban settings.

Bisanzio|Donal|D|
McMillan|Joseph R|JR|
Barreto|Josafá Gonçalves|JG|
Blitvich|Bradley J|BJ|
Mead|Daniel G|DG|
O'Connor|Josh|J|
Kitron|Uriel|U|

West Nile Virus
Gray squirrels
Arbovirus(es)
Culex
Rodents
Zoonosis


Low-Profile Dual Small Plate Fixation Is Biomechanically Similar to Larger Superior or Anteroinferior Single Plate Fixation of Midshaft Clavicle Fractures.

Abstract:
BACKGROUND
Limited biomechanical data exist for dual small plate fixation of midshaft clavicle fractures, and no prior study has concurrently compared dual small plating to larger superior or anteroinferior single plate and screw constructs.

PURPOSE
To biomechanically compare dual small orthogonal plating, superior plating, and anteroinferior plating of midshaft clavicle fractures by use of a cadaveric model.

STUDY DESIGN
Descriptive laboratory study.

METHODS
The study used 18 cadaveric clavicle specimens (9 pairs total), and 3 plating techniques were studied: anteroinferior, superior, and dual. The dual plating technique used smaller diameter plates and screws (1.6-mm thickness) than the other, single plate techniques (3.3-mm thickness). Each of the 9 clavicle pairs was randomly assigned a combination of 2 plating techniques, and randomization was used to determine which techniques were used for the right and left specimens. Clavicles were plated and then osteotomized to create an inferior butterfly fracture model, which was then fixed with a single interfragmentary screw. Clavicle specimens were then potted for mechanical testing. Initial bending, axial, and torsional stiffness of each construct was determined through use of a randomized nondestructive cyclic testing protocol followed by load to failure.

RESULTS
No significant differences were found in cyclical axial (P = .667) or torsional (P = .526) stiffness between plating groups. Anteroinferior plating demonstrated significantly higher cyclical bending stiffness than superior plating (P = .005). No significant difference was found in bending stiffness between dual plating and either anteroinferior (P = .129) or superior plating (P = .067). No significant difference was noted in load to failure among plating methods (P = .353).

CONCLUSION
Dual plating with a smaller plate-screw construct is biomechanically similar to superior and anteroinferior single plate fixation that uses larger plate-screw constructs. No significant differences were found between dual plating and either superior or anteroinferior single plating in axial, bending, or torsional stiffness or in bending load to failure. Dual small plating is a viable option for fixing midshaft clavicle fractures and may be a useful low-profile technique that avoids a larger and more prominent plate-screw construct.

CLINICAL RELEVANCE
Plate prominence and hardware irritation are commonly reported complaints and reasons for revision surgery after plate fixation of midshaft clavicle fractures. Dual small plate fixation has been used to improve cosmetic acceptability, minimize hardware irritation, and decrease reoperation rate. Biomechanically, dual small plate fixation performed similarly to larger single plate fixation in this cadaveric model of butterfly fracture.

Ziegler|Connor G|CG|
Aman|Zachary S|ZS|
Storaci|Hunter W|HW|
Finch|Hannah|H|
Dornan|Grant J|GJ|
Kennedy|Mitchell I|MI|
Provencher|Matthew T|MT|
Hackett|Thomas R|TR|

clavicle fracture open reduction internal fixation


Uveal Melanoma Regression after Brachytherapy: Relationship with Chromosome 3 Monosomy Status.

Abstract:
AIM
The objective was to evaluate the relationship between the regression rate of ciliary body melanoma and choroidal melanoma after brachytherapy and chromosome 3 monosomy status.

METHODS
We conducted a prospective and consecutive case series of patients who underwent biopsy and brachytherapy for ciliary/choroidal melanoma. Tumor biopsy performed at the time of radiation plaque placement was analyzed with fluorescence in situ hybridization to determine the percentage of tumor cells with chromosome 3 monosomy. The regression rate was calculated as the percent change in tumor height at months 3, 6, and 12. The relationship between regression rate and tumor location, initial tumor height, and chromosome 3 monosomy (percentage) was assessed by univariate linear regression (R version 3.1.0).

RESULTS
Of the 75 patients included in the study, 8 had ciliary body melanoma, and 67 were choroidal melanomas. The mean tumor height at the time of diagnosis was 5.2 mm (range: 1.90-13.00). The percentage composition of chromosome 3 monosomy ranged from 0-20% (n = 35) to 81-100% (n = 40). The regression of tumor height at months 3, 6, and 12 did not statistically correlate with tumor location (ciliary or choroidal), initial tumor height, or chromosome 3 monosomy (percentage).

CONCLUSION
The regression rate of choroidal melanoma following brachytherapy did not correlate with chromosome 3 monosomy status.

Salvi|Sachin M|SM|
Aziz|Hassan A|HA|
Dar|Suhail|S|
Singh|Nakul|N|
Hayden-Loreck|Brandy|B|
Singh|Arun D|AD|

Uveal melanoma
Chromosome 3 monosomy
Metastasis
Prognostic factor


Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial.

Abstract:
BACKGROUND/PURPOSE
Family history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

MATERIALS/METHODS
Baseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%).

RESULTS
These patients were younger (median 56.7 vs. 62.1years, P<0.0001) and more often current smokers (52.4% vs. 43.5%, P<0.0001), had more dyslipidemia (47.7% vs. 41.1%, P=0.0003), less diabetes mellitus (14.1% vs. 17.5%, P=0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P=0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P=0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P=0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P=0.046 and 4.8% vs. 7.7%, P=0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI]=1.00 [0.70, 1.44], P=0.98).

CONCLUSIONS
A family history of premature CAD is not an independent predictor of higher mortality.

Ertelt|Konstanze|K|
Généreux|Philippe|P|
Mintz|Gary S|GS|
Brener|Sorin J|SJ|
Kirtane|Ajay J|AJ|
McAndrew|Thomas C|TC|
Francese|Dominic P|DP|
Ben-Yehuda|Ori|O|
Mehran|Roxana|R|
Stone|Gregg W|GW|

Coronary artery disease
Percutaneous coronary intervention
Heredity


Speaking of That: Terms to Avoid or Reconsider in the Eating Disorders Field.

Abstract: Inspired by an article on 50 terms that, in the interest of clarity in scientific reasoning and communication in psychology, psychiatry, and allied fields, "should be avoided or at most be used sparingly and only with explicit caveats,"(1) we propose a list of terms to avoid or think twice about before using when writing for the International Journal of Eating Disorders (IJED). Drawing upon our experience as reviewers or editors for the IJED, we generated an abridged list of such terms. For each term, we explain why it made our list and what alternatives we recommend. We hope that our list will contribute to improved clarity in scientific thinking about eating disorders, and that it will stimulate discussion of terms that may need to be reconsidered in our field's vocabulary to ensure the use of language that is respectful and sensitive to individuals who experience an eating disorder.

eating disorders
anorexia
anorexia nervosa
anorexic
binge eating
binge-eating disorder
bulimia nervosa
bulimic
subclinical eating disorder
subthreshold eating disorder


Identification and analysis of short open reading frames (sORFs) in the initially annotated noncoding RNA LINC00493 from human cells.

Abstract: Whole transcriptome analyses have revealed that mammalian genomes are massively transcribed, resulting in the production of huge numbers of transcripts with unknown functions (TUFs). Previous research has categorized most TUFs as noncoding RNAs (ncRNAs) because most previously studied TUFs do not encode open reading frames (ORFs) with biologically significant lengths [>100 amino acids (AAs)]. Recent studies, however, have reported that several transcripts harbouring small ORFs that encode peptides shorter than 100 AAs are translated and play important biological functions. Here, we examined the translational capacity of transcripts annotated as ncRNAs in human cells, and identified several hundreds of ribosome-associated transcripts previously annotated as ncRNAs. Ribosome footprinting and polysome profiling analyses revealed that 61 of them are potentially translatable. Among them, 45 were nonnonsense-mediated mRNA decay targets, suggesting that they are productive mRNAs. We confirmed the translation of one ncRNA, LINC00493, by luciferase reporter assaying and western blotting of a FLAG-tagged LINC00493 peptide. While proteomic analysis revealed that the LINC00493 peptide interacts with many mitochondrial proteins, immunofluorescence assays showed that its peptide is mitochondrially localized. Our findings indicate that some transcripts annotated as ncRNAs encode peptides and that unannotated peptides may perform important roles in cells.

Yeasmin|Fouzia|F| Imamachi|Naoto|N| Tanu|Tanzina|T| Taniue|Kenzui|K| Kawamura|Takeshi|T| Yada|Tetsushi|T| Akimitsu|Nobuyoshi|N|

D006367:HeLa Cells
D006801:Humans
D016366:Open Reading Frames
D010455:Peptides
D062085:RNA, Long Noncoding
D012333:RNA, Messenger

sORFs
TUFs
ncRNAs
ribosomes
short peptides


Long-term residential exposure to air pollution is associated with hair cortisol concentration and differential leucocyte count in Flemish adolescent boys.

Abstract:
BACKGROUND
Exposure to air pollution and traffic noise are associated with adverse health outcomes in adolescents. Chronic endocrine stress and systemic inflammation have been hypothesized to underlie the adverse health effects. Simultaneous assessment of inflammation and chronic endocrine stress in epidemiological studies is lacking. The aim of the study was to investigate biomarkers of chronic endocrine stress and inflammation in relation to long-term residential exposure to air pollution and traffic noise in adolescents.

METHODS
In Flemish adolescents (14-15 years), we determined hair cortisol concentration (HCC) as a chronic stress biomarker in 3-cm scalp-near hair sections (n = 395), and leucocyte and leucocyte subtype counts (neutrophils, monocytes, lymphocytes) as inflammatory biomarkers in peripheral blood (n = 385). Daily particulate matter (PM2.5, PM10), nitrogen dioxide (NO2) and black carbon (BC) concentrations were modelled at the residential address and averaged over 3-month and 1-year periods prior to sampling. Residential traffic noise level was estimated and classified in 5 dB intervals. Sex-specific associations between residential exposures and effect biomarkers were studied using linear regression models, adjusted for a priori selected covariates.

RESULTS
In boys, HCC increased with a factor 1.30 (95% CI: 1.10, 1.54) for an increase in 1-year mean NO2 from the 25th to 75th percentile (p75/p25), after adjustment for age, BMI, personal and neighborhood socioeconomic status. The corresponding estimate for PM10 was 1.24 (95% CI: 1.02, 1.51). Total leucocyte count in boys, adjusted for the aforementioned covariates and recent health complaints, was positively associated with PM2.5, PM10, NO2 and BC. In particular, the neutrophil count increased with a factor 1.11 (95% CI: 1.03, 1.19) for a (p75/p25)-factor increase in 1-year mean BC, corresponding estimates for PM2.5, PM10 and NO2 were 1.10 (95% CI: 1.01, 1.19), 1.10 (95% CI: 1.01, 1.20) and 1.08 (95% CI: 1.00, 1.16). Lymphocyte count increased with a factor 1.05 (95% CI: 1.01, 1.10) for a (p75/p25)-factor increase in 1-year mean NO2. Similar results were observed for 3-month mean exposures. Results were robust to adjustment for recent air pollution exposure. In girls, air pollutants were not associated with HCC or differential leucocyte count. Residential traffic noise level was not associated with HCC or leucocyte counts in boys nor girls.

CONCLUSIONS
Long-term residential exposure to air pollutants was positively associated with chronic endocrine stress and inflammation in adolescent boys, not in girls. This study may contribute to a better understanding of the early pathophysiological changes that may underlie adverse health effects of air pollution exposure in adolescents.

Verheyen|Veerle J|VJ|
Remy|Sylvie|S|
Bijnens|Esmée M|EM|
Colles|Ann|A|
Govarts|Eva|E|
Martin|Laura Rodriguez|LR|
Koppen|Gudrun|G|
Bruckers|Liesbeth|L|
Nielsen|Flemming|F|
Vos|Stijn|S|
Morrens|Bert|B|
Coertjens|Dries|D|
De Decker|Annelies|A|
Franken|Carmen|C|
Den Hond|Elly|E|
Nelen|Vera|V|
Covaci|Adrian|A|
Loots|Ilse|I|
De Henauw|Stefaan|S|
van Larebeke|Nicolas|N|
Teughels|Caroline|C|
Nawrot|Tim S|TS|
Schoeters|Greet|G|

Flemish Environment and Health Study (FLEHS)


Small-cell neuroendocrine tumor of the bladder: A rare disease in a low-risk woman.

Abstract: Bladder cancer is the fourth most common malignancy in men and ninth most in woman. Most bladder cancers are urothelial, and the neuroendocrine sub-types make up 0.5-1.0% of cases. Here we present a 70-year-old female with poorly differentiated small cell carcinoma of the bladder who complains of an extensive history of gross hematuria. She was started on a neoadjuvant chemotherapy regimen of 21-day Etoposide with Carboplatin and radical cystectomy. More work needs to be done when it comes to the best treatment method for this rare cohort of patients.

Neuroendocrine tumor
Bladder cancer
Neoadjuvant chemotherapy
Oncology


Chinese Mongolian horses may retain early domestic male genetic lineages yet to be discovered.

Abstract: The Mongolian horse represents one of the most ancient extant horse populations. In this study we determined the male-specific region of the Y chromosome (MSY) haplotype distribution in 60 Chinese Mongolian horses representing five distinct populations. Cosmopolitan male lineages were predominant in horses from one improved (Sanhe), one Chinese Mongolian subtype (Baicha Iron Hoof) and one indigenous (Abaga Black) population. In contrast, autochthonous Y chromosome diversity was evident among the two landrace populations (Wushen and Wuzhumuqin), as the majority of their MSY haplotypes were situated at root nodes in a network. Our results also suggest gene flow between Chinese Mongolian and Arabian horses, as an appreciable number of Wuzhumuqin horses carried haplotypes that are typically observed in Arabian horses. Although most horses carried modern haplotypes as a direct result of recent breed improvement, authentic Chinese Mongolian horses retain an ancient signature of paternal lineages that has not previously been described in extant horse populations. Therefore, further characterization of MSY variation in these populations will be important for the discovery of lost diversity in modern domestic horses and also for understanding the evolutionary history of equine paternal lineages.

haplotype
Domestic horse
Y chromosome variation


Institutional and technological barriers to the use of open educational resources (OERs) in physiology and medical education.

Abstract: Open educational resources (OERs) are becoming increasingly common as a tool in education, particularly in medical and biomedical education. However, three key barriers have been identified to their use: 1) lack of awareness of OERs, 2) lack of motivation to use OERs, and 3) lack of training in the use of OERs. Here, we explore these three barriers with teachers of medical and biomedical science to establish how best to enhance the use of OERs to improve pedagogical outcomes. An online survey was completed by 209 educators, many of whom (68.4%) reported using OERs in their teaching and almost all (99.5%) showing awareness of at least one OER. The results suggest that key problems that prevent educators from adopting OERs in their teaching include suitability for particular classes, time, and copyright. Most (81.8%) educators were somewhat, very, or extremely comfortable with OERs so there is no innate motivational barrier to adoption. A lack of training was reported by 13.9% of respondents, and 40% of respondents stated that there was little or no support from their institutions. OER users were no more comfortable with technology or better supported by departments but tended to be aware of a greater number of sources of OERs. Our study illustrates key opportunities for the expansion of OER use in physiology and medical teaching: increased breadth of awareness, increased institutional support (including time, training, and copyright support), and greater sharing of diverse OERs to suit the range of teaching challenges faced by staff in different subdisciplines.

technology
open educational resource
physiology
online
blended learning
medicine
pedagogy


In silico identification and validation of miRNA and their DIR specific targets in Oryza sativa Indica under abiotic stress.

Abstract: Several biotic (bacterial and viral pathogenesis) and abiotic stress factors like salt, drought, cold, and extreme temperatures significantly reduce crop productivity and grain quality throughout the world. MicroRNAs (miRNAs) are small (~22 nucleotides) non-coding endogenous RNA molecules which negatively regulate gene expression at the post-transcriptional level either by degrading the target protein-coding mRNA genes or suppressing translation in plants. Dirigent (DIR) gene protein plays a crucial role as they are involved to dictate the stereochemistry of a compound synthesized by other enzymes as well as in lignifications against biotic and abiotic stress. In plants, several miRNAs, as well as their targets, are known to regulate stress response but systematic identification of the same is limited. The present work has been designed for in silico identification of miRNAs against a total of sixty-one DIR genes in Oryza sativa Indica followed by target prediction of identified miRNAs through the computational approach and thereafter validation of potential miRNAs in rice genotypes. We systematically identified 3 miRNA and their respective DIR specific target gene in Oryza sativa Indica. The expression of these three miRNAs and their respective DIR specific targets were validated in rice seedlings subjected to five different abiotic stress conditions (heavy metal, high temperature, low temperature, salinity and drought) by quantitative Real-Time PCR (qRT-PCR). Expression analysis indicated that miRNA under stress conditions regulates the gene expression of the DIR gene in rice. To the best of our knowledge this is this is the first report in any organism showing the expression of ath-miRf10317-akr, and osamiRf10761-akr miRNAs in response to various abiotic stresses.

Singh|Deepak Kumar|DK|
Mehra|Shourya|S|
Chatterjee|Sayan|S|
Purty|Ram Singh|RS|

Oryza sativa
Abiotic stress
microRNA
Gene expression
Dirigent proteins
Molecular phylogeny
Motif analysis


Enhanced Biosynthesis of Dihydromyricetin in Saccharomyces cerevisiae by Coexpression of Multiple Hydroxylases.

Abstract: Dihydromyricetin (DHM) is a traditional plant-extracted flavonoid with some health benefits. This study aimed to metabolically engineer the strains for DHM bioproduction. Two strains of BK-11 and BQ-21 were integrated with flavonoid 3-hydroxylase (F3H) or both F3H and flavonoid 3'-hydroxylase (F3'H). The resulting strains have expressed the enzymes of GmCPR and SlF3'5'H, and then, the promoters of INO1p and TDH1p were used to enhance further the DHM production from naringenin in Saccharomyces cerevisiae. Through multiple-copy integration, 709.6 mg/L DHM was obtained by adding 2.5 g/L naringenin in a 5 L bioreactor, implying that the synergistic effect between F3'H and flavonoid 3'5'-hydroxylase is likely to promote the DHM production. An yield of 246.4 mg/L DHM was obtained from glucose by deleting genes for branch pathways and integrating PhCHS, MsCHI, Pc4CL, and FjTAL. To our knowledge, this is the highest production reported for the de novo biosynthesis of DHM.

dihydromyricetin
Saccharomyces cerevisiae
metabolic engineering
cytochrome P450 reductase
flavonoid 3′5′-hydroxylase


The transcription factor LSF: a novel oncogene for hepatocellular carcinoma.

Abstract: The transcription factor LSF (Late SV40 Factor), also known as TFCP2, belongs to the LSF/CP2 family related to Grainyhead family of proteins and is involved in many biological events, including regulation of cellular and viral promoters, cell cycle, DNA synthesis, cell survival and Alzheimer's disease. Our recent studies establish an oncogenic role of LSF in Hepatocellular carcinoma (HCC). LSF overexpression is detected in human HCC cell lines and in more than 90% cases of human HCC patients, compared to normal hepatocytes and liver, and its expression level showed significant correlation with the stages and grades of the disease. Forced overexpression of LSF in less aggressive HCC cells resulted in highly aggressive, angiogenic and multi-organ metastatic tumors in nude mice. Conversely, inhibition of LSF significantly abrogated growth and metastasis of highly aggressive HCC cells in nude mice. Microarray studies revealed that as a transcription factor LSF modulated specific genes regulating invasion, angiogenesis, chemoresistance and senescence. LSF transcriptionally regulates thymidylate synthase (TS) gene, thus contributing to cell cycle regulation and chemoresistance. Our studies identify a network of proteins, including osteopontin (OPN), Matrix metalloproteinase-9 (MMP-9), c-Met and complement factor H (CFH), that are directly regulated by LSF and play important role in LSF-induced hepatocarcinogenesis. A high throughput screening identified small molecule inhibitors of LSF DNA binding and the prototype of these molecules, Factor Quinolinone inhibitor 1 (FQI1), profoundly inhibited cell viability and induced apoptosis in human HCC cells without exerting harmful effects to normal immortal human hepatocytes and primary mouse hepatocytes. In nude mice xenograft studies, FQI1 markedly inhibited growth of human HCC xenografts as well as angiogenesis without exerting any toxicity. These studies establish a key role of LSF in hepatocarcinogenesis and usher in a novel therapeutic avenue for HCC, an invariably fatal disease.

Santhekadur|Prasanna K|PK|
Rajasekaran|Devaraja|D|
Siddiq|Ayesha|A|
Gredler|Rachel|R|
Chen|Dong|D|
Schaus|Scott E|SE|
Hansen|Ulla|U|
Fisher|Paul B|PB|
Sarkar|Devanand|D|

hepatocellular carcinoma (HCC)
metastasis
angiogenesis
thymidylate synthase (TS)
cell cycle regulation
osteopontin (OPN)
matrix metalloproteinase-9 (MMP-9)
c-Met
small molecule inhibitors
FQI1
Late SV40 Factor (LSF)


Investigation on Plugging and Profile Control of Polymer Microspheres as a Displacement Fluid in Enhanced Oil Recovery.

Abstract: Polymer microspheres (PMs) are used as a new material to recover residual oil left in unswept oil areas after secondary recovery methods. The fact that the PMs plug the macropores causes the flow direction of the injection fluid to be transferred from macropores to micropores. In order to investigate the plugging and profile control mechanisms of PMs in reservoirs, four kinds of PMs with different particle sizes and four kinds of artificial cores with different permeability were selected for flooding tests, including plugging experiments and profile control experiments. The pore throat size distribution of cores was characterized by nuclear magnetic resonance (NMR) technology. The particle size distribution of PMs used in the experiment was characterized using a laser particle size analyzer. The results showed that there are six matching relationships existing simultaneously between pore throats and PMs based on theoretical analysis, which are completely plugging, single plugging, bridge plugging, smooth passing, deposition, and deformable passing. A key principle for optimizing PMs in profile control is that the particle size of the selected PMs can enter the high permeability layer well, but it is difficult for it to enter the low permeability layer. The results of this paper provide a theoretical basis for the optimal particle size of PMs during the oil field profile control process.

Nie|Xiangrong|X| Chen|Junbin|J| Cao|Yi|Y| Zhang|Jinyuan|J| Zhao|Wenjing|W| He|Yanlong|Y| Hou|Yunyi|Y| Yuan|Shaomin|S|

plugging
profile control
polymer microspheres
enhanced oil recovery
pore throat


Infection by Parorchis acanthus (Trematoda) decreases grazing by the keystone gastropod, Littoraria irrorata.

Abstract: Parasites are well-known to alter the behavior of their hosts, but there is still a paucity of knowledge about how parasites modify the behavior of many ecologically influential host species. I studied the keystone grazer, the salt marsh periwinkle (Littoraria irrorata), to determine the influence of infection by the digenetic trematode, Parorchis acanthus, on its grazing behavior. Comparative laboratory grazing studies of wild-collected and experimentally infected snails revealed that Parorchis decreased grazing on live Spartina by more than 80%. Because of the large ecological influence of Littoraria in southern U.S. marshes, parasite modification of snail grazing may have ramifications for marsh ecosystem stability if parasite prevalence is sufficiently high.

Grazing
Parasitism
Salt marsh
Trematode
Behavior modification


Did you mean to do that? Infants use emotional communication to infer and re-enact others' intended actions.

Abstract: Infants readily re-enact others' intended actions during the second year of life. However, the role of emotion in appreciating others' intentions and how this understanding develops in infancy remains unstudied. In the present study, 15- and 18-month-old infants observed an experimenter repeatedly attempt but fail to produce a target action on an object and express either frustration or neutral affect after each attempt. Analyses of infants' responses revealed that 18-month-old infants, but not 15-month-olds, produced more target actions in the frustration condition than the neutral condition. These results suggest that infants use emotional communication to disambiguate and re-enact others' intended actions and that this ability develops in the second year of life.

Reschke|Peter J|PJ|0000-0002-1711-8385
Walle|Eric A|EA|
Dukes|Daniel|D|

emotion
Imitation
infancy
intentionality
social cognition


Video-assisted thoracoscopic surgical wedge resection using multiplanar computed tomography reconstruction-fluoroscopy after CT guided microcoil localization.

Abstract:
BACKGROUND
When early-stage lung cancer is diagnosed, the recommended treatment is anatomical resection using video-assisted thoracoscopic surgery (VATS) or robotic lobectomy. However, nonanatomical resection, known as wedge resection (WR), which is performed to diagnose pulmonary nodules, can be problematic for clinicians performing VATS or robotic-assisted thoracic surgery (RATS). The purpose of this study was to evaluate the safety and effectiveness of VATS WR using multiplanar computed tomography reconstruction (CT MPR)-fluoroscopy after CT guided microcoil localization to achieve complete pulmonary nodule resection.

METHODS
Between January 2016 to December 2020, the medical records of patients who underwent CT-guided microcoil localization for suspicious malignant pulmonary nodules and VATS WR with CT MPR and intraoperative fluoroscopy were retrospectively reviewed.

RESULTS
All 130 patients successfully underwent CT-guided localization. The success rate of VATS WR with CT MPR-intraoperative fluoroscopy was 98.5%. Mean operation time was 58 min (range 50-84 min). The postoperative complication rate was 3.1%, and no major postoperative complications were reported. The mean postoperative length of hospital stay was 4.7 days (range 4-8 days).

CONCLUSIONS
VATS WR using CT MPR-fluoroscopy after CT guided microcoil localization is a safe and highly effective approach for complete pulmonary nodule resection. However, even in uniport VATS or recently performed robotic surgery, localization and resection of nonvisible, nonpalpable pulmonary nodules is a challenging problem. Consequently, satisfactory outcomes can be expected if this technique is used for suspicious malignant pulmonary nodule resection.

Lee|Moon Ok|MO|
Jin|Sung Yup|SY|
Lee|Sang Kyung|SK|
Hwang|Sangwon|S|
Kim|Tae Gyu|TG|
Song|Yun Gyu|YG|0000-0003-0164-6914

computed tomography multiplanar reconstruction


Carbonation dysgeusia associated with topiramate.

Abstract:
PURPOSE
A case of carbonation dysgeusia associated with the use of topiramate is reported in order to bring awareness to a lesser-known adverse effect of the medication so that providers may be able to more effectively counsel patients and provide potential solutions.

SUMMARY
A 39-year-old Caucasian woman with longstanding epilepsy was initiated on topiramate therapy after experiencing a generalized seizure (she reported not taking any antiepileptic medication for years). Topiramate was started at a dosage of 25 mg by mouth twice daily and after 3 weeks titrated to a dosage of 100 mg by mouth twice daily for maintenance therapy. After initiation of topiramate therapy, the patient began to experience an immediate change in her carbonation perception when drinking carbonated beverages; all carbonated beverages, including seltzer and beer, tasted "flat." The patient remained on topiramate for the subsequent 12 months without her carbonation perception returning to normal but noted that drinking carbonated beverages through straws slightly mitigated the adverse effect. Case assessment using the adverse drug reaction probability scale of Naranjo et al indicated that topiramate was the probable cause of the patient's carbonation taste perversion.

CONCLUSION
A 39-year-old Caucasian woman developed chronic carbonation dysgeusia after initiation of topiramate following a generalized seizure.

Charbonneau|Maria|M| Doyle-Campbell|Courtney|C| Laskey|Corey|C| Capoccia|Kam|K|

dysgeusia
topiramate
carbonation taste perversion


The Developmental Shift of NMDA Receptor Composition Proceeds Independently of GluN2 Subunit-Specific GluN2 C-Terminal Sequences.

Abstract: The GluN2 subtype (2A versus 2B) determines biophysical properties and signaling of forebrain NMDA receptors (NMDARs). During development, GluN2A becomes incorporated into previously GluN2B-dominated NMDARs. This "switch" is proposed to be driven by distinct features of GluN2 cytoplasmic C-terminal domains (CTDs), including a unique CaMKII interaction site in GluN2B that drives removal from the synapse. However, these models remain untested in the context of endogenous NMDARs. We show that, although mutating the endogenous GluN2B CaMKII site has secondary effects on GluN2B CTD phosphorylation, the developmental changes in NMDAR composition occur normally and measures of plasticity and synaptogenesis are unaffected. Moreover, the switch proceeds normally in mice that have the GluN2A CTD replaced by that of GluN2B and commences without an observable decline in GluN2B levels but is impaired by GluN2A haploinsufficiency. Thus, GluN2A expression levels, and not GluN2 subtype-specific CTD-driven events, are the overriding factor in the developmental switch in NMDAR composition.

McKay|Sean|S|
Ryan|Tomás J|TJ|
McQueen|Jamie|J|
Indersmitten|Tim|T|
Marwick|Katie F M|KFM|
Hasel|Philip|P|
Kopanitsa|Maksym V|MV|
Baxter|Paul S|PS|
Martel|Marc-André|MA|
Kind|Peter C|PC|
Wyllie|David J A|DJA|
O'Dell|Thomas J|TJ|
Grant|Seth G N|SGN|
Hardingham|Giles E|GE|
Komiyama|Noboru H|NH|

D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2

NMDA receptor
synaptogenesis
neurodevelopment
synaptic plasticity


Physical and Mental Health Issues among Homeless Youth in British Columbia, Canada: Are they Different from Older Homeless Adults?

Abstract:
OBJECTIVES
Youth homelessness is on the rise in North America, yet this vulnerable population is rarely studied and compared with adults. This paper aimed to study the homeless youth and identify specific vulnerabilities, which rendered them different from the adult homeless population. It also aimed to describe the youth homeless population and their significant co-morbidities.

METHODS
DATA WAS DERIVED FROM THE BC HEALTH OF THE HOMELESS STUDY (BCHOHS), CARRIED OUT IN THREE CITIES IN BRITISH COLUMBIA, CANADA: the large urban centre Vancouver (n=250); the mid-sized city and capital of the province Victoria (n=150). Measures included socio-demographic information, the Maudsley Addiction Profile (MAP), the Childhood Trauma Questionnaire (CTQ) and the Mini International Neuropsychiatric Interview (MINI) Plus.

RESULTS
Youth constituted 16.5% (n=82) of the homeless population. Compared to the adult homeless, the homeless youth were more often female (55%), were Aboriginal (47.6%), had greater substance abuse of alcohol (70.7%), amphetamines (8.5%) and cannabis (75.6%). A lower prevalence of sexually transmitted diseases (0.2%) and psychotic disorders (13.4%) was also observed. The prevalence of traumatic experiences, other psychiatric disorders and physical illnesses were similar between the adult and homeless youth.

CONCLUSION
Homeless youth have high rates of physical and psychiatric comorbidity, similar to the adult homeless, despite being 20 years younger. An urgent need for interventions that go beyond the standardized ones being offered to homeless populations as a whole, and to derive specific strategies that target this vulnerable population is required.

Saddichha|Sahoo|S|
Linden|Isabelle|I|
Krausz|Michael Reinhardt|MR|

physical
homeless
youth
trauma
substance abuse
psychiatric


The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

Abstract: The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices.

Bouffler|S D|SD|
Peters|S|S|
Gilvin|P|P|
Slack|K|K|
Markiewicz|E|E|
Quinlan|R A|RA|
Gillan|J|J|
Coster|M|M|
Barnard|S|S|
Rothkamm|K|K|
Ainsbury|E|E|

Exposure
Medical
Radiation
Cataract
Eye lens
Mechanisms


Effects of levosimendan on heart failure in normotensive patients: does loading dose matter?

Abstract:
BACKGROUND
Levosimendan is a calcium sensitizer and K(+)-ATP channel opener with inotropic and vasodilatatory effects irrespective of myocardial oxygen consumption, used for treatment of heart failure (HF). A loading dose is usually given by infusion for 12 h; however, profound lowering of blood pressure often disrupts or prolongs the infusion. The aim of this study was to assess clinical, biochemical and myocardial differences between different regimes of levosimendan therapy, with or without loading dose, and compared to standard therapy in heart failure.

METHODS
Fifty-seven patients (mean age ± SD: 60.9 ± 9.3 years, 45 males) with HF, New York Heart Association (NYHA) III-IV, reduced left ventricular ejection fraction (LVEF) were included. Twenty patients (NB group) were given levosimendan without loading dose, 14 patients (B group) were given levosimendan with loading dose, and 23 patients (C group) were given standard therapy. Clinical, biochemical and echocardiographic characteristics at baseline and one week after treatment were evaluated.

RESULTS
Groups were similar at baseline. After one week NHYA class (P < 0.001), NT pro-BNP (P < 0.001), LVEF (P = 0.045), E/A (P = 0.048) E/e' (P < 0.001), and PAPs (P < 0.001) decreased. DT (P = 0.011) and TAPSE (P = 0.035) increased in all groups.

CONCLUSIONS
Levosimendan, as well as standard therapy, improves myocardial function and symptoms of HF, irrespective of the loading dose administration. Treatment options for patients with end-stage heart failure refractory to conventional medical therapy are limited. Inotropic drugs play an important role in heart failure (HF).

Palmerini|Elisabetta|E| Söderberg|Stefan|S| Mondillo|Sergio|S| Favilli|Roberto|R| Lunghetti|Stefano|S|

heart failure
Echocardiography
natriuretic peptides


Distribution, antimicrobial resistance and predictors of mortality in neonatal sepsis.

Abstract:
OBJECTIVE
The aim of this study is to investigate etiological agents, patterns of antimicrobial resistance and predictors of mortality in culture proven neonatal sepsis.

METHOD
This is a twenty-four month retrospective cohort study of infants with culture proven sepsis. Demographic data, type of isolates and its sensitivity pattern were recorded. Multidrug resistant gram-negative isolates were defined as resistance to any three of five antibiotic classes: extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and piperacillin-tazobactam.

RESULT
A total of 183 case with culture positive sepsis were identified. Early onset sepsis occurred in 59% of cases. The majority of isolates (56.2%) were gram-positive but the most common individual isolates were klebsiella spp. (31.1%), Staphylococcus aureus (24.5%) and coagulase-negative staphylococci (CONS) (22.9%). The pathogen mix in early-onset did not differ from late-onset sepsis. High rates of multidrug resistance were observed in klebsiella spp. (49.1%), Escherichia coli (50%), citrobacter spp (50%), acinetobacter spp. (28.5%), pseudomonas spp. (100%) isolates. Methicillin resistance prevailed in 16.6% of coagulase-negative staphylococci, 24.4% of Staphylococcus aureus and 62.5% of enterococcus spp. Multivariate analysis revealed invasive ventilation and early onset sepsis to be independently associated with increased risk of mortality in contrast to breast milk feeding which is associated with decreased risk of mortality.

CONCLUSION
A high degree of antimicrobial resistance underscores the need to understand the pathogenesis of resistance, curtail the irrational prescription of antibiotics in neonates and the requirement for measures to prevent it in low-income and middle-income countries.

Bandyopadhyay|T|T|
Kumar|A|A|
Saili|A|A|
Randhawa|V S|VS|

D024901:Drug Resistance, Multiple, Bacterial

Antimicrobial resistance
mortality
neonates


Utility of gradient recalled echo magnetic resonance imaging for the study of myelination in cuprizone mice treated with fingolimod.

Abstract: The availability of high-field-strength magnetic resonance imaging (MRI) systems has brought about the development of techniques that aim to map myelination via the exploitation of various contrast mechanisms. Myelin mapping techniques have the potential to provide tools for the diagnosis and treatment of diseases, such as multiple sclerosis. In this study, we evaluated the sensitivity of T2 *, frequency shift and susceptibility measures to myelin levels in a cuprizone mouse model of demyelination. The model was supplemented with two different dosages of fingolimod, a drug known to positively affect demyelination. A decrease in grey-white matter contrast with the cuprizone diet was observed for T2 *, frequency shift and susceptibility measures, together with myelin basic protein antibody findings. These results indicate that T2 *, frequency shift and susceptibility measures have the potential to act as biomarkers for myelination. Susceptibility was found to be the most sensitive measure to changes in grey-white matter contrast. In addition, fingolimod treatment was found to reduce the level of demyelination, with a larger dosage exhibiting a greater reduction in demyelination for the in vivo MRI results. Overall, susceptibility mapping appears to be a more promising tool than T2 * or frequency shift mapping for the early diagnosis and treatment of diseases in which myelination is implicated.

Ziser|Laura|L|
Meyer-Schell|Naja|N|
Kurniawan|Nyoman D|ND|
Sullivan|Robert|R|
Reutens|David|D|
Chen|Min|M|
Vegh|Viktor|V|0000-0002-4310-1421

magnetic resonance imaging
myelination
magnetic susceptibility
ultra-high field


A randomized, double-blind placebo-controlled study on acceptability, safety and efficacy of oral administration of sacha inchi oil (Plukenetia volubilis L.) in adult human subjects.

Abstract: The study was designed to assess acceptability and side-effects of consumption of sacha inchi oil, rich in α-linolenic acid and sunflower oil, rich in linoleic acid, in adult human subjects. Thirty subjects received 10 or 15ml daily of sacha inchi or sunflower oil for 4months. Acceptability was assessed with daily self-report and with a Likert test at the end of the study. Safety was assessed with self- recording of side-effects and with hepatic and renal markers. Primary efficacy variables were the change in lipid profile. Subjects reported low acceptability of sacha inchi oil at week-1 (37.5%). However, since week-6, acceptability was significantly increased to 81.25-93.75%. No differences were observed in acceptability with respect to sex or oil volume (P>0.05). Most frequent adverse effects during first weeks of consuming sacha inchi oil or sunflower oil were nauseas. The side-effects were reduced with time. Biochemical markers of hepatic and kidney function were maintained unchanged. Serum total cholesterol and LDL cholesterol levels and arterial blood pressure were lowered with both oils (P<0.05). Higher HDL-cholesterol was observed with sacha inchi oil at month-4. In conclusion, sacha inchi oil consumed has good acceptability after week-1 of consumption and it is safety.

Linoleic acid
Lipid profile
Adverse effects
Clinical trial
Linolenic acid
Toxicity


Diagnosing skull fracture in children with closed head injury using point-of-care ultrasound vs. computed tomography scan.

Abstract: Diagnostic and therapeutic interventions in children for traumatic brain injury, which is known as the most important complication in trauma, require special attention. This study aimed to evaluate the accuracy of point-of-care ultrasound (POCUS) in diagnosing skull fracture in children with closed head injury in comparison with computed tomography (CT) scan. The current prospective cross-sectional study was conducted on children (0-14 years old), who were referred to the emergency department of a general teaching hospital in Shiraz, southern Iran (January-March 2018), with close head injury and were suspected of bone fracture. The participants were selected using a convenience sampling. The results of POCUS performed by emergency medicine (EM) residents were compared with the results of CT scan, which was reported by radiologists and considered a gold standard. Then, diagnostic tests were calculated. A total of 168 children were enrolled, with the mean ± standard deviation age of 6.21 ± 3.99. The most affected areas in the skull were the frontal (34.5%) and occipital areas (33.3%). POCUS had a sensitivity and specificity of 81.8% (95%CI, 48.2-97.7%) and 100% (95%CI, 97.7-100%), respectively. Positive and negative predictive values were 100% and 98.7%, with an accuracy of 98.8% in comparison with CT scan in the diagnosis of skull fracture.Conclusion: The results showed that POCUS with a portable ultrasonography machine, performed by the EM's physicians, have high diagnostic precision and can be considered a tool in the management of patients with closed head injury. What is Known: • Some studies have investigated the accuracy of ultrasound in diagnosing skull bone fractures in children with closed head injury, but before conducting this survey, no definite evidence recommended POCUS for skull fracture in children with closed head trauma in the ED. What is New: • POCUS with a portable ultrasonography machine, performed by the EM's physicians, has high diagnostic precision and can be considered a tool in the management of patients with closed head injury.

Dehbozorgi|Afsaneh|A|
Mousavi-Roknabadi|Razieh Sadat|RS|
Hosseini-Marvast|Seyed Rouhollah|SR|
Sharifi|Mehrdad|M|
Sadegh|Robab|R|
Farahmand|Faramarz|F|
Damghani|Fatemeh|F|

Skull fracture
Closed head injury
Traumatic brain injuries
Emergency department
Ultrasonography


Ex vivo treatment of prostate tumor tissue recapitulates in vivo therapy response.

Abstract:
BACKGROUND
In vitro models of prostate cancer (PCa) are not always reliable to evaluate anticancer treatment efficacy. This limitation may be overcome by using viable tumor slice material. Here we report on the establishment of an optimized ex vivo method to culture tissue slices from patient-derived xenografts (PDX) of prostate cancer (PCa), to assess responses to PCa treatments.

METHODS
Three PDX models were used that are characterized by different androgen receptor (AR) expression and different homology directed DNA repair capacities, due to a breast cancer associated two (BRCA2) wild-type or mutated status. Tumors were removed from mice, sliced using a vibratome and cultured for a maximum of 6 days. To test the sensitivity to androgen antagonist, tumor slices from the AR-expressing and AR-negative PDX tumors were treated with the anti-androgen enzalutamide. For sensitivity to DNA repair intervention, tumors slices from BRCA2 wild-type and mutated PDXs were treated with the poly (ADP-ribose) polymerase-1 inhibitor olaparib. Treatment response in these tumor slices was determined by measuring slice morphology, cell proliferation, apoptosis, AR expression level, and secretion of prostate specific antigen (PSA).

RESULTS
We compared various culture conditions (support materials, growth media, and use of a 3D smooth rocking platform) to define the optimal condition to maintain tissue viability and proliferative capacity up to least 6 days. Under optimized conditions, enzalutamide treatment significantly decreased proliferation, increased apoptosis, and reduced AR-expression and PSA secretion of AR-expressing tumor slices compared to AR-negative slices, that did not respond to the intervention. Olaparib treatment significantly increased cell death in BRCA2 mutated tumors slices as compared to slices from BRCA2 wild type tumors.

CONCLUSIONS
Ex vivo treatment of PCa PDX tumor slices with enzalutamide and olaparib recapitulates responses previously observed in vivo. The faithful retention of tissue structure and function in this ex vivo model offers an ideal opportunity for treatment efficacy screening, thereby reducing costs and numbers of experimental animals.

Zhang|Wenhao|W|
van Weerden|Wytske M|WM|
de Ridder|Corrina M A|CMA|
Erkens-Schulze|Sigrun|S|
Schönfeld|Edgar|E|
Meijer|Titia G|TG|
Kanaar|Roland|R|
van Gent|Dik C|DC|
Nonnekens|Julie|J|0000-0002-9644-7522

D023041:Xenograft Model Antitumor Assays

prostate cancer
tissue slices
enzalutamide
olaparib
ex vivo culture


Doxorubicin-Loaded Gold Nanoarchitectures as a Therapeutic Strategy against Diffuse Intrinsic Pontine Glioma.

Abstract: Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG.

nanoarchitectures
DIPG
paediatric brain tumours
doxorubicin
gold nanoparticles
orthotopic animal models


Joint estimation of growth and survival from mark-recapture data to improve estimates of senescence in wild populations.

Abstract: Understanding age-dependent patterns of survival is fundamental to predicting population dynamics, understanding selective pressures, and estimating rates of senescence. However, quantifying age-specific survival in wild populations poses significant logistical and statistical challenges. Recent work has helped to alleviate these constraints by demonstrating that age-specific survival can be estimated using mark-recapture data even when age is unknown for all or some individuals. However, previous approaches do not incorporate auxiliary information that can improve age estimates of individuals. We introduce a survival estimator that combines a von Bertalanffy growth model, age-specific hazard functions, and a Cormack-Jolly-Seber mark-recapture model into a single hierarchical framework. This approach allows us to obtain information about age and its uncertainty based on size and growth for individuals of unknown age when estimating age-specific survival. Using both simulated and real-world data for two painted turtle (Chrysemys picta) populations, we demonstrate that this additional information substantially reduces the bias of age-specific hazard rates, which allows for the testing of hypotheses related to aging. Estimating patterns of senescence is just one practical application of jointly estimating survival and growth; other applications include obtaining better estimates of the timing of recruitment and improved understanding of life-history trade-offs between growth and survival.

Reinke|Beth A|BA|
Hoekstra|Luke|L|
Bronikowski|Anne M|AM|
Janzen|Fredric J|FJ|
Miller|David|D|

growth
survival
senescence
hazard
mark-recapture model
painted turtle


Antiapoptotic Bcl-2 protein as a potential target for cancer therapy: A mini review.

Abstract: Bcl-2, an antiapoptotic protein, is considered as a potential target in cancer treatment since its oncogenic potential has been proven and is well documented. Antisense technology and RNA interference (RNAi) have been used to reduce the expression of the Bcl-2 gene in many types of cancer cells and are effective as adjuvant therapy along with the chemotherapeutic agents. The lack of appropriate delivery systems is considered to be the main hurdle associated with the RNAi. In this review, we discuss the antiapoptotic Bcl-2 protein, its oncogenic potential, and various approaches utilized to target Bcl-2 including suitable delivery systems employed for successful delivery of siRNA.

Jagani|Hitesh|H|
Kasinathan|Narayanan|N|
Meka|Sreenivasa Reddy|SR|
Josyula|Venkata Rao|VR|

Bcl-2
cancer
RNA interference
Antisense oligonucleotide
apoptosis
drug delivery


AREL1 E3 ubiquitin ligase inhibits TNF-induced necroptosis via the ubiquitination of MTX2.

Abstract: Previously, we reported on a novel anti-apoptotic E3 ubiquitin ligase, apoptosis-resistant E3 ubiquitin protein ligase 1 (AREL1), that ubiquitinates inhibitors of apoptosis proteins antagonists. The present study demonstrated that AREL1 ubiquitinated Metaxin 2 (MTX2), which was involved in TNF-induced necroptosis. MTX2 has been identified as a protein that belongs to the Metaxin family. It interacts with another Metaxin protein, Metaxin 1 (MTX1), which is localized in the outer membrane of mitochondria, and is involved in TNF-induced necroptosis. This study found that AREL1 interacted with MTX2, but not MTX1, while the amino-terminal domain of MTX2 interacted with MTX1, AREL1 interacted with the carboxyl-terminal domain of MTX2. Furthermore, AREL1 expression led to a decrease in the protein expression of MTX2, but not MTX1. However, a mutant form of AREL1, AREL1C790A, which is deficient for E3 activity, did not cause MTX2 degradation. Moreover, the protein levels of MTX2 were increased by AREL1 knockdown. Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. The expression of MTX2, together with MTX1, enhanced TNF-induced necroptosis. However, AREL1 inhibited necroptosis even in cells expressing Metaxin proteins. Therefore, these results suggested that the inhibition of AREL1-dependent ubiquitination of MTX2 could be beneficial to sensitize tumor cells to TNF-induced necroptosis.

Jo|Yongsam|Y|
Kim|Byeongmo|B|
Shin|Deug Y|DY|


MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

Abstract: Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy. We elucidate that MET promotes GSC radioresistance through a novel mechanism, relying on AKT activity and leading to (i) sustained activation of Aurora kinase A, ATM kinase, and the downstream effectors of DNA repair, and (ii) phosphorylation and cytoplasmic retention of p21, which is associated with anti-apoptotic functions. We show that MET pharmacological inhibition causes DNA damage accumulation in irradiated GSCs and their depletion in vitro and in GBMs generated by GSC xenotransplantation. Preclinical evidence is thus provided that MET inhibitors can radiosensitize tumors and convert GSC-positive selection, induced by radiotherapy, into GSC eradication.

De Bacco|Francesca|F|
D'Ambrosio|Antonio|A|
Casanova|Elena|E|
Orzan|Francesca|F|
Neggia|Roberta|R|
Albano|Raffaella|R|
Verginelli|Federica|F|
Cominelli|Manuela|M|
Poliani|Pietro L|PL|
Luraghi|Paolo|P|
Reato|Gigliola|G|
Pellegatta|Serena|S|
Finocchiaro|Gaetano|G|
Perera|Timothy|T|
Garibaldi|Elisabetta|E|
Gabriele|Pietro|P|
Comoglio|Paolo M|PM|
Boccaccio|Carla|C|0000-0003-2620-9083

D064007:Ataxia Telangiectasia Mutated Proteins

D050759:Cyclin-Dependent Kinase Inhibitor p21

glioblastoma
radiotherapy
radiosensitization
MET oncogene
glioblastoma stem‐like cells


Effects of transition on HIV and non-HIV services and health systems in Kenya: a mixed methods evaluation of donor transition.

Abstract:
BACKGROUND
In 2015 the US President's Emergency Plan for AIDS Relief (PEPFAR) initiated its Geographic Prioritization (GP) process whereby it prioritized high burden areas within countries, with the goal of more rapidly achieving the UNAIDS 90-90-90 targets. In Kenya, PEPFAR designated over 400 health facilities in Northeastern Kenya to be transitioned to government support (known as central support (CS)).

METHODS
We conducted a mixed methods evaluation exploring the effect of GP on health systems, and HIV and non-HIV service delivery in CS facilities. Quantitative data from a facility survey and health service delivery data were gathered and combined with data from two rounds of interviews and focus group discussions (FGDs) conducted at national and sub-national level to document the design and implementation of GP. The survey included 230 health facilities across 10 counties, and 59 interviews and 22 FGDs were conducted with government officials, health facility providers, patients, and civil society.

RESULTS
We found that PEPFAR moved quickly from announcing the GP to implementation. Despite extensive conversations between the US government and the Government of Kenya, there was little consultation with sub-national actors even though the country had recently undergone a major devolution process. Survey and qualitative data identified a number of effects from GP, including discontinuation of certain services, declines in quality and access to HIV care, loss of training and financial incentives for health workers, and disruption of laboratory testing. Despite these reports, service coverage had not been greatly affected; however, clinician strikes in the post-transition period were potential confounders.

CONCLUSIONS
This study found similar effects to earlier research on transition and provides additional insights about internal country transitions, particularly in decentralized contexts. Aside from a need for longer planning periods and better communication and coordination, we raise concerns about transitions driven by epidemiological criteria without adaptation to the local context and their implication for priority-setting and HIV investments at the local level.

D006078:Government Programs
D015658:HIV Infections
D006268:Health Facilities
D006296:Health Services
D006801:Humans
D007630:Kenya

HIV
Health systems
Kenya
Donor transition
Mixed-methods evaluation
Sustainability


Comparison of the Nutritional Status Assessment Methods for Hemodialysis Patients.

Abstract: Protein-energy wasting (PEW) is prevalent among hemodialysis (HD) patients and is associated with poor outcomes. There are various methods for nutritional status evaluation in HD patients. Each method has its own advantages and disadvantages. We aimed at comparing the method validities of normalized protein catabolic ratio (nPCR) and malnutrition universal screening tool (MUST) with subjective global assessment (SGA) in HD patients. We examined 88 HD patients using SGA and MUST questionnaires. The nPCRs were calculated using pre-dialysis and post-dialysis BUN and Kt/v. Also, PEW of patients was assessed based on the criteria of the International Society of Renal Nutrition and Metabolism. Methods' specificity, sensitivity, and precision rates were assessed. Correlations between methods were analyzed using Pearson-correlation. Based on the SGA, MUST, and nPCR methods, almost 41%, 30%, and 60% of patients had malnutrition, respectively. According to the criteria, more than 90% of patients had PEW. SGA was positively and significantly associated with MUST (p ≤ 0.001). Sensitivity for SGA, MUST, and nPCR methods were 100%,100%, 1.8%, and their specificity were 98%, 98%, and 4%, and their precision rates were 99.7%, 98.7%, and 3%, respectively. From various methods of nutritional assessment (SGA, MUST, and nPCR), compared to SGA as the common method of nutrition assessment in hemodialysis patients, MUST had the nearest specificity, sensitivity, and precision rate and nPCR method had the lowest ones. nPCR seems to be a flawed marker of malnutrition and it should be more investigated if MUST can be used instead of SGA.

Malnutrition
Nutrition assessment
Cachexia
Kidney failure


Evaluation of the expression level of 12/15 lipoxygenase and the related inflammatory factors (CCL5, CCL3) in respiratory syncytial virus infection in mice model.

Abstract: Human respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection during early childhood and imposes a great burden on patients, parents, and society. Disease is thought to be caused, at least partially, by an excessive immune response. Pulmonary leukocyte infiltration is the result of a coordinated expression of diverse chemokines with distinct cellular specificities. Lipoxygenases (LOXs), as a key enzyme catalyzing deoxygenation of poly unsaturated fatty acids, regulate inflammation and have been suggested to play an important role in the immune response in viral infection. To expand our understanding on the possible role of LOX in respiratory viral infection, we studied the 12/15- lipoxygenase expression in RSV-related airway inflammation, and the related inflammatory chemokines, Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (C-C motif) ligand 3(CC L3) in both lung tissue and Bronchoalveolar lavage (BAL) fluid during experimental RSV infection. RSV infection induced mRNA expression of CCL5 and CCL3 in both BAL and lung tissue cells. In addition RSV infection enhanced expression of 12/15-LOX in both BAL and lung cells. In conclusion, we confirm that RSV infection leads to the increased expression of 12/15 LOX and the related chemokines CCL5 and CCL3 in BAL fluid and lung tissue cells suggesting that the 12/15 LOX pathway could serve as a candidate target for prevention and treatment of RSV infection.

Salimi|Vahid|V| Ramezani|Ali|A| Mirzaei|Habibollah|H| Tahamtan|Alireza|A| Faghihloo|Ebrahim|E| Rezaei|Farhad|F| Naseri|Maryam|M| Bont|Louis|L| Mokhtari-Azad|Talat|T| Tavakoli-Yaraki|Masoumeh|M|

D018357:Respiratory Syncytial Virus Infections

12/15 lipoxygenases
Respiratory syncytial virus
Chemokine
Inflammation


Diabetes mellitus might be a protective factor of glioma.

Abstract:
Aims
Several studies suggested that diabetes mellitus (DM) was associated with the risk of glioma. However, other studies did not confirm the result. Therefore, I conducted this meta-analysis.

Materials and Methods
I retrieved the PubMed, Embase, and Web of Science database, by adopting keywords "glioma," and "diabetes," "DM." The strength of the associations between DM and the risk of glioma was measured by odds ratios (ORs) with 95% confidence intervals (95% CIs).

Results
Ten relevant studies were identified in the final analysis. A statistically significant association between DM and glioma risk was fond (OR = 0.84; 95% CI, 0.73-0.97; P = 0.02). In the subgroup analysis of age group, young population with DM showed decreased glioma risk (OR = 0.83; 95% CI, 0.70-0.98; P = 0.02), whereas old population with DM did not show a significant association (OR = 0.87; 95% CI, 0.65-1.16; P = 0.34). In the subgroup analysis of gender, male patients with DM showed decreased glioma risk (OR = 0.82; 95% CI, 0.68-0.99; P = 0.04), whereas female population with DM did not show a significant association (OR = 0.93; 95% CI, 0.70-1.24; P = 0.63).

Conclusions
This meta-analysis suggested that DM may be associated with the reduced glioma risk.

diabetes mellitus
glioma
Association
meta-analysis


Clarification of phosphorus fractions and phosphorus release enhancement mechanism related to pH during waste activated sludge treatment.

Abstract: This study aimed to clarify phosphorus (P) fractions in waste activated sludge (WAS) and explore release performance and enhancement mechanism of different P species related to pH. Results showed that inorganic P (IP) was the major P fraction in raw sludge (87.86% of total solid P), and non-apatite inorganic P (NAIP), the most labile P forms, occupied 81.30% of IP, suggesting that WAS could be selected as potential substitution of phosphate rock. The optimized acid and alkaline conditions were pH=4 and pH=12 for molybdate reactive P accumulation, increased by 311.20mg/L and 479.18mg/L compared to raw sludge, which were 3.80 and 5.84 times higher than that of control, respectively. The mechanism study demonstrated that high pH promoted NAIP release, and apatite P was sensitive to low pH. Moreover, the releasable and recoverable P depended on both fractions of different P species in sludge and pH adjustment for sludge treatment.

He|Zhang-Wei|ZW| Liu|Wen-Zong|WZ| Wang|Ling|L| Tang|Cong-Cong|CC| Guo|Ze-Chong|ZC| Yang|Chun-Xue|CX| Wang|Ai-Jie|AJ|

Enhancement mechanism
pH
Waste activated sludge
Molybdate reactive P accumulation
Phosphorus species


Ethics skills laboratory experience for surgery interns.

Abstract:
INTRODUCTION AND PURPOSE
Ethics curricula are nearly universal in residency training programs, but the content and delivery methods are not well described, and there is still a relative paucity of literature evaluating the effect of ethics curricula. Several commentators have called for more ethics curriculum development at the postgraduate level, and specifically in surgery training. We detail our development and implementation of a clinical ethics curriculum for surgery interns.

METHODS
We developed curricula and simulated patient cases for 2 core clinical ethics skills--breaking bad news and obtaining informed consent. Educational sessions for each topic included (1) framework development (discussion of interns' current experience, development of a consensus framework for ethical practice, and comparison with established frameworks) and (2) practice with simulated patient followed by peer and faculty feedback. At the beginning and end of each session, we administered a test of confidence and knowledge about the topics to assess the effect of the sessions.

RESULTS
A total of 98 surgical interns participated in the ethics skills laboratory from Spring 2008 to Spring 2011. We identified significant improvement in confidence regarding the appropriate content of informed consent (<0.001) and capacity to break bad news (<0.001). We also identified significant improvement in overall knowledge regarding informed consent (<0.01), capacity assessment (<0.05), and breaking bad news (0.001). Regarding specific components of informed consent, capacity assessment, and breaking bad news, significant improvement was shown in some areas, while we failed to improve knowledge in others.

CONCLUSIONS
Through faculty-facilitated small group discussion, surgery interns were able to develop frameworks for ethical practice that paralleled established frameworks. Skills-based training in clinical ethics resulted in an increase in knowledge scores and self-reported confidence. Evaluation of 4 annual cohorts of surgery interns demonstrates significant successes and some areas for improvement in this educational intervention.

Moon|Margaret R|MR|
Hughes|Mark T|MT|
Chen|Jiin-Yu|JY|
Khaira|Kiran|K|
Lipsett|Pamela|P|
Carrese|Joseph A|JA|

D002983:Clinical Competence
D003479:Curriculum
D004503:Education, Medical, Graduate
D004521:Educational Measurement
D004992:Ethics, Medical
D013502:General Surgery
D006801:Humans
D007258:Informed Consent
D007396:Internship and Residency
D014342:Truth Disclosure

clinical ethics
informed consent
breaking bad news
Interpersonal and Communication Skills
Patient Care
Professionalism
graduate medical education


Complete mitochondrial genome and phylogenetic analysis of the chimney swift, Chaetura pelagica.

Abstract: The chimney swift (Chaetura pelagica) is a bird belonging to the swift family, Apodidae, a member of the genus Chaetur. Here, we report the complete mitogenome sequence of C. pelagica, which was 16 892 bp and contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 non-coding control region. Phylogenic tree was constructed based on the complete mitogenome of C. pelagica and closely related 11 closely related species to estimate their phylogenic relationship and to approve the accuracy. The complete mitochondrial genome of the C. pelagica would provide more information for the research of C. pelagica and the evolution of Apodidae family.


Differentiation of S. chartarum (Ehrenb.) S. Hughes Chemotypes A and S via FT-IR Spectroscopy.

Abstract: Stachybotrys (S.) chartarum is a cellulolytic mould with the ability to produce highly cytotoxic macrocyclic trichothecenes. Two chemotypes are defined according to their ability to produce either atranones or satratoxins. S. chartarum has been well known as the causative agent of the lethal disease stachybotryotoxicosis in horses. Further investigations revealed that this disease is strictly correlated with the presence of macrocyclic trichothecenes. Furthermore, their occurrence in water-damaged buildings has been linked to adverse health effects such as the sick building syndrome. As the chemotypes cannot be characterized via phenotypic criteria, different methods such as PCR, MALDI-TOF MS, LC-MS/MS, thin-layer chromatography and cytotoxicity assays have been used so far. Fourier-transform-infrared spectroscopy (FT-IR) is commonly used for the differentiation of bacteria and yeasts, but this technique is also applicable to filamentous fungi. Hence, this study aimed at evaluating to which extent a reliable differentiation of S. chartarum chemotypes A and S is possible. Besides, another objective was to verify if the recently introduced third genotype of S. chartarum can be identified. Therefore, 28 strains including the two chemotypes and the third genotype H were cultivated on malt extract agar (MEA) and potato dextrose agar in three biological replicates. Each sample was applied to FT-IR measurements on day 7, 14 and 21 of cultivation. In this study, we achieved a distinction of the chemotypes A and S via FT-IR spectroscopy after incubation for 7 days on MEA. In terms of genotype differentiation, the PCR detecting satratoxin- and atranone-gene clusters remained the only applicable method.

D017550:Spectroscopy, Fourier Transform Infrared

Macrocyclic trichothecenes
Fourier-transform-infrared spectroscopy
Stachybotrys chartarum
Triplex PCR


Time-motion analysis of acceleration demands of 4v4 small-sided soccer games played on different pitch sizes.

Abstract: We aimed to quantify the time-motion characteristics and technical demands of small-sided soccer games (SSGs) played on small, medium and large pitches using a high frequency non-differential global positioning system (NdGPS) that allowed assessment of acceleration and deceleration patterns. Eight male soccer players competed in SSGs comprising 4×4min quarters (3min recovery) on small (30×20m) medium (40×30m) and large (50×40m) pitch sizes. Time motion analysis using a NdGPS positioning system quantified distance covered sprinting (⩾6.7ms(-1)), high speed running (⩾5.8ms(-1)) and low (1-2ms(-2)), medium (2-3ms(-2)) and high (>3ms(-2)) acceleration. The frequency of common technical actions (passing, turning, dribbling, shooting, tackling, heading and interceptions) was performed using a hand notation system. SSGs played on medium and large pitches had a greater physical demand than on small pitches, with significantly more distance covered in all movement categories. Total distance covered in acceleration categories ranged from 230±111 (small pitch) to 356±72m (medium pitch). The small pitch imposed a greater technical demand on players (more passes, shots and tackles) compared to medium and large pitches. The study provides novel data demonstrating the acceleration patterns observed in SSGs are relatively greater than those observed during professional match play. Thus SSGs might offer a "density" type conditioning stimulus. Practitioners should be aware that changes in pitch size impact both the physical and technical demands of SSGs.

Fitness training
Football
GPS
Technical abilities
Time–motion analysis


Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar.

Abstract: The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection. Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019. What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities. Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality. The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body's innate immune response, and the vascular response to cytokine production. The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.

Giustino|Gennaro|G|
Pinney|Sean P|SP|
Lala|Anuradha|A|
Reddy|Vivek Y|VY|
Johnston-Cox|Hillary A|HA|
Mechanick|Jeffrey I|JI|
Halperin|Jonathan L|JL|
Fuster|Valentin|V|


The weight status of school-age children and its association with gross domestic product.

Abstract:
THE AIM
To examine the possible relationship between the prevalence of underweight, overweight and obesity of Polish children and adolescents and the gross domestic product per capita (GDP).

MATERIAL AND METHODS
This report is based on the results of a nationwide, representative population study. An area of the country, the so-called Eastern Poland, where GDP per capita is less than 80% of the national average, was designated, based on the data from the Central Statistical Office of Poland (CSOP) and was compared with the rest of the country. The frequency of underweight, normal weight, overweight and obesity, as well as the odds ratio were calculated for gender and region of residence. The body mass index (BMI) for age and sex was standardized and expressed as z-score. The statistical significance of standardized mean differences of BMI depending on the area was examined using the t-test.

RESULTS
There were significant differences in the prevalence of underweight, overweight and obesity between the regions analyzed. The region of Eastern Poland was characterized by a lower risk of overweight and obesity and an increased risk of underweight in comparison with the rest of the country.

CONCLUSIONS
Identification of the diverse prevalence of overweight and underweight depending on the region and determined according to the economic status is an opportunity to modify and adapt the strategy of implementing programs aimed at promoting healthy behaviours.

Grajda|Aneta|A| Kułaga|Zbigniew|Z| Gurzkowska|Beata|B| Góźdź|Magdalena|M| Wojtyło|Małgorzata|M| Litwin|Mieczysław|M|

D017195:Adolescent Nutritional Physiological Phenomena

D002664:Child Nutritional Physiological Phenomena

school-age children
underweight
overweight
obesity
GDP per capita


Transient Receptor Potential Channel 4 Small-Molecule Inhibition Alleviates Migraine-Like Behavior in Mice.

Abstract: Migraine is a common neurological disorder with few available treatment options. Recently, we have demonstrated the role of transient receptor potential cation channel subfamily C member 4 (TRPC4) in itch and the modulation of the calcitonin gene-related peptide (CGRP), a biomarker and emerging therapeutic target for migraine. In this study, we characterized the role of TRPC4 in pain and evaluated its inhibition as anti-migraine pain therapy in preclinical mouse models. First, we found that TRPC4 is highly expressed in trigeminal ganglia and its activation not only mediates itch but also pain. Second, we demonstrated that the small-molecule inhibitor ML204, a specific TRPC4 antagonist, significantly reduced episodic and chronic migraine-like behaviors in male and female mice after injection of nitroglycerin (NTG), a well-known migraine inducer in rodents and humans. Third, we found a significant decrease in CGRP protein levels in the plasma of both male and female mice treated with ML-204, which largely prevented the development of chronic migraine-like behavior. Using sensory neuron cultures, we confirmed that activation of TRPC4 elicited release of CGRP, which was significantly diminished by ML-204. Collectively, our findings identify TRPC4 in peripheral sensory neurons as a mediator of CGRP release and NTG-evoked migraine. Since a TRPC4 antagonist is already in clinical trials, we expect that this study will rapidly lead to novel and effective clinical treatments for migraineurs.

Cohen|Cinder Faith|CF|
Prudente|Arthur Silveira|AS|
Berta|Temugin|T|
Lee|Sang Hoon|SH|

transient receptor potential channels
migraine
TRPC4
CGRP
peripheral sensory neurons
headache


Does Organomineral Fertilizer Combined with Phosphate-Solubilizing Bacteria in Sugarcane Modulate Soil Microbial Community and Functions?

Abstract: Soil bacterial and fungal communities are suitable soil ecosystem health indicators due to their sensitivity to management practices and their role in soil ecosystem processes. Here, information on composition and functions of bacterial and fungal communities were evaluated at two phenological stages of sugarcane (six and twelve months, equivalent to the most intensive vegetative stage and to final maturation, respectively) when organomineral fertilizer, combined with phosphate-solubilizing bacteria (PSB), was added into the soil. Organic compost enriched with apatite (C + A) or phosphorite (C + P) and compost without phosphate enrichment (C) were used in the presence or absence of PSB. In addition, we used a control fertilized with soluble triple superphosphate. The differences were more related to the sampling period than to the type of organomineral fertilizer, being observed higher available phosphorus at six months than at twelve months. Only in the C treatment we observed the presence of Bacillaceae and Planococcaceae, while Pseudomonadaceae were only prevalent in inoculated C + A. As for fungi, the genera Chaetomium and Achroiostachys were only present in inoculated C + P, while the genus Naganishia was most evident in inoculated C + A and in uninoculated C + P. Soliccocozyma represented 75% of the total fungal abundance in uninoculated C while in inoculated C, it represented 45%. The bacterial community was more related to the degradation of easily decomposable organic compounds, while the fungal community was more related to degradation of complex organic compounds. Although the microbial community showed a resilient trait, subtle changes were detected in microbial community composition and function, and this may be related to the increase in yield observed.

Cardoso|Elke Jurandy Bran Nogueira|EJBN|http://orcid.org/0000-0003-3938-0373

Inoculants
Biofertilizer
Microbial dynamics
Phosphorus recovery
Soil organic matter