High Acute Myeloid Leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow

Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the relationship between vascular morphology within AML bone marrow biopsies and AML derived VEGFA levels. Vessel count and surface area (Chalkley count) were calculated in AML bone marrow biopsies at diagnosis (n = 32), at remission (n = 8) and Normal Bone Marrow (n = 32) using immunohistochemical staining for FVIII, CD31, CTIV, SMA and VEGFA. VEGFA protein levels were measured. High vessel count was associated with an immature vessel status. Combining vessel count and Chalkley count different vessel morphology patterns were quantified within AML bone marrow biopsies. Three different subgroups could be distinguished. The subgroup (37.5% of the samples) exhibiting a high vessel count and vessels with predominantly large lumen (normal Chalkley count) was associated with high secreted VEGFA protein levels. Different vasculature patterns are seen in AML bone marrow biopsies, defined by combining number and size of vessel. These quantified morphology patterns, combined with VEGFA levels, might be of value in the success of VEGF/VEGFR-signaling interference approaches

Attachment, infidelity, and loneliness in college students involved in a romantic relationship: the role of relationship satisfaction, morbidity and prayer for partner

This study examined the mediating effects of relationship satisfaction, prayer for a partner, and morbidity in the relationship between attachment and loneliness, infidelity and loneliness, and psychological morbidity and loneliness, in college students involved in a romantic relationship. Participants were students in an introductory course on family development. This study examined only students (n = 345) who were involved in a romantic relationship. The average age of participants was 19.46 (SD = 1.92) and 25 % were males. Short-form UCLA Loneliness Scale (ULS-8), (Hays and DiMatteo in J Pers Assess 51:69–81, doi:10.1207/s15327752jpa5101_6, 1987); Relationship Satisfaction Scale (Funk and Rogge in J Fam Psychol 21:572–583, doi:10.1037/0893-3200.21.4.572, 2007); Rotterdam Symptom Checklist (De Haes et al. in Measuring the quality of life of cancer patients with the Rotterdam Symptom Checklist (RSCL): a manual, Northern Centre for Healthcare Research, Groningen, 1996); Prayer for Partner Scale, (Fincham et al. in J Pers Soc Psychol 99:649–659, doi:10.1037/a0019628, 2010); Infidelity Scale, (Drigotas et al. in J Pers Soc Psychol 77:509–524, doi:10.1037/0022-3514.77.3.509, 1999); and the Experiences in Close Relationship Scale-short form (Wei et al. in J Couns Psychol 52(4):602–614, doi:10.1037/0022-0167.52.4.602, 2005). Results showed that relationship satisfaction mediated the relationship between avoidance attachment and loneliness and between infidelity and loneliness. Physical morbidity mediated the relationship between anxious attachment and psychological morbidity. Psychological morbidity mediated the relationship between anxious attachment and physical morbidity. The present results expand the literature on attachment by presenting evidence that anxious and avoidant partners experience loneliness differently. Implications for couple’s therapy are addressed. Future research should replicate these results with older samples and married couples.Acknowledgments This research was supported by Grant Number 90FE0022 from the United States Department of Health and Human Services awarded to the last author

Diversity and Seasonal Dynamics of an Assemblage of Sarcophagid Diptera in a Gradient of Urbanization

Sarcophagid species inhabiting different locations in a rural-urban gradient were surveyed in the east central Argentine district of the Almirante Brown, Buenos Aires province. The main objectives of this research were to identify the most prevalent sarcophagid species and to describe community richness and diversity according to the degree of urbanization and the environmental variables measured in three locations within a rural-urban gradient sampled during two years from May 2005 to April 2007. Spatial and seasonal variations were the main factors involved in structuring the sarcophagid communities. Diversity was lower in urbanized areas than in rural ones. Bait and microhabitat preferences (sunny or shady places) and seasonal fluctuations were described for 17 sarcophagid species

Enhanced genetic maps from family-based disease studies: population-specific comparisons

Abstract Background Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps. Results We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths. Conclusions Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.http://deepblue.lib.umich.edu/bitstream/2027.42/112826/1/12881_2010_Article_748.pd

Correlates of women's cancer screening and contraceptive knowledge among female emergency department patients

<p>Abstract</p> <p>Background</p> <p>Lack of knowledge regarding preventive health services for women might impede campaigns to expand these services in the emergency department setting. For 18–55-year-old English-speaking women visiting an urban emergency department, we aimed to: (1) Ascertain their knowledge regarding the applicability, purpose, and recommended intervals of three women's cancer screening and three contraceptive methods; and (2) Determine if patient age, race/ethnicity, medical insurance status, and current or recent usage of these methods are associated with greater or lesser knowledge about them.</p> <p>Methods</p> <p>Emergency department-based survey on recent or current usage and knowledge about Pap smears, breast self-examinations, mammograms, condoms, birth control, and emergency contraception. Analyses included calculation of summary statistics and creation of multivariable logistic regression models.</p> <p>Results</p> <p>Of 1,100 patients eligible for the study, 69.9% agreed to participate. Most of the participants were < age 35, white, single (never married and no partner), Catholic, and had private medical insurance. Participant's recent or current usage of a particular cancer screening or contraceptive method varied by type of method: Pap smear within the past year (69.1%), breast self-exam within the past month (45.5%), mammogram within the past year (65.7% for women age 45–55), condom usage during every episode of sexual intercourse (15.4%), current usage of birth control pills (17.8%), and ever use of emergency contraception (9.3%). The participants correctly answered 87.9% of all survey questions about condoms, 82.5% about birth control pills, 78.5% about breast self-exams, 52.9% about Pap smears, 35.4% about mammograms, and 25.0% about emergency contraception. In multivariable logistic regression models, survey participants who had private medical insurance and those who recently or currently used a given screening or contraceptive method had a greater odds of correctly answering all questions about each cancer screening or contraceptive method.</p> <p>Conclusion</p> <p>Although these female ED patients demonstrated strong knowledge on some women's cancer screening and contraceptive methods, there were several areas of knowledge deficit. Women without private medical insurance and those who have not used a particular cancer screening or contraceptive method demonstrated less knowledge. Reduced knowledge about women's cancer screening and contraceptive methods should be considered during clinical encounters and when instituting or evaluating emergency department-based initiatives that assess the need for these methods.</p

Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability

Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O2 responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca2+ transients, at least in some neurons: in maco-1 mutants the O2-sensing neuron PQR is unable to generate a Ca2+ response to a rise in O2. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O2, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca2+ channels, also fails to disrupt Ca2+ responses in the PQR cell body to O2 stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca2+ channel α1 subunit, recapitulate the Ca2+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or traffic of ion channels or ion channel regulators

Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system

A novel strategy for profiling Caenorhabditis elegans cells identifies transcripts highly enriched in either the embryonic or larval C. elegans nervous system, including 19 conserved transcripts of unknown function that are also expressed in the mammalian brain

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs