Mental health disparities of sexual minority refugees and asylum seekers: Provider perspectives on trauma exposure, symptom presentation, and treatment approach.

Refugees and asylum seekers who identify as sexual minorities and/or who have been persecuted for same-sex acts maneuver through multiple oppressive systems at all stages of migration. Sexual minority refugees and asylum seekers (SM RAS) report experiencing a greater number of persecutory experiences and worse mental health symptoms than refugees and asylum seekers persecuted for reasons other than their sexual orientation (non-SM RAS). SM RAS are growing in numbers, report a need and desire for mental health treatment, and are often referred to therapy during the asylum process. However, little research has been conducted on the treatment needs of SM RAS in therapy or the strategies therapists use to address these needs. This study sought to identify these factors through qualitative interviews with providers at a specialty refugee mental health clinic (N = 11), who had experience treating both SM RAS and non-SM RAS. Interviews were transcribed and coded for themes of similarities and differences between SM RAS and non-SM RAS observed during treatment and factors that could be leveraged to reduce mental health disparities between SM RAS and non-SM RAS. Clinicians reported that compared to the non-SM RAS, SM RAS reported greater childhood trauma exposure, increased isolation, decreased support, identity-related shame, difficulty trusting others, and continued discrimination due to their SM identitiy. Suggested adaptations included reducing isolation, preparing for ongoing identity-based challenges, creating safe spaces to express SM identity, and a slower treatment pace. Providers reported benefits and drawbacks to centering the client's SM identity in treatment and encouraging community involvement for SM RAS, and noted additional training in cultural awareness would be beneficial. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Demographic characteristics, torture experiences, and posttraumatic stress disorder symptoms among asylum seekers and refugees persecuted for same-sex behaviors.

Increasingly, lesbian, gay, and bisexual (LGB) individuals are fleeing the 67 countries that criminalize consensual same-sex intimate relationships, seeking asylum in countries such as the United States. Minority stress theory posits that compared with non-LGB refugees and asylum seekers (RAS), LGB RAS are likely to face persecution, rejection, and discrimination and have a higher risk of experiencing posttraumatic stress disorder (PTSD) symptoms. This study assessed differences in sociodemographic characteristics, persecution experiences, and mental health outcomes among 959 RAS persecuted for same-sex behavior (pLGB RAS) who presented for care and social services at the Boston Center for Refugee Health and Human Rights. Data were derived from intake interviews with RAS clients that elicited torture experiences and assessed PTSD symptoms using the Short Screening Scale for PTSD. Over 11% of the total sample were pLGB RAS. Compared with non-pLGB RAS, pLGB RAS reported higher PTSD symptom levels, ß = .08, p = .031; more difficulty loving others, d = 0.13, p < .001; and feeling more isolated, d = 0.10, p = .005. pLGB RAS reported more persecution, d = 0.31, p = .002; physical assaults, d = 0.22, p = .029; and psychological assaults, d = 0.20, p = .047; and were more likely to be asylum seekers, d = 0.11, p = .001, and have experienced persecution in Uganda, d = 0.39, p < .001, and other countries that criminalize same-sex acts, d = 0.26, p < .001. More research is needed to understand clinical outcomes and implications of treatment for this population.

Going against the Norm: A Mixed Methods Analysis of College Students' Arguments against the College Drinking Culture.

College alcohol beliefs (e.g. "College is a time for experimentation with alcohol") are highly predictive of heavy drinking and its consequences. Yet, current college alcohol interventions do not address this belief system even though researchers have recommended that these beliefs be targeted.Using a mixed methods approach, we conducted two studies to generate arguments against the college drinking culture and to evaluate the effectiveness of such arguments.In Study 1, freshman students (N = 104, 65% women) wrote an essay to a fictitious roommate presenting arguments against the college drinking culture. Responses were reliably coded into a 19-category scheme. The most common arguments included that (1) one's focus should be on academics, (2) drinking will lead to academic consequences, and (3) drinking is not a rite of passage in college. In Study 2, college students (N = 488) rated the effectiveness of prototype arguments drawn from each Study 1 category. According to their ratings, the most effective arguments were that (1) one's focus should be on academics, (2) drinking could have a negative impact on one's career, and (3) one could do potential harm to others.The student-generated arguments against the college drinking culture identified in his research have inherent ecological validity and will help inform the development of new interventions to counter such beliefs. We offer suggestions for translating our findings into clinical interventions.The problem of college student drinking has been long-standing (Kilmer et al., 2014) and remains a significant public health issue today (Hingson et al., 2017). Decades of research on college student drinking and its consequences have identified key cognitive factors that underlie drinking and its consequences, such as the misperception of norms for drinking (Borsari & Carey, 2003) and the positive expectancies students hold about the effects of drinking (Jones et al., 2001; Monk & Heim, 2013). The robust relationships between these cognitive variables and alcohol consumption among college students have led to the development of interventions that target these variables. Social norms marketing campaigns (DeJong et al., 2006), personalized normative feedback (Lewis & Neighbors, 2006), and expectancy challenge techniques (Scott-Sheldon et al., 2012) have been a part of interventions designed to correct students' misperceptions about the percentage of and amount students drink and the effects that alcohol has on their functioning in social situations. Reviews of the literature have demonstrated that interventions containing these components are effective for first year students (Scott-Sheldon et al., 2014) and mandated students (Carey et al., 2016), except for interventions targeting student members of Greek letter organizations (Scott-Sheldon et al., 2016). Effect sizes in most interventions across freshman and mandated students tend to be modest and not very durable in the long-term (Carey et al., 2016; Scott-Sheldon et al., 2014). However, recent research reveals that a variety of new intervention strategies may be useful in addressing the problem of college student drinking (Dunn et al., 2020; Kazemi et al., 2020; King et al., 2020; Magill et al., 2017; Pedrelli et al., 2020; Young & Neighbors, 2019). Aside from social norms and positive alcohol expectancies, another cognitive variable has been found to be a very robust predictor, mediator, and moderator of college student drinking and its consequences - college alcohol beliefs (Crawford & Novak, 2006; Osberg et al., 2010).

Accuracy of Home-Based Ultrasonographic Diagnosis of Obstetric Risk Factors by Primary-Level Health Care Workers in Rural Nepal.

OBJECTIVE: To assess the feasibility of ultrasonographic task shifting by estimating the accuracy at which primary-level health care workers can perform community-based third-trimester ultrasound diagnosis for selected obstetric risk factors in rural Nepal. METHODS: Three auxiliary nurse-midwives received two 1-week ultrasound trainings at Tribhuvan University Teaching Hospital in Kathmandu. At a study site in rural Nepal, pregnant women who were 32 weeks of gestation or greater were enrolled and received ultrasound examinations from the auxiliary nurse-midwives during home visits. Each auxiliary nurse-midwife screened for noncephalic presentation, multiple gestation, and placenta previa. Deidentified digital ultrasonograms were stored and uploaded onto an online server, where certified sonologists and ultrasonographers reviewed the images and made their own diagnoses for the three conditions. Accuracy of auxiliary nurse-midwife diagnoses was then calculated. RESULTS: A total of 804 women contributed to the analysis. Each auxiliary nurse-midwife's κ statistic for diagnosis of noncephalic presentation was above 0.90 compared with the ultrasonogram reviewers. Sensitivity, specificity, and positive and negative predictive values were between 90% and 100% for all auxiliary nurse-midwives. For multiple gestation, the auxiliary nurse-midwives were in perfect agreement with both the ultrasonogram reviewers and maternal postpartum self-report. Two placenta previa cases were detected, and the ultrasonogram reviewers agreed with both. CONCLUSION: With limited training, primary-level health care workers in rural Nepal can accurately diagnose selected third-trimester obstetric risk factors using ultrasonography.

Mutation spectrum revealed by breakpoint sequencing of human germline CNVs.

Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 1-30 bp of microhomology, whereas 33% of deletion breakpoints contain 1-367 bp of inserted sequence. The co-occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible.

Population genomics of human gene expression.

Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants. Here we have used gene expression profiling of Epstein-Barr virus-transformed lymphoblastoid cell lines of all 270 individuals genotyped in the HapMap Consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find that gene expression is heritable and that differentiation between populations is in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency in HapMap) with gene expression identified at least 1,348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis signals and 15% of trans signals, respectively. Our results strongly support an abundance of cis-regulatory variation in the human genome. Detection of trans effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. We also explore several methodologies that improve the current state of analysis of gene expression variation.

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21.

The goals of the human genome project did not include sequencing of the heterochromatic regions. We describe here an initial sequence of 1.1 Mb of the short arm of human chromosome 21 (HSA21p), estimated to be 10% of 21p. This region contains extensive euchromatic-like sequence and includes on average one transcript every 100 kb. These transcripts show multiple inter- and intrachromosomal copies, and extensive copy number and sequence variability. The sequencing of the "heterochromatic" regions of the human genome is likely to reveal many additional functional elements and provide important evolutionary information.

Fast-evolving noncoding sequences in the human genome.

BACKGROUND: Gene regulation is considered one of the driving forces of evolution. Although protein-coding DNA sequences and RNA genes have been subject to recent evolutionary events in the human lineage, it has been hypothesized that the large phenotypic divergence between humans and chimpanzees has been driven mainly by changes in gene regulation rather than altered protein-coding gene sequences. Comparative analysis of vertebrate genomes has revealed an abundance of evolutionarily conserved but noncoding sequences. These conserved noncoding (CNC) sequences may well harbor critical regulatory variants that have driven recent human evolution. RESULTS: Here we identify 1,356 CNC sequences that appear to have undergone dramatic human-specific changes in selective pressures, at least 15% of which have substitution rates significantly above that expected under neutrality. The 1,356 'accelerated CNC' (ANC) sequences are enriched in recent segmental duplications, suggesting a recent change in selective constraint following duplication. In addition, single nucleotide polymorphisms within ANC sequences have a significant excess of high frequency derived alleles and high F(ST) values relative to controls, indicating that acceleration and positive selection are recent in human populations. Finally, a significant number of single nucleotide polymorphisms within ANC sequences are associated with changes in gene expression. The probability of variation in an ANC sequence being associated with a gene expression phenotype is fivefold higher than variation in a control CNC sequence. CONCLUSION: Our analysis suggests that ANC sequences have until very recently played a role in human evolution, potentially through lineage-specific changes in gene regulation.

Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials.

X inactivation, the transcriptional silencing of one of the two X chromosomes in female mammals, achieves dosage compensation of X-linked genes relative to XY males. In eutherian mammals X inactivation is regulated by the X-inactive specific transcript (Xist), a cis-acting non-coding RNA that triggers silencing of the chromosome from which it is transcribed. Marsupial mammals also undergo X inactivation but the mechanism is relatively poorly understood. We set out to analyse the X chromosome in Monodelphis domestica and Didelphis virginiana, focusing on characterizing the interval defined by the Chic1 and Slc16a2 genes that in eutherians flank the Xist locus. The synteny of this region is retained on chicken chromosome 4 where other loci belonging to the evolutionarily ancient stratum of the human X chromosome, the so-called X conserved region (XCR), are also located. We show that in both M. domestica and D. virginiana an evolutionary breakpoint has separated the Chic1 and Slc16a2 loci. Detailed analysis of opossum genomic sequences revealed linkage of Chic1 with the Lnx3 gene, recently proposed to be the evolutionary precursor of Xist, and Fip1, the evolutionary precursor of Tsx, a gene located immediately downstream of Xist in eutherians. We discuss these findings in relation to the evolution of Xist and X inactivation in mammals.

Relative impact of nucleotide and copy number variation on gene expression phenotypes.

Extensive studies are currently being performed to associate disease susceptibility with one form of genetic variation, namely, single-nucleotide polymorphisms (SNPs). In recent years, another type of common genetic variation has been characterized, namely, structural variation, including copy number variants (CNVs). To determine the overall contribution of CNVs to complex phenotypes, we have performed association analyses of expression levels of 14,925 transcripts with SNPs and CNVs in individuals who are part of the International HapMap project. SNPs and CNVs captured 83.6% and 17.7% of the total detected genetic variation in gene expression, respectively, but the signals from the two types of variation had little overlap. Interrogation of the genome for both types of variants may be an effective way to elucidate the causes of complex phenotypes and disease in humans.

Functional variation and evolution of non-coding DNA.

The focus of large genomic studies has shifted from only looking at genes and protein-coding sequences to exploring the full set of elements in each genome. The explosion of comparative sequencing data has led to an increase in methodologies, approaches and ideas on how to analyze the unknown fraction of the genome, namely the non-protein-coding fraction. The main issues relate to the discovery, evolutionary analysis and natural variation of non-coding DNA, and the parameters that prevent us from fully understanding the properties of non-coding DNA.

Conserved noncoding sequences are selectively constrained and not mutation cold spots.

Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals, suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new (derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation.

Progressive proximal expansion of the primate X chromosome centromere.

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the functional centromere. We analyzed the finished sequence of this human genomic region to investigate its evolutionary history. Phylogenetic analysis of >1,500 alpha-satellite monomers from the region revealed the presence of five physical domains, each containing monomers from a distinct phylogenetic clade. The most distal domain contains long interspersed nucleotide element repeats that were active >35 million years ago, whereas the four proximal domains contain more recently active long interspersed nucleotide element repeats. An out-of-register, unequal recombination (i.e., crossover) detected at the edge of the X chromosome-specific alpha-satellite array (DXZ1) may reflect the most recent of a series of punctuating events during evolution that resulted in a proximal physical expansion of the X centromere. The first 18 kb of this array has 97-99% pairwise identity among all 2-kb repeat units. To perform more detailed evolutionary comparisons, we sequenced the junction between the ancient DNA of Xp and the primate-specific alpha satellite in chimpanzee, gorilla, orangutan, vervet, macaque, and baboon. The striking conservation found in all cases supports the ancestral nature of the alpha satellite at this location. These studies demonstrate that the primate X centromere appears to have evolved through repeated expansion events occurring within the central, active region of centromeric DNA, with the newly added sequences then conferring centromere function.

The DNA sequence of the human X chromosome.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Complete nucleotide sequence of the conjugative tetracycline resistance plasmid pFBAOT6, a member of a group of IncU plasmids with global ubiquity.

This study presents the first complete sequence of an IncU plasmid, pFBAOT6. This plasmid was originally isolated from a strain of Aeromonas caviae from hospital effluent (Westmorland General Hospital, Kendal, United Kingdom) in September 1997 (G. Rhodes, G. Huys, J. Swings, P. McGann, M. Hiney, P. Smith, and R. W. Pickup, Appl. Environ. Microbiol. 66:3883-3890, 2000) and belongs to a group of related plasmids with global ubiquity. pFBAOT6 is 84,748 bp long and has 94 predicted coding sequences, only 12 of which do not have a possible function that has been attributed. Putative replication, maintenance, and transfer functions have been identified and are located in a region in the first 31 kb of the plasmid. The replication region is poorly understood but exhibits some identity at the protein level with replication proteins from the gram-positive bacteria Bacillus and Clostridium. The mating pair formation system is a virB homologue, type IV secretory pathway that is similar in its structural organization to the mating pair formation systems of the related broad-host-range (BHR) environmental plasmids pIPO2, pXF51, and pSB102 from plant-associated bacteria. Partitioning and maintenance genes are homologues of genes in IncP plasmids. The DNA transfer genes and the putative oriT site also exhibit high levels of similarity with those of plasmids pIPO2, pXF51, and pSB102. The genetic load region encompasses 54 kb, comprises the resistance genes, and includes a class I integron, an IS630 relative, and other transposable elements in a 43-kb region that may be a novel Tn1721-flanked composite transposon. This region also contains 24 genes that exhibit the highest levels of identity to chromosomal genes of several plant-associated bacteria. The features of the backbone of pFBAOT6 that are shared with this newly defined group of environmental BHR plasmids suggest that pFBAOT6 may be a relative of this group, but a relative that was isolated from a clinical bacterial environment rather than a plant-associated bacterial environment.

Dispersal of NK homeobox gene clusters in amphioxus and humans.

The Drosophila melanogaster genome has six physically clustered NK-related homeobox genes in just 180 kb. Here we show that the NK homeobox gene cluster was an ancient feature of bilaterian animal genomes, but has been secondarily split in chordate ancestry. The NK homeobox gene clusters of amphioxus and vertebrates are each split and dispersed at two equivalent intergenic positions. From the ancestral NK gene cluster, only the Tlx-Lbx and NK3-NK4 linkages have been retained in chordates. This evolutionary pattern is in marked contrast to the Hox and ParaHox gene clusters, which are compact in amphioxus and vertebrates, but have been disrupted in Drosophila.

Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting.

Comparative genomic sequence analysis is a powerful technique for identifying regulatory regions in genomic DNA. However, its utility largely depends on the evolutionary distances between the species involved. Here we describe the screening of a genomic BAC library from the stripe-faced dunnart, Sminthopsis macroura, formerly known as the narrow-footed marsupial mouse. We isolated a clone containing the LYL1 locus, completely sequenced the 60.6-kb insert, and compared it with orthologous human and mouse sequences. Noncoding homology was substantially reduced in the human/dunnart analysis compared with human/mouse, yet we could readily identify all promoters and exons. Human/mouse/dunnart alignments of the LYL1 candidate promoter allowed us to identify putative transcription factor binding sites, revealing a pattern highly reminiscent of critical regulatory regions of the LYL1 paralogue, SCL. This newly identified LYL1 promoter showed strong activity in myeloid progenitor cells and was bound in vivo by Fli1, Elf1, and Gata2-transcription factors all previously shown to bind to the SCL stem cell enhancer. This study represents the first large-scale comparative analysis involving marsupial genomic sequence and demonstrates that such comparisons provide a powerful approach to characterizing mammalian regulatory elements.