Clinical Audit of Sexual Abuse Referral Forms to the Sexual Assault Follow-up and Evaluation Clinic, Nassau, The Bahamas, among Females Aged 13 to 19 Years / Auditoría clínica de los formularios de remisión de abuso sexual a la Clínica de Evaluación y Seguimiento de Agresiones Sexuales, Nassau, Bahamas, entre mujeres de 13 a 19 años

ABSTRACT Objective: To evaluate the adequacy of the documentation of referral forms for sexually abused females aged 13-19 years directed to the Sexual Assault Follow-up and Evaluation (SAFE) Clinic at the Agape Family Medicine Clinic, Nassau, The Bahamas, for interim management. Methods: An approved review was performed on 123 referral forms regarding sexually abused females aged 13-19 years who attended the SAFE Clinic from 2011 to 2015. The exercise focussed on documentation adequacy based on a scoring system developed by the researchers (> 50% was assessed to be adequate; records of the referee's disposition of the patient, the date of the incident and evidence of sexually transmitted infection (STI) screening were considered vital for adequacy). Descriptive and inferential statistics were calculated. Results: The median age of the participants was 14 years (interquartile range: 13-15). Of the 63.4% (78) with documented nationality, 88.5% (69) were Bahamian and 11.5% (9) Haitian. Documentation status did not differ statistically significantly by nationality. Regarding documentation, 74% (91) recorded the name of the patient's school, 59.3% (73) recorded that the patient knew the assailant and 17.9% (22) indicated that the patient did not know the assailant, while 22.8% (28) did not document this latter information. Type of sexual penetration was indicated by 65.9% (81). Of the vital variables, 18.7% (23) recorded the referee's disposition of the patient, 29.8% (36) the date of the incident and 60.2% (74) evidence of STI screening; 7.3% (9) documented all three and 22.8% (28) two. The mean percentage of documentation for vital variables was 49.3% (± 3.6) for the Accident and Emergency (A&E) Department, Princess Margaret Hospital, Nassau, versus 30.5% (± 4.0) for public health clinics (PHCs) (p = 0.001). Overall, 69.9% (86 of 123) of the referral forms were deemed inadequate: 64.7% (33 of 51) from the A&E Department versus 73.4% (47 of 64) from PHCs among the 115 patients who provided referral information. Conclusion: Documentation deficiencies of the sexual abuse referral forms demand reform. Complete and consistent documentation is required.

RESUMEN Objetivo: Evaluar la idoneidad de la documentación de los formularios de remisión para mujeres de 13 a 19 años sexualmente abusadas, dirigidas a la Clínica de Evaluación y Seguimiento de Agresiones Sexuales (ESAS) en la Clínica Ágape de Medicina Familiar, Nassau, Bahamas, para la administración interina. Métodos: Se aprobó una revisión para examinar 123 formularios de remisión con respecto a las mujeres de 13 a 19 años sexualmente abusadas, que asistieron a la clínica de ESAS de 2011 a 2015. El ejercicio se centró en la idoneidad de la documentación basada en un sistema de puntuación desarrollado por los investigadores (50% fue adecuado según la valoración; los registros de la disposición de la paciente en el arbitraje, la fecha del incidente y la evidencia del tamizaje de la infección de transmisión sexual (ITS), fueron todos vitales a la hora de determinar la idoneidad). Se calcularon las estadísticas descriptivas e inferenciales. Resultados: La edad promedio de las participantes fue 14 años (rango intercuartil: 13-15). De 63.4% (78) con nacionalidad documentada, el 88.5% (69) fueron bahameñas y el 11.5% (9) haitianas. El estado de la documentación en término de las estadísticas no difirió significativamente por nacionalidad. Con respecto a la documentación, el 74% (91) registró el nombre de la escuela de la paciente, 59.3% (73) registró que la paciente conocía al agresor, y el 17.9% (22) indicó que la paciente no conocía al agresor, mientras que el 22.8% (28) no documentó esta última información. El tipo de penetración sexual fue indicado por 65.9% (81). De las variables vitales, 18.7% (23) registró la disposición de la paciente en el arbitraje, 29.8% (36) la fecha del incidente, y el 60.2% (74) evidencia del tamizaje de las ITS; 7.3% (9) documentó tres de ellas y 2.8% (28) dos. El porcentaje medio de documentación de las variables vitales fue 49.3% (± 3.6) para el Departamento de Accidentes y Emergencias (A&E), Hospital Princess Margaret, Nassau, frente al 30.5% (± 4.0) de las clínicas de salud pública (CSP) (p = 0.001). En general, el 69.9% (86 de 123) de los formularios de referencia se consideró inadecuado: 64.7% (33 de 51) del Departamento de A&E frente al 73.4% (47 de 64) de las CSP entre las 115 pacientes que proporcionaron la información de la remisión. Conclusión: Las deficiencias de la documentación de los formularios de remisión de abuso sexual exigen reformas. Se requiere una documentación completa y consistente.

Behavioral, transcriptomic and epigenetic responses to social challenge in honey bees.

Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer-term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting 2 and 1 h, respectively. Previous research also documented the whole-brain transcriptomic response; we now show that in the mushroom bodies (MBs) there are 2 waves of gene expression, the first highlighted by genes related to cytoskeleton remodeling, and the second highlighted by genes related to hormones, stress response and transcription factors (TFs). Overall, 16 of 37 (43%) of the TFs whose cis-motifs were enriched in the promoters of the differentially expressed genes (DEGs) were also predicted from transcriptional regulatory network analysis to regulate the MB transcriptional response, highlighting the strong role played by a relatively small subset of TFs in the MB's transcriptomic response to social challenge. Whole brain histone profiling showed few changes in chromatin accessibility in response to social challenge; most DEGs were 'ready' to be activated. These results show how biological embedding of a social challenge involves temporally dynamic changes in the neurogenomic state of a prominent region of the insect brain that are likely to influence future behavior.

Clinical audit of referrals for sexual abuse among females ages 13–19 years attending the Agape Family Medicine Clinic, Nassau, Bahamas, 2011–2015

OBJECTIVE: To evaluate the adequacy of the documentation of referrals for sexually abused females ages 13–19 years directed to the Agape Family Medicine Clinic for interim management. SUBJECTS AND METHODS: An approved review was performed on 123 referral forms regarding sexually abused females 13–19 years old who attended Agape’s Sexual Assault Follow-up and Evaluation (SAFE) clinic, Nassau, Bahamas. The exercise focussed on documentation adequacy based on a scoring system developed by the researchers: > 50% was assessed to be adequate, and recording disposition, date of incident and sexually transmitted infection (STI) screening was considered vital for adequacy. A current version of Statistical Package for the Social Sciences (IBM SPSS, v 21) generated descriptive and inferential statistics. RESULTS: Participants’ median age was 14 (IQR: 13, 15) years old. Of 63.4% (n = 78) with documented nationality, 88.5% (n = 69) were Bahamian and 11.5% (n = 9) Haitian. Documentation status did not differ statistically significantly by nationality. Regarding documentation, 74% (n =91) recorded school, 59.3% (n = 73) recorded knowing the assailant and 17.9% (n = 22) indicated not knowing. Approximately two-thirds (65.9%; n = 81) indicated penetration type; 18.7% recorded disposition, 29.8% (n =36) incident date and 60.2% STI screening; 7.3% (n = 9) documented all three and 22.8% (n = 28) two. Among public health clinics (PHCs), 45.3% (n = 29) did not indicate any of the three vital variables versus 7.8% (n = 4) for Accident and Emergency (A&E) referrals. Mean percent documentation for vital variables was 49.3 (± 3.6)%for A&E versus 30.5 (± 4.0)% for PHCs (p = 0.001). CONCLUSION: The deficient documentation status of referral forms demands the need for reform. Complete, consistent documentation is required.

Extent of linkage disequilibrium in chicken.

Many of the economically important traits in chicken are multifactorial and governed by multiple genes located at different quantitative trait loci (QTLs). The optimal marker density to identify these QTLs in linkage and association studies is largely determined by the extent of linkage disequilibrium (LD) around them. In this study, we investigated the extent of LD on two chromosomes in a white layer and two broiler chicken breeds. Pairwise levels of LD were calculated for 33 and 36 markers on chromosomes 10 and 28, respectively. We found that useful LD (i.e. an r(2) value higher than 0.3) in Nutreco chicken breed E5 (inbred) can extend to around 1 cM on chromosomes 10 and 28, although in a second region on chromosome 28 it extends to about 2.5 cM. The extent in breed Nutreco E3 (outbred) was very short in chromosome 10 (15 kb) but very much larger on chromosome 28, particularly in one region of depressed heterozygosity. The layer breed E2 (inbred) showed an extent of useful LD up to 4 cM on chromosome 10; the extent on chromosome 28 could not be assessed due to an erratic pattern of LD on that chromosome, although in one region LD appears to be in the order of 0.8 cM. This indicates that there may be very large differences in patterns of LD between different chicken breeds and different genomic regions.

Characterization of the region containing the jcpk PKD gene on mouse Chromosome 10.

The jcpk gene on mouse Chromosome 10 causes a severe, early onset form of polycystic kidney disease (PKD) when inherited in an autosomal recessive manner. In order to positionally clone this gene, high resolution genetic and radiation hybrid maps were generated along with a detailed physical map of the approximately 500-kb region containing the jcpk gene. Additionally, sixty-nine kidney-specific ESTs were evaluated as candidates for jcpk and subsequently localized throughout the mouse genome by radiation hybrid mapping analysis. Previous studies indicating non-complementation of the jcpk mutation and 67Gso, a new PKD translocation mutant had suggested that 67Gso represents a new allele of jcpk. Fluorescence in situ hybridization (FISH) analysis using key bacterial artificial chromosome clones from the jcpk critical region, refined the 67Gso breakpoint and provided support for the allelism of jcpk and 67Gso.

Imprinting and evolution of two Kruppel-type zinc-finger genes, ZIM3 and ZNF264, located in the PEG3/USP29 imprinted domain.

We have isolated Kruppel-type (C2H2) zinc-finger genes, ZIM3 (zinc-finger gene 3 from imprinted domain) and ZNF264, located downstream of human and mouse USP29 genes (encoding ubiquitin-specific processing protease 29). In human, both ZIM3 and ZNF264 encode zinc-finger proteins with Kruppel-associated box (KRAB) A and B domains at the amino-terminal regions of the predicted proteins. In contrast, mouse Zim3 and Zfp264 seem to have lost protein-coding capability based on the lack of open reading frames (ORFs) in their cDNA sequences. In particular, the 3' end of the Zim3 transcript overlaps with the coding region of the adjacent gene Usp29 in an antisense orientation, indicating the conversion of mouse Zim3 into an antisense transcript gene for Usp29. The expression patterns of ZIM3 and ZNF264 have been largely conserved between human and mouse, with testis-specific expression of ZIM3 and ubiquitous expression of ZNF264, but high expression levels in adult testes in both species. Our studies also demonstrate that both mouse genes are imprinted with maternal expression of Zim3 in adult testes and paternal expression of Zfp264 in neonatal and adult brain. The reciprocal imprinting of two neighboring mouse genes, Zim3 and Zfp264, is consistent with a pattern observed frequently in other imprinted domains, and suggests that the imprinting of these two genes might be coregulated.

Human chromosome 19 and related regions in mouse: conservative and lineage-specific evolution.

To illuminate the function and evolutionary history of both genomes, we sequenced mouse DNA related to human chromosome 19. Comparative sequence alignments yielded confirmatory evidence for hypothetical genes and identified exons, regulatory elements, and candidate genes that were missed by other predictive methods. Chromosome-wide comparisons revealed a difference between single-copy HSA19 genes, which are overwhelmingly conserved in mouse, and genes residing in tandem familial clusters, which differ extensively in number, coding capacity, and organization between the two species. Finally, we sequenced breakpoints of all 15 evolutionary rearrangements, providing a view of the forces that drive chromosome evolution in mammals.

Homology-driven assembly of a sequence-ready mouse BAC contig map spanning regions related to the 46-Mb gene-rich euchromatic segments of human chromosome 19.

Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.

Cryptic translocation identification in human and mouse using several telomeric multiplex fish (TM-FISH) strategies.

Experimental data published in recent years showed that up to 10% of all cases of mild to severe idiopathic mental retardation may result from small rearrangements of the subtelomeric regions of human chromosomes. To detect such cryptic translocations, we developed a "telomeric" multiplex fluorescence in situ hybridization (M-FISH) assay, using a set of previously published and commercially available subtelomeric probes. This set of probes includes 41 cosmid/PAC/P1 clones located from less than 100 kilobases to approximately 1 megabase from the end of the chromosomes. Similarly, a published mouse probe set, comprised of BACs hybridizing to the closest known marker toward the centromere and telomere of each mouse chromosome, was used to develop a mouse-specific "telomeric" M-FISH. Three different combinatorial labeling strategies were used to simultaneously detect all human subtelomeric regions on one slide. The simplest approach uses only three fluors and can be performed in laboratories lacking sophisticated imaging equipment or personnel highly trained in cytogenetics. A standard fluorescence microscope equipped with only three filters is sufficient. Fluor-dUTPs and labeled probes can be custom made, thus dramatically reducing costs. Images can be prepared using imaging software (Adobe Photoshop) and analysis performed by simple visual inspection.

Defining the minimal length of sequence homology required for selective gene isolation by TAR cloning.

The transformation-associated recombination (TAR) cloning technique allows selective and accurate isolation of chromosomal regions and genes from complex genomes. The technique is based on in vivo recombination between genomic DNA and a linearized vector containing homologous sequences, or hooks, to the gene of interest. The recombination occurs during transformation of yeast spheroplasts that results in the generation of a yeast artificial chromosome (YAC) containing the gene of interest. To further enhance and refine the TAR cloning technology, we determined the minimal size of a specific hook required for gene isolation utilizing the Tg.AC mouse transgene as a targeted region. For this purpose a set of vectors containing a B1 repeat hook and a Tg.AC-specific hook of variable sizes (from 20 to 800 bp) was constructed and checked for efficiency of transgene isolation by a radial TAR cloning. When vectors with a specific hook that was >/=60 bp were utilized, approximately 2% of transformants contained circular YACs with the Tg.AC transgene sequences. Efficiency of cloning dramatically decreased when the TAR vector contained a hook of 40 bp or less. Thus, the minimal length of a unique sequence required for gene isolation by TAR is approximately 60 bp. No transgene-positive YAC clones were detected when an ARS element was incorporated into a vector, demonstrating that the absence of a yeast origin of replication in a vector is a prerequisite for efficient gene isolation by TAR cloning.

Neuroepithelial defects of the inner ear in a new allele of the mouse mutation Ames waltzer.

This report presents new findings regarding a recessive insertional mutation in the transgenic line TgN2742Rpw that causes deafness and circling behavior in mice homozygous for the mutation. The mutant locus was mapped to a region on mouse chromosome 10 close to three spontaneous recessive mutations causing deafness: Ames waltzer (av), Waltzer (v), and Jackson circler (jc). Complementation testing revealed that the TgN2742Rpw mutation is allelic with av. Histological and auditory brainstem response (ABR) evaluation of animals that have the new allele balanced with the av(J) allele (called compound heterozygotes, TgN2742Rpw/av(J)) supports our genetic analysis. ABR evaluation shows complete absence of auditory response throughout the life span of TgN2742Rpw/av(J) compound heterozygotes. Scanning electron microscopy revealed abnormalities of inner and outer hair cell stereocilia in the cochleae of TgN2742Rpw mutants at 10 days after birth (DAB). The organ of Corti subsequently undergoes degeneration, leading to nearly complete loss of the cochlear neuroepithelium in older mutants by about 50 DAB. The vestibular neuroepithelia remain morphologically normal until at least 30 DAB. However, by 50 days, degenerative changes are evident in the saccular macula, which progresses to total loss of the saccular neuroepithelium in older animals. The new allele of av reported here will be designated av(TgN2742Rpw).

Discovery of a novel, paternally expressed ubiquitin-specific processing protease gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4.

Using mouse BAC clones spanning an imprinted interval of proximal mouse chromosome 7 and the genomic sequence of the related interval of human chromosome 19q13.4, we have identified a novel mouse gene, Usp29 (ubiquitin-specific processing protease 29), near two known imprinted genes, Peg3 and Zim1. Gene Usp29 is located directly adjacent to Peg3 in a "head-to-head" orientation, and comprises exons distributed over a genomic distance of at least 400 kb. A similar human gene is also found in the homologous location in human chromosome 19q13.4. The mouse Usp29 gene is also imprinted and is transcribed mainly from the paternal allele with highest expression levels in adult brain, especially in the cerebral cortex and hippocampus, and in the forebrain, face, and limb buds of midgestation mouse embryos. Analysis of a full-length 7.6-kb cDNA clone revealed that Usp29 encodes an 869-amino-acid protein that displays significant homology with yeast and nematode ubiquitin carboxyl-terminal hydrolases. These data suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase), Usp29 may represent another imprinted gene involved in the ubiquitination pathway. This identification of a third imprinted gene, Usp29, from the Peg3/Zim1-region confirms the presence of a conserved imprinted domain spanning at least 500 kb in the proximal portion of mouse chromosome 7 (Mmu7).

Exon sharing of a novel human zinc-finger gene, ZIM2, and paternally expressed gene 3 (PEG3).

We have identified a novel human gene, ZIM2 (zinc-finger gene 2 from imprinted domain), located 25 kb downstream of PEG3 (paternally expressed gene 3). ZIM2 produces two different-size transcripts, 2.5 and 9.0 kb in length, with highest levels of expression in adult testis and modest levels in fetal kidney and brain. The 2.5-kb transcript of ZIM2 consists of 11 exons and encodes a Kruppel-type (C2H2) zinc-finger protein with a conserved Kruppel-associated box (KRAB) domain. Rapid amplification of cDNA ends and cDNA sequencing studies showed that ZIM2 and PEG3 transcripts share identical 5'-ends, composed of 7 small exons. Alternative splicing events connect these 7 exons either with the remaining 2 exons of PEG3 or with the remaining 4 exons of ZIM2. Interestingly, the third among the 7 shared exons exhibits sequence similarity to leucine-rich domains that are found at the N-terminal region of a subset of KRAB-containing zinc-finger genes. Sequencing of the 5'-termini of both transcripts indicates that ZIM2 and PEG3 share identical transcription start sites and may also share upstream regulatory elements, although the two genes show distinct patterns of tissue-specific expression.

Expression specificity of the mouse exonuclease 1 (mExo1) gene.

Genetic recombination involves either the homo-logous exchange of nearly identical chromosome regions or the direct alignment, annealing and ligation of processed DNA ends. These mechanisms are involved in repairing potentially lethal or mutagenic DNA damage and generating genetic diversity within the meiotic cell population and antibody repertoire. We report here the identification of a mouse gene, termed mExo1 for mouse exonuclease 1, which encodes a approximately 92 kDa protein that shares homology to proteins of the RAD2 nuclease family, most notably human 5' to 3' exonuclease Hex1/hExo1, yeast exonuclease 1 (Exo1) proteins and Drosophila melanogaster Tosca. The mExo1 gene maps to distal chromosome 1, consistent with the recent mapping of the orthologous HEX1 / hEXO1 gene to chromosome 1q42-q43. mExo1 is expressed prominently in testis, an area of active homologous recombination, and spleen, a prominent lymphoid tissue. An increased level of mExo1 mRNA was observed during a stage of testis development where cells that are actively involved in meiotic recombination arise first and represent a significant proportion of the germ cell population. Comparative evaluation of the expression patterns of the human and mouse genes, combined with previous biochemical and yeast genetic studies, indicate that the Exo1-like proteins are important contributors to chromosome processing during mammalian DNA repair and recombination.

A new mouse insertional mutation that causes sensorineural deafness and vestibular defects.

This article describes a new recessive insertional mutation in the transgenic line TgN2742Rpw that causes deafness and circling behavior in mice. Histologic analysis revealed virtually complete loss of the cochlear neuroepithelium (the organ of Corti) in adult mutant mice. In association with the neuroepithelial changes, there is a dramatic reduction of the cochlear nerve supply. Adult mutants also show morphological defects of the vestibular apparatus, including degeneration of the saccular neuroepithelium and occasional malformation of utricular otoconia. Audiometric evaluations demonstrated that the mice displaying the circling phenotype are completely deaf. Molecular analysis of this mutant line revealed that the transgenic insertion occurred without creating a large deletion of the host DNA sequences. The mutant locus was mapped to a region on mouse chromosome 10, where other spontaneous, recessive mutations causing deafness in mice have been mapped.

Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice.

The juvenile development and fertility-2 (jdf2) locus, also called runty-jerky-sterile (rjs), was originally identified through complementation studies of radiation-induced p-locus mutations. Studies with a series of ethylnitrosourea (ENU)-induced jdf2 alleles later indicated that the pleiotropic effects of these mutations were probably caused by disruption of a single gene. Recent work has demonstrated that the jdf2 phenotype is associated with deletions and point mutations in Herc2, a gene encoding an exceptionally large guanine nucleotide exchange factor protein thought to play a role in vesicular trafficking. Here we describe the molecular characterization of a collection of radiation- and chemically induced jdf2/Herc2 alleles. Ten of the 13 radiation-induced jdf2 alleles we studied are deletions that remove specific portions of the Herc2 coding sequence; DNA rearrangements were also detected in two additional mutations. Our studies also revealed that Herc2 transcripts are rearranged, not expressed, or are present in significantly altered quantities in animals carrying most of the jdf2 mutations we analyzed, including six independent ENU-induced alleles. These data provide new molecular clues regarding the wide range of jdf2 and p phenotypes that are expressed by this collection of recently generated and classical p-region mutations.