Prevalence and correlates of depression, posttraumatic stress disorder, and suicidality in Jordanian youth in institutional care.

Youth in institutional care centers have higher mental illness rates compared with community populations. Research examining mental illness among youth in institutional care in the Middle East is lacking. This study examines the prevalence and correlates of depression, posttraumatic stress disorder (PTSD), and suicidality of youth in institutional care in Jordan. Data were collected through youth interviews, staff-caregiver surveys, and administrative files. Prevalence rates and logistic regressions were used to model suicidality across depression, PTSD, and comorbid depression/PTSD, controlling for youth characteristics, case history, and social support factors. Institutionalized youth endorsed high rates of mental illness (45% depression, 24% PTSD, 17% depression/PTSD, 27% suicidality). The odds of suicidality for depressed youth were 3.6 times higher. Abuse was significant, with the odds of suicidality for abused youth 4 times higher. Elevated rates of mental illness and suicidality indicate the importance of addressing these needs within institutions. Developing institutional programs that foster peer relationships is recommended.

Stigma and mental health treatment of adolescents with depression in jordan.

Stigma is a fundamental barrier to seeking and engaging in mental health treatment for individuals managing depression. This study examines stigma perceptions of mental health treatment for Arab adolescents managing depression using a vignette survey completed by adults in public spaces in Amman, Jordan (n = 108). The vignette was systematically changed across four different conditions that varied the described youth's gender and whether or not they were receiving treatment for their depression. Two-way ANOVAs found that gender and receipt of mental health treatment influenced perceptions of stigma. Seeking treatment, however, did not increase perceived stigma, and receiving mental health treatment rather than no treatment was found as more likely to be a helpful approach for both males and females. Findings indicate that personal level stigma may have greater effects on females whereas public stigma may exert more influence on males. Participants endorsed that adolescents with depression are most likely to be helped when a family sought treatment rather than not seeking treatment. Findings also indicate that the community seems to appreciate the need for treatment and the likelihood of benefiting from formal mental health services.

Assessment of adolescent mental health and behavioral problems in institutional care: discrepancies between staff-reported CBCL scores and adolescent-reported YSR scores.

For children residing in institutional settings, staff act as primary caregivers and often provide assessment of child psychopathology. Minimal research exists on how and when staff-caregivers are best positioned to report on youth mental health. This study examines differences between 60 staff-reported and 60 adolescent-reported Child Behavioral Checklist/Youth Self-Report (CBCL/YSR) scores in Jordanian care centers, and the associations between adolescent-staff agreement, demographic characteristics and child-caregiver relationship factors. Results indicated small to modest correlations between informant scores. Additionally, staff-caregivers who know the child over 1 year and have a high perceived fit are better able to approximate the adolescent's self-report of psychopathology.

Rates of evolution of hominoid seminal proteins are correlated with function and expression, rather than mating system.

In species where females mate with multiple males during a single ovulatory cycle, sperm competition is hypothesized to increase the rate of adaptive evolution of proteins expressed in male reproductive tissues through recurrent selective sweeps (positive selection). The hominoids, comprising apes and humans, are a group of closely related primates with extensive variation in mating behaviors and predicted levels of sperm competition. Since previous studies of individual male reproductive genes have shown evidence of positive selection, we estimated rates of evolution of a comprehensive set of proteins expressed in ejaculated semen. Our results show that these proteins in hominoids do not have elevated rates of nonsynonymous substitutions (Ka) compared with a control dataset of nonreproductive genes. Species with greater sperm competition do not have faster rates of seminal protein evolution. Although at these broad levels our hypotheses were not confirmed, further analyses indicate specific patterns of molecular evolution. Namely, the Ka of seminal genes is more strongly correlated with measures of tissue specificity than nonreproductive genes, suggesting that the former may more readily adapt to tissue-specific functions. Proteins expressed from the seminal vesicles evolve more rapidly than those from other male reproductive tissues. Also, several gene ontology categories show elevated rates of protein evolution, not seen in the control data set. While the generalization that male reproductive genes evolve rapidly in hominoids is an oversimplification, a subset of proteins can be identified that are likely targets for adaptive evolution driven by sexual selection.

The effectiveness of booster sessions in CBT treatment for child and adolescent mood and anxiety disorders.

BACKGROUND: To investigate the effects of booster sessions in cognitive behavioral therapy (CBT) for children and adolescents with mood or anxiety disorders, whereas controlling for youth demographics (e.g., gender, age), primary diagnosis, and intervention characteristics (e.g., treatment modality, number of sessions). METHODS: Electronic databases were searched for CBT interventions for youth with mood and anxiety disorders. Fifty-three (k = 53) studies investigating 1,937 youth met criteria for inclusion. Booster sessions were examined using two case-controlled effect sizes: pre-post and pre-follow-up (6 months) effect sizes and employing weighted least squares (WLSs) regressions. RESULTS: Meta-analyses found pre-post studies with booster sessions had a larger effect size r = .58 (k = 15; 95% CI = 0.52-0.65; P < .01) than those without booster sessions r = .45 (k = 38; 95% CI = 0.41-0.49; P < .001). In the WLS regression analyses, controlling for demographic factors, primary diagnosis, and intervention characteristics, studies with booster sessions showed larger pre-post effect sizes than those without booster sessions (B = 0.13, P < .10). Similarly, pre-follow-up studies with booster sessions showed a larger effect size r = .64 (k = 10; 95% CI = 0.57-0.70; P < .10) than those without booster sessions r = .48 (k = 20; 95% CI = 0.42-0.53; P < .01). Also, in the WLS regression analyses, pre-follow-up studies showed larger effect sizes than those without booster sessions (B = 0.08, P < .01) after accounting for all control variables. CONCLUSIONS: Result suggests that CBT interventions with booster sessions are more effective and the effect is more sustainable for youth managing mood or anxiety disorders than CBT interventions without booster sessions.

Stigma and adolescents with psychosis in the Middle East: implications for engaging in mental health treatment.

Stigma is a fundamental barrier to individuals seeking out mental health treatment in the Middle East. The impact of stigma may be amplified if the engagement in and utilization of mental health services for psychosis further stigmatizes individuals and their families. One hundred four Jordanians (N = 104) participated in an experimental vignette survey examining stigma perceptions and social exclusion related to adolescents with psychosis, with the vignettes varying in sex of the youth and whether their family had sought mental health services. The results found that seeking treatment did not add to perceived stigma, and both the male and female adolescents receiving mental health treatment were viewed as significantly more likely to be helped than those not in treatment (p < 0.001). Therefore, receiving mental health treatment did not further stigmatize these Arab youth with psychosis. In addition, seeking out and engaging adolescents and their family in mental health treatment were positively perceived and may help to improve the youth's prognosis and outcomes.

Foster care as a viable alternative to institutional care in the Middle East: community acceptance and stigma across type of placement in Jordan.

OBJECTIVE: Utilizing an experimental vignette design, this study assessed attitudes in the Hashemite Kingdom of Jordan toward the implementation of foster care as an alternative to institutions for children in need of care and protection. METHODS: A sample of 111 adults were surveyed in Amman and presented with a vignette describing a 14-year-old boy who came into the care of the Ministry of Social Development when he was a baby after being placed by the grandfather because of shame surrounding the mother being unwed. The vignettes systematically varied as to whether the child was described as raised in an orphanage, with a relative in a kinship foster placement, or with a nonkin foster family. Participants were then asked a series of questions about their acceptance of the child, stigma that the community might attach to the child, and potential outcomes for the child. RESULTS: We found no differences across the acceptance and stigma questions between the kinship and non-kin foster conditions. The 2 foster care options were at least as acceptable as current institutional models across all domains, and participants were more likely to accept the child going to school with or being friends with their child if they were in foster care rather than an institution. CONCLUSIONS: These results represent the first evidence of public acceptance of foster care as a model of care in Jordan and may inform the process of local stakeholders implementing alternatives to institutional care on a meaningful and sustainable scale in the Kingdom and regionally.

Intravenous zoledronic acid and oral alendronate in patients with a low trauma fracture: experience from an osteoporosis clinic.

BACKGROUND/AIMS: Oral bisphosphonates have been shown to be effective in treating osteoporosis. However, there has been a significant problem with compliance. Newer intravenous bisphosphonates are available for osteoporosis management, but have not been compared with oral bisphosphonates in a clinical setting. The aim of this study was to compare the safety and effectiveness of intravenous zoledronic acid (ZOL) and oral alendronate (ALN) in osteoporotic patients following a low trauma fracture. METHODS: A non-randomized, retrospective cohort study was conducted of 169 patients with a low trauma fracture and reduced bone mineral density (BMD). Patients were treated with either an infusion of 4 mg ZOL or ALN 70 mg weekly. The outcomes measured were change in BMD after 12 months of treatment with either bisphosphonate, and new osteoporotic fractures. All adverse events were documented. RESULTS: Lumbar spine BMD (L2-L4) improved 5.6% in the ZOL group (P < 0.001) and 5.5% in the ALN group (P < 0.001). Total hip BMD improved 2% in the ZOL group (P < 0.01) and 2.5% in the ALN group (P < 0.001). There was no significant difference in BMD change between the groups. There were significantly more new fractures (P < 0.001) in the ZOL group (7.2%) than the ALN group (1%). The ZOL group were significantly older (P < 0.01) and had a significantly higher proportion of males (P < 0.05) at baseline. There were no serious adverse reactions in either group. CONCLUSION: ZOL and ALN both produce a significant increase in BMD and are well tolerated in patients with osteoporotic, low trauma fractures. Yearly ZOL provides a safe, convenient alternative to weekly oral bisphosphonates.

Pulmonary bioavailability of a phosphorothioate oligonucleotide (CGP 64128A): comparison with other delivery routes.

PURPOSE: Phosphorothioate antisense oligodeoxynucleotides are promising therapeutic candidates. When given systemically in clinical trials they are administered via slow intravenous infusion to avoid their putative plasma concentration-dependent haemodynamic side-effects. In this study, we have evaluated alternative parenteral and non-parenteral administration routes which have the potential to enhance the therapeutic and commercial potential of these agents. METHODS: The delivery of CGP 64128A by intravenous, subcutaneous, intra-peritoneal, oral and intra-tracheal (pulmonary) routes was investigated in rats using radiolabelled compound and supported by more specific capillary gel electrophoretic analyses. RESULTS: Intravenously administered CGP 64128A exhibited the rapid blood clearance and distinctive tissue distribution which are typical for phosphorothioate oligodeoxynucleotides. Subcutaneous and intraperitoneal administration resulted in significant bioavailabilities (30.9% and 28.1% over 360 min, respectively) and reduced peak plasma levels when compared with intravenous dosing. Administration via the gastrointestinal tract gave negligible bioavailability (< 2%). Intra-tracheal administration resulted in significant but dose-dependent bioavailabilities of 3.2, 16.5 and 39.8% at 0.06, 0.6 and 6.0 mg/kg, respectively. CONCLUSIONS: Significant bioavailabilities of CGP 64128A were achieved following subcutaneous, intra-peritoneal and intra-tracheal administration. Pulmonary delivery represents a promising mode of non-parenteral dosing for antisense oligonucleotides. The dose-dependent increase in pulmonary bioavailability suggests that low doses may be retained in the lungs for local effects whereas higher doses may be suitable for the treatment of a broader spectrum of systemic diseases.

Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration.

The pharmacokinetics, tissue distribution and metabolism of CGP 69846A, a 20-mer phosphorothioate oligodeoxynucleotide targeted against the 3'-untranslated region of human c-raf-1 kinase mRNA, were investigated in vivo in rats after intravenous and subcutaneous administration. Intravenous disposition studies with [3H]CGP 69846A were supported with analysis by capillary gel electrophoresis and electrospray mass spectrometry. In combination, these techniques provide a detailed account of the pharmacokinetic and metabolic profile for this compound. The elimination of CGP 69846A after a single intravenous dose was studied over extended periods in mice using whole-body autoradiography and capillary gel electrophoresis. Subcutaneous administration to rats resulted in a significant bioavailability with peak plasma levels 4.5-fold lower than after intravenous dosing. This dose route resulted in low interanimal variability and only slightly greater metabolism of the oligonucleotide compared to the intravenous administration.

Use of electroejaculation to collect semen samples from wild seals.

Semen samples were obtained from 7 adult male gray seals (Halichoerus grypus) at a colony on Sable Island, Nova Scotia, Canada, using a portable electroejaculation system. Males were anesthetized with tiletamine-zolazepam. A probe was inserted in the rectum, and a progressive series of 10 to 15 stimulations (1 to 9 V, 25 to 750 mA) was applied. Males ejaculated after 15 to 29 minutes of stimulation and produced ejaculates with volumes of 4 to 17 ml that had vigorous, motile spermatozoa. Although trials were performed in winter conditions (0 to -15 C), simple storage methods (semen samples collected into plastic bags and placed in a warm pocket or an insulated cooler) kept spermatozoa motile for up to 4 hours after ejaculation. The procedure described here provides a means for collection of semen samples for genetic analyses and tests of reproductive competence in seals.

Enhanced immunoreactivity and preferential heterodimer formation of reassociated Fel d I recombinant chains.

In this study we have addressed the question of whether reassociating the two recombinant protein chains that comprise the major cat dander allergen, Fel d I, would change the overall IgE and allergic patient T cell immunoreactivity compared to the native molecule. To accomplish this, the chains were combined under reducing and denaturing conditions, then allowed to reassociate by dilution and extensive dialysis against a physiological buffer. An initial examination of the reaction products using quantitative capture ELISA demonstrated comparable reactivity to Fel d I. Further analysis, using a pool of cat allergic patient plasma, showed that the products of the reassociation reaction (rFel d I) also possessed an enhanced IgE binding capacity. Depletion ELISA results gave only a 5% difference in reactivity between rFel d I and the native protein versus a 20% difference with the mixture of the two chains. Comparative secondary T cell stimulation assays were subsequently performed using cat allergic patient peripheral blood lymphocytes. Here the results demonstrated no loss of reactivity with the reassociated chains as compared to Fel d I or the two mixed recombinant chains. To biochemically characterize the products of the reassociation reaction we have performed reverse phase HPLC and then analysed the isolated fractions by mass spectrometry. It was clear from these results that like the native Fel d I, the products of the reassociation reaction favored heterodimer formation, with no homodimer being detected. This implies that the reassociated protein chains had preferentially adopted a native-like conformation.

Mass spectrometry of the humanized monoclonal antibody CAMPATH 1H.

Two mass spectrometric techniques, electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) have been used to study the intact humanized monoclonal antibody CAMPATH 1H, its fully and partially deglycosylated species, and 13 fragments prepared from it. The transformed ESI mass spectra of the glycosylated species gave complex patterns of molecular masses (M(r's). These have been substantially assigned to the presence of a mixture of glycoforms, each resulting from the combination of a single protein species with specific glycans of four distinct masses. The MALDI mass spectra of the glycosylated species, with the exception of that of the smallest fragment Fc/2, which indicated the presence of three of the glycans, gave single M(r) values comparable to the mean M(r) calculated from the ESI results. The M(r) values for the 10 prepared nonglycosylated species support the validity of the published amino acid sequence for the antibody and define the cleavage sites for the enzymic fragmentations. It is concluded that mass measurement of the Fc/2 fragment using ESI techniques provides a convenient means of preliminary assessment of the major glycosylated entities.

Potential therapeutic recombinant proteins comprised of peptides containing recombined T cell epitopes.

The complete primary structure of Fel d I2 has been determined and shown to be comprised of two separate polypeptide chains (designated chain 1 and 2). Overlapping peptides covering the entire sequence of both chains of Fel d I have been used to map the major areas of human T cell reactivity. The present study describes three non-contiguous T cell reactive regions of < 30 aa in length that were assembled in all six possible configurations using PCR and recombinant DNA methods. These six recombinant proteins comprised of defined non-contiguous T cell epitope regions artificially combined into single polypeptide chains have been expressed in E. coli, highly purified, and examined for their ability to bind to human cat-allergic IgE and for human T cell reactivity. Several of these recombined T cell epitope-containing polypeptides exhibit markedly reduced IgE binding as compared to the native Fel d I. Importantly, the human T cell reactivity to individual T cell epitope-containing regions is maintained even though each was placed in an unnatural position as compared to the native molecule. In addition, T cell responses to potential junctional epitopes were not detected. It was also demonstrated in mice that s.c. injection of T cell epitope-containing polypeptides inhibits the T cell response to the individual peptides upon subsequent challenge in vitro. Thus, these recombined T cell epitope-containing polypeptides, which harbor multiple T cell reactive regions but have significantly reduced reactivity with allergic human IgE, constitute a novel potential approach for desensitization to important allergens.