Clients' experiences with a specialized sexual assault service.

INTRODUCTION: Specialized services have been developed to meet the unique needs of survivors of sexual assault, and yet little research has been conducted to investigate clients' experiences with these services. An interpretive study was conducted to (1) understand the experience of women who were sexually assaulted and then cared for in an emergency setting by professionals associated with a specialized sexual assault service; (2) discover themes in the experiences of these women; and (3) discern implications of this experience for delivery of care to women who have been sexually assaulted. METHODS: Eight women who had been cared for at a specialized sexual assault service were interviewed 2 months later. RESULTS: Nine themes emerged from latent content analysis of the interviews. DISCUSSION: Conclusions drawn include the importance of holistic woman-centered care, the importance of having one caregiver focus on the client's emotional needs, the importance of touch, and the need for an effective, sensitive, and coordinated response by police and community services.     

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth

The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (DeltaPsim) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases DeltaPsim, increases mitochondrial H2O2, and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent.     

Identification of RL-TGR,a coreceptor involved in aversive chemical signaling

Chemical signaling plays an important role in predator–prey interactions and feeding dynamics. Like other organisms that are sessile or slow moving, some marine sponges contain aversive compounds that defend these organisms from predation. We sought to identify and characterize a fish chemoreceptor that detects one of these compounds. Using expression cloning in Xenopus oocytes coexpressing the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, the beta-2 adrenergic receptor (β₂AR), and fractions of a zebrafish cDNA library, we isolated a cDNA clone encoding receptor activity–modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), a novel coreceptor involved in signaling in response to triterpene glycosides. This coreceptor appears to be structurally and functionally related to RAMPs, a family of coreceptors that physically associate with and modify the activity of G protein–coupled receptors (GPCRs). In membranes from formoside-responsive oocytes, RL-TGR was immunoprecipitated in an apparent complex with β₂AR. In HEK293 cells, coexpression of β₂AR induced the trafficking of RL-TGR from the cytoplasm to the plasma membrane. These results suggest that RL-TGR in the predatory fish physically associates with the β₂AR or another, more physiologically relevant GPCR and modifies its pharmacology to respond to triterpene glycosides found in sponges that serve as a potential food source for the fish. RL-TGR forms a coreceptor that responds to a chemical defense compound in the marine environment, and its discovery might lead the way to the identification of other receptors that mediate chemical defense signaling.     

The introduction of confidential enquiries into maternal deaths and near-miss case reviews in the WHO European Region

Most maternal deaths can be averted with known, effective interventions but countries require information about which women are dying and why, and what can been done to prevent such deaths in future. This paper describes the introduction of two approaches to reviewing maternal deaths and severe obstetric complications in 12 countries in transition in the WHO European Region - national-level confidential enquiries into maternal deaths and facility-based near-miss case reviews. Initially, two regional meetings involving stakeholders from 12 countries were held in 2004-2005, followed by national meetings in seven of the countries. The Republic of Moldova was the first to pilot the review process, preceded by a technical workshop to make detailed plans, provide training in how to facilitate and carry out a review, finalise clinical guidelines against which the findings of the confidential enquiry and near-miss case review could be judged, and a range of other preparatory work. To date, near-miss case reviews have been carried out in the three main referral hospitals in Moldova, and a national committee appointed by the Ministry of Health to conduct the confidential enquiry has met twice. Several other countries have begun a similar process, but progress may remain slow due to continuing fears of punitive actions against health professionals who have a mother or baby die in their care.     

Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted.     

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.