Challenges of connectedness in personal recovery for rural mothers with mental illness

Social connection is a fundamental human need, but challenging for individuals with characteristics that are socially stigmatized. Parenting with mental illness presents obstacles, as well as opportunities, for connection. In the present study, we examined connectedness within a personal recovery paradigm for rural mothers with a mental illness. In‐depth interviews with 17 mothers with a mental illness, utilizing constructivist grounded theory, resulted in six categories of meaning, including ‘yearning for connection’, ‘connecting intensely’, ‘encountering rejection and exclusion’, ‘choosing isolation’, ‘being known’, and ‘finding peers/helping others’. Women expressed a strong desire for connection, but for many, prior experiences of trauma and rejection created barriers to the development of trust, preventing some women from seeking opportunities for connection. Connectedness to self and significant others, and a broader life meaning and purpose can support and expedite personal recovery from mental illness for rural women. However the factors that contribute to the mental illness might also inhibit the development of trust needed to attain social connection. Increasing connectedness in mothers with mental illness is a complex endeavour requiring concerted focus as distinct from other service‐delivery goals. The perinatal period could be a key time for intervention.     

Prevalence of mental illness within families in a regional child‐focussed mental health service

Nearly 50% of all mental illnesses begin in childhood before the age of 14 years, and over 20% of parents have a mental illness. Few studies have examined the co‐occurrence of mental illnesses in parents and children. In the present study, we examined the extent of mental illness within families of 152 clients attending an Australian regional child and adolescent mental health service (CAMHS). A cross‐sectional study design was employed involving a case record review and clinician‐completed questionnaire of the children and youth attending a CAMHS. It was found that 79% of these children were living with a parent with mental illness. The predominant diagnosis of both child and parent was an anxiety or mood disorder, and many families had co‐occurring risk factors of domestic violence and limited social supports. The findings in this Australian cohort are similar to those of other international research. While novel in nature, the present study has highlighted the extent of both mental illness and scarce supports for both children and parents in the same family. The findings indicate the need for a coordinated multiservice delivery of appropriate and consistent family‐focussed interventions, responding to both mental illness and social supports for children and parents. Further research should examine specific components of family need and support, as seen through the eyes of the child and their parent.     

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a ⁶⁴Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of ⁶⁴Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from ⁶⁴Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to ⁶⁴Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D₁₀ values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that ⁶⁴Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from ⁶⁴Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after ⁶⁴Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that ⁶⁴Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of ⁶⁴Cu-ATSM as a cancer treatment modality for hypoxic tumors.     

Lack of Protection Against Ebola Virus from Chloroquine in Mice and Hamsters

The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes.     

Many alphaIIbbeta3 autoepitopes in chronic immune thrombocytopenic purpura are localized to alphaIIb between amino acids L1 and Q459

In chronic immune thrombocytopenic purpura (ITP), autoantibodies bind to platelet surface proteins, particularly alphaIIb, resulting in platelet destruction by the reticulo-endothelial system. In order to better localize the autoepitopes on alphaIIb, we studied the binding of antibodies to Chinese hamster ovary (CHO) cells expressing either alphaIIbbeta3 or alphaIIb-alphavbeta3 chimaeras in which a segment of alphaIIb (either amino acids L1-Q459, L1-F223 or F223-Q459) was substituted for that portion of alphav. We evaluated platelet-associated autoantibodies from 14 ITP patients with alphaIIb-dependent antibodies. Ten of 14 bound to alphaIIb (L1-Q459)-alphavbeta3, showing that autoepitopes were often localized to this region of alphaIIb. In addition, each of the autoantibodies binding to alphaIIb (L1-Q459)-alphavbeta3, also bound to CHO cells expressing either alphaIIb(L1-F223)-alphavbeta3 or alphaIIb(F223-Q459)-alphavbeta3). In two of the three eluates tested, > 95% of the autoantibody binding to alphaIIb could be adsorbed using CHO cells expressing any of the three chimaeras, showing that the epitope(s) have contact points on either side of amino acid F223; in the third eluate, only a portion ( approximately 40%) could be adsorbed by the chimaeric cell lines showing that, in this patient, an additional antibody was also present, directed to a site distal to amino acid Q459. The remaining four eluates bound to CHO cells expressing alphaIIbbeta3 but to none of the chimaeras, suggesting that these epitopes are also distal to amino acid Q459. We conclude that the binding of many anti-alphaIIbbeta3 autoantibodies is dependent on the presence of alphaIIb amino acids L1-Q459.     

A specific assay for anti-HLA antibodies: application to platelet donor selection

Alloimmunization to donor class I HLA antigens represents a major obstacle to successful platelet transfusion therapy. It is desirable to distinguish alloimmunization from nonimmunologic causes of poor platelet survival to assess the need for HLA-matched, single-donor platelets. We describe a new in vitro assay for anti-HLA antibodies and report its application to the problem of platelet crossmatching. In contrast to previously described crossmatch techniques, the immunobead assay is specific for anti-HLA antibodies. The assay was used to evaluate 51 single-donor platelet transfusions given to seven patients from 35 different donors. Recipient plasma was assayed for antibodies directed against HLA antigens present on donor platelets. A one-hour posttransfusion corrected count increment of greater than or equal to 7,500 was considered a successful outcome. Twenty-nine of 33 (87.9%) transfusion episodes associated with a negative immunobead assay had successful outcomes. The four unsuccessful transfusions were associated with potential nonimmunologic causes of poor platelet survival. Only two of 18 (11.1%) episodes associated with a positive assay had successful outcomes. Only one unsuccessful transfusion episode was associated with a negative immunobead assay and a positive radiolabeled antiglobulin test result, which suggested that isolated alloantibodies to antigens other than class I HLA antigens are not a common cause of platelet refractoriness. Platelets stored in suspension at 4 degrees C or frozen in liquid nitrogen were found suitable for crossmatch testing.     

Percutaneous coronary intervention versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: The VA AWESOME multicenter registry: comparison with the randomized clinical trial.

OBJECTIVES: This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND: The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS: Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS: The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS: Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients.