The Neurobehavioral Symptom Inventory: Psychometric Properties and Symptom Comparisons in Women With and Without Brain Injuries Due to Intimate Partner Violence.

This study psychometrically evaluated the Neurobehavioral Symptom Inventory (NSI) among women survivors of intimate partner violence (IPV) and compared symptoms between women with no brain injury history (n = 93) and women with IPV-related brain injury history (n = 112). Women completed the NSI and questionnaires on traumatic brain injury (TBI), hypoxic-ischemic brain injury (HI-BI), and lifetime IPV history. A four-factor NSI model, including affective, somatosensory, cognitive, and vestibular factors, had the best fit (comparative fit index = 0.970, root mean square error of approximation = 0.064), with strong reliability for the total score (ω = .93) and subscale scores (ω range = .72-.89). In group comparisons, women with IPV-related brain injuries reported greater total, affective, and cognitive symptom severity after adjusting for age and education; however, no group differences were observed after adjusting for IPV severity. When examining lifetime number of brain injuries, HI-BI count was independently predictive of total, cognitive, and vestibular symptom severity after adjusting for age, education, and IPV severity; whereas TBI count did not independently predict any NSI scores after adjusting for these covariates. The NSI had acceptable psychometric properties for measuring neurobehavioral symptoms among women survivors of IPV. The association between HI-BI count and cognitive and vestibular symptoms may indicate the importance of studying repetitive nonfatal strangulation as an injury mechanism in this population.

Head Injury Due to Intimate Partner Violence: Injury Characteristics, Subacute Symptoms, and Receipt of Care.

Women survivors of intimate partner violence (IPV) have increased risk of repetitive neurotrauma in their lifetime but have received less research focus compared with populations of athletes, veterans, and emergency department patients. The current study examined the importance of IPV as a contextual mechanism of injury, by comparing women survivors of IPV based on whether they experienced a head injury due to IPV or a head injury not due to IPV. The analyses involved archival data from in-person interviews conducted with women who received a protective order against an intimate partner in Kentucky from 2001 to 2004 (n = 641). Women were excluded if they reported no head injury history (n = 268), resulting in two groups compared based on a retrospective cohort design: 255 women with at least one self-reported IPV-related head injury (M = 33.8 ± 9.0 years old, range: 19-65; 87.5% White) and 118 women with self-reported head injuries due to reasons other than IPV (M = 32.2 ± 9.1 years old, range: 18-62; 89.0% White). Participants were compared on injury characteristics, lifetime physical and sexual IPV severity, subacute symptoms of head injury, and receipt of care for head injury. Compared with women with head injuries unrelated to IPV, women with IPV-related head injuries reported a higher number of lifetime head injuries (Mdn[range]: IPV-related = 3[1-515] vs. non-IPV-related = 1[1-13], p < 0.001, r = 0.51) and a higher number of head injuries involving loss of consciousness (Mdn[range]: IPV-related = 1[1-35] vs. non-IPV-related = 1[1-4], p < 0.001, r = 0.27), but lower rates of hospitalization (IPV-related = 56.1% vs. non-IPV-related = 73.7%, p = 0.001, odds ratio [OR] = 2.20 [95% confidence interval (CI): 1.36, 3.55]) and formal rehabilitation (IPV-related = 3.2% vs. non-IPV-related = 9.4%, p = 0.011, OR = 3.18 [1.24, 8.13]) following head injury. Women with IPV-related head injuries had greater lifetime severity of physical IPV (p < 0.001, d = 0.64 [0.41, 0.86]) and sexual IPV (p < 0.001, d = 0.38 [0.16, 0.60]). Women with IPV-related head injuries endorsed all symptoms at greater rates than women with non-IPV-related head injuries (ps < 0.001), including physical (e.g., headaches: OR = 3.15 [1.81, 5.47]; dizziness: OR = 2.65 [1.68, 4.16]), cognitive (e.g., trouble problem solving: OR = 2.66 [1.53, 4.64]; inattention: OR = 2.39 [1.52, 3.78]), and emotional symptoms (e.g., depression: OR = 7.39 [4.48, 12.20]; anxiety: OR = 4.60 [2.82, 7.51]). The total count of symptoms endorsed was higher for women with IPV-related head injury than women with head injuries unrelated to IPV (p < 0.001, d = 0.71 [0.49, 0.94]). When controlling for lifetime physical and sexual IPV, IPV-related head injury was independently associated with symptom count (ß = 0.261, p < 0.001) and accounted for additional variance in symptom count (ΔR2 = 0.06, p < 0.001). Among women survivors of IPV, those reporting IPV-related head injuries reported greater subacute symptoms, but a lower likelihood of being hospitalized or receiving rehabilitative care. Women with self-reported IPV-related head injuries represent an underserved population that is often unevaluated following injury and may have many unmet care needs. Future studies should examine persistent symptoms following IPV-related head injuries and interventions that would be most beneficial for this population.

Repetitive Head Injury and Cognitive, Physical, and Emotional Symptoms in Women Survivors of Intimate Partner Violence.

Many women survivors of intimate partner violence (IPV) experience repetitive head injuries in their lifetime, but limited research has examined the cumulative effects of multiple head injuries on post-concussion symptom severity in this population. This study examined how number of lifetime head injuries and episodes of loss of consciousness (LOC) due to head injuries were related to current cognitive, physical, and emotional symptoms among women survivors of IPV. Cisgender women from Kentucky were recruited following a protective order against an intimate partner, including 268 women with no reported lifetime head injuries and 250 women with one or more IPV-related head injuries (mean [M] = 17.2 head injuries, standard deviation [SD] = 50.5, median [Mdn] = 4, range = 1-515; M = 1.8 LOC episodes, SD = 4.3, Mdn = 1, range = 0-35, respectively). Participants underwent in-person interviews about lifetime physical and sexual IPV history, head injury history, and current cognitive, physical, and emotional symptoms. Sociodemographic characteristics, physical and sexual IPV severity, and current symptom severity were examined in relation to number of head injuries and LOC episodes. A higher number of head injuries was associated with greater age, White race, less than high school education, unemployment, and rural residence. No sociodemographic variables differed based on number of LOC episodes. Greater number of lifetime head injuries and LOC episodes correlated significantly with physical IPV severity (rho = 0.35, p < 0.001; rho = 0.33, p < 0.001, respectively) and sexual IPV severity (rho = 0.22, p < 0.001; rho = 0.19, p = 0.003). Greater number of head injuries and LOC episodes correlated significantly with greater cognitive (rho = 0.33, p < 0.001; rho = 0.23, p < 0.001, respectively), physical (rho = 0.36, p < 0.001; rho = 0.31, p < 0.001), emotional (rho = 0.36, p < 0.001; rho = 0.18, p = 0.004), and total symptom severity (rho = 0.39, p < 0.001; rho = 0.26, p < 0.001). In group comparisons, participant groups stratified by number of head injuries (i.e., 0, 1-3, 4+) differed in total symptom severity (p < 0.001, η2 = 0.15), with greater symptom burden associated with more head injuries. Participants with and without LOC differed in symptom severity: cognitive (p < 0.001, d = 0.45), physical (p < 0.001, d = 0.60), emotional (p = 0.004, d = 0.37), and total symptom severity (p < 0.001, d = 0.53). Group differences between participants with and without LOC remained significant after controlling for sociodemographic variables and IPV severity. There was no cumulative effect of LOC, in that participants with 1 LOC episode did not differ from participants with 2 + LOC episodes (p > 0.05). Based on hierarchical regression analyses, only physical symptoms were independently related to number of head injuries (p = 0.008, ΔR2 = 0.011) and number of LOC episodes (p = 0.014, ΔR2 = 0.021) after controlling for sociodemographic characteristics and IPV severity. Among women survivors of IPV, cumulative head injuries appear related to greater symptom severity. Greater head injury history was independently related to worse physical symptoms (e.g., headaches, dizziness, sleep problems), whereas cognitive and emotional symptoms were, in part, attributable to cumulative physical and emotional trauma due to IPV. Women survivors of IPV with repetitive head injuries have unmet neurobehavioral health needs that may benefit from targeted interventions.

iTRAQ-based proteomic profiling of breast cancer cell response to doxorubicin and TRAIL.

Breast cancer is a molecularly heterogeneous disease, and predicting response to chemotherapy remains a major clinical challenge. To minimize adverse side-effects or cumulative toxicity in patients unlikely to benefit from treatment, biomarkers indicating treatment efficacy are critically needed. iTRAQ labeling coupled with multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum fraction, key organelles regulating apoptosis, has led to the discovery of several differentially abundant proteins in breast cancer cells treated with the chemotherapeutic agent doxorubicin followed by the death receptor ligand, TRAIL, among 571 and 801 unique proteins identified in ZR-75-1 and MDA-MB-231 breast cancer cell lines, respectively. The differentially abundant proteins represent diverse biological processes associated with cellular assembly and organization, molecular transport, oxidative stress, cell motility, cell death, and cancer. Despite many differences in molecular phenotype between the two breast cancer cell lines, a comparison of their subproteomes following drug treatment revealed three proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in these proteins, detected by iTRAQ, were confirmed by immunofluorescence, visualized by confocal microscopy. These novel potential biomarkers may have clinical utility for assessing response to cancer treatment and may provide insight into new therapeutic targets for breast cancer.

Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL.

Treatment of breast cancer is complex and challenging due to the heterogeneity of the disease. To avoid significant toxicity and adverse side-effects of chemotherapy in patients who respond poorly, biomarkers predicting therapeutic response are essential. This study has utilized a proteomic approach integrating 2D-DIGE, LC-MS/MS, and bioinformatics to analyze the proteome of breast cancer (ZR-75-1 and MDA-MB-231) and breast epithelial (MCF-10A) cell lines induced to undergo apoptosis using a combination of doxorubicin and TRAIL administered in sequence (Dox-TRAIL). Apoptosis induction was confirmed using a caspase-3 activity assay. Comparative proteomic analysis between whole cell lysates of Dox-TRAIL and control samples revealed 56 differentially expressed spots (≥2-fold change and p < 0.05) common to at least two cell lines. Of these, 19 proteins were identified yielding 11 unique protein identities: CFL1, EIF5A, HNRNPK, KRT8, KRT18, LMNA, MYH9, NACA, RPLP0, RPLP2, and RAD23B. A subset of the identified proteins was validated by selected reaction monitoring (SRM) and Western blotting. Pathway analysis revealed that the differentially abundant proteins were associated with cell death, cellular organization, integrin-linked kinase signaling, and actin cytoskeleton signaling pathways. The 2D-DIGE analysis has yielded candidate biomarkers of response to treatment in breast cancer cell models. Their clinical utility will depend on validation using patient breast biopsies pre- and post-treatment with anticancer drugs.

Profiling of apoptotic changes in human breast cancer cells using SELDI-TOF mass spectrometry.

Apoptosis is a key process in the response of tumours to chemotherapeutic agents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many tumor cells, while sparing most normal cells. Several chemotherapeutic drugs synergize with TRAIL in reducing tumor growth and inducing apoptosis. Because some tumour cells respond poorly to these treatments, biomarkers that predict clinical responsiveness are needed. This study used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify novel apoptotic markers in TRAIL and etoposide (T+E)-treated MDA-MB-231 and ZR-75-1 breast cancer cells and MCF-10A non-transformed breast cells. T+E induced apoptosis, increasing caspase-3 activity at 4-8h, in all cell lines. Protein profiles revealed two prominent peaks, m/z 10090 and 8560, which decreased significantly during apoptosis. Mass spectrometry sequencing of tryptic peptides identified these proteins as S100A6 (confirmed immunologically) and ubiquitin (confirmed against a purified standard), respectively. Caspase inhibition prevented the decrease in both proteins during T+E-induced apoptosis whereas proteasome inhibition combined with T+E further decreased ubiquitin, possibly by preventing its recycling. Using SELDI-TOF MS we have identified S100A6 and ubiquitin as potential protein markers of apoptosis. Further validation using patient samples is required to confirm their potential utility in monitoring the effectiveness of anti-cancer drugs in inducing tumour cell apoptosis.