Numbing symptoms as predictors of unremitting posttraumatic stress disorder

This prospective longitudinal study examined the ability of re-experiencing, avoidance, numbing, and hyperarousal symptoms to predict persistence of posttraumatic stress disorder (PTSD) in disaster workers followed for 2 years. Cluster analyses suggested that overall severity was the best predictor of PTSD at follow up, but for groups with PTSD of moderate severity, numbing symptoms were also associated with PTSD at the 2-year follow up. Regression analyses with all four symptom groups as independent variables found that only numbing and re-experiencing symptoms predicted PTSD at the 1 year follow up, and only numbing symptoms predicted PTSD at the 2-year follow up. Findings suggest that numbing symptom severity could be used as a risk index of very chronic PTSD, especially when the overall PTSD severity falls in the moderate range.     

Lymphoid and fibroblastic cell lineages from radiosensitive cancer patients: molecular analysis of DNA double strand break repair by major non-homologous end-joining sub-pathways

Aims: Radiation therapy (RT) is used in the treatment of approximately half of all cancer patients. Although there have been great improvements in tumor localization and the technical accuracy of RT delivery, some RT patients still have idiosyncratic hypersensitivity to ionizing radiation (IR) in their normal tissues. Although much effort has been expended in the search for assays that could detect radiosensitive individuals prior to treatment and facilitate tailored therapy; a suitable and clinically practical predictive assay has yet to be realized. Since DNA double‐strand breaks (DSB) are a major lesion caused by IR, we hypothesized that radiation hypersensitive individuals might be deficient in the repair of such lesions. Methods: To test this hypothesis we quantitatively and functionally characterized DSB repair of the two major non‐homologous end‐joining (NHEJ) sub‐pathways in a pilot study using a plasmid repair reconstitution assay in lymphoblastoid and fibroblast cell lines from radiosensitive cancer patients and controls. Experiments using well‐characterized mammalian DSB repair mutants demonstrated the ability of the assay to distinguish NHEJ sub‐pathways. The proportion of direct end‐joining repair compared with that of microhomology‐directed repair was used as a functional end‐point of DSB repair competence in the different cell lines. Results: We found that the overall level of NHEJ sub‐pathway repair competency was similar in cell lines from radiosensitive patients and controls. Conclusion: These data suggest that this assay in these cell lineages has limited usefulness as a predictive screen for the endogenous DNA DSB repair competency of radiosensitive cancer patients' cells but can usefully characterize major cellular DSB repair phenotypes.     

Predictors of responses to psychotherapy referral of WTC utility disaster workers

This study examined male utility disaster workers' responses to referral for trauma-specific psychotherapy. Among 328 workers offered referral for symptoms related to the World Trade Center (WTC) attacks during psychological screening, approximately 48% chose to accept, 28% chose to consider only, and 24% chose to decline. Analyses examined predisposing factors, i.e., age, race/ethnicity, marital status, education, previous mental health treatment, and previous disorder; as well as illness level; i.e., posttraumatic stress disorder (PTSD), depression, and general psychiatric distress; current treatment; and time of referral as predictors of referral response. PTSD (specifically reexperiencing and hyperarousal symptoms), depressive symptoms, and previous mental health treatment were positively associated with workers' accepting referral. Implications and limitations of these findings are discussed.     

The longitudinal course of PTSD among disaster workers deployed to the World Trade Center following the attacks of September 11th

This study examined the long-term mental health outcomes of 2,960 nonrescue disaster workers deployed to the World Trade Center site in New York City following the September 11, 2001 (9/11) terrorist attacks. Semistructured interviews and standardized self-report measures were used to assess the prevalence of posttraumatic stress disorder (PTSD) and other psychopathology 4 and 6 years after the attacks. Clinician-measured rates of PTSD and partial PTSD 4-years posttrauma were 8.4% and 8.9%, respectively, in a subsample of 727 individuals. Rates decreased to 5.8% and 7.7% for full and partial PTSD 6 years posttrauma. For the larger sample, self-report scores revealed probable PTSD and partial PTSD prevalence to be 4.8% and 3.6% at 4 years, and 2.4% and 1.8% at 6 years. Approximately 70% of workers never met criteria for PTSD. Although PTSD rates decreased significantly over time, many workers remained symptomatic, with others showing delayed-onset PTSD. The strongest predictors of ongoing PTSD 6 years following 9/11 were trauma history (odds ratio (OR) = 2.27, 95% confidence interval (CI) [1.06, 4.85]); the presence of major depressive disorder 1-2 years following the trauma (OR = 2.80, 95% CI [1.17, 6.71]); and extent of occupational exposure (OR = 1.31, 95% CI [1.13, 1.51]). The implications of the findings for both screening and treatment of disaster workers are discussed.     

Cathepsin B inhibition limits bone metastasis in breast cancer

Metastasis to bone is a major cause of morbidity in breast cancer patients, emphasizing the importance of identifying molecular drivers of bone metastasis for new therapeutic targets. The endogenous cysteine cathepsin inhibitor stefin A is a suppressor of breast cancer metastasis to bone that is coexpressed with cathepsin B in bone metastases. In this study, we used the immunocompetent 4T1.2 model of breast cancer which exhibits spontaneous bone metastasis to evaluate the function and therapeutic targeting potential of cathepsin B in this setting of advanced disease. Cathepsin B abundancy in the model mimicked human disease, both at the level of primary tumors and matched spinal metastases. RNA interference-mediated knockdown of cathepsin B in tumor cells reduced collagen I degradation in vitro and bone metastasis in vivo. Similarly, intraperitoneal administration of the highly selective cathepsin B inhibitor CA-074 reduced metastasis in tumor-bearing animals, a reduction that was not reproduced by the broad spectrum cysteine cathepsin inhibitor JPM-OEt. Notably, metastasis suppression by CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth. Together, our findings established a prometastatic role for cathepsin B in distant metastasis and illustrated the therapeutic benefits of its selective inhibition in vivo.     

Clear cell papulosis of the skin: a case report from Singapore

Clear cell papulosis of the skin is a rare condition; to our knowledge only 12 cases have been reported. Here, we report for the first time a case of clear cell papulosis with cytokeratin 7 expression and provide a comprehensive literature review. A 16-month-old girl presented with 3 hypopigmented lesions in the pubic region that were 3 to 9 mm in diameter; 1 lesion was papular, and the other 2 were macular. A skin biopsy revealed acanthosis with a proliferation of clear cells along the basal and suprabasal layers of the epidermis occurring in small clusters and singly. The cells had round to oval regular nuclei with abundant to moderate lightly eosinophilic to clear cytoplasm and intracytoplasmic mucin. Immunostaining produced positive results for carcinoembryonic antigen, AE1/3, epithelial membrane antigen, cell adhesion molecule 5.2, and cytokeratin 7 and negative results for gross cystic fluid disease protein, S100, and HMB-45. Clear cells of clear cell papulosis are mucin-positive and S100-negative glandular-secretory epithelial cells with histogenetic features of Toker cells of nipple and Paget cells. Immunohistochemical features support an eccrine secretory cell origin because the clear cells are consistently and strongly positive for carcinoembryonic antigen, positive for cell adhesion molecule 5.2, and negative or rarely positive for gross cystic fluid disease protein.     

Hyperkeratotic flexural erythema responding to amoxicillin–clavulanic acid therapy: Report of four cases

Hyperkeratotic eruptions in the flexures, especially in the inguinal region, often pose a diagnostic and therapeutic dilemma. Inguinal keratotic eruptions may be caused by various infections, inflammatory dermatoses, vesico-bullous dermatoses, nutrient deficiencies, medication allergies and other miscellaneous causes such as granular parakeratosis. We hereby report four patients who presented with idiopathic hyperkeratotic erythematous eruptions with a migratory nature involving the inguinal region and occasionally showing the histopathologic features of granular parakeratosis. All four patients showed a dramatic therapeutic response to amoxicillin–clavulanic acid combination. We suggest that ‘granular parakeratosis’ should be considered as a histopathologic feature rather than the diagnosis. We would prefer to label our cases as ‘Hyperkeratotic Flexural Erythema’. We recommend that detailed study of skin microbiome may help identify a possible alteration in skin microbiome contributing to the pathogenesis. We briefly review strategies on characterising the skin microbiome and the latest knowledge surrounding how alterations to the skin microbial populations can contribute to some diseases.