Financial and social circumstances and the incidence and course of PTSD in Mississippi during the first two years after Hurricane Katrina

Hurricane Katrina was the most devastating natural disaster to hit the United States in the past 75 years. The authors conducted interviews of 810 persons who were representative of adult residents living in the 23 southernmost counties of Mississippi before Hurricane Katrina. The prevalence of posttraumatic stress disorder (PTSD) since Hurricane Katrina was 22.5%. The determinants of PTSD were female gender, experience of hurricane-related financial loss, postdisaster stressors, low social support, and postdisaster traumatic events. Kaplan-Meier survival curves suggest that exposure to both hurricane-related traumatic events and to financial and social stressors influenced the duration of PTSD symptoms. Postdisaster interventions that aim to improve manipulable stressors after these events may influence the onset and course of PTSD.     

HLA class II antigen presentation by prostate cancer cells

Prostate cancer is the second most commonly diagnosed cancer in men. Recent evidence suggests that reduced expression of target protein antigens and human leukocyte antigen (HLA) molecules is the predominant immune escape mechanism of malignant prostate tumor cells. The purpose of this study was to investigate the prospect of antigen specific immunotherapy against prostate cancer via the HLA class II pathway of immune recognition. Here, we show for the first time that prostate cancer cells express HLA class II proteins that are recognized by CD4+ T cells. Prostate tumor cells transduced with class II molecules efficiently presented tumor-associated antigens/peptides to CD4+ T cells. This data suggests that malignant prostate tumors can be targeted via the HLA class II pathway, and that class II-positive tumors could be employed for direct antigen presentation, and CD4+ T-cell mediated tumor immunotherapy.Prostate Cancer and Prostatic Diseases (2008) 11, 334-341; doi:10.1038/sj.pcan.4501021; published online 16 October 2007.     

Comparison of Phaconit Rollable IOL with Acrylic Foldable IOL

Background

Phaconit or ultra micro incision phacoemulsification cataract surgery involves phacoemulsification through a 0.9 millimetre sleeveless phaco tip and irrigating chopper followed by implantation of a rollable intraocular lens. The procedure leads to negligible astigmatism and faster visual recovery as compared to phacoemulsification with a foldable intraocular lens.

Methods

This prospective study analysed 80 cases of sub millimetre phaconit surgery with implantation of rollable intraocular lenses(IOL) in 40 cases and acrylic foldable IOL in the remaining 40 cases. Evaluation of efficacy and adaptability of procedure, equipment settings, operative constraints, postoperative complications, keratometric and topographic evaluation of induced astigmatism with visual outcome and patient''s rehabilitation were studied.

Results

The intraoperative complications were surge/ chamber collapse in 16 (20%), iris chaffing in one and corneal burns in two cases. All cases had an induced astigmatism of less than or equal to ± 0.25 D in four to six weeks after rollable IOL and ± 0.5 D to ± 0.75 D after acrylic IOL implantation. All patients had best-corrected visual acuity of 6/6 by third post operative day.

Conclusion

Phaconit with rollable IOL is a perfect blend of surgical skill, application of technology and ultra thin IOL.Key Words: Phaconit, Ultra micro phaco, Submillimetre incision, Rollable IOL implantation     

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.     

Development of an in vitro keratinocyte model for use in the study of HSV specific cytotoxicity

Herpes simplex virus (HSV) specific immune mediated cytotoxicity may be involved in control of HSV infections and in the tissue damage induced by HSV infection or HSV related skin disease such as herpes associated erythema multiforme. Developing an in vitro model to study this process has proved difficult due to the lack of an appropriate target cell that will express HSV antigens but is not simultaneously subject to viral induced cell death. The purpose of this study was to develop a model in which keratinocytes express cell surface HSV specific antigens but at the same time are protected from death due to viral infection. We found that keratinocytes infected with HSV in the presence of acyclovir (ACV) expressed such antigens yet remained viable for a period of time after the onset of antigen expression such that cytotoxicity studies could be successfully performed. Rabbit skin cells, a transformed keratinocyte line, or second passage human neonatal foreskin keratinocytes were grown in culture medium with or without 200 microM ACV and were infected with HSV. Examination by direct immunofluorescence with anti-HSV antibody revealed uniform HSV antigen expression by cells both with and without ACV by 8 h after infection. Cells infected without ACV exhibited marked structural abnormalities including formation of multinucleated giant cells, while cells with ACV showed fewer such changes throughout a 24-h period. An Ethidium Bromide-Acridine Orange cytotoxicity assay demonstrated significant increases in the cytotoxicity of infected cells not protected by ACV compared to that of cells with ACV (p less than .001). This in vitro model should prove useful in the investigation of HSV specific immune mediated cytotoxicity.     

The state of differentiation of cultured human keratinocytes determines the level of intercellular adhesion molecule-1 (ICAM-1) expression induced by gamma interferon.

Inducing the expression of ICAM-1 (CD54) on the surface of epidermal keratinocytes is an important step in initiating leukocyte interaction with the epidermis. We studied the effect of keratinocyte differentiation and of drugs used to treat epidermal inflammation on the induction of this important adhesion molecule. Cell membrane expression of ICAM-1 in cultured human keratinocytes was analyzed using both immunofluorescence and FACS analysis of staining with anti-ICAM-1 monoclonal antibody and was correlated with markers of keratinocyte differentiation. Cell-surface ICAM-1 expression was induced by gamma interferon in all culture conditions, but was significantly greater (p less than 0.014) in cells grown in low-calcium medium ([Ca++] 0.03 mM), and correlated with increased staining for the basal cell keratin K5. The synthetic retinoid Etretin (Ro 10-1670) enhanced the interferon-induced ICAM-1 expression over a wide concentration range (10(-8)-10(-5) M); however, this effect was only seen in the more differentiated cells grown in 0.15 mM and 1.0 mM calcium and not in the cells grown in 0.03 mM calcium. The Etretin effects on intracellular K5 staining paralleled those on cell-surface ICAM-1. Anti-inflammatory glucocorticoids had no effect on ICAM-1 expression in cultured human keratinocytes, even at suboptimal gamma interferon doses (5 U/ml). beta-estradiol, on the other hand, mimicked the Etretin effect, increasing both IFN induction of ICAM-1 expression and K5 staining in more differentiated keratinocytes in 0.15 and 1.0 mM calcium, but not in those in 0.03 mM calcium. Both Etretin and beta-estradiol decreased staining of involucrin, a marker of terminal differentiation, supporting the proposition that in this experimental system these drugs suppress keratinocyte differentiation. The enhanced ICAM-1 induction in keratinocytes with a basal level of differentiation correlates with the in vivo effects of interferon on ICAM-1 and may be a principal determinant in the patterns of ICAM-1 seen in inflammatory skin diseases.     

BH3 mimetic ABT-737 and a proteasome inhibitor synergistically kill melanomas through Noxa-dependent apoptosis

The Bcl-2 family is important in modulating sensitivity to anticancer drugs in many cancers, including melanomas. The BH3 mimetic ABT-737 is a potent small molecule inhibitor of the anti-apoptotic proteins Bcl-2/Bcl-X(L)/Bcl-w. In this report, we examined whether ABT-737 is effective in killing melanoma cells in combination with the proteasome inhibitor MG-132, and further evaluated the mechanisms of action. Viability, morphological, and Annexin V apoptosis assays showed that ABT-737 alone exhibited little cytotoxicity, yet it displayed strong synergistic lethality when combined with MG-132. In addition, the detection of Bax/Bak activation indicated that the combination treatment synergistically induced mitochondria-mediated apoptosis. Furthermore, mechanistic analysis revealed that this combination treatment induced expression of the pro-apoptotic protein Noxa- and caspase-dependent degradation of the anti-apoptotic protein, Mcl-1. Finally, siRNA-mediated inhibition of Mcl-1 expression significantly increased sensitivity to ABT-737 in these cells, and knocking down Noxa expression protected the cells from cytotoxicity induced by the combination treatment. These findings demonstrate that ABT-737 combined with MG-132 synergistically induced Noxa-dependent mitochondrial-mediated apoptosis. In summary, this study indicates promising therapeutic potential of targeting anti-apoptotic Bcl-2 family members in treating melanoma, and it validates rational molecular approaches that target anti-apoptotic defenses when developing cancer treatments.     

Acceptability and feasibility of continuous diaphragm use among sex workers in Madagascar

OBJECTIVES: The diaphragm, a woman controlled, reusable contraceptive device, might prevent some sexually transmitted infections (STIs). We assessed the acceptability and feasibility of use of silicone Wide-Seal Arcing Diaphragms (Milex Products, Chicago, IL, USA) by sex workers in Madagascar. METHODS: Over 8 weeks, we evaluated method acceptability by examining patterns of and problems with women's diaphragm use. We also evaluated several measures of study feasibility, including recruitment and follow up methods. RESULTS: 91 women from three cities (Antananarivo, Tamatave, and Mahajanga) participated, and 87 (96%) completed follow up. At enrolment, participants reported a median of six sex acts with five clients in the previous week. During the follow up period, participants reported a median of three sex acts with three clients during the previous 2 days, and self reported continuous diaphragm use during the previous day increased from 87% to 93%. Seven women became pregnant (incidence 53 pregnancies per 100 woman years). Self reported use of male condoms and diaphragms was fairly constant over the study period: women reported condom use in 61% to 70% of acts and diaphragms in 95% to 97% of acts. The number of participants reporting diaphragm problems decreased from 15 (16%) at the first visit to six (7%) at the final visit. 20 women (22%) needed replacement devices during follow up because their original diaphragms were lost, were the wrong size, or became seriously damaged. CONCLUSIONS: Given the high use and steady decrease in reported problems during the study, we believe diaphragms are acceptable and feasible in this resource poor, low education sex worker population.     

Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol

Summary Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol- augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16--hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus.