The Online Sharing of Instagram Images for Rheumatoid Arthritis.

Social media use related to chronic disease has become pervasive, yet little research has been done to examine how social media is currently used by healthcare consumers or how to best use various social media platforms to improve health outcomes. The purpose of this study was to gain an understanding of Instagram use for image sharing related to #rheumatoidarthritis. A visual ethnography approach using content analysis was completed. Images for analysis (n = 106) were randomly selected, using the Instagram public search feature, during seven distinct periods. Content analysis, conducted by two coders, was used to identify categories and provide a sentiment analysis of the images. Approximately 75% of the images were determined to be positive by both coders. Social interaction and self-expression were the most frequently identified categories, suggesting that individuals use Instagram primarily for sharing awareness, sharing encouragement, and self-expression regarding rheumatoid arthritis. This finding is consistent with the use of Instagram for social networking and self-promotion. This study reveals new insights about how Instagram serves as a social, personal, and health-related information sharing platform particularly for those who may be socially isolated due to rheumatoid arthritis.

The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension.

OBJECTIVE: We sought to compare the rates of superimposed preeclampsia and adverse outcomes in women with chronic hypertension with or without prior preeclampsia. STUDY DESIGN: We conducted secondary analysis of 369 women with chronic hypertension (104 with prior preeclampsia) enrolled at 12-19 weeks as part of a multisite trial of antioxidants to prevent preeclampsia (no reduction was found). Outcome measures were rates of superimposed preeclampsia and other adverse perinatal outcomes. RESULTS: Prepregnancy body mass index, blood pressure, and smoking status at enrollment were similar between groups. The rates of superimposed preeclampsia (17.3% vs 17.7%), abruptio placentae (1.0% vs 3.1%), perinatal death (6.7% vs 8.7%), and small for gestational age (18.4% vs 14.3%) were similar between groups, but preterm delivery <37 weeks was higher in the prior preeclampsia group (36.9% vs 27.1%; adjusted risk ratio, 1.46; 95% confidence interval, 1.05-2.03; P = .032). CONCLUSION: In women with chronic hypertension, a history of preeclampsia does not increase the rate of superimposed preeclampsia, but is associated with an increased rate of delivery at <37 weeks.

Tobacco use and secondhand smoke exposure during pregnancy in two African countries: Zambia and the Democratic Republic of the Congo.

OBJECTIVE: To study pregnant women's knowledge, attitudes and behaviors towards tobacco use and secondhand smoke (SHS) exposure, and exposure to advertising for and against tobacco products in Zambia and the Democratic Republic of the Congo (DRC). DESIGN: Prospective cross-sectional survey between November 2004 and September 2005. SETTING: Antenatal care clinics in Lusaka, Zambia, and Kinshasa, DRC. POPULATION: Pregnant women in Zambia (909) and the DRC (847). METHODS: Research staff administered a structured questionnaire to pregnant women attending antenatal care clinics. MAIN OUTCOME MEASURES: Pregnant women's use of tobacco, exposure to SHS, knowledge of the harms of tobacco and exposure to advertising for and against tobacco products. RESULTS: Only about 10% of pregnant women reported ever having tried cigarettes (6.6% Zambia; 14.1% DRC). However, in the DRC, 41.8% of pregnant women had tried other forms of tobacco, primarily snuff. About 10% of pregnant women and young children were frequently or always exposed to SHS. Pregnant women's knowledge of the hazards of smoking and SHS exposure was extremely limited. About 13% of pregnant women had seen or heard advertising for tobacco products in the last 30 days. CONCLUSIONS: Tobacco use and SHS exposure pose serious threats to the health of women, infants and children. In many African countries, maternal and infant health outcomes are often poor and will likely worsen if maternal tobacco use increases. Our findings suggest that a 'window of opportunity' exists to prevent increased tobacco use and SHS exposure of pregnant women in Zambia and the DRC.

Prevalence of anxiety, depression and associated factors among pregnant women of Hyderabad, Pakistan.

BACKGROUND: Few studies have examined the relationship between antenatal depression, anxiety and domestic violence in pregnant women in developing countries, despite the World Health Organization's estimates that depressive disorders will be the second leading cause of the global disease burden by 2020. There is a paucity of research on mood disorders, their predictors and sequelae among pregnant women in Pakistan. AIMS: To determine the prevalence of anxiety and depression and evaluate associated factors, including domestic violence, among pregnant women in an urban community in Pakistan. METHODS: All pregnant women living in identified areas of Hyderabad, Pakistan were screened by government health workers for an observational study on maternal characteristics and pregnancy outcomes. Of these, 1,368 (76%) of eligible women were administered the validated Aga Khan University Anxiety Depression Scale at 20-26 weeks of gestation. RESULTS: Eighteen per cent of the women were anxious and/or depressed. Psychological distress was associated with husband unemployment (p = 0.032), lower household wealth (p = 0.027), having 10 or more years of formal education ( p = 0.002), a first (p = 0.002) and an unwanted pregnancy ( p < 0.001). The strongest factors associated with depression/anxiety were physical/sexual and verbal abuse; 42% of women who were physically and/or sexually abused and 23% of those with verbal abuse had depression/anxiety compared to 8% of those who were not abused. CONCLUSIONS: Anxiety and depression commonly occur during pregnancy in Pakistani women; rates are highest in women experiencing sexual/physical as well as verbal abuse, but they are also increased among women with unemployed spouses and those with lower household wealth. These results suggest that developing a screening and treatment programme for domestic violence and depression/anxiety during pregnancy may improve the mental health status of pregnant Pakistani women.

Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile.

OBJECTIVE: Left ventricular hypertrophy is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of left ventricular hypertrophy regression rather than its progression and hypothesize that left ventricular hypertrophy regression is associated with a distinct genomic profile. METHODS: Minimally invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed physiologically by means of transthoracic echocardiographic analysis, structurally by means of histology, and molecularly by means of real-time polymerase chain reaction. Mouse hearts were genomically analyzed with Agilent (Santa Clara, Calif) mouse 44k developmental gene chips. RESULTS: Compared with control animals, animals banded for 28 days had a robust hypertrophic response, as determined by means of heart weight/body weight ratio, histologic analysis, echocardiographic analysis, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole-genome arrays on left ventricular tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structure-related patterns associated with left ventricular hypertrophy progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production. CONCLUSIONS: This study demonstrates an effective model for characterizing left ventricular hypertrophy and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of left ventricular hypertrophy and provide a novel therapeutic paradigm focused on promoting regression of left ventricular hypertrophy and not just halting its progression.

Inhibitory kappa B kinase-beta is a target for specific nuclear factor kappa B-mediated delayed cardioprotection.

OBJECTIVE: Myocardial ischemia/reperfusion injury remains a vexing problem. Translating experimental strategies that deliver protective agents before the ischemic insult limits clinical applicability. We targeted 2 proteins in the nuclear factor-kappaB pathway, inhibitory kappa B kinase-beta, and 26S cardiac proteasome to determine their cardioprotective effects when delivered during reperfusion. METHODS: C57BL/6 mice underwent left anterior descending artery occlusion for 30 minutes. An inhibitory kappa B kinase-beta inhibitor (Compound A), a proteasome inhibitor (PS-519), or vehicle was administered at left anterior descending artery release or 2 hours afterward. Infarct size was analyzed 24 hours later. Pressure-volume loops were performed at 72 hours. Serum and left ventricular tissue were collected 1 hour after injury to examine protein expression by enzyme-linked immunosorbent assay and Western blot. RESULTS: Inhibitory kappa B kinase-beta and proteasome inhibition significantly attenuated infarct size and preserved ejection fraction compared with the vehicle groups. When delivered even 2 hours after reperfusion, Compound A, but not PS-519, still decreased infarct size in mice. Finally, when delivered at reperfusion, successful inhibition of phosphorylated-p65 and decreased interleukin-6 and tumor necrosis factor-alpha levels occurred in mice given the inhibitory kappa B kinase-beta inhibitor, but not in mice with proteasome inhibition. CONCLUSION: Although inhibitory kappa B kinase-beta and proteasome inhibition at reperfusion attenuated infarct size after acute ischemia/reperfusion, only inhibitory kappa B kinase-beta inhibition provided cardioprotection through specific suppression of nuclear factor-kappaB signaling. This feature of highly targeted nuclear factor-kappaB inhibition might account for its delayed protective effects, providing a clinically relevant option for treating myocardial ischemia/reperfusion associated with unknown periods of ischemia and reperfusion as seen in cardiac surgery and acute coronary syndromes.

Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.

OBJECTIVE: The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM). STUDY DESIGN: A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo. RESULTS: Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group. CONCLUSION: Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.

Domestic violence prior to and during pregnancy among Pakistani women.

OBJECTIVE: Abuse of women has been associated with adverse pregnancy outcomes. Data about abuse from developing countries are scarce, especially from Muslim societies. Our objective was to investigate domestic violence before and during pregnancy among women in an urban area of Pakistan. DESIGN: Population-based cohort study. SETTING: An urban community in Hyderabad, Pakistan. POPULATION: Thousand three hundred and twenty-four pregnant women at 20-26 weeks gestation. METHODS: Socio-demographic and reproductive history data were obtained through structured interviews. We used a modified World Health Organization screening instrument to assess women's experience of domestic violence. MEASURES: Physical, sexual, and verbal abuse and demographic characteristics. RESULTS: The majority of women had received some schooling and in most households the husbands were employed; by Pakistani standards, they were middle class. Young maternal age, having an unemployed husband and one with other wives/partners, and having had a prior pregnancy were significant predictors of abuse. In the six months prior to and/or during pregnancy, 51% reported experiencing verbal, physical or sexual abuse. Twenty percent reported physical or sexual abuse alone. Sixteen percent of women considered suicide as a response to the abuse. CONCLUSIONS: Domestic violence is common among urban Pakistani women of reproductive age, suggesting a need for universal screening during antenatal care, and for support and referral. Further research is needed to determine factors that place women at greatest risk, and to assess the impact of domestic violence on pregnancy outcomes.

Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan.

BACKGROUND: Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. OBJECTIVE: To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan. METHODS: This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation and followed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and during pregnancy were obtained by trained interviewers within 1 week of enrollment. RESULTS: The prevalence of anemia (defined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobin from 9.0 to 10.9 g/dL) and 14.8% had moderate anemia (hemoglobin from 7.0 to 8.9 g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/ dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustment for education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt during pregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1.7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia (aPOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p = .05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger. CONCLUSIONS: A high percentage of women at 20 to 26 weeks of pregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught how food choices can either enhance or interfere with iron absorption.

Variation in the postpartum hemorrhage rate in a clinical trial of oral misoprostol.

OBJECTIVE: The main objective of this study was to identify factors associated with variation in the rate of acute postpartum hemorrhage (PPH), defined as blood loss >or= 500 mL within 2 hours of delivery, observed in a randomized clinical trial of misoprostol for the prevention of PPH, conducted in rural India. Although the women in the misoprostol group had a significantly lower probability of having a PPH, we also noted a reduction in the rate of PPH in the placebo group over the course of the study. We hypothesized that this was due to the changing skills of the auxiliary nurse midwives (ANMs) over the course of the study. METHODS: We conducted a post-hoc analysis examining variation in PPH rates over the duration of the trial among the women randomized to the placebo arm (n = 808). Descriptive, correlation analysis and generalized estimating equations (GEE) were used to predict PPH rates. With no direct measure of ANM skills, we used proxy measures, including: (1) the ANM's point of entry into the study (original ANMs at the initiation of the trial were less skilled than replacement ANMs); (2) the study duration, representing exposure of the ANM to ongoing training and monitoring; and (3) duration of the second stage of labor as a measure of improved delivery practices. RESULTS: As the study duration increased, the duration of the second stage of labor decreased (-0.12, p = 0.001) and as the duration of the second stage of labor decreased, the rate of PPH decreased (0.0282; 95% CI 0.0201-0.0363). For each 10-minute increase in the duration of second stage labor increased PPH odds by 7.1% and each 30-day duration of the trial decreased PPH odds by 3.4%. Additionally, a patient delivered by an original ANM was 3.14 times more likely to have a PPH compared to a patient delivered by a replacement ANM. CONCLUSIONS: Declining PPH rates were associated with improved skills and delivery practices that decreased duration of the second stage of labor. These improvements appeared to be consistent with the introduction of the more skilled replacement ANMs as well as ongoing training and monitoring for all ANMs over the duration of the trial.

A behavioral intervention to improve obstetrical care.

BACKGROUND: Implementation of evidence-based obstetrical practices remains a significant challenge. Effective strategies to disseminate and implement such practices are needed. METHODS: We randomly assigned 19 hospitals in Argentina and Uruguay to receive a multifaceted behavioral intervention (including selection of opinion leaders, interactive workshops, training of manual skills, one-on-one academic detailing visits with hospital birth attendants, reminders, and feedback) to develop and implement guidelines for the use of episiotomy and management of the third stage of labor or to receive no intervention. The primary outcomes were the rates of prophylactic use of oxytocin during the third stage of labor and of episiotomy. The main secondary outcomes were postpartum hemorrhage and birth attendants' readiness to change their behavior with regard to episiotomies and management of the third stage of labor. The outcomes were measured at baseline, at the end of the 18-month intervention, and 12 months after the end of the intervention. RESULTS: The rate of use of prophylactic oxytocin increased from 2.1% at baseline to 83.6% after the end of the intervention at hospitals that received the intervention and from 2.6% to 12.3% at control hospitals (P=0.01 for the difference in changes). The rate of use of episiotomy decreased from 41.1% to 29.9% at hospitals receiving the intervention but remained stable at control hospitals, with preintervention and postintervention values of 43.5% and 44.5%, respectively (P<0.001 for the difference in changes). The intervention was also associated with reductions in the rate of postpartum hemorrhage of 500 ml or more (relative rate reduction, 45%; 95% confidence interval [CI], 9 to 71) and of 1000 ml or more (relative rate reduction, 70%; 95% CI, 16 to 78). Birth attendants' readiness to change also increased in the hospitals receiving the intervention. The effects on the use of episiotomy and prophylactic oxytocin were sustained 12 months after the end of the intervention. CONCLUSIONS: A multifaceted behavioral intervention increased the prophylactic use of oxytocin during the third stage of labor and reduced the use of episiotomy. (ClinicalTrials.gov number, NCT00070720 [ClinicalTrials.gov]; Current Controlled Trials number, ISRCTN82417627 [controlled-trials.com].).

Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations.

OBJECTIVES: We examined pregnant women's use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa. METHODS: Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005. RESULTS: At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home. CONCLUSIONS: Pregnant women's tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.

Factors associated with acute postpartum hemorrhage in low-risk women delivering in rural India.

OBJECTIVE: Postpartum hemorrhage (PPH), a major cause of maternal mortality and morbidity in low-income countries, can occur unpredictably. This study examined the sociodemographic, clinical, and perinatal characteristics of low-risk women who experienced PPH. METHODS: This analysis was conducted using data on 1620 women from a randomized trial testing oral misoprostol for prevention of PPH in rural India. RESULTS: Of the women, 9.2% experienced PPH. No maternal or sociodemographic factors and few perinatal factors differed between women with PPH and those without, other than treatment with misoprostol. Having fewer than 4 prenatal visits and lack of iron supplementation increased the risk for PPH (P<0.001 and P=0.037, respectively). Several factors unknown until the second stage of labor (perineal tear and birth weight) were also associated (P=0.003). CONCLUSIONS: Among women at low risk for PPH, there were few factors associated with further risk. Given that PPH can occur without warning, rural communities should consider ways to increase both primary prevention (iron supplementation, AMTSL) and secondary prevention of PPH (availability of obstetric first aid, availability of transport, and availability of emergency obstetric care).

Proteasome inhibition promotes regression of left ventricular hypertrophy.

Current research in left ventricular hypertrophy (LVH) has largely focused on its progression and therapeutic mechanisms to prevent or slow its development. Few studies have centered on the regression or treatment of existing LVH. Nuclear factor-kappaB (NF-kappaB) is an inflammatory transcription factor that has been shown to be involved in LVH development. We hypothesized that proteasome-mediated NF-kappaB inhibition would prevent the development of LVH and promote its regression. A murine model of reversible hypertrophy was employed by administering isoproterenol (Iso) subcutaneously for 7-14 days. The proteasome inhibitor, PS-519, was delivered both concurrently and after Iso treatment. LVH was quantified by heart weight-to-body weight ratios, histology, transthoracic echocardiography, and hypertrophic gene expression. After 7 days of Iso treatment, all measures indicated successful development of LVH. Another group was treated for 7 days and then observed for an additional 7 days. This group experienced normalization of Iso-induced cell size, wall thickness, and beta-myosin heavy chain expression. When administered concurrently, PS-519 prevented Iso-induced LVH at 7 days. Furthermore, when PS-519 was given to animals during the second week of continued Iso treatment, these animals also experienced regression of hypertrophy by several measures. The success of proteasome inhibition in preventing LVH development and in promoting LVH regression, even in the face of continued hypertrophic stimulation, demonstrates its potential use as a clinically accessible strategy for treating patients with a variety of LVH-associated cardiomyopathies.

Antioxidant therapy to prevent preeclampsia: a randomized controlled trial.

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The alpha level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110 LEVEL OF EVIDENCE: I.

Stillbirths in an urban community in Pakistan.

OBJECTIVE: The purpose of this study was to determine stillbirth risk factors and gestational age at delivery in a prospective developing country birth cohort. STUDY DESIGN: At 20-26 weeks of gestation, 1369 Pakistani women were prospectively enrolled in the study; the gestational age was determined by ultrasound evaluation, and risk factors and pregnancy outcomes were assessed. RESULTS: The stillbirth rate was 33.6 of 1000 births, despite the fact that 96% of the women received prenatal care, 83% of the women were attended by skilled providers in the hospital, and a 20% of the women underwent cesarean delivery. Fifty-one percent of stillbirths occurred at > or = 37 weeks of gestation and 19% occurred from 34-36 weeks of gestation. Only 4% of the births had congenital anomalies. Hemoglobin of < 8 g/dL, vaginal bleeding, and preeclampsia were associated with increased stillbirth risk. CONCLUSION: In this developing country with reasonable technical resources defined by hospital delivery and a high cesarean delivery rate, stillbirth rates were much higher than rates in the United States. That most of the stillbirths were term and did not have congenital anomalies and that the death appeared to be recent suggests that many Pakistani stillbirths may be preventable with higher quality obstetric care.

IKKbeta inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury.

Despite years of experimental and clinical research, myocardial ischemia-reperfusion (IR) remains an important cause of cardiac morbidity and mortality. The transcription factor nuclear factor-kappaB (NF-kappaB) has been implicated as a key mediator of reperfusion injury. Activation of NF-kappaB is dependent upon the phosphorylation of its inhibitor, IkappaBalpha, by the specific inhibitory kappaB kinase (IKK) subunit, IKKbeta. We hypothesized that specific antagonism of the NF-kappaB inflammatory pathway through IKKbeta inhibition reduces acute myocardial damage following IR injury. C57BL/6 mice underwent left anterior descending (LAD) artery ligation and release in an experimental model of acute IR. Bay 65-1942, an ATP-competitive inhibitor that selectively targets IKKbeta kinase activity, was administered intraperitoneally either prior to ischemia, at reperfusion, or 2 h after reperfusion. Compared with untreated animals, mice treated with IKKbeta inhibition had significant reduction in left ventricular infarct size. Cardiac function was also preserved following pretreatment with IKKbeta inhibition. These findings were further associated with decreased expression of phosphorylated IkappaBalpha and phosphorylated p65 in myocardial tissue. In addition, IKKbeta inhibition decreased serum levels of TNF-alpha and IL-6, two prototypical downstream effectors of NF-kappaB activity. These results demonstrate that specific IKKbeta inhibition can provide both acute and delayed cardioprotection and offers a clinically accessible target for preventing cardiac injury following IR.

Proteasome inhibition attenuates infarct size and preserves cardiac function in a murine model of myocardial ischemia-reperfusion injury.

BACKGROUND: Despite improvements in protection, myocardial ischemia-reperfusion remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally; few are clinically accessible. Nuclear factor kappa-B (NF-kappaB) is a transcription factor central to the inflammatory response and is implicated in reperfusion injury. Its activation relies on the degradation of its inhibitory molecule, IkappaB, by the 20S proteasome. We hypothesized that proteasome inhibition would decrease the extent of infarction after temporary coronary occlusion. METHODS: C57Bl6 mice received a specific proteasome inhibitor (PS-519) and were subjected to 30 minutes of transient occlusion of the left anterior descending artery. After 24 hours of reperfusion, echocardiography was performed to evaluate ventricular function and hearts were excised and analyzed for infarct size, areas at risk, and molecular markers of injury and NF-kappaB activation. RESULTS: Compared with controls, PS-519 delivered before left anterior descending (coronary artery) ligation reduced the area of infarct without a change in the area at risk. Similar results were seen with PS-519 delivered at reperfusion. Echocardiography demonstrated a relative reduction in fractional shortening in the vehicle group of 9.8% versus only 2.7% in the PS-519 group. Markers of myocardial stress and injury were accordingly suppressed with PS-519. These physiologic findings were associated with PS-519 decreasing p65 and TNF expression while preserving IkappaB alpha expression. CONCLUSIONS: In this murine infarct model PS-519 significantly preserved regional myocardial function, reduced the size of infarction, and attenuated expression of myocardial inflammatory response genes. These data demonstrate that a currently available and well-tolerated inhibitor of NF-kappaB can decrease the risk of myocardial injury associated with ischemia-reperfusion.

Diagnostic validity of two instruments for assessing anxiety and depression among pregnant women in Hyderabad, Pakistan.

The objective of this study was to compare the diagnostic validity of two measures, the Aga Khan University Anxiety and Depression Scale (AKUADS) and the How I Feel scale, for assessing anxiety and depression among pregnant women in Pakistan. The sample included 200 pregnant women in Hyderabad, Pakistan. Using psychiatrist-administered Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria, 71 (36%) of the women were diagnosed with depression or anxiety or both. Receiver operating characteristic (ROC) analyses indicated that the two scales had similar levels of discrimination. This study represents an important initial step in developing measures to assess the psychological well-being of Pakistani pregnant women. Additional research is needed, however, to improve the sensitivity and specificity of these scales by removing items that do not function well in this population.

The use of chlorhexidine to reduce maternal and neonatal mortality and morbidity in low-resource settings.

Of the 4 million neonatal deaths and 500,000 maternal deaths that occur annually worldwide, almost 99% are in developing countries and one-third are associated with infections. Implementation of proven interventions and targeted research on a select number of promising high-impact preventative and curative interventions are essential to achieve Millennium Development Goals for reduction of child and maternal mortality. Feasible, simple, low-cost interventions have the potential to significantly reduce the mortality and severe morbidity associated with infection in these settings. Studies of chlorhexidine in developing countries have focused on three primary uses: 1) intrapartum vaginal and neonatal wiping, 2) neonatal wiping alone, and 3) umbilical cord cleansing. A study of vaginal wiping and neonatal skin cleansing with chlorhexidine, conducted in Malawi in the 1990s suggested that chlorhexidine has potential to reduce neonatal infectious morbidity and mortality. A recent trial of cord cleansing conducted in Nepal also demonstrated benefit. Although studies have shown promise, widespread acceptance and implementation of chlorhexidine use has not yet occurred. This paper is derived in part from data presented at a conference on the use of chlorhexidine in developing countries and reviews the available evidence related to chlorhexidine use to reduce mortality and severe morbidity due to infections in mothers and neonates in low-resource settings. It also summarizes issues related to programmatic implementation.