Six Recommendations for Provider Behavior Change in Family Planning.

Health care provider behavior has the power to influence family planning and reproductive health outcomes positively and negatively, underlining the importance of provider behavior change (PBC) initiatives. However, global health practitioners lack a shared understanding of PBC interventions and what influences provider behavior. Furthermore, PBC interventions in family planning and reproductive health have tended to address individual and workplace environmental factors rather than the full breadth of factors that influence provider behavior, including the broader systems and contexts where providers operate. This commentary contributes to a common understanding of PBC, including the determinants of provider behavior, and describes actions to advance PBC efforts in family planning and reproductive health. To inform these considerations, we conducted a narrative review of more than 70 articles and project materials describing interventions that aimed to change provider behaviors pertaining to family planning and reproductive health and used the review to identify the most and least common provider cadres addressed, behavioral determinants targeted, and strategies implemented. We strongly encourage global health practitioners to design future PBC interventions for a more diverse set of cadres and contexts, consider the full set of factors that influence provider behavior, pair provider- and client-side interventions, shift the narrative around PBC from "blaming" to supporting providers, move beyond training-only interventions, and improve the rigor of measurement and evidence-building efforts for PBC. These considerations can be used to advance the field of PBC in family planning and reproductive health to improve outcomes across the service delivery continuum.

A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes.

PURPOSE: Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. METHODS: A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts. RESULTS: Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10-9 . Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10-8 and 1.23 × 10-8 , respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429). CONCLUSION: This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.

Platelet transfusion does not improve outcomes in patients with brain injury on antiplatelet therapy.

INTRODUCTION: Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI. METHODS: An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted. RESULTS: Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality. CONCLUSION: Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy.

Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferative diabetic retinopathy (PDR) as cases and 13 patients with no diabetic retinopathy despite at least 10years of type 2 diabetes as controls. Thirty-one out of the 57 cases and all 13 controls were from the African American Proliferative Diabetic Retinopathy Study (AA). The rest of the cases were of mixed ethnicities (ME). WES identified 721 candidate genes with rare or novel non-synonymous variants found in at least one case with PDR and not present in any controls. After filtering for genes with null alleles in greater than two cases, 28 candidate genes were identified in our ME cases and 16 genes were identified in our AA cases. Our analysis showed rare and novel variants within these genes that could contribute to the development of PDR, including rare non-synonymous variants in FAM132A, SLC5A9, ZNF600, and TMEM217. We also found previously unidentified variants in VEGFB and APOB. We found that VEGFB, VPS13B, PHF21A, NAT1, ZNF600, PKHD1L1 expression was reduced in human retinal endothelial cells (HRECs) cultured under high glucose conditions. In an exome sequence analysis of patients with PDR, we identified variants in genes that could contribute to pathogenesis. Six of these genes were further validated and found to have reduced expression in HRECs under high glucose conditions, suggestive of an important role in the development of PDR.

Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes.

PURPOSE: Previous studies have yielded conflicting results regarding whether serum lipid levels are associated with retinal hard exudates in diabetic retinopathy. The majority of studies have assessed hard exudates only as a dichotomous trait (presence vs. absence) and included limited numbers of African Americans (AA). The purpose of this study was to determine if there are any associations between serum lipid levels and hard exudates in AA with type 2 diabetes (T2D). METHODS: 890 AA participants with T2D were enrolled from 5 sites. Macular fundus photographs were graded by masked ophthalmologist investigators. Hard exudate areas were measured using a semi-automated algorithm and ImageJ software. Multivariate regression models were used to determine the association between serum lipid levels and (1) presence of hard exudate and (2) area of hard exudate. RESULTS: Presence of hard exudates was associated with higher total cholesterol [(odds ratio (OR) = 1.08, 95 % confidence interval (CI) 1.03-1.13, P = 0.001)] and higher low-density lipoprotein (LDL) cholesterol (OR = 1.08, 95 % CI 1.03-1.14, P = 0.005) in models controlling for other risk factors. Hard exudate area was also associated with both higher total and LDL cholesterol levels (P = 0.04 and 0.01, respectively) in multivariate models controlling for other risk factors. CONCLUSIONS: Higher total and LDL cholesterol were associated with the presence of hard exudates and a greater hard exudate area in AA with T2D. This information can be used to counsel diabetic patients regarding the importance of lipid control to decrease the risk of macular hard exudates.

OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF MACULAR EDEMA AND HARD EXUDATES AND THEIR ASSOCIATION WITH LIPID SERUM LEVELS IN TYPE 2 DIABETES.

PURPOSE: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. METHODS: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. RESULTS: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95% confidence interval = 1.01-1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95% confidence interval = 1.02-1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. CONCLUSION: Higher total and low-density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels.

Risk Factors for Proliferative Diabetic Retinopathy in African Americans with Type 2 Diabetes.

PURPOSE: To assess personal and demographic risk factors for proliferative diabetic retinopathy in African Americans with type 2 diabetes. METHODS: In this prospective, non-interventional, cross-sectional case-control study, 380 African Americans with type 2 diabetes were enrolled. Participants were recruited prospectively and had to have either: (1) absence of diabetic retinopathy after ≥10 years of type 2 diabetes, or (2) presence of proliferative diabetic retinopathy when enrolled. Dilated, 7-field fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study scale. Covariates including hemoglobin A1C (HbA1C), blood pressure, height, weight and waist circumference were collected prospectively. Multivariate regression models adjusted for age, sex and site were constructed to assess associations between risk factors and proliferative diabetic retinopathy. RESULTS: Proliferative diabetic retinopathy was associated with longer duration of diabetes (odds ratio, OR, 1.62, p < 0.001), higher systolic blood pressure (OR 1.65, p < 0.001) and insulin use (OR 6.65, p < 0.001) in the multivariate regression analysis. HbA1C was associated with proliferative diabetic retinopathy in the univariate analysis (OR 1.31, p = 0.002) but was no longer significant in the multivariate analysis. CONCLUSIONS: In this case-control study of African Americans with type 2 diabetes, duration of diabetes, systolic hypertension and insulin use were strong risk factors for the development of proliferative diabetic retinopathy. Interestingly, HbA1C did not confer additional risk in this cohort.

Increased Adipocyte Area in Injured Muscle With Aging and Impaired Remodeling in Female Mice.

We demonstrated that young male and female mice similarly regenerated injured skeletal muscle; however, female mice transiently increased adipocyte area within regenerated muscle in a sex hormone-dependent manner. We extended these observations to investigate the effect of aging and sex on sarcopenia and muscle regeneration. Cardiotoxin injury to the tibialis anterior muscle of young, middle, and old-aged C57Bl/6J male and female mice was used to measure regenerated myofiber cross-sectional area (CSA), adipocyte area, residual necrosis, and inflammatory cell recruitment. Baseline (uninjured) myofiber CSA was decreased in old mice of both sexes compared to young and middle-aged mice. Regenerated CSA was similar in male mice in all age groups until baseline CSA was attained but decreased in middle and old age female mice compared to young females. Furthermore, adipocyte area within regenerated muscle was transiently increased in young females compared to young males and these sex-dependent increases persisted in middle and old age female mice and were associated with increased Pparg Young female mice had more pro-inflammatory monocytes/macrophages in regenerating muscle than young male mice and increased Sca-1(+)CD45(-)cells. In conclusion, sex and age influence pro-inflammatory cell recruitment, muscle regeneration, and adipocyte area following skeletal muscle injury.

African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.

PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.

Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy.

The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 and Rad9, regulating double-strand break (DSB) repair and the DNA damage response (DDR). TLKs maintain genomic stability and are important therapeutic intervention targets. We identified specific inhibitors of TLKs from several compound libraries, some of which belong to the family of phenothiazine antipsychotics. The inhibitors prevented the TLK-mediated phosphorylation of Rad9(S328) and impaired checkpoint recovery and DSB repair. The inhibitor thioridazine (THD) potentiated tumor killing with chemotherapy and also had activity alone. Staining for γ-H2AX revealed few positive cells in untreated tumors, but large numbers in mice treated with low doxorubicin or THD alone, possibly the result of the accumulation of DSBs that are not promptly repaired as they may occur in the harsh tumor growth environment.

Childbirth traditions and cultural perceptions of safety in Nepal: critical spaces to ensure the survival of mothers and newborns in remote mountain villages.

OBJECTIVE: to uncover local beliefs regarding pregnancy and birth in remote mountainous villages of Nepal in order to understand the factors which impact on women's experiences of pregnancy and childbirth and the related interplay of tradition, spiritual beliefs, risk and safety which impact on those experiences. DESIGN: this study used a qualitative methodological approach with in-depth interviews framework within social constructionist and feminist critical theories. SETTING: the setting comprised two remote Nepalese mountain villages where women have high rates of illiteracy, poverty, disadvantage, maternal and newborn mortality, and low life expectancy. Interviews were conducted between February and June, 2010. PARTICIPANTS: twenty five pregnant/postnatal women, five husbands, five mothers-in-law, one father-in-law, five service providers and five community stakeholders from the local communities were involved. FINDINGS: Nepalese women, their families and most of their community strongly value their childbirth traditions and associated spiritual beliefs and they profoundly shape women's views of safety and risk during pregnancy and childbirth, influencing how birth and new motherhood fit into daily life. These intense culturally-based views of childbirth safety and risk conflict starkly with the medical view of childbirth safety and risk. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: if maternity services are to improve maternal and neonatal survival rates in Nepal, maternity care providers must genuinely partner with local women inclusive of their cultural beliefs, and provide locally based primary maternity care. Women will then be more likely to attend maternity care services, and benefit from feeling culturally safe and culturally respected within their spiritual traditions of birth supported by the reduction of risk provided by informed and reverent medicalised care.

Effects of the tropical ginger compound,1'-acetoxychavicol acetate, against tumor promotion in K5.Stat3C transgenic mice.

The purpose of the current study was to determine whether a tropical ginger derived compound 1'-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr705Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action.

Intracutaneous or subcutaneous sterile water injection compared with blinded controls for pain management in labour.

BACKGROUND: Intracutaneous or subcutaneous injection of sterile water is rapidly gaining popularity as a method of pain relief in labour and it is therefore essential that it is properly evaluated. Adequate analgesia in labour is important to women worldwide. Sterile water injection is inexpensive, requires basic equipment, and appears to have few side effects. It is purported to work for labour pain. OBJECTIVES: To determine the efficacy of sterile water injections for relief of pain (both typical contraction pain and intractable back pain) during labour compared to placebo (isotonic saline injections) or non-pharmacological interventions, and to identify any relevant effects on mode and timing of delivery, or safety of both mother and baby. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2011), MEDLINE, and EMBASE (January 2010 to 30 May 2011), together with reference lists in retrieved studies and review articles. SELECTION CRITERIA: We included randomised, double blind, controlled studies using intracutaneous or subcutaneous sterile water injections for pain relief during labour. There were no restrictions on birth place, parity, risk, age, weight, gestation, or stage of labour. Potential comparators were placebo (saline) and non-pharmacological interventions (e.g. hypnosis or biofeedback). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials, and extracted data. We resolved any disagreements or uncertainties by discussion with a third review author. Primary outcome measures were at least 50% pain relief, or at least 30%, pain relief, patient global impression of change of at least 'good', mode of delivery, perinatal morbidity and mortality, maternal complications and adverse events. Secondary outcomes were women with any pain relief, use of rescue analgesia, and treatment group average pain relief. We made explicit judgements about potential biases in the studies. MAIN RESULTS: We included seven studies, with 766 participants: four used intracutaneous injections, two subcutaneous, and one both. All reported on low back pain in labour only. Methodological quality was good, but four studies were at high risk of bias due to small size of treatment groups, incomplete outcome data, and performance bias.All studies reported treatment group mean or median scores, finding greater reduction in pain for sterile water. However, failure to demonstrate a normal distribution for pain intensity or relief, and use of different scales, meant meta-analysis was inappropriate. No study reported primary dichotomous efficacy outcomes. One reported the number self-scoring 4/10 cm or more reduction in pain; significantly more had this outcome with sterile water (50% to 60%) than with placebo (20% to 25%).There was no significant difference between sterile water and saline for rates of caesarean section (risk ratio (RR) 0.58, 95% confidence interval (CI) 0.33 to 1.02), instrumental delivery (RR 1.31, 95% CI 0.79 to 2.18), rescue analgesia (RR 0.86, 95% CI 0.44 to 1.69), timing of delivery, or Apgar scores. Two studies reported that more women treated with sterile water would request the same analgesia in future.No study reported on women's satisfaction with pain relief, women's sense of control in labour, women's satisfaction with the childbirth experience, mother/baby interaction, rates of breastfeeding, maternal morbidity, infant long-term outcomes, or cost. No adverse events were reported other than transient pain with injection, which was worse with sterile water. AUTHORS' CONCLUSIONS: The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Effects of Auraptene on IGF-1 Stimulated Cell Cycle Progression in the Human Breast Cancer Cell Line, MCF-7.

Auraptene is being investigated for its chemopreventive effects in many models of cancer including skin, colon, prostate, and breast. Many mechanisms of action including anti-inflammatory, antiproliferative, and antiapoptotic effects are being suggested for the chemopreventive properties of auraptene. We have previously shown in the N-methylnitrosourea induced mammary carcinogenesis model that dietary auraptene (500 ppm) significantly delayed tumor latency. The delay in time to tumor corresponded with a significant reduction in cyclin D1 protein expression in the tumors. Since cyclin D1 is a major regulator of cell cycle, we further studied the effects of auraptene on cell cycle and the genes related to cell cycle in MCF-7 cells. Here we show that auraptene significantly inhibited IGF-1 stimulated S phase of cell cycle in MCF-7 cells and significantly changed the transcription of many genes involved in cell cycle.

Women's knowledge of options for birth after Caesarean Section.

OBJECTIVE: In Australia, the Caesarean Section rate has risen from 21.8% to 31.1% (2010) in a decade; in South Australia the rate was 32.2% in 2009. Caesarean Section is a life saving intervention in certain circumstances, but also a major surgical procedure with potential adverse effects on both mother and baby. The aim of this study was to ascertain the determinants of knowledge regarding options for subsequent birth in women who have experienced a previous Caesarean Section with a live baby. METHOD: A sample of 33 women in South Australia who had a previous Caesarean Section were surveyed to assess their awareness of birth options and their advantages versus disadvantages as well as the possible factors influencing their information gathering and decision-making on birth options for their subsequent pregnancy. FINDINGS: Most women perceived Caesarean Section to be major surgery but 69.6% were not aware that babies might have problems with breastfeeding, 60.6% did not know the rarity of uterine rupture during labour and/or birth and 48.5% were not aware that a caesarean may involve any complications for the baby at or after birth. CONCLUSION: Women's knowledge deficits relating to risks and benefits of birth options after previous caesarean can constrain them as most women chose caesarean rather than normal birth in their subsequent pregnancy.

Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea.

Clearly new breast cancer models are necessary in developing novel therapies. To address this challenge, we examined mammary tumor formation in the Syrian hamster using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50mg/kg intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A and HMAM4B, were derived from one of the primary mammary tumors induced by MNU. The morphology of the primary tumor was similar to a high-grade poorly differentiated adenocarcinoma in human breast cancer. The primary tumor stained positively for both HER-2/neu and pancytokeratin, and negatively for both cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor derived from HMAM4B cells implanted into a syngeneic hamster was further propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female syngeneic hamsters with a 70% take rate of tumor formation. These cells proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44). To determine responsiveness to the estrogen receptor (ER), a cell proliferation assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and human MCF-7 (ER positive) cells showed a similar decrease at 24h. However, MDA-MB-231 (ER negative) cells were relatively insensitive to any decrease in proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell line was likely derived from a luminal B subtype of mammary tumor. These results also represent characterization of the first mammary tumor cell line available from the Syrian hamster. The HMAM5 cell line is likely to be useful as an immunocompetent model for human breast cancer in developing novel therapies.

A porcine model for evaluating the management of noncompressible torso hemorrhage.

BACKGROUND: Noncompressible hemorrhage from central vascular injuries remains the leading cause of preventable death in modern combat. This report introduces a large animal model of noncompressible torso hemorrhage, which permits assessment of the various approaches to this problem. METHODS: Yorkshire swine were anesthetized and monitoring devices for central aortic pressure, carotid flow, and intracerebral and transcutaneous brain oximetry were applied. Class IV hemorrhagic shock was induced through an iliac arterial injury and animals were subjected to different vascular control methods including thoracic aortic clamping, supraceliac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. After vascular control, the injury was shunted, and damage control resuscitation was continued. Serum markers, intravenous fluid volumes, and vasopressor requirements were tracked over a subsequent resuscitation period. Postmortem tissue analysis was performed to compare levels of acute ischemic injury between groups. RESULTS: The protocol for animal preparation, hemorrhage volume, open surgical technique, and posthemorrhage resuscitation was developed using four animals. The endovascular approach was developed using two additional animals. After model development, treatment animals subsequently underwent noncompressible hemorrhage with thoracic aortic clamping, supraceliac aortic clamping, direct vascular control, and endovascular aortic occlusion. Premature death occurred in one animal in the direct vascular control group. CONCLUSION: This study presents a large animal model of class IV hemorrhagic shock from noncompressible hemorrhage, which permits comparison of various vascular control methods to address this challenging problem. Future studies using this model as the standard will allow further development of strategies for the management of noncompressible hemorrhage.