Essential trauma management training: addressing service delivery needs in active conflict zones in eastern Myanmar

Introduction  

Access to governmental and international nongovernmental sources of health care within eastern Myanmar's conflict regions is virtually nonexistent. Historically, under these circumstances effective care for the victims of trauma, particularly landmine injuries, has been severely deficient. Recognizing this, community-based organizations (CBOs) providing health care in these regions sought to scale up the capacity of indigenous health workers to provide trauma care.     

Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in ApcMin/+ mouse

Cancer chemopreventive agent sulforaphane (SFN) and dibenzoylmethane (DBM) showed antitumorigenesis effects in several rodent carcinogenesis models. In this study, we investigated the cancer chemopreventive effects and the underlying molecular mechanisms of dietary administration of SFN and DBM alone or in combination in the ApcMin/+ mice model. Male ApcMin/+ mice (12 per group) at age of 5 weeks were given control AIN-76A diet, diets containing 600 ppm SFN and 1.0% DBM, or a combination of 300 ppm SFN and 0.5% DBM for 10 weeks. Mice were then sacrificed, and tumor numbers and size were examined. Microarray analysis, Western blotting, ELISA, and immunohistochemical staining were done to investigate the underlying molecular mechanisms of cancer chemopreventive effects of SFN and DBM. Dietary administrations of SFN and DBM alone or in combination significantly inhibited the development of intestinal adenomas by 48% (P=0.002), 50% (P=0.001), and 57% (P<0.001), respectively. Dietary administration of 600 ppm SFN and 1.0% DBM also reduced colon tumor numbers by 80% (P=0.016) and 60% (P=0.103), respectively, whereas the combination of SFN and DBM treatment blocked the colon tumor development (P=0.002). Both SFN and DBM treatments resulted in decreased levels of prostaglandin E2 or leukotriene B4 in intestinal polyps or apparently normal mucosa. Treatments also led to the inhibition of cell survival and growth-related signaling pathways (such as Akt and extracellular signal-regulated kinase) or biomarkers (such as cyclooxygenase-2, proliferating cell nuclear antigen, cleaved caspases, cyclin D1, and p21). In conclusion, our results showed that both SFN and DBM alone as well as their combination are potent natural dietary compounds for chemoprevention of gastrointestinal cancers.     

Decreasing Disparities in Breast Cancer Screening in Refugee Women Using Culturally Tailored Patient Navigation

BACKGROUND

Patient navigator (PN) programs can improve breast cancer screening in low income, ethnic/racial minorities. Refugee women have low breast cancer screening rates, but it has not been shown that PN is similarly effective.

OBJECTIVE

Evaluate whether a PN program for refugee women decreases disparities in breast cancer screening.

DESIGN

Retrospective program evaluation of an implemented intervention.

PARTICIPANTS

Women who self-identified as speaking Somali, Arabic, or Serbo-Croatian (Bosnian) and were eligible for breast cancer screening at an urban community health center (HC). Comparison groups were English-speaking and Spanish-speaking women eligible for breast cancer screening in the same HC.

INTERVENTION

Patient navigators educated women about breast cancer screening, explored barriers to screening, and tailored interventions individually to help complete screening.

MAIN MEASURES

Adjusted 2-year mammography rates from logistic regression models for each calendar year accounting for clustering by primary care physician. Rates in refugee women were compared to English-speaking and Spanish-speaking women in the year before implementation of the PN program and over its first 3 years.

RESULTS

There were 188 refugee (36 Somali, 48 Arabic, 104 Serbo-Croatian speaking), 2,072 English-speaking, and 2,014 Spanish-speaking women eligible for breast cancer screening over the 4-year study period. In the year prior to implementation of the program, adjusted mammography rates were lower among refugee women (64.1 %, 95 % CI: 49–77 %) compared to English-speaking (76.5 %, 95 % CI: 69 %–83 %) and Spanish-speaking (85.2 %, 95 % CI: 79 %–90 %) women. By the end of 2011, screening rates increased in refugee women (81.2 %, 95 % CI: 72 %–88 %), and were similar to the rates in English-speaking (80.0 %, 95 % CI: 73 %–86 %) and Spanish-speaking (87.6 %, 95 % CI: 82 %–91 %) women. PN increased screening rates in both younger and older refugee women.

CONCLUSION

Linguistically and culturally tailored PN decreased disparities over time in breast cancer screening among female refugees from Somalia, the Middle East and Bosnia.     

Autoimmune hepatitis: new paradigms in the pathogenesis,diagnosis, and management

Autoimmune hepatitis (AIH), primary biliary cirrhosis, and primary sclerosing cholangitis are the three major autoimmune diseases affecting the liver, and of these three, AIH is the most typical autoimmune disease being characterized by a T-cell-rich infiltrate, raised circulating γ-globulins, autoantibodies, HLA associations, and links with other autoimmune diseases. It is the only one, of the three diseases, that responds well to immunosuppressive therapy. AIH is caused by dysregulation of immunoregulatory networks and the consequent emergence of autoreactive T cells that orchestrate a progressive destruction of hepatocytes leading untreated to liver failure. T cells play a major role in the immunopathogenesis, and both CD4⁺ and CD8⁺ T cells are involved together with effector responses mediated by NK cells, γδ T cells, and macrophages. A number of triggering factors have been proposed including viruses, xenobiotics, and drugs, but none have been conclusively shown to be involved in pathogenesis.     

Hypoglycaemic activity of commelina africana and ageratum conyzoides in relation to their mineral composition

Background

Many plants with antidiabetic properties probably act in part through their content of fibre, vitamins, bioactive or mineral content

Objectives

This study investigated the mineral, proximate, phytochemical compositions and hypoglycaemic effect of Commelina africana and Ageratum conyzoides extracts in diabetic rats, and the likely relationship between this property and the mineral, proximate and phytochemical compositions of the plants.

Methods

The plants were subjected to mineral, proximate composition and phytochemical analysis. Attempt was made to see (if any) the relationship between the hypoglycaemic effect and the mineral, proximate compositions and phytochemistry of the plants. Alloxan-induced diabetic animals were administered 500mg/kg body weight aqueous extracts of the plants and glibenclamide as the reference hypoglycaemic agent.

Results

Aqueous extract of Ageratum conyzoides reduced fasting blood glucose of experimental animals by 39.1% while Commelina africana reduced the same by 78.0%. Alkaloids, cardenolides, saponins, and tannins were detected in both plants. Anthraquinones was absent in C. africana but a trace of it was detected in A. conyzoides. The hypoglycaemic effect of Commelina africana was comparable with the reference hypoglycaemic agent. Ageratum conyzoides showed comparably weaker hypoglycaemic effect than exhibited by reference hypoglycaemic agent. Comparatively, Commelina africana had higher mineral concentrations (except Na) than Ageratum conyzoides.

Conclusions

Plants'' extracts minerals (magnesium, potassium and iron) and bioactive components (alkaloids and cardenolides) seemingly enhanced their hypoglycaemic effect. Furthermore, these minerals, alkaloids and cardenolides could be helpful in ameliorating complications of diabetes like hypertension and cardiovascular disease.     

Engagement of S1P₁-degradative mechanisms leads to vascular leak in mice

GPCR inhibitors are highly prevalent in modern therapeutics. However, interference with complex GPCR regulatory mechanisms leads to both therapeutic efficacy and adverse effects. Recently, the sphingosine-1-phosphate (S1P) receptor inhibitor FTY720 (also known as Fingolimod), which induces lymphopenia and prevents neuroinflammation, was adopted as a disease-modifying therapeutic in multiple sclerosis. Although highly efficacious, dose-dependent increases in adverse events have tempered its utility. We show here that FTY720P induces phosphorylation of the C-terminal domain of S1P receptor 1 (S1P₁) at multiple sites, resulting in GPCR internalization, polyubiquitinylation, and degradation. We also identified the ubiquitin E3 ligase WWP2 in the GPCR complex and demonstrated its requirement in FTY720-induced receptor degradation. GPCR degradation was not essential for the induction of lymphopenia, but was critical for pulmonary vascular leak in vivo. Prevention of receptor phosphorylation, internalization, and degradation inhibited vascular leak, which suggests that discrete mechanisms of S1P receptor regulation are responsible for the efficacy and adverse events associated with this class of therapeutics.