Status of breast cancer screening strategies and indicators in Iran: A scoping review.

Background: This scoping review aimed to investigate the status of breast cancer (BC) preventive behaviors and screening indicators among Iranian women in the past 15 years. BC, as the most common cancer in women, represents nearly a quarter (23%) of all cancers. Presenting the comprehensive view of preventive modalities of BC in the past 15 years in Iran may provide a useful perspective for future research to establish efficient services for timely diagnosis and control of the disease. Materials and Methods: The English and Persian articles about BC screening modalities and their indicators in Iran were included from 2005 to 2020. English electronic databases of Web of Science, PubMed, and Scopus, and Persian databases of Scientific Information Database (SID) and IranMedex were used. The critical information of articles was extracted and classified into different categories according to the studied outcomes. Results: A total of 246 articles were assessed which 136 of them were excluded, and 110 studies were processed for further evaluation. Performing breast self-examination, clinical breast examination, and mammography in Iranian women reported 0%-79.4%, 4.1%-41.1%, and 1.3%-45%, respectively. All of the educational interventions had increased participants' knowledge, attitude, and practice in performing the screening behaviors. The most essential screening indicators included participation rate (3.8% to 16.8%), detection rate (0.23-8.5/1000), abnormal call rate (28.77% to 33%), and recall rate (24.7%). Conclusion: This study demonstrated heterogeneity in population and design of research about BC early detection in Iran. The necessity of a cost-effective screening program, presenting a proper educational method for increasing women's awareness and estimating screening indices can be the priorities of future researches. Establishing extensive studies at the national level in a standard framework are advised.

Familial genetic and environmental risk profile and high blood pressure event: a prospective cohort of cardio-metabolic and genetic study.

BACKGROUND AND AIMS: High blood pressure is the heritable risk factor for cardiovascular diseases. We investigated whether the presence of familial genetic and environmental risk factors are associated with increased risk of high blood pressure. METHODS: A total of 4,559 individuals from 401 families were included in this study. Familial aggregation analysis was carried out on systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC), and heritability was estimated for SBP and DBP. The association between familial risk factors and blood pressure traits including, incidence of hypertension, SBP and DBP was estimated separately using regression-based two-level Haseman-Elston (HE) method, with individual and familial BMI and WC as environmental exposures and familial genetic profile of known variants as genetic risk factors in 210 index families (≥2 hypertensive cases). Models were adjusted for the two nested sets of covariates. RESULTS: During a follow-up of 15 years, the SBP, DBP, BMI and WC were highly correlated in inter class of mother-offspring and intraclass of sister-sister with heritability of 30 and 25% for DBP and SBP, respectively. Among index families, those whose members with higher familial BMI or WC had significantly increased risk of hypertension and consistent, strong signals of rs2493134 (AGT) linked with SBP and DBP, rs976683 (NLGN1) linked with SBP and HTN, and epistasis of rs2021783 (TNXB) and known genetic variants linked with all blood pressure traits. CONCLUSIONS: Findings from this study show that familial genetic and environmental risk profile increase risk for high blood pressure beyond the effect of the individuals' own risk factors.

Generality of genomic findings on blood pressure traits and its usefulness in precision medicine in diverse populations: A systematic review.

Remarkable findings from genome-wide association studies (GWAS) on blood pressure (BP) traits have made new insights for developing precision medicine toward more effective screening measures. However, generality of GWAS findings in diverse populations is hampered by some technical limitations. There is no comprehensive study to evaluate source(s) of the non-generality of GWAS results on BP traits, so to fill the gap, this systematic review study was carried out. Using MeSH terms, 1545 records were detected through searching in five databases and 49 relevant full-text articles were included in our review. Overall, 749 unique variants were reported, of those, majority of variants have been detected in Europeans and were associated to systolic and diastolic BP traits. Frequency of genetic variants with same position was low in European and non-European populations (n = 38). However, more than 200 (>25%) single nucleotide polymorphisms were found on same loci or linkage disequilibrium blocks (r2 ≥ 80%). Investigating for locus position and linkage disequilibrium of infrequent unique variants showed modest to high reproducibility of findings in Europeans that in some extent was generalizable in other populations. Beyond theoretical limitations, our study addressed other possible sources of non-generality of GWAS findings for BP traits in the same and different origins.

Exercise training, circulating cytokine levels and immune function in cancer survivors: A meta-analysis.

BACKGROUND: Anti-cancer therapies lead to chronic non-resolving inflammation and reduced immune function. One potential therapy is exercise training, but the effectiveness of these interventions to improve immune-related outcomes, the gaps in the literature, and recommendations to progress the field need to be determined. OBJECTIVES: (1) to conduct separate meta-analyses in cancer survivors to determine the effects of exercise training on pro- and anti-inflammatory markers, and immune cell proportions and function; and (2) to perform subgroup analyses to determine whether exercise modality, cancer type, and specific markers help to explain heterogeneity in each meta-analysis. DATA SOURCES: Electronic databases (PubMed/MEDLINE, EMBASE, CENTRAL, and CINAHL) from inception to March 2018. The reference lists of eligible articles and relevant reviews were also checked. STUDY SELECTION: Inclusion criteria were adult cancer survivors from randomized controlled trials performing structured exercise intervention (aerobic, resistance or combined training or Tai Chi/yoga) compared to usual care control group and included pro-inflammatory, anti-inflammatory, and/or immune cell outcomes. APPRAISAL AND SYNTHESIS METHODS: A total of 5349 potentially eligible articles were identified, of which 26 articles (27 trials) met the inclusion criteria. Effect sizes were calculated as standardized mean differences (SMD), where <0.2 was defined as trivial, 0.2-0.3 as small, 0.4-0.8 as moderate, and >0.8 as a large effect. RESULTS: Exercise training decreased pro-inflammatory markers (SMD: -0.2, 95% CI: -0.4, -0.1, p < 0.001). Sub-group analysis for the pro-inflammatory markers indicated that combined aerobic and resistance training had the greatest effect (SMD: -0.3, 95% CI: -0.5, -1.9, p < 0.001), that prostate (SMD: -0.5, 95% CI: -0.8, 0.1, p = 0.004) and breast cancer populations were most responsive (SMD: -0.2, 95% CI: -0.3, -0.1, p = 0.001), and that C-reactive protein (SMD: -0.5, 95% CI: -0.9, -0.06, p = 0.025) and tumor necrosis factor (SMD: -0.3, 95% CI: -0.5, -0.06, p = 0.004) were the most sensitive to change. Exercise training tended to decrease anti-inflammatory markers (p = 0.072) but had no effect on natural killer or natural killer T cell proportions or cytotoxic activity. CONCLUSIONS: Exercise training reduces pro-inflammatory markers in cancer survivors, with the strongest evidence for combined training and for prostate and breast cancer survivors. Further research is warranted to determine if these changes are clinically relevant or are associated with improvements in symptoms. To strengthen future research, focusing on novel immune populations that include functional parameters and standardized reporting of key immune outcomes is recommended.

Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the electrophysiologic function of retina.

CONTEXT: Since we had observed electroretinographic (ERG) abnormalities in some patients undergoing photochemotherapy with normal eye examination, we decided to investigate the effects of this therapy on retinal function. OBJECTIVE: To investigate the effects of oral photochemotherapy (8-methoxypsoralen + Ultraviolet-A) on electrophysiologic function of retina. MATERIALS AND METHODS: Patients with vitiligo, psoriasis or eczema were enrolled. Patients with any abnormal eye exam or a positive drug or family history for retinal disease were excluded. Baseline standard ERG was provided with the RETIport32 device. The second ERG was performed 6 months after the first and at least 1 week after the last photochemotherapy session (mean number of sessions: 45 ± 11). The outcome measures were changes in rod response, standard combined response, single-flash cone response, 30-Hz flicker (N1-P1) and oscillatory potentials amplitudes. RESULTS: Forty patients were enrolled; 20 of them (mean age: 31.1 ± 12 years) completed the study. The mean rod response b-wave amplitude decreased from 88.9 ± 47.5 to 86.4 ± 36.6 and standard combined response b-wave amplitude decreased from 266.52 to 261.85 µV (p = 0.422 and p = 0.968, respectively) and the standard combined response a-wave amplitude increased from 155.4 ± 40.0 at baseline to 165.1 ± 48.4 in the follow-up ERG (p = 0.092). The mean single-flash cone response a-wave amplitude decreased insignificantly in the follow-up ERG trace (34.5 ± 13.7 and 29 ± 15.4, respectively, p = 0.242). The mean single-flash cone response b-wave amplitude showed an insignificant increase (p = 0.087). The amplitudes of 30-Hz flicker wave and oscillatory potentials did not change significantly in the follow-up ERG (p = 0.551 and p = 0.739, respectively). CONCLUSION: Since no significant change in ERG traces was observed, oral photochemotherapy seems safe for retinal electrophysiologic function.

Electrophysiologic evaluation of retinal function in patients with psoriasis and vitiligo.

PURPOSE: To investigate the relation between psoriasis and vitiligo with the electrophysiologic function of the retinal photoreceptors. METHODS: Patients with psoriasis or vitiligo referred for PUVA therapy were enrolled. Complete eye examination was performed. Patients with any drug or familial history or abnormal eye examination that might affect the retinal function were excluded. Standardized full-field electroretinogram (ERG) elicited with Ganzfeld stimuli using the commercial ERG system (Retiport32; Roland Consult) according to International Society for Clinical Electrophysiology of Vision guidelines was performed. The outcome measures were the difference between the mean rod response, standard combined response, single-flash cone response and 30-Hz flicker wave amplitudes of the patients and normal population. RESULTS: Seventy-six eyes of 38 patients (vitiligo: 21; psoriasis: 17) and 40 eyes of 20 normal subjects were enrolled in this study. The mean age of patients was 31.3 ± 11.3 years (range 16-54 years). Twenty-two patients (58 %) were female. The mean rod response b-wave, standard combined a- and b-waves, single-flash cone response b-wave and the 30-Hz flicker (N1-P1) amplitudes were significantly lower than the normal population in the same range of age as the study group. There was no significant difference between the patients with vitiligo and those with psoriasis in all wave amplitudes (P = 0.094). CONCLUSION: This study showed that overall retinal electrophysiologic function in patients with vitiligo or psoriasis is significantly impaired compared with normal population, independent of age and sex.

Effectiveness of home-based exercise in breast cancer survivors: a randomized clinical trial.

BACKGROUND: Breast cancer patients are recommended to engage in regular exercise. In developing countries, where there is a lack of facilities to offer specialized, supervised exercise for this population, regularly exercising might be a challenge. We aimed to evaluate the effectiveness of a home-based intervention in this population. METHODS: Breast cancer survivors were randomly assigned to either the home-based exercise program or the usual care group. Exercise intervention included walking, balance, and stretch exercises, along with weekly follow-up telephone calls. Quality of life (QOL) was evaluated using EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and the predicted VO2 peak was measured using the Ebbeling submaximal treadmill test. RESULTS: Eighty-nine patients were enrolled in the study. Reported minutes of exercise gradually increased from 40.7 min per week in week 1 to 116.9 min per week in week 12. This intervention improved global QOL (P = 0.001), social functioning (P = 0.04), and the predicted VO2 peak (P = 0.01). CONCLUSION: This home-based exercise regime effectively increased quality of life and physical activity levels. TRIAL REGISTRY: Iranian Registry of Clinical Trials identifier: IRCT20140810018746N1, prospectively registered 08/01/2018, https://en.irct.ir/trial/27959 .

Toll-like receptors 2, 4, and 9 modulate promoting effect of COPD-like airway inflammation on K-ras-driven lung cancer through activation of the MyD88/NF-ĸB pathway in the airway epithelium.

Introduction: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable Haemophilus influenzae (NTHi) promotes tumorigenesis in a K-ras mutant mouse model of lung cancer, CCSPCre/LSL-K-rasG12D (CC-LR) mouse. Methods: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on K-ras-driven lung adenocarcinoma. Results: We found that knockout of TLR 2, 4, or 9 results in a lower tumor burden, reduced angiogenesis, and tumor cell proliferation, accompanied by increased tumor cell apoptosis and reprogramming of the tumor microenvironment to one that is antitumorigenic. Additionally, knocking out of downstream signaling pathways, MyD88/NF-κB in the airway epithelial cells further recapitulated this initial finding. Discussion: Our study expands the current knowledge of the roles that TLR signaling plays in lung cancer, which we hope, can pave the way for more reliable and efficacious prevention and treatment modalities for lung cancer.

Exercise-induced modulation of monocytes in breast cancer survivors.

BACKGROUND: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. OBJECTIVES: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. METHODS: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. RESULTS: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß+CD14+CD16+ MFI (-11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (-63, p=0.002) and CD14+CD16+ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. CONCLUSIONS: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

P-Selectin Is Critical for De Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma.

BACKGROUND: Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS: A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS: Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION: P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.

Heritability of blood pressure traits in diverse populations: a systematic review and meta-analysis.

To understand the genetic architecture and make inferences about transmissible resemblance of systolic and diastolic blood pressure (SBP and DBP) traits in relatives, the polygenic effect of individual alleles in terms of narrow heritability (h2) is usually assessed. The heritability estimates for BP traits are population specific parameters with a wide range in different studies (6-68%), and there is no comprehensive evidence comparing its source(s) of heterogeneity. To fill the gap, this systematic review and meta-analysis study was carried out. Using MeSH terms, 647 records were detected through searching, "Pubmed," "Ebsco," "Web of Science," and "Scopus" databases. From these, 24 relevant full-text articles with 47 comparisons for final quantitative meta-analysis were included in our review over the five continents. The additive genetic effects of both traits showed a widespread distribution (h2SBP: 17-52%, h2DBP:19-41%). Different categories of transmissible resemblance for BP traits were explained by ethnicity; higher heritability was estimated in Europeans and Mexican Americans, while lower heritability was seen in the Middle Eastern, Asians, Africans, Latinos, Hispanics, and American Indians. Low heterogeneity of polygenic effects was seen for both traits in subgroups of the Middle East, Asians, Africans, and Latinos, Hispanics, American Indians. However, there was a substantial heterogeneity of h2 within European and Mexican American studies. Neither pedigree type nor other covariates explained the variance of additive genetic effects of BP traits in different ethnicities.

Effect of 6 months of aerobic training on adipokines as breast cancer risk factors in postmenopausal women: A randomized controlled trial.

PURPOSE: Physical activity has been introduced as an inexpensive and effective behavior to reduce postmenopausal breast cancer risk. Decreased concentrations of adipokines such as leptin and resistin may be a possible mechanism. This study aimed to investigate the effects of 6 months of aerobic training on leptin and resistin levels in postmenopausal women. MATERIALS AND METHODS: The study participants were 50-74 years old, sedentary and postmenopausal women. Forty-one women met the inclusion criteria and were randomly assigned to the training (n = 22) or the control group (n = 19). Participants in intervention group engaged in a moderate supervised aerobic training, 3 days per week for 6 months, while controls were asked not to change their physical activity levels for the duration of the trial. Plasma concentrations of leptin and resistin, aerobic fitness, and anthropometric measures were assessed at baseline and after 6 months. RESULTS: Twenty-seven out of 41 participants completed the study. Plasma leptin decreased by 0.6% in exercisers and increased by 8.2% in controls; however, the exercise effect was not statistically significant. Plasma concentrations of resistin also decreased by 16.1% and 15.1% in exercise and control group, respectively. Aerobic fitness increased, and body mass index (BMI) decreased significantly in the intervention group. CONCLUSIONS: The exercise intervention did not have a statistically significant impact on the concentrations of the adipokines in question; however, this long-term aerobic training reduced BMI and body fat percentage and enhanced aerobic fitness. Thus, exercise programs can be considered as an effective behavioral modification in breast cancer prevention.

Pulmonary Arterial Thrombosis in a Murine Model of Blunt Thoracic Trauma.

Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.

IL22 Promotes Kras-Mutant Lung Cancer by Induction of a Protumor Immune Response and Protection of Stemness Properties.

Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-κB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on nonhematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells. Here, we found that higher expression of IL22R1 in patients with KRAS-mutant lung adenocarcinoma was an independent indicator of poor recurrence-free survival. We then showed that genetic ablation of Il22 in CC-LR mice (CC-LR/IL22KO mice) caused a significant reduction in tumor number and size. This was accompanied by significantly lower tumor cell proliferation, angiogenesis, and STAT3 activation. Il22 ablation was also associated with significant reduction in lung-infiltrating inflammatory cells and expression of protumor inflammatory cytokines. Conversely, this was accompanied with increased antitumor Th1 and cytotoxic CD8+ T-cell responses, while suppressing the protumor immunosuppressive T regulatory cell response. In CC-LR/IL22KO mice, we found significantly reduced expression of core stemness genes and the number of prototypical SPC+CCSP+ stem cells. Thus, we conclude that IL22 promotes Kras-mutant lung tumorigenesis by driving a protumor inflammatory microenvironment with proliferative, angiogenic, and stemness contextual cues in epithelial/tumor cells. Cancer Immunol Res; 6(7); 788-97. ©2018 AACR.

COPD-Type lung inflammation promotes K-ras mutant lung cancer through epithelial HIF-1α mediated tumor angiogenesis and proliferation.

Chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung, is an independent risk factor for lung cancer. Lung tissues obtained from human smokers with COPD and lung cancer demonstrate hypoxia and up-regulated hypoxia inducible factor-1 (HIF-1). HIF-1 activation is the central mechanism for controlling the cellular response to hypoxia during inflammation and tumor development. These facts suggest a link between COPD-related airway inflammation, HIF-1, and lung cancer. We have previously established a mouse model of COPD-like airway inflammation that promotes lung cancer in a K-ras mutant mouse model (CC-LR). Here we show that tumors in the CC-LR model have significantly elevated levels of HIF-1α and HIF-1 activity. To determine the tumor-promoting functions of HIF-1 in CC-LR mice, the gene Hif1a which encodes HIF-1α and is required for HIF-1 activity, was disrupted in the lung epithelium of CC-LR animals. Airway epithelial specific HIF-1α deficient mice demonstrated significant reductions in lung surface tumor numbers, tumor angiogenesis, and tumor cell proliferation in the absence or presence of COPD-like airway inflammation. In addition, when CC-LR mice were bred with transgenic animals that overexpress a constitutively active mutant form of human HIF-1α in the airway epithelium, both COPD- and adenocarcinoma-like phenotypes were observed. HIF-1α overexpressing CC-LR mice had significant emphysema, and they also showed potentiated tumorigenesis, angiogenesis, and cell proliferation accompanied by an invasive metastatic phenotype. Our gain and loss of function studies support a key role for HIF-1α in the promotion of lung cancer by COPD-like inflammation.

Requirement for MUC5AC in KRAS-dependent lung carcinogenesis.

With more than 150,000 deaths per year in the US alone, lung cancer has the highest number of deaths for any cancer. These poor outcomes reflect a lack of treatment for the most common form of lung cancer, non-small cell lung carcinoma (NSCLC). Lung adenocarcinoma (ADC) is the most prevalent subtype of NSCLC, with the main oncogenic drivers being KRAS and epidermal growth factor receptor (EGFR). Whereas EGFR blockade has led to some success in lung ADC, effective KRAS inhibition is lacking. KRAS-mutant ADCs are characterized by high levels of gel-forming mucin expression, with the highest mucin levels corresponding to worse prognoses. Despite these well-recognized associations, little is known about roles for individual gel-forming mucins in ADC development causatively. We hypothesized that MUC5AC/Muc5ac, a mucin gene known to be commonly expressed in NSCLC, is crucial in KRAS/Kras-driven lung ADC. We found that MUC5AC was a significant determinant of poor prognosis, especially in patients with KRAS-mutant tumors. In addition, by using mice with lung ADC induced chemically with urethane or transgenically by mutant-Kras expression, we observed significantly reduced tumor development in animals lacking Muc5ac compared with controls. Collectively, these results provide strong support for MUC5AC as a potential therapeutic target for lung ADC, a disease with few effective treatments.

Prophylactic efficacy of primaquine for preventing Plasmodium falciparum and Plasmodium vivax parasitaemia in travelers: A meta-analysis and systematic review.

BACKGROUND: With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. Although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. To fill the gap, this systematic review and meta-analysis study was carried out. METHODS: Using MeSH terms, 756 records were detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane" databases. From these,7 relevant full-text articles with 14 comparisons for final quantitative meta-analysis were included in our review. In order to make a comparison between the studies, Risk Ratios(RRs) and their 95% confidence intervals(CIs) were estimated. RESULTS: Overall,74% reduction in the incidence of parasitaemia by primaquine versus other prophylactic regimens was estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36--RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse effects showed no statistically significant difference between primaquine and control groups (p > 0.05). CONCLUSIONS: For persons without G6PD deficiency, who are not pregnant, primaquine is the most effective presently available prophylactic for P. vivax malaria and comparable to such regimens as doxycycline, mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.

Spatial and non-spatial determinants of successful tuberculosis treatment outcomes: An implication of Geographical Information Systems in health policy-making in a developing country.

This retrospective study aimed to address whether or to what extent spatial and non-spatial factors with a focus on a healthcare delivery system would influence successful tuberculosis (TB) treatment outcomes in Urmia, Iran. In this cross-sectional study, data of 452 new TB cases were extracted from Urmia TB Management Center during a 5-year period. Using the Geographical Information System (GIS), health centers and study subjects' locations were geocoded on digital maps. To identify the statistically significant geographical clusters, Average Nearest Neighbor (ANN) index was used. Logistic regression analysis was employed to determine the association of spatial and non-spatial variables on the occurrence of adverse treatment outcomes. The spatial clusters of TB cases were concentrated in older, impoverished and outskirts areas. Although there was a tendency toward higher odds of adverse treatment outcomes among urban TB cases, this finding after adjusting for distance from a given TB healthcare center did not reach statistically significant. This article highlights effects of spatial and non-spatial determinants on the TB adverse treatment outcomes, particularly in what way the policies of healthcare services are made. Accordingly, non-spatial determinants in terms of low socio-economic factors need more attention by public health policy makers, and then more focus should be placed on the health delivery system, in particular men's health.