Prognostic Value of Lymphocyte Vascular Density and E-Cadherin in Inflammatory Breast Cancer

Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients. Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and survival data were available for up to 17 years. Overall survival (OS) was analyzed through the Kaplan-Meier method stratified by E-cadherin, LVD, VEGF-D, and response to chemotherapy. The differences in OS curves were compared using the log-rank test. Results: The median OS for patients with high LVD was 6.63 years (95% CI: 4.06 to 10.14), compared to median at 10 years not reached in those with low LVD (p = 0.03). There was a trend towards a longer median OS in patients with high E-cadherin (10.14, 95% CI: 6.63 to 11.67), compared with those with low E-cadherin (6.26, 95% CI: 3.42 to undeterminable). VEGF-D levels showed no correlation with survival. Conclusion: Low LVD significantly predicts better survival. High E-cadherin expression, as with non-IBC breast cancer and several other malignancies, tends to be associated with a better prognosis.

Nationwide seroprevalence, spatial distribution and risk factors of Leishmania in Jordan

Objective:To explore the seroprevalence,spatial distribution and risk factors for Leishmania seropositivity in Jordan.Methods:Blood samples from 872 apparently healthy participants were randomly selected from 11 governorates in Jordan and tested for anti-Leishmania K39 IgG.Risk factors(animal ownership and agriculture practices)and demographic data were also collected using pre-tested and validated questionnaire.Results:Overall,2.52% of participants were seropositive for Leishmania spp.Participants living in the Jordan Valley plateau had significantly greater odds(adjusted odds ratio= 3.70,95% CI 1.37-9.93)of seropositivity than those living in the Highlands after adjustment for age.Conclusions:This study supports the intermittent reports of cutaneous leishmaniasis outbreaks in the Jordan Valley.Vector control measures in the Jordan Valley should be considered,including insecticide treated bed nets,sugar baits and using flowering plants to attract and trap Phlebotomus papatasi sand flies.Active surveillance in the Jordan Valley is also recommended in light of this and other reports.

What do teachers see?Perceptions of school-time physical activity programs on student behavior

In the United States, children are not meeting daily recommendationsfor 60 min of moderate・to・vigorous activity.1Because children spend a large portion of their days in school, ithas been further recommended that children accumulate 30 minof their physical activity (PA) during school hours.2 Our previousresearch has demonstrated with objective measures that only8%—9% of elementary school children meet this goal, with anaverage accumulation of 18 min/day.3,4 This finding is of concerngiven the numerous benefits that PA has not only on healthoutcomes,5-8 but also on academic achievement.9 For example,there is heightened awareness that children benefit from PAthroughout the school day in terms of attention to task, memory,behavior, and, ultimately, academic performance.10 Schooladministrators acknowledge this link, but still face barriers toincorporating PA for schoolchildren, including limited time andresources for physical education (PE) and recess.

Outdoor air pollution as a possible modifiable risk factor to reduce mortality in post-stroke population

Outdoor air pollution is a known risk factor for mortality and morbidity.The type of air pollutant most reliably associated with disease is particulate matter（PM）,especially finer particulate matter that can reach deeper into the lungs like PM_（2.5）（particulate matter diameter 〈 2.5 μm）.Some subpopulations may be particularly vulnerable to PM pollution.This review focuses on one subgroup,long-term stroke survivors,and the emerging evidence suggesting that survivors of a stroke may be at a higher risk from the deleterious effects of PM pollution.While the mechanisms for mortality are still under debate,long-term stroke survivors may be vulnerable to similar mechanisms that underlie the well-established association between PM pollution and cardiovascular disease.The fact that long-term stroke survivors of ischemic,but not hemorrhagic,strokes appear to be more vulnerable to the risk of death from higher PM pollution may also bolster the connection to ischemic heart disease.Survivors of an ischemic stroke may be more vulnerable to dying from higher concentrations of PM pollution than the general population.The clinical implications of this association suggest that reduced exposure to PM pollution may result in fewer deaths amongst stroke survivors.

New scientific basis for the 2018 U.S. Physical Activity Guidelines

The U.S.Department of Health and Human Services convened the 2018 Physical Activity Guidelines Advisory Committee(PAGAC)and charged it with reviewing and summarizing the current scientific evidence linking physical activity to human health and function.The 2018 PAGAC Scientific Report1 serves as the basis for the Physical Activity Guidelines for Americans,2nd edition3 The 2018 Scientific Report extends the findings of the 2008 Scientific Report3 by examining a broader range of health outcomes and special populations that benefit from increased physical activity.In addition,the 2018 Scientific Report more closely examined the specific types,volumes,and intensities of physical activity that are associated with those benefits and now describes novel strategies for physical activity promotion at the population level.

Evaluation of disinfection byproducts for their ability to affect mitochondrial function

In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs) in water;evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential( Δψm) and cytoplasmic adenosine triphosphate(C-ATP) was investigated with human carcinoma(Hep G2) cells. Within 90 min of cell exposure, only the haloacetic acid(HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups(haloacetonitriles(HANs), trihalomethanes(THMs), nitrosamines(NOAs), and HAAs) responded well to Δψm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in Δψm, the response gradient was HANs >> HAAs ~ THM > NOAs. The inhibition of the Δψm by HANs is driven by dibromoacetonitrile(DBAN), while dichloroacetonitrile(DCAN) did not cause a significant change in the Δψm at less than 2000 μM. A mixture of HANs exhibited an antagonistic behavior on the Δψm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then Δψm could be used as a biomonitoring tool for DBP toxicity.

Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity

Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.

Implementation and evaluation of Exercise is Medicine in primary care clinics within a large academic health system

Objective Exercise is Medicine(EIM)is a global initiative encouraging healthcare providers to routinely assess and promote physical activity(PA)among patients.The objective of this study was to evaluate the feasibility,adoption,implementation and effectiveness of EIM from patient,clinician and healthcare staff perspectives using a combination of electronic health record(EHR),survey and interview data.Design This study used a combination of the Practical Robust Implementation and Sustainability Model(PRISM)and the Learning Evaluation model to implement EIM.Data captured from the EHR,including Physical Activity Vital Sign(PAVS)scores,and data collected from qualitative surveys and interviews were used to evaluate the programme’s Reach,Effectiveness,Adoption,Implementation,Maintenance(RE-AIM,which is embedded within PRISM)from provider,staff and patient perspectives.Setting Five primary care clinics within a large academic health system.Participants A total of 24443 patients from all participating clinics had at least one PAVS score during the study period.A total of 17 clinicians completed surveys,and 4 clinicians,8 medical assistants and 9 patients completed interviews.Results Implementation fidelity metrics varied widely between components and across clinics but were generally consistent over time,indicating a high degree of programme maintenance.Fidelity was highest during the first 6 months of the COVID-19 pandemic when most visits were virtual.Mean PAVS scores increased from 57.7(95%CI:56 to 59.4)to 95.2(95%CI:91.6 to 98.8)min per week at 6 months for patients not meeting PA guidelines at baseline and decreased from 253.84(95%CI:252 to 255.7)to 208.3(95%CI:204.2 to 212.4)min per week at 6 months for patients meeting PA guidelines at baseline.After EIM implementation,clinician-estimated time spent discussing PA with patients increased for 35%of providers and stayed the same for 53%.Conclusion Overall,this study established EIM’s feasibility,adoption,implementation and maintenance in routine primary care practice within a large academic health system.From a population health perspective,EIM is a model to emulate to help primary care providers efficiently address healthy lifestyle behaviours in routine primary care visits.

Use of prostate-specific antigen testing in Medicare beneficiaries:Association with previous evaluation

Objective:Determine uptake of prostate-specific antigen(PSA)testing in Medicare benefi-ciaries according to previous receipt of PSA testing.Methods:A 5%random sample of men aged 67 years or older without a previous diagnosis of prostate cancer was identified through 2009-2012 Medicare claims.We measured the annualized frequency of PSA screening among men due for PSA testing,stratified by PSA testing use in the previous 2 years,and clustered by ordering provider.Results:Throughout the study period,PSA testing use was consistently higher for men with previous screening than for men without previous screening.For men without previous screening,there was a decline in testing that was most pronounced in 2012.Compared with 2009,the cor-responding odds ratios were 0.98[95%confidence interval(CI)(0.96-1.00)]in 2010,0.94[95%CI(0.92-0.95)]in 2011,and 0.66[95%CI(0.65-0.68)]in 2012.In contrast,for men with previous screening,PSA testing frequency was stable from 2009 to 2011,and declined to a lesser extent in 2012[odds ratio 0.80,95%CI(0.79-0.81)].Conclusion:Receipt of PSA testing is highly dependent on whether an individual was tested in the recent past.In previously unscreened men,the largest decrease occurred in 2012,which may reflect in part the publication of US Preventive Services Task Force guidelines,but there was much less impact among men already being screened.