Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice

Aging is an inevitable process associated with immune imbalance, which is characterized by a progressive functional decline in major organs, including lung. However, effects of altered Th1/Th2 commitment on lung senescence are largely unknown. To examine effects of altered Th1/Th2 balance on lung aging, we measured proportions of Th1 and Th2 cells and expression of cytokines, chemokines, collagen deposition and other relevant physiological and pathological parameters in 2- and 20-months-old (mo) CXCR3-deficient (CXCR3^−/−) C57BL/6J mice compared with wild-type (WT) mice. There was a significant weight-loss observed in 20-mo CXCR3^−/− mice compared with the same aged WT group. Although lung function and structure changed with age in both groups, central airway resistance (Rn), tissue elastance (H) and damping (G) were significantly lower in 20-mo CXCR3^−/− mice than those of WT mice. In contrast, the whole lung volume (V_L), the mean linear intercept length of alveolar (L_m), and the total lung collagen content were significantly elevated in 20-mo CXCR3^−/− mice. With aging, the lungs of WT mice had typical Th1-type status (increased population of Th1 cells and concentrations of cytokine IFN-γ and CXCR3 ligands) while CXCR3^−/− mice showed Th2-type polarization (decreased proportion of Th1 cells and concentrations of CXCR3 ligands but increased level of IL-4). Our data suggest that Immunosenescence is associated with lung aging, and that altered Th1/Th2 imbalance favors Th2 predominance in CXCR3^−/− mice, which contributes to the process of accelerated lung aging in this model.     

婴幼儿汞暴露相关影响因素分析

目的调查福建省厦门市婴幼儿汞暴露现状,并分析其相关因素,为采取干预措施提供依据。方法采用整群分层法选取10个社区的1 041名婴幼儿,对其日常家庭社会环境进行问卷调查,同时采集其发样进行发汞含量测定。结果婴幼儿发汞均值为0.985 μg/g,几何均数为0.724 μg/g,>1 μg/g者占31.70%;海岛社区婴幼儿的发汞均值最高,为1.559 μg/g,超标率为53.26%,偏僻农村最低,为0.684 μg/g,超标率为14.42%;鱼类与贝类辅食摄入频率与婴幼儿发汞含量呈正相关,差异均有统计学意义(F=12.68,P<0.01;F=6.867,P=0.009);家中有人使用染发剂时婴幼儿发汞含量较高(t=3.165,P=0.002);婴幼儿的月龄与婴幼儿发汞含量呈正相关(β=6.186,t=2.220,P=0.027),婴幼儿性别、睡眠等因素与发汞含量无关。结论厦门市婴幼儿发汞水平接近临界值,居住在海岛的儿童发汞值高于偏僻乡村,随着年龄的增长,婴幼儿的发汞值逐渐增高;鱼类、贝类辅食的摄入及家庭环境中染发剂等的使用是婴幼儿汞暴露的主要来源。     

Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study

PurposeThe estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR_6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR_6m <60 mL/min/1.73 m² (eGFR_6m <60) and identify the risk factors that can predict the occurrence of eGFR_6m <60 in living kidney donors.Materials and MethodsLiving kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR_6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR_6m <60 occurrence were determined using the Youden index.ResultsThe eGFR_6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR_6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR_6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863–0.908] vs. 0.862 (95% CI, 0.838–0.887), p<0.001}.ConclusionThe incidence of eGFR_6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR_6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR_6m <60.     

Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

ObjectiveSecond-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents.MethodsTen second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction.ResultsIn the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R² = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R² = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared stronger than the correlation of response (76%, Қ = 0.17) with OS12 in the external validation dataset.ConclusionsPFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC.     

Mass media based health behavior change: televised smoking cessation program

This report describes the 1-year follow-up assessment of a television-based smoking cessation program shown as a part of local news in the Los Angeles area. The post-broadcast experiences of two distinct samples was considered: individuals who wrote in for additional materials (Registrants) and a cross section sample (CS) contacted by a random survey method. Results showed significant between-group differences in demographic characteristics and smoking behavior outcomes. Compared to the CS sample, registrants displayed more quitting attempts during the 1-year follow-up period (70.7% and 49.8%) and more abstinence (6.2% and 2.4%, respectively). When compared to results from a comparison survey, both registrant and CS subjects made significantly more quitting attempts in the three week period following broadcast. In terms of abstinence, only registrant results significantly differed from the comparison survey (6.2% vs. 2.9%). Few correlates of outcome were identified. Overall, analyses suggest that the televised quit smoking program encouraged viewers to initiate more numerous attempts to quit smoking than otherwise would have been expected. In terms of maintaining nonsmoking over time, however, only registrants experienced significantly greater success than might have been observed in the general population. Implications for research and policy recommendations of televised health promotion programs are proposed.     

Formulas providing adequate pantothenic acid,vitamin D,manganese, iron and vitamin A for infants fed with mother's milk (aged 6–11 months) according to the Japanese Dietary Reference Intakes prepared by the Ministry of Health,Labour and Welfare (2005 edition)

Weaning formulas served in hospitals and care facilities in Japan should conform to dietary reference intakes (DRIs). We examined whether the DRI for breastfed infants aged 6–11 months can be satisfied in dietary practice, with a particular focus on the fulfilment rates for vitamins, minerals, trace elements and electrolytes in weaning formulas containing energy and protein at levels either greater than or equal to the DRIs, as well as on the dietary profiles of weaning formulas to achieve the DRI for every nutrient. The results showed that no weaning formulas examined in this study fulfilled the DRI for pantothenic acid (5 mg), vitamin D (4 µg), manganese (1.2 mg) or iron (5.5 mg). Furthermore, their vitamin A content exceeded the DRI (350 µg RE). The discrepancy between the guidelines and actual dietary practice is probably because of the fact that the estimated reference values poorly reflect the actual dietary intake in the target population; for example, the pantothenic acid and manganese DRIs for breastfed infants aged 6–11 months were set based on the breast milk intake of younger infants (0–5 months) in combination with the breast milk contents. Our results suggest that dietary guidance for infants should include information to promote proper intakes of vitamins A and D, and iron by reducing the amount of vitamin A‐rich foods and utilizing dietary vitamin D and iron supplements including government‐approved specified health foods.     

The course of maternal depressive symptomatology during the first 18 months postpartum in an Italian sample

Postnatal depression (PND) affects about 10-15% of women and can last more than a year in chronic cases. The Edinburgh Postnatal Depression Scale (EPDS) is a well-known questionnaire for screening PND symptomatology during the first weeks after birth, but its use in later periods is rare, reflecting a tendency to pay more attention to the onset of PND instead of its course. The study aimed to explore stability of PND symptomatology at 3, 9 and 18 months after birth, using the EPDS. Depression rate decreased from 3 to 18 months postpartum. Onset of symptoms was mainly within the first 3 months; 23.4% of 167 women showed an EPDS score > or =13 on at least one of the assessments, and 7.2% of women did so on at least two assessments. Over the 18-month period, the number of women who had recovered in the period from one assessment to the following was not significantly different from the number of women becoming depressed. Our findings underline the need to consider the existence of different courses of depressive symptomatology in research and clinical practice; women with persistent or recurrent depressive symptoms need forms of preventive intervention that cover at least the first postpartum year.     

Latent Tuberculosis Infection: Treatment Initiation and Completion Rates in Persons Seeking Immigration and Health Care Workers

BackgroundWe assessed the factors associated with initiation and completion rates of latent tuberculosis (TB) infection treatment in persons evaluated at an infectious diseases outpatient clinic in central Massachusetts. The Centers for Disease Control and Prevention (CDC) estimates that there may be up to 14 million persons in the United States with a latent TB infection. The risk of developing active TB in these persons can range from 5% to 15%. Hence, treatment of latent TB infection is an important aspect of any plan attempting to eradicate TB from the United States.MethodsWe performed a retrospective chart review of patients referred to our outpatient infectious diseases clinic from December 2006 to October 2010.ResultsOverall treatment initiation and completion rates were 76% and 68%, respectively, in our cohort. Two factors that were statistically significant for higher rates of treatment completion were 4 or more follow-up visits during the course of treatment (P < 0.001) and persons seeking immigration (PSI) to the United States (P < 0.02). Rate of treatment refusal was higher in health care workers as compared to workers not in health care (35% vs 13%, P = 0.004, 95% confidence interval [CI]: 1.38-4.91).ConclusionOur study reveals findings not previously reported in the US literature. We noted a high rate of treatment completion in persons seeking immigration to the United States. The second unique observation is the higher treatment completion rates in persons with 4 or more follow-up visits. We suggest that an emphasis on at least 4 follow-up visits can be an intervention that could improve the overall rates of treatment completion.     

24月龄幼儿心理行为预警征筛查现状及影响因素分析

目的 了解24月龄幼儿心理行为预警征筛查情况并分析可能的影响因素,为临床有效筛查提供参考。方法 在全国4个省的5个县区采用随机抽样的方法选取2016年内出生的2 731例婴儿作为研究对象,追踪随访收集孕产妇基本情况和幼儿基本情况、喂养情况、生长发育和健康情况。以国家预警征筛查表为工具对儿童进行心理行为发育迟缓筛查。结果 追踪随访到2岁幼儿心理行为预警征筛查阳性率为6.65%,在性别和地区间差异有统计学意义(P＜0.05)。单因素分析结果显示,母乳喂养至6月龄及以上、家庭居住环境、幼儿每天室外活动时间和每天与儿童互动玩耍时间差异有统计学意义(P＜0.05)。多因素Logistic回归分析结果显示,男童(OR=2.169,95%CI:1.516~3.103)、生活在北方(OR=2.308,95%CI:1.630~3.267)、母乳喂养未到6月龄(OR=1.645,95%CI:1.088~2.489)、幼儿每天在室外活动时间低于4 h(OR=2.715,95%CI:1.548~4.761)是2岁幼儿心理行为预警征筛查阳性的危险因素。结论 应注重幼儿早期心理行为预警征筛查,早发现、早转诊、早干预,提倡母乳喂养,家长在养育幼儿过程中要加强对幼儿的陪伴、多参加室外活动等,从而促进儿童健康成长。     

Addressing Food Insecurity: An Evaluation of Factors Associated with Reach of a School-Based Summer Meals Program

BackgroundOne in six US households with children experiences food insecurity, with higher rates in the summer. Approximately 3 million children receive free meals each summer weekday through the US Department of Agriculture’s Summer Nutrition Programs. However, participation in these programs has been declining in recent years and is lower than participation in programs that serve free or reduced-price meals during the school year.ObjectiveTo identify school and site characteristics associated with greater reach by school-based free summer meals program sites.DesignThis observational study combined program data, public school data, and Google Maps data to determine factors associated with site reach.Participants/settingLunchStop Summer Meals Program sites (N=100) and schools at which they were based during summer 2018 in Chicago, IL.Main outcome measuresReach of sites was measured by the mean daily meals served at each site throughout summer 2018.Statistical analyses performedAssociations between site reach and each independent variable were evaluated using Mann-Whitney tests and simple linear regressions. Variables significantly associated with site reach in bivariate analyses (P<0.05) were included in a multivariate linear regression.ResultsIn bivariate analyses, sites with greater reach were significantly more likely to be based at schools with higher attendance percentages, higher percentages of Hispanic/Latino students, larger student populations, and locations in a network of southwest Chicago schools. Those with greater reach were also significantly more likely to have continuity in program staff and more years of site operation (all P values ≤0.01). The last four factors remained significant in multivariate analysis.ConclusionsSchool-based summer meals programs may be able to reach more vulnerable children by taking into account continuity among sites and staff. Further research is needed to clarify whether the relationships between these variables and increased reach is causal.