Linking between ambient pollution and metals concentration in blood. Nationwide study based on the national blood banking system.

This study was aimed to describe the chemical traces of air pollution in blood of residents and evaluate the association between ambient pollution and its dose absorbed internally by a human body. The national Magen David Adom Blood Services blood donation collection platform and the National Public Health Laboratory's testing services were utilized to conduct a human biomonitoring study among blood donors in Israel. The donors' residential addresses and donations sites' locations were geocoded and merged with the levels of pollutants recorded by the nearby monitoring stations. Pollutants included nitrogen dioxide (NO2), sulfate dioxide (SO2), ozone (O3), carbon monoxide (CO) and particulate matter of size <10 and 2.5 µm in diameter (PM10 & PM2.5). Metal concentrations were statistically analyzed by ratio t-test and a lognormal regression, and adjusted to age, gender and smoking (defined based on Cadmium values). The findings indicate an independent positive association between pollutants and metals' concentrations in blood. Specifically, an increase in interquartile range (IQR) of NO2 was associated with 9.5 % increase in As in blood. The increase in one IQR of PM10 and SO2 was associated with an increase in Pb, of 16.6 % and 12.4 %, respectively. SO2 was also adversely associated with Cd concentrations, by increasing its levels by 5.7 %. The donors' proximity to quarries was related to the Pb blood levels higher 1.47 times compared to donors without quarries close to their residence (p-value = 0.013). To conclude, ambient pollution levels are associated with internal metals' concentrations, reaffirming the link between the two in the pathological pathway from air pollution to morbidity.

National blood bank services as a platform for national human biomonitoring - A proof-of-concept study.

BACKGROUND: Human biomonitoring (HBM) is crucial for identifying potential risks to human health from exposure to environmental hazards. However, it is an expensive and labor-intensive endeavor. To save on samples' collection process we suggested using a national blood banking system as a platform for a national HBM program. For the case study, we used a comparison of blood donors from heavily industrialized Haifa Bay region, northern Israel, with donors from the rest of the country. METHODS: The study population comprised a random sample of blood donors donating blood all over Israel. Samples of whole blood were tested for arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb). Donors' donations sites and residential locations were geocoded. Smoking status was verified based on Cd levels, after calibrating their concentrations vs Cotinine in a sub-sample of 45 subjects. Metal concentrations were compared between regions using a lognormal regression, while controlling for age, gender, and predicted probability of smoking. RESULTS: During Mar 2020-Feb 2022, we collected 6230 and tested 911 samples. Concentrations of most of the metals were modified by age, gender, and smoking. Cr and Pb appeared to be 1.08-1.10 times higher among Haifa Bay residents than in the rest of the country (although with borderline significance of 0.069 for Cr). Cr and Pb were 1.13-1.15 times higher for those who donated blood in the Haifa Bay region, but not necessarily resided in the area. Donors from Haifa Bay had lower levels of As and Cd as compared to other donors in Israel. CONCLUSIONS: Using a national blood banking system for HBM proved to be feasible and efficient. Blood donors from Haifa Bay area were characterized by elevated levels of Cr and Pb and lower levels of As and Cd. An extensive investigation of industries in the area is warranted.

Exposure to metals and morbidity at eight years follow-up in women of childbearing age.

This exploratory study was aimed to investigate the link between toxic metal content in women's urine and their morbidity 2 years before and 6 years after the test. Concentrations of 25 metals in urine were analyzed for 111 pregnant women collected prior to delivery. All women were of Arab-Bedouin origin. Information on primary care and hospital visits during the study period was obtained. In a Poisson regression model, a health outcome was regressed over metal exposure and other factors. A Weighted Quantile Sum Regression (WQS) approach was used to indicate metals dominating in their possible impact on women's morbidity. Obesity was the most frequently diagnosed condition in this population (27.9%). Diagnoses in a neurological category accounted for 36.0%, asthma or respiratory-25.2%, psychiatric-12.6%, cardiovascular-14.4% and cancer or benign growth-for 13.5%. Based on WQS analysis, cancer and benign growth were mostly attributed to the increased levels of cadmium, cardiovascular outcomes were linked with lead, and obesity was found associated with elevated levels of nickel. Hematological, neurological and respiratory outcomes were attributed to multiple non-essential metals. The health and exposure profile of women in the study warrants a periodic biomonitoring in attempt to identify and reduce exposure to potentially dangerous elements.

Atrial Fibrillation and Mortality in the Oldest Old after Surgery for Hip Fractures.

INTRODUCTION: One-year mortality following hip fractures increases steeply with age, from 2% in the 60- to 69-year-old population up to 28% in the oldest old (older than 90 years). Of the various factors that contribute to hip fractures, atrial fibrillation (AF) is an independent risk factor at any age. OBJECTIVE: The objective of this study was to assess the association of AF with mortality among the oldest old with hip fractures. METHOD: This is a retrospective cohort study of 701 persons above age 90 years who underwent orthopedic repair for a hip fracture during 2000-2018. Of them, 218 (31%) had AF at hospital admission. The primary outcome was survival following surgery. We compared patient characteristics and 30-day, 180-day, 1-year, and 3-year survival between patients with and without AF. RESULTS: The adjusted odds ratio for 30-day postoperative mortality for those with AF versus without AF group was 1.03 (95% confidence interval [CI] 0.63-1.66). Survival estimates were higher among those without AF than with AF at 180 days postoperative: 0.85 (95% CI 0.82-0.89) versus 0.68 (95% CI 0.61-0.74), p < 0.001; at 1 year postoperative: 0.68 (95% CI 0.63-0.72) versus 0.48 (95% CI 0.42-0.55), p < 0.001; and at 3 years postoperative: 0.47 (95% CI 0.42-0.52) versus 0.28 (95% CI 0.27-0.34), p < 0.001. CONCLUSIONS: Among individuals aged >90 years, operated for hip fractures, mortality was similar for those with and without AF at 30 days postoperative. However, the survival curves diverged sharply after 180 days. Our findings suggest that AF is not an immediate surgical risk factor, but rather confers increased long-term risk in this population.

Autophagy differentially regulates macrophage lipid handling depending on the lipid substrate (oleic acid vs. acetylated-LDL) and inflammatory activation state.

The regulation of lipid droplet (LD) dynamics by autophagy in naïve macrophages is complex: Inhibiting autophagosome initiation steps attenuates oleic acid (OA) induced LD (OA-LD) biogenesis, whereas interfering with later-autophagosome maturation/lysosomal steps accelerates OA-LD biogenesis rate, but not OA-LD degradation. Here we hypothesized that regulation of macrophage lipid handling by autophagy may be lipid-substrate and activation-state-specific. Using automated quantitative live-cell imaging, initial LD biogenesis rate was ~30% slower when the lipid source was acetylated low density lipoprotein (acLDL) compared to OA. Yet, both were similarly affected by triacsin-C, an inhibitor of acyl-CoA synthase, which inhibited, and etomoxir, an inhibitor of acylcarnitine palmitoyl transferase (fatty acid oxidation), which augmented, LD biogenesis rates. An autophagy inducing peptide, Tat-Beclin1, enhanced the degradation, and inhibited (by 37%) the biogenesis of acLDL induced LD (acLDL-LD). Yet, Tat-Beclin1 increased OA-LD biogenesis rate by 70%. When macrophages were pre-activated with LPS + INFG they exhibited increased autophagosome number and area, and reduced BECN1 and ATG14 protein levels, which associated with a markedly attenuated autophagic flux. Concomitantly, OA-LD and acLDL-LD biogenesis rates increased 3 and 7.4-fold, respectively, but could not be further modulated by Tat-Beclin1, as observed in non-activated/naïve macrophages. We propose that macrophage autophagy, and/or components of its machinery, differentially regulate LD/foam-cell biogenesis depending on the lipid-source, and that inflammatory activation uncouples autophagy from LD biogenesis.

SCAPER localizes to primary cilia and its mutation affects cilia length, causing Bardet-Biedl syndrome.

Studies of ciliopathies have served in elucidating much of our knowledge of structure and function of primary cilia. We report humans with Bardet-Biedl syndrome who display intellectual disability, retinitis pigmentosa, obesity, short stature and brachydactyly, stemming from a homozyogous truncation mutation in SCAPER, a gene previously associated with mitotic progression. Our findings, based on linkage analysis and exome sequencing studies of two remotely related large consanguineous families, are in line with recent reports of SCAPER variants associated with intellectual disability and retinitis pigmentosa. Using immuno-fluorescence and live cell imaging in NIH/3T3 fibroblasts and SH-SY5Y neuroblastoma cell lines over-expressing SCAPER, we demonstrate that both wild type and mutant SCAPER are expressed in primary cilia and co-localize with tubulin, forming bundles of microtubules. While wild type SCAPER was rarely localized along the ciliary axoneme and basal body, the aberrant protein remained sequestered to the cilia, mostly at the ciliary tip. Notably, longer cilia were demonstrated both in human affected fibroblasts compared to controls, as well as in NIH/3T3 cells transfected with mutant versus wildtype SCAPER. As SCAPER expression is known to peak at late G1 and S phase, overlapping the timing of ciliary resorption, our data suggest a possible role of SCAPER in ciliary dynamics and disassembly, also affecting microtubule-related mitotic progression. Thus, we outline a human ciliopathy syndrome and demonstrate that it is caused by a mutation in SCAPER, affecting primary cilia.