Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.

Exposure of individuals aged 18-44 years to personal care products in Beijing, China: Exposure profiles, possible influencing factors, and risk assessment.

Personal care products (PCPs) are a class of emerging pollutants that have attracted public concern owing to their harmful effects on humans and the environment. Biomonitoring data is valuable for insight the levels of PCPs in the human body and can be crucial for identifying potential health hazards. To gain a better understanding of timely exposure profiles and health risk of reproductive-age population to PCPs, we determined six parabens, six benzophenone-type ultraviolet filters, and three disinfectants in 256 urine samples collected from young adults aged 18-44 years in Beijing, China. The urinary levels of benzophenone-3 (BP-3) and 4-hydroxybenzophenone (4-OHBP) were significantly higher in summer compared to winter, suggesting these compounds have different seasonal usage patterns. Moreover, the total concentration of 15 PCPs in female was 430 ng/mL, approximately two times higher than that in male. P­chloro-m-xylenol (PCMX), as a new type of antibacterial agent, has the greatest level among all target analytes, indicating the increasingly use of this antibacterial alternative recently. Five potential influencing factors that lead to the elevated exposure level of PCPs were identified. Over 19% of the target population had a high hazard index value (greater than 1) which was attributed to exposure to propyl paraben (PrP), benzophenone-1 (BP-1), BP-3 and PCMX, indicating that PCPs may pose a relatively high exposure risk at environmental levels that should be a cause for concern.

Determination of Cotinine, 3'-Hydroxycotinine and Nicotine 1'-Oxide in Urine of Passive and Active Young Smokers by LC-Orbitrap-MS/MS Technique.

Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3'-hydroxycotinine, and (2'S)-nicotine 1'-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans-3'-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1'S,2'S)-nicotine 1'-oxide in the samples of individuals from various groups.

Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension: An observational study among 1162 healthy men.

Disinfection byproducts (DBPs) have demonstrated cardiovascular and reproductive toxicity. However, the associations and mechanisms of DBP exposure in relation to hypertension among healthy young men, which are critical for gaining new insights into the prevention and treatment of male subfertility, remain unclear. In 2017-2018, we recruited 1162 healthy Chinese men. A single blood sample was collected and measured for trihalomethane (THM) concentrations (n = 956). Up to 2930 repeated urinary samples were collected at baseline and during follow-up periods and determined for haloacetic acid concentrations. Oxidative stress (OS) biomarkers were measured in within-subject pooled urinary samples (n = 1003). In total, 403 (34.68 %) participants were diagnosed with stage 1-2 hypertension (≥130/80 mmHg) and 108 (9.29 %) stage 2 hypertension (≥140/90 mmHg). In adjusted models, blood bromodichloromethane (BDCM) concentrations were positively associated with the risk of stage 1-2 and stage 2 hypertension [ORs= 1.48 (95 % CI: 1.15, 1. 91) and 1.65 (95 % CI: 1.08, 2.51), respectively, per 2.7-fold increase in BDCM concentrations]. Additionally, we found positive associations between DBP exposure biomarkers and urinary concentrations of 4-hydroxy-2-nonenal-mercapturic acid and 8-hydroxy-2-deoxyguanosine. However, these OS biomarkers were unrelated to hypertension. Our results suggest that BDCM exposure may be associated with a greater risk of hypertension among healthy young men.

A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats.

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin-angiotensin-aldosterone system.

PHENOTYPING REPAIR AFTER ACUTE KIDNEY INJURY: PRECISION MEDICINE TO CLINICAL TRIALS.

Acute kidney injury (AKI) is common during hospitalization and is associated with long-term risk of readmissions and chronic kidney disease (CKD). Preclinical studies and novel urine biomarkers have demonstrated that subclinical inflammation and repair continue for several months after AKI. We conducted three clinical and translational studies to alleviate long-term sequelae after AKI. First, we assessed repair in deceased donor kidneys which can assist with organ allocation and reduce discard. In an ongoing study, organ procurement organizations are measuring repair biomarkers via lateral flow devices to assess organ quality and adding it to their workflow. Second, we performed research biopsies during AKI to interrogate kidney tissue with novel transcriptomic and proteomic techniques to advance therapeutic development. Third, we initiated pragmatic clinical trials to reduce readmissions after an episode of AKI by providing nurse navigator and pharmacist support to optimize blood pressure, fluid, and medication management.

Panel miRNAs are potential diagnostic markers for chronic kidney diseases: a systematic review and meta-analysis.

BACKGROUND: Accurate detection of kidney damage is key to preventing renal failure, and identifying biomarkers is essential for this purpose. We aimed to assess the accuracy of miRNAs as diagnostic tools for chronic kidney disease (CKD). METHODS: We thoroughly searched five databases (MEDLINE, Web of Science, Embase, Scopus, and CENTRAL) and performed a meta-analysis using R software. We assessed the overall diagnostic potential using the pooled area under the curve (pAUC), sensitivity (SEN), and specificity (SPE) values and the risk of bias by using the QUADAS-2 tool. The study protocol was registered on PROSPERO (CRD42021282785). RESULTS: We analyzed data from 8351 CKD patients, 2989 healthy individuals, and 4331 people with chronic diseases. Among the single miRNAs, the pooled SEN was 0.82, and the SPE was 0.81 for diabetic nephropathy (DN) vs. diabetes mellitus (DM). The SEN and SPE were 0.91 and 0.89 for DN and healthy controls, respectively. miR-192 was the most frequently reported miRNA in DN patients, with a pAUC of 0.91 and SEN and SPE of 0.89 and 0.89, respectively, compared to those in healthy controls. The panel of miRNAs outperformed the single miRNAs (pAUC of 0.86 vs. 0.79, p < 0.05). The SEN and SPE of the panel miRNAs were 0.89 and 0.73, respectively, for DN vs. DM. In the lupus nephritis (LN) vs. systemic lupus erythematosus (SLE) cohorts, the SEN and SPE were 0.84 and 0.81, respectively. Urinary miRNAs tended to be more effective than blood miRNAs (p = 0.06). CONCLUSION: MiRNAs show promise as effective diagnostic markers for CKD. The detection of miRNAs in urine and the use of a panel of miRNAs allows more accurate diagnosis.

Frequencies of chromosomal aberrations and related biochemical parameters in welders.

Stainless steel welders are exposed to heavy filler metals. We evaluated the concentration of these metals in whole blood and urine, and the relevant biochemical parameters in relation to the total chromosomal aberrations (CAs), chromatid-type (CTA-type, CTAs) and chromosome-type (CSA-type, CSAs), in 117 welders and control individuals. Statistically higher concentrations of the total Cr, Ni and Mn were observed in whole blood and urine of welders, and the concentrations were higher in welders who smoked. On the contrary, concentrations of urinary heavy metals Cr and Mn adjusted for creatinine were significantly higher in the control groups. A statistically higher frequency of total CAs was observed in the whole group of welders, and also in the non-smoking welders, as compared to controls. The frequency of total CAs significantly correlated with the concentration of Cr, Ni and Mn in whole blood (R=0.61, P˂0.0001, R=0.33, P˂0.0001 and R=0.66, P˂0.0001, respectively), with urinary concentrations of Ni and Mn (R=0.27, P=0.003 and R=0.28, P=0.003, respectively) and with urinary concentrations of Cr, Ni and Mn adjusted for creatinine (R=0.22, P=0.029, R=0.26, P=0.005 and R=0.20, P=0.030, respectively). Likewise, the frequency of CTA-types significantly correlated with the concentration of Cr and Mn in whole blood (R=0.31, P=0.0007 and R=0.34, P=0.0002). The frequency of CSA-types significantly correlated with concentrations of Cr, Ni and Mn in whole blood (R=0.43, P˂0.0001, R=0.38, P˂0.0001 and R=0.46, P˂0.0001, respectively). The statistically higher values of serum creatinine and total bilirubin were detected in all welders, as well as in smokers when compared to the corresponding controls. The exposure to heavy metals in welders increased the frequencies of CAs and altered the balance between urinary excretion of heavy metals and their possible accumulation.

Detection of Subclinical Rejection in Pediatric Kidney Transplantation: Current and Future Practices.

INTRODUCTION: The successes in the field of pediatric kidney transplantation over the past 60 years have been extraordinary. Year over year, there have been significant improvements in short-term graft survival. However, improvements in longer-term outcomes have been much less apparent. One important contributor has been the phenomenon of low-level rejection in the absence of clinical manifestations-so-called subclinical rejection (SCR). METHODS: Traditionally, rejection has been diagnosed by changes in clinical parameters, including but not limited to serum creatinine and proteinuria. This review examines the shortcomings of this approach, the effects of SCR on kidney allograft outcome, the benefits and drawbacks of surveillance biopsies to identify SCR, and new urine and blood biomarkers that define the presence or absence of SCR. RESULTS: Serum creatinine is an unreliable index of SCR. Surveillance biopsies are the method most utilized to detect SCR. However, these have significant drawbacks. New biomarkers show promise. These biomarkers include blood gene expression profiles and donor derived-cell free DNA; urine gene expression profiles; urinary cytokines, chemokines, and metabolomics; and other promising blood and urine tests. CONCLUSION: Specific emphasis is placed on studies carried out in pediatric kidney transplant recipients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03719339.

Tailored portable electrochemical sensor for dopamine detection in human fluids using heteroatom-doped three-dimensional g-C3N4 hornet nest structure.

BACKGROUND: There is widespread interest in the design of portable electrochemical sensors for the selective monitoring of biomolecules. Dopamine (DA) is one of the neurotransmitter molecules that play a key role in the monitoring of some neuronal disorders such as Alzheimer's and Parkinson's diseases. Facile synthesis of the highly active surface interface to design a portable electrochemical sensor for the sensitive and selective monitoring of biomolecules (i.e., DA) in its resources such as human fluids is highly required. RESULTS: The designed sensor is based on a three-dimensional phosphorous and sulfur resembling a g-C3N4 hornet's nest (3D-PS-doped CNHN). The morphological structure of 3D-PS-doped CNHN features multi-open gates and numerous vacant voids, presenting a novel design reminiscent of a hornet's nest. The outer surface exhibits a heterogeneous structure with a wave orientation and rough surface texture. Each gate structure takes on a hexagonal shape with a wall size of approximately 100 nm. These structural characteristics, including high surface area and hierarchical design, facilitate the diffusion of electrolytes and enhance the binding and high loading of DA molecules on both inner and outer surfaces. The multifunctional nature of g-C3N4, incorporating phosphorous and sulfur atoms, contributes to a versatile surface that improves DA binding. Additionally, the phosphate and sulfate groups' functionalities enhance sensing properties, thereby outlining selectivity. The resulting portable 3D-PS-doped CNHN sensor demonstrates high sensitivity with a low limit of detection (7.8 nM) and a broad linear range spanning from 10 to 500 nM. SIGNIFICANCE: The portable DA sensor based on the 3D-PS-doped CNHN/SPCE exhibits excellent recovery of DA molecules in human fluids, such as human serum and urine samples, demonstrating high stability and good reproducibility. The designed portable DA sensor could find utility in the detection of DA in clinical samples, showcasing its potential for practical applications in medical settings.

Ultrasound probe enhanced enzymatic hydrolysis for rapid separation of ß2-adrenergic agonists from animal urine and livestock wastewater: Applicability to biomonitoring investigation.

BACKGROUND: An increasing number of ß2-adrenergic agonists are illicitly used for growth promoting and lean meat increasing in animal husbandry in recent years, but the development of analytical methods has lagged behind these emerging drugs. RESULTS: Here, we designed and developed an ultrasound probe enhanced enzymatic hydrolysis reactor for quick separation and simultaneously quantification of 22 ß2-adrenergic agonists in animal urine and livestock wastewater. Owing to the enhancement of the conventional enzymatic digestion through the ultrasound acoustic probe power, only 2 min was required for the comprehensively separation of ß2-adrenergic agonists from the sample matrices, making it a much more desirable alternative tool for high-throughput investigation. The swine, bovine and sheep urines (n = 287), and livestock wastewater (n = 15) samples, collected from both the north and south China, were examined to demonstrate the feasibility and capability of the proposed approach. Six kinds of ß2-adrenergic agonists (clenbuterol, salbutamol, ractopamine, terbutaline, clorprenaline and cimaterol) were found in animal urines, with concentrations ranged between 0.056 µg/L (terbutaline) and 5.79 µg/L (clenbuterol). Up to nine ß2-adrenergic agonists were detected in wastewater samples, of which four were found in swine farms and nine in cattle/sheep farms, with concentration levels from 0.069 µg/L (tulobuterol) to 2470 µg/L (clenbuterol). SIGNIFICANCE: Interestingly, since ß2-adrenergic agonists are usually considered to be abused mainly in the pig farms, our data indicate that both the detection frequencies and concentrations of these agonists in the ruminant farms were higher than the pig farms. Furthermore, the findings of this work indicated that there is a widespread occurrence of ß2-adrenergic agonists in livestock farms, especially for clenbuterol and salbutamol, which may pose both food safety and potential ecological risks. We recommend that stricter controls should be adopted to prevent the illegally usage of these ß2-adrenergic agonists in agricultural animals, especially ruminants, and they should also be removed before discharging to the environment.

Proteomics and metabolomics analyses of urine for investigation of gallstone disease in a high-altitude area.

BACKGROUND: The incidence of gallstones is high in Qinghai Province. However, the molecular mechanisms underlying the development of gallstones remain unclear. METHODS: In this study, we collected urine samples from 30 patients with gallstones and 30 healthy controls. The urine samples were analysed using multi-omics platforms. Proteomics analysis was conducted using data-independent acquisition, whereas metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Among the patients with gallstones, we identified 49 down-regulated and 185 up-regulated differentially expressed proteins as well as 195 up-regulated and 189 down-regulated differentially expressed metabolites. Six pathways were significantly enriched: glycosaminoglycan degradation, arginine and proline metabolism, histidine metabolism, pantothenate and coenzyme A biosynthesis, drug metabolism-other enzymes, and the pentose phosphate pathway. Notably, 10 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION: The findings of our metabolomics and proteomics analyses provide new insights into novel biomarkers for patients with cholelithiasis in high-altitude areas.

Variability of urinary albumin to creatinine ratio and eGFR are independently associated with eGFR slope in Japanese with type 2 diabetes: a three-year, single-center, retrospective cohort study.

BACKGROUND: To evaluate the seasonal variability of urinary albumin to creatinine ratio (UACR) and eGFR and these effects on three-year eGFR slope in persons with type 2 diabetes (T2D). METHODS: A total of 1135 persons with T2D were analyzed in this single-center, retrospective cohort study in Japan. The standard deviation (SD) of UACR (SD [UACR]) and SD of eGFR (SD [eGFR]) were calculated for each person's 10-point data during the three years, and a multiple linear regression analysis was performed to evaluate associations with eGFR slope. A sensitivity analysis was performed in a group with no medication changes (n = 801). RESULTS: UACR exhibited seasonal variability, being higher in winter and lower in spring, early summer, and autumn especially in the UACR ≥ 30 mg/g subgroup, while eGFR showed no seasonal variability. The eGFR slope was significantly associated with SD (eGFR) (regression coefficient -0.170 [95% CI -0.189--0.151]) and SD (UACR) (0.000 [-0.001-0.000]). SGLT-2 inhibitors, baseline eGFR, and baseline systolic blood pressure (SBP) were also significantly associated. These associated factors, except baseline SBP, were still significant in the sensitivity analysis. CONCLUSIONS: The UACR showed clear seasonal variability. Moreover, SD (UACR) and SD (eGFR) were independently associated with a three-year eGFR slope in persons with T2D. TRIAL REGISTRATION: This study was not registered for clinical trial registration because it was a retrospective observational study.

Mitochondrial HMG-CoA Synthase Deficiency: A Cyclic Vomiting Mimic Without Reliable Biochemical Markers.

Here, we report an individual, eventually diagnosed with HMG-CoA synthase deficiency, who presented with a cyclic vomiting phenotype. HMG-CoA synthase deficiency is a rare disorder affecting ketone body synthesis in which affected individuals typically present at a young age with hypoketotic hypoglycemia, lethargy, encephalopathy, and hepatomegaly, usually triggered by catabolism (e.g., infection or prolonged fasting). This individual presented with recurrent episodes of vomiting and lethargy, often associated with hypoglycemia or hyperglycemia, at 3 years of age. Metabolic labs revealed nonspecific abnormalities in her urine organic acids (showing mild elevation of dicarboxylic acids with relatively low excretion of ketones) and a normal acylcarnitine profile. Given her clinical presentation, as well as a normal upper gastrointestinal series, esophagogastroduodenoscopy with biopsies, and abdominal ultrasound, she was diagnosed with cyclic vomiting syndrome at 3 years of age. Molecular testing completed at 7 years of age revealed a previously reported pathogenic sequence variant (c.1016+1G>A) and a novel likely pathogenic deletion (1.57 kB deletion, including exon 1) within HMGCS2 consistent with HMG-CoA synthase deficiency. This individual's presentation, mimicking cyclic vomiting syndrome, widens the clinical spectrum of HMG-CoA synthase deficiency. In addition, this case highlights the importance of molecular genetic testing in such presentations, as this rare disorder lacks specific metabolic markers.

Are Metal Ion Levels Elevated After Dual Mobility Acetabular Systems Minimum Five-Year Analysis.

INTRODUCTION: Dual mobility acetabular systems for total hip arthroplasty (THA) have been shown to have decreased dislocation rates and reduced revision rates, but there is controversy over the potential release of sufficient levels of metal ions into the blood to cause adverse local tissue reactions. However, there is a lack of long-term studies analyzing these levels of cobalt and chromium. Therefore, the purpose of this study was to investigate the levels these metal ions at a minimum 5-year follow-up after dual mobility implantation. Specifically, we analyzed: 1. overall blood and urine cobalt levels; 2. overall blood and urine chromium levels; 3. cobalt levels stratified by length of follow-up and various implant-related metrics (i.e., offset, cup size, stem, and neck angle); as well as 4. chromium levels stratified by length of follow-up and these various implant-related metrics. METHODS: A total of 41 patients who underwent THA with modular dual mobility acetabular systems between January 1, 2011, and December 31, 2016, were identified and followed for a mean time of 6 years (range: 5 to 10 years). All patients had well-functioning hips (Harris Hip Scores greater than 90 points (range: 90 to 100 points) and had no evidence of impending radiographic failure or progressive radiolucencies. Cobalt and chromium serum and plasma, blood, as well as urine levels were obtained at final followup. Additional parameters analyzed included: head material and size, stem offset, cup size, as well as stem-neck angle. RESULTS: Concentrations of cobalt were low as the mean blood and urine levels for all patients were 0.6 ± 0.5 µg/L (normal < 1.8 µg/L) and 0.8 ± 0.8 µg/L (normal < 2.8 µg/L), respectively. Only one patient had a minimally elevated blood cobalt level by 0.1 µg/L. These levels were not substantially different when subgroup analyses were performed for ceramic and cobalt-chrome heads. The mean chromium levels in blood and urine were also found to be low for all patients as values were 0.8 ± 0.2 µg/L (normal: < 1.2 µg/L) and 1.2 ± 0.5 ng/milliliter (normal: < 2 ng/L), respectively. Similarly, only one patient had a very slightly elevated blood chromium level of 1.3 µg/L. Additionally, analyses of ceramic or cobalt-chrome heads separately did not demonstrate differences in blood or urine levels. Blood cobalt or chromium concentrations had minimal changes with longer lengths of follow-ups, and with different stem offsets, cup sizes, stems, or neck angles. CONCLUSION: Dual mobility acetabular systems when combined with the two stems studied produced low levels of blood as well as urine cobalt and chromium levels at a minimum follow-up of 5 years (mean: 6 years; range: 5 to 10 years). These results remained below the threshold of normal and clinically insignificant regardless of length of follow-up, head material, or various implant measurements. To the best of our knowledge, this is the first study to demonstrate low levels of metal ions at longer than 4-year follow-up. These data may be of importance to surgeons deciding on the appropriate implants to use for their high-risk patients.

Biodetection of an odor signature in white-tailed deer associated with infection by chronic wasting disease prions.

Chronic wasting disease (CWD) has become a major concern among those involved in managing wild and captive cervid populations. CWD is a fatal, highly transmissible spongiform encephalopathy caused by an abnormally folded protein, called a prion. Prions are present in a number of tissues, including feces and urine in CWD infected animals, suggesting multiple modes of transmission, including animal-to-animal, environmental, and by fomite. CWD management is complicated by the lack of practical, non-invasive, live-animal screening tests. Recently, there has been a focus on how the volatile odors of feces and urine can be used to discriminate between infected and noninfected animals in several different species. Such a tool may prove useful in identifying potentially infected live animals, carcasses, urine, feces, and contaminated environments. Toward this goal, dogs were trained to detect and discriminate CWD infected individuals from non-infected deer in a laboratory setting. Dogs were tested with novel panels of fecal samples demonstrating the dogs' ability to generalize a learned odor profile to novel odor samples based on infection status. Additionally, dogs were transitioned from alerting to fecal samples to an odor profile that consisted of CWD infection status with a different odor background using different sections of gastrointestinal tracts. These results indicated that canine biodetectors can discriminate the specific odors emitted from the feces of non-infected versus CWD infected white-tailed deer as well as generalizing the learned response to other tissues collected from infected individuals. These findings suggest that the health status of wild and farmed cervids can be evaluated non-invasively for CWD infection via monitoring of volatile metabolites thereby providing an effective tool for rapid CWD surveillance.

Neutrophil-percentage-to-albumin ratio is associated with chronic kidney disease: Evidence from NHANES 2009-2018.

INTRODUCTION: The neutrophil-percentage-to-albumin ratio (NPAR), a novel inflammatory biomarker, has been used to predict the prognosis of patients with cancer and cardiovascular disease. However, the relationship between NPAR and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible association between NPAR and CKD. METHODS: The cross-sectional study included participants with complete information on NPAR, serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear associations between NPAR and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest. RESULTS: A total of 25,236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.19 (95% CI = 1.07-1.31, p <0.05) for the Q2 group, 1.53 (95% CI = 1.39-1.69, p < 0.001) for the Q3 group, and 2.78 (95% CI = 2.53-3.05, p < 0.001) for the Q4 group. There was a significant interaction between age and diabetes mellitus on the association between NPAR and CKD (both p for interaction < 0.05). And there was a non-linear association between NPAR levels and CKD in the whole population (p for non-linear < 0.001). All sensitivity analyses supported the positive association between NPAR and CKD. CONCLUSIONS: NPAR was positively correlated with increased risk of CKD. The NPAR may serve as an available and cost-effective tool for identifying and intervening the individuals at risk of CKD.

Rapid nanomolar detection of cocaine in biofluids by electrochemical aptamer-based sensor with low-temperature effect for drugged driving screening.

Cocaine is one of the most abused illicit drugs, and its abuse damages the central nervous system and can even lead directly to death. Therefore, the development of simple, rapid and highly sensitive detection methods is crucial for the prevention and control of drug abuse, traffic accidents and crime. In this work, an electrochemical aptamer-based (EAB) sensor based on the low-temperature enhancement effect was developed for the direct determination of cocaine in bio-samples. The signal gain of the sensor at 10 °C was greatly improved compared to room temperature, owing to the improved affinity between the aptamer and the target. Additionally, the electroactive area of the gold electrode used to fabricate the EAB sensor was increased 20 times by a simple electrochemical roughening method. The porous electrode possesses more efficient electron transfer and better antifouling properties after roughening. These improvements enabled the sensor to achieve rapid detection of cocaine in complex bio-samples. The low detection limits (LOD) of cocaine in undiluted urine, 50% serum and 50% saliva were 70 nM, 30 nM and 10 nM, respectively, which are below the concentration threshold in drugged driving screening. The aptasensor was simple to construct and reusable, which offers potential for drugged driving screening in the real world.

Caffeine and Ovariectomy Debilitate Bone Health in Rats on Calcium-deficient Diet.

This study investigated the effects of ovariectomy and caffeine intake on bone health in rats on calcium-deficient diet. Forty adults female Wistar rats were divided into 4 groups in a 2x2 factorial design: Ovary (OVX/SHAM) and Caffeine (placebo/caffeine). The animals were housed in individual cages for 8 weeks, receiving 18-20g of AIN-93M diet per day, containing 50% of the daily recommended intake of calcium. The rats underwent ovariectomy (OVX) or laparotomy (SHAM) surgery. Caffeine groups received 6mg of caffeine/kg/day. After euthanasia, the tibia and femur were dissected to determine the calcium content and bone fracture strength, respectively. Blood sample was collected to determine serum Ostase. 24-hour urine was analyzed for excreted calcium and NTx. Reduced bone fracture strength and calcium content were observed in OVX and Caffeine groups. When observed separately, OVX group showed increased urinary NTx and lower bone weight, blood ostase, and urinary calcium. Caffeine groups showed elevated urinary calcium. There was a positive correlation between bone fracture strength and calcium content. NTx correlated negatively with bone calcium, fracture strength and thickness. In conclusion, both OVX and caffeine intake debilitate bone health in rats on calcium-deficient diet.